Introduction: Acute pyelonephritis (APN) is a serious bacterial infection requiring hospitalization during childhood. This study investigated whether hospitalization for APN is associated with increased subsequent autoimmune disease risk. Methods: In this nationwide, population-based retrospective cohort study using the Korean National Health Insurance Service database, we included children born between 2002 and 2005. Children hospitalized for APN (identified by inpatient ICD-10 codes) were matched by birth year and sex to controls without APN. Clinical data including microbiological outcomes were unavailable. The primary outcome was incident autoimmune disease after a 1-year lag period. Results: The study included 31,856 children with APN and 318,560 matched controls. Autoimmune disease incidence was 98.35 and 59.91 per 10,000 person-years, respectively. APN was associated with increased risk, with heterogeneity across diseases; the strongest association was for IgA nephropathy (aHR 2.14; 95% CI 1.92–2.29). Risks were elevated for autoimmune thyroiditis, Behçet disease, and acute disseminated encephalomyelitis. Recurrent APN carried higher risk than a single episode. Conclusions: Hospitalization for childhood APN was associated with increased autoimmune disease risk through early adolescence. The stronger association with recurrence suggests a dose–response relationship. However, exposure misclassification, unmeasured urinary tract anomalies, and antibiotic-related microbiome effects limit causal inference.
Brucella infections are associated with gestational complications in both humans and animals, including spontaneous abortion, premature delivery, and infertility. Successful pregnancy requires the proper invasion and functional integrity of extravillous trophoblasts (EVTs), specialized fetal cells that remodel the maternal decidua. However, the direct impact of the major human-pathogenic species on human EVT biology remains incompletely characterized. Here, we investigated in vitro the effects of B. abortus, B. melitensis, and B. suis infections on the fitness of a human EVT cell line (Swan71). Infection with all three species induced a proinflammatory profile in EVT, with increased CXCL8, CCL2 and IL-6 production. Infection markedly impaired EVT migration (wound closure) and reduced EVT invasive capacity in a matrix invasion assay. EVT tubulogenesis was affected by the infection, with all the species reducing master segments and B. suis and B. melitensis additionally reducing master junctions and meshes. Blastocyst-like spheroids derived from infected EVTs showed reduced outgrowth on decidualized endometrial cell monolayers, with B. suis exhibiting the most consistent effect. Antiproliferative effects were observed at 24 h for B. abortus and B. suis and at 48 h for B. melitensis, preceding marked cell death (late apoptotic features became pronounced only at 72 h post-infection). Collectively, our findings demonstrate that major human-pathogenic Brucella species induce an early dysfunctional state in human EVTs, affecting cellular processes involved in implantation and placental vascular remodeling.
Klebsiella oxytoca is an emerging opportunistic pathogen capable of causing bovine mastitis and neonatal colonization. This study provides a comprehensive molecular and phenotypic characterization of K. oxytoca across dairy supply nodes and pediatric host matrices while evaluating a probiotic-based bio-intervention strategy. K. oxytoca was isolated from 27.9% (39/140) of examined samples across dairy supply nodes and infant stool in Egypt, with equal peak prevalence in clinical mastitic milk (40.0%, 8/20) and infant fecal specimens (40.0%, 8/20). High rates of multidrug resistance (MDR; 66.7%, 26/39) were observed, with all isolates (100%) confirmed as extended-spectrum β-lactamase (ESBL) producers. Colistin (CT) and azithromycin resistance reached 46.2% (18/39) overall, peaking in commercial milk (69.2% for CT). Molecular screening revealed high frequencies of the mobile colistin resistance gene mcr-1 (41.0%, 16/39) and the ESBL determinant blaCTX-M (66.7%, 26/39), alongside fimbrial adhesion (mrkA, 76.9%) and iron acquisition (kfuBC, 82.1%) loci. All isolates (100%) exhibited strong biofilm-forming capacity (mean OD570 = 0.63 ± 0.016), while toxin-antitoxin (TA) modules (symE, ccdB, relE) correlated positively with MDR profiles (p = 0.024). Bacterial virulence gene burden showed strong statistical associations with host tissue damage and inflammatory markers, including elevated milk lactate dehydrogenase (LDH; r = 0.918), haptoglobin (r = 0.954), and neonatal fecal calprotectin (FC; 83.34 ± 21.13 μg/g vs. 22.4 ± 2.0 μg/g in controls, p = 0.02). Crucially, milk-based cell-free metabolic supernatant (CFS) from Lactobacillus acidophilus demonstrated superior antagonistic activity compared to broth-based CFS (inhibition zones up to 40 mm vs. 12 mm against CT-resistant isolates). In silico molecular docking predicted strong binding affinities of putative L. acidophilus bioactive peptides (Acidocin 8912 score: −108.07 kcal/mol; Acidocin B score: 80.63 kcal/mol) to K. oxytoca outer membrane porin CymA and transport targets. These findings highlight the co-occurrence of resilient K. oxytoca lineages across food and pediatric matrices and demonstrate the therapeutic potential of probiotic-derived CFS as a non-antibiotic control strategy within a One Health framework.
Porcine circovirus type 3 (PCV3) is an emerging circovirus detected worldwide in pigs with and without clinical disease, including reproductive and systemic disorders. However, baseline information on PCV3 exposure in Philippine swine populations remains limited. A cross-sectional serosurvey was conducted in selected provinces of Central Luzon, Philippines, from May to June 2025. A total of 337 serum samples from slaughter pigs were tested using an indirect enzyme-linked immunosorbent assay based on recombinant PCV3 open reading frame 2 (ORF2) capsid antigen. Samples with sample-to-positive (S/P) ratios ≥ 0.5 were classified as seropositive. Overall, 143 of 337 pigs were seropositive, corresponding to an apparent seroprevalence of 42.4% (95% confidence interval [CI]: 37.1–47.9%). Province-level apparent seroprevalence was 46.1% in Bulacan, 38.0% in Nueva Ecija, and 42.2% in Pampanga, with no significant difference among provinces (p = 0.470). However, seroprevalence differed significantly between slaughterhouses in Bulacan (66.1% in Malolos versus 27.3% in Meycauayan; p < 0.0001). These findings provide the first serological evidence of PCV3 exposure in slaughter pigs from selected provinces of Central Luzon. Because molecular testing was not performed, the results should be interpreted as evidence of an antibody response to PCV3 rather than confirmation of active infection. Expanded surveillance integrating serology, qPCR, sequencing, farm-level epidemiological data, and clinicopathological investigations is warranted.
Sepsis is characterized by a dysregulated immune response, and hemogram-derived inflammatory indices have emerged as potential complementary biomarkers of disease severity and prognosis. However, their longitudinal behavior and clinical relevance during sepsis remain poorly characterized in people living with HIV (PLWH). This longitudinal retrospective study included PLWH with sepsis and three comparison groups: PLWH with comorbidities, PLWH without comorbidities, and HIV-negative controls. Hemogram-derived inflammatory indices and clinical severity scores were evaluated at sepsis diagnosis and on days 3 and 7. Longitudinal comparisons, correlations, ROC, Kaplan–Meier, and regression analyses were performed. Among the 22 patients with complete serial measurements through day 7, hemogram-derived inflammatory indices exhibited distinct temporal patterns, whereas cross-sectional analyses at days 0, 3, and 7 were influenced by progressively selected survivor subsets. Lower SII was associated with a shorter time from sepsis diagnosis to death. Component-level analyses showed that low SII predominantly reflected thrombocytopenia and reduced circulating neutrophils, with platelet count accounting for a substantial proportion of the time-to-death information captured by SII. Thus, the clinical meaning of SII depends not only on its absolute value but also on the hematological phenotype underlying it. As a low-cost and widely accessible index, SII warrants further evaluation as a complementary marker of hematological vulnerability in PLWH with sepsis.
