Search Results (717)

This study describes extracellular vesicles (EVs) isolated from the culture supernatant of a Kluyveromyces marxianus strain deriving from an artisanal sourdough. Previous work had clearly shown the probiotic properties of the yeast isolate and its antagonistic activities against clinical fluconazole-resistant Candida albicans strains. Characterization of the isolated EVs by nanotracking particle analysis showed they had a mean diameter of 157.7 nm. Proteomic characterization of the purified EVs identified a complex array of 100 proteins. Both C. albicans planktonic growth and biofilm formation were inhibited by K. marxianus EVs, as well as adhesion and invasion of Candida cells in the vaginal epithelial A-431 cells. In the same cell model, K. marxianus EVs exerted an immunomodulatory effect affecting the secretion of pro-inflammatory and anti-inflammatory cytokines. Further, the expression of C. albicans SAP2 and SAP6 genes, coding for two aspartyl proteases involved in the invasion and damage of the epithelial mucosa, was affected by the presence of the yeast EVs. Overall, the results of this study show that K. marxianus EVs retain, at least in part, the beneficial features of the live microorganism, representing a postbiotic cell-free alternative preparation potentially useful for the management of C. albicans vaginal infections. Full article

Background: Aerobic vaginitis (AV) is characterized by dysbiotic vaginal microflora with overgrowth of aerobic pathogens of enteric origin, presence of vaginal inflammation and immature epithelial cells. This study aimed to evaluate, over a period of 10 years, women of reproductive age (non-pregnant and pregnant) as well as menopausal women affected by AV. Methods: We included non-pregnant, pregnant and menopausal women diagnosed with AV over a period of 10 years. Diagnosis of AV was determined according to the criteria proposed by Donders in 2002. The isolated pathogens were identified with the rapid identification system I-dOne (Alifax S.r.l, Polverara, Italy) and the automated system VITEK2 (Biomerieux, Marcy l’Etoile, France), which was used for antimicrobial susceptibility testing. Results: The overall aerobic vaginitis prevalence rate during the studied period was 9.5%. The most common isolated pathogens were Escherichia coli 27.3%, Enterococcus faecalis 25.0%, Streptococcus agalactiae 22.2%, Klebsiella pneumoniae 8.9%, Proteus spp 4.7%, and Staphylococcus aureus 3.5%. E. coli infection significantly increased the odds of mild AV by 1.65 times (p = 0.002) and Proteus species infection was over 6 times more likely to progress to severe disease (p < 0.001). Furthermore, pregnant women were more likely to be infected with E. faecalis (p < 0.001) while menopausal women were diagnosed significantly more with severe AV (p < 0.001) compared to the other groups. Conclusions: The prevalence of aerobic vaginitis in the population studied was in concordance with global rates. Menopausal women displayed increased severe AV cases while, in contrast, mild cases were recorded during pregnancy. The most commonly isolated pathogens were of enteric origin. Full article

Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the persistent burden of HPV-related disease. In recent years, increasing attention has focused on molecular biomarkers and the vaginal microbiome as complementary approaches for improving cervical cancer prevention strategies. This systematic review aimed to evaluate recent evidence regarding HPV genotype distribution, molecular biomarkers, vaginal microbiome composition, and their implications for cervical cancer prevention in Eastern Europe. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library for studies published between January 2020 and May 2026. This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261391136). Studies from Eastern European populations reporting data on HPV genotype distribution, screening strategies, vaccination, molecular biomarkers, or vaginal microbiome composition were included. HPV prevalence in screening populations ranged from approximately 12% to over 20%, with HPV16 consistently identified as the predominant genotype across all included studies. However, non-16/18 high-risk genotypes, particularly HPV31, HPV51, HPV52, HPV66, and HPV68, represented a substantial proportion of infections in several Eastern European cohorts. Studies evaluating CINtec PLUS cytology and HPV E6/E7 mRNA testing demonstrated improved specificity for identifying clinically significant cervical lesions compared with HPV DNA testing alone. Emerging evidence also suggested associations between vaginal dysbiosis, increased microbial diversity, persistent high-risk HPV infection, and progression to cervical intraepithelial neoplasia. Although the 9-valent HPV vaccine provides coverage for most circulating high-risk genotypes identified in the region, vaccination uptake remains inconsistent throughout Eastern Europe. The findings of this systematic review support the growing importance of extended HPV genotyping, molecular biomarkers, and microbiome-related approaches in cervical cancer prevention strategies in Eastern Europe. Strengthening organized screening programs, expanding vaccination coverage, and improving access to molecular diagnostic technologies remain essential priorities for reducing the regional burden of HPV-related disease. Full article

During pregnancy, hormonal, metabolic, and immunological changes influence the composition and function of maternal microbial communities. Increasing evidence suggests that the maternal microbiota—particularly in the vaginal, gut, and oral environments—plays a significant role in maintaining pregnancy homeostasis and supporting fetal development. In healthy pregnancies, the vaginal microbiota is typically dominated by Lactobacillus species, which help maintain a low vaginal pH and protect against ascending infections. However, disruption of this balance (vaginal dysbiosis) has been associated with obstetrical complications such as intrauterine infection and preterm birth. Similarly, the maternal gut microbiota undergoes trimester-specific changes that contribute to metabolic adaptations required for fetal growth, while alterations in microbial composition have been linked to metabolic disorders including gestational diabetes mellitus and preeclampsia. Changes in oral microbiota and periodontal disease have also been associated with adverse pregnancy outcomes through systemic inflammatory pathways and potential microbial translocation to the placenta. Recent advances in sequencing technologies have improved the understanding of host–microbiome interactions in pregnancy, although the existence of a placental microbiome remains controversial. Overall, maternal microbiota plays an important role in pregnancy physiology, and its dysregulation may contribute to obstetrical complications. Understanding these mechanisms may facilitate the development of microbiome-based diagnostic and therapeutic strategies in maternal–fetal medicine. Full article

Background/Objectives: This study aimed to evaluate the association between the clinical parameters of vaginal infection—specifically the presence, type, number of concurrent symptoms, and recurrence frequency—and cervical cytology findings, including inflammation severity, Candida, bacterial vaginosis, cellular abnormalities, and Human Papillomavirus (HPV) positivity. Methods: This prospective, cross-sectional, observational study included 458 women attending our gynecology outpatient clinic for Pap smear screening. Vaginal symptoms were documented through face-to-face interviews using a structured data collection form. Cervical samples were evaluated via liquid-based cytology by a single, experienced cytopathologist, who was blinded to the clinical data; cellular abnormalities, the degree of inflammation and cytomorphological findings indicative of infection were reported. HPV analysis was performed on the 218 women for whom results were available. Chi-square and trend chi-square tests were used in the statistical analysis. Results: No significant association was found between the clinical parameters of vaginal symptoms—specifically presence, concurrency, and recurrence frequency—and cytological abnormalities, HPV positivity and bacterial vaginosis (p > 0.05). In contrast, the prevalence of moderate-to-severe inflammation was significantly higher in women with vaginal discharge and a greater symptom burden (p < 0.05). Pruritus, dysuria, and vaginal burning were significantly associated with Candida positivity (p < 0.05). However, no significant association was found between the severity of cervical inflammation and abnormal cytology or HPV positivity (p > 0.05). In multivariable logistic regression analyses, neither symptom burden nor cervical inflammation severity was independently associated with abnormal cytology or HPV positivity. Conclusions: Our findings indicate that vaginal symptoms and the severity of cervical inflammation may not serve as definitive or independent discriminatory markers for cellular abnormalities or HPV positivity in this context. Nevertheless, specific symptom patterns may assist clinicians in evaluating localized infectious processes. Consequently, while standard cytological and molecular protocols remain essential for oncogenic screening, evaluating the overall symptom burden provides clinicians with a valuable framework for identifying benign dysbiotic and inflammatory processes. These findings remained consistent after adjustment for major clinical confounders. Full article

Vulvovaginal candidiasis (VVC) is a common fungal infection among reproductive-age women and is increasingly challenged by the emergence of non-albicans Candida species and reduced azole susceptibility. This prospective cross-sectional study investigated 235 symptomatic reproductive-age women attending two healthcare facilities in Ho Chi Minh City, Vietnam, to determine VVC prevalence, Candida species distribution, pregnancy-associated patterns, antifungal susceptibility, and diagnostic performance. Vaginal swabs were cultured on Sabouraud Dextrose Agar and CHROMagar™ Candida, while species identification was confirmed by PCR-RFLP targeting the ITS region. Susceptibility to fluconazole and clotrimazole was assessed using the disk diffusion method. Candida spp. was detected in 55.7% of participants. C. albicans accounted for 50.3% of isolates, whereas non-albicans Candida species represented 49.7%, indicating a substantial species shift. VVC was more frequent among pregnant women, particularly in the third trimester. Most C. albicans, C. tropicalis, and C. parapsilosis isolates remained susceptible to azoles; however, C. glabrata showed markedly reduced susceptibility to fluconazole and clotrimazole. CHROMagar™ Candida reliably identified C. albicans but misclassified several non-albicans Candida isolates compared with PCR-RFLP. These findings highlight the need for routine species-level diagnosis, antifungal susceptibility testing, and strengthened VVC surveillance in reproductive and antenatal healthcare settings in Vietnam. Full article

Dairy cows are frequently affected by postpartum uterine infections, such as metritis and endometritis, which negatively impact fertility and cause significant economic losses. The extensive use of antibiotics may alter the reproductive microbiota and contribute to the emergence of antibiotic resistance. This study aimed to isolate lactic acid bacteria (LAB) from healthy vaginal samples of cows and evaluate their antimicrobial activity against uterine pathogens such as Escherichia coli and Salmonella spp. Phenotypic characterization and antibiotic susceptibility testing were performed, along with antagonistic assays using both overlay and well diffusion methods. The results demonstrated strain-dependent inhibitory activity against E. coli, with inhibition zones ranging from 2 to 4 mm depending on the LAB strain and the method used, whereas no inhibitory activity was observed against Salmonella. These findings support the potential application of selected LAB strains in bovine reproductive health management. However, further in vitro and in vivo studies are required to confirm their efficacy, safety, and stability under physiological conditions. Full article

Objectives: Recurrent vulvovaginal candidiasis (RVVC) is a difficult-to-treat infection, most likely due to the growth of Candida biofilms on the human vaginal epithelium. We assessed in vitro efficacy of conventional antifungals and complementary and alternative medicine (CAM) used in clinical settings, and sought for Candida biofilm-effective single or combination therapies. Methods: Standard broth microdilution assay and XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay were used for antifungal and anti-biofilm efficacies of three conventional antifungals, and selected CAM including boric acid, povidone-iodine, and allicin (garlic extract), against Candida clinical isolates grown at neutral and acidic pHs respectively. Fractional inhibitory concentration (FIC) indices were assessed to evaluate interactions between fluconazole and different CAM. Viable count-based cell enumeration and confocal laser scanning microscopy (CLSM) were performed to confirm the efficacy of single or combination therapies against Candida biofilms. Results: All selected conventional antifungals and CAM showed efficacies against planktonic Candida cells. Acidic vaginal microenvironments provided agent-specific protection to Candida cells against conventional antifungals and the CAM. Synergistic or additive interactions were observed between fluconazole at serum achievable concentrations and povidone-iodide at topically achievable concentrations against all tested Candida strains. Most antifungal agents except caspofungin had very limited activities against Candida biofilms. Combining fluconazole at 8 mg/L with povidone-iodine at 2048 mg/L effectively killed Candida biofilms in an acidic vaginal microenvironment to a level that is comparable to that of caspofungin. Conclusions: We provided robust in vitro evidence supporting the combinational use of oral fluconazole and topical CAM povidone-iodine against Candida biofilms in managing RVVC. Full article

Background/Objectives: Trichomonas vaginalis is one of the most prevalent non-viral sexually transmitted infections worldwide. Although Gram staining is routinely performed in clinical microbiology laboratories for the evaluation of vaginal samples, it is not considered a diagnostic method for T. vaginalis, which represents a missed diagnostic opportunity in routine practice. This study aimed to evaluate an artificial intelligence (AI)-assisted diagnostic approach for the identification of T. vaginalis directly from routine Gram-stained vaginal smears. Methods: A retrospective dataset of Gram-stained vaginal smear images was analysed using a cascaded AI-based framework combining image processing and classification. The image selection and quality control were performed under the supervision of a specialised clinical microbiologist. All cases were independently confirmed by polymerase chain reaction (PCR), which served as the reference diagnostic standard. Model performance was assessed using standard diagnostic metrics, including accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), Cohen’s kappa, and Matthews correlation coefficient (MCC). Held-out independent testing was used to assess generalisability beyond the internal validation subset. Results: The proposed AI-assisted approach demonstrated high diagnostic performance for the identification of T. vaginalis, achieving an AUC of 0.973, Cohen’s kappa of 0.87, and an MCC of 0.87. The system showed high diagnostic concordance with PCR results across both internal and external validation datasets, supporting the feasibility and reproducibility of the approach under routine laboratory conditions. Conclusions: This study shows that artificial intelligence may enhance the diagnostic utility of routinely performed Gram-stained vaginal smears by enabling reliable identification of T. vaginalis. The proposed approach could be integrated into standard microbiology workflows as an objective decision-support or triage adjunct, facilitating early identification and supporting clinical decision-making without altering existing laboratory procedures. Full article

Background/Objectives: Adolescent pregnancy, defined as pregnancy occurring between ages 10 and 19, remains a pressing global health concern with significant disparities in prevalence and outcomes across countries. Early and systematic diagnostic screening may allow timely risk stratification and adequate management. Methods: We conducted this retrospective cohort study at a tertiary referral center from January 2015 through December 2024, including all women who delivered live fetuses at our facility, analyzing adolescent pregnancy outcomes in our region and comparing them with adult pregnancy outcomes. Results: Younger adolescents have higher rates of vaginal infections (45.3% vs. 38.1%), chorioamnionitis, urinary tract infections (6% vs. 4.9%), preterm birth, higher cesarean section rates, SGA and FGR fetuses, with more frequent NICU admissions than older adolescents. Adolescent pregnancies more often resulted in vaginal births compared to adult pregnancies but also showed higher rates of operative vaginal delivery, episiotomy, perineal tears, vaginal tears, and cervical lacerations. Gestational diabetes and excessive gestational weight gain were overall less common in adolescents, but pre-pregnancy maternal obesity was significantly more prevalent in the older adolescent group than in the younger ones. Gestational hypertension was about twice as frequent in adult pregnancies, while HELLP syndrome was approximately six times more common in adults than in adolescents. Conclusions: In summary, adolescent pregnancy presents both potential biological advantages and notable disadvantages, with outcomes resulting from the complex interplay of biological immaturity and socioeconomic factors. These results highlight the critical importance of implementing comprehensive early diagnostic screening protocols and structured antenatal care to facilitate earlier identification and mitigation of modifiable risk factors to improve both maternal and fetal outcomes. Full article

Background and Clinical Significance: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Among its various etiologies, uterine atony accounts for approximately 70% of cases, while other causes include genital tract trauma, pathologic placentation, and intrapelvic arterial injury. Uterine artery embolization (UAE) has emerged as a preferred management option for severe PPH due to its high success rates of 89–98% and fertility preservation benefit. Despite its efficacy, UAE can lead to complications, such as pain, re-bleeding, infection, persistent vaginal discharge, ovarian insufficiency, and uterine necrosis—a rare but serious complication occurring in 1.4–2.7% of cases. Case Presentation: We present three cases of uterine necrosis following UAE from a single center (CHA Bundang Medical Center) between 2003 and 2024. All patients developed persistent high-grade fever approximately two weeks after the procedure, despite an initial response to antibiotic therapy. Imaging studies, including contrast-enhanced CT and MRI, revealed uterine ischemia and necrosis, and all patients ultimately required total hysterectomy. Conclusions: Uterine necrosis is a rare but potentially life-threatening complication of UAE that should be suspected in patients with persistent high-grade fever beyond the typical post-procedural course. Early imaging evaluation, particularly with contrast-enhanced modalities, is essential for prompt diagnosis. Timely surgical intervention, including hysterectomy, may be required to prevent severe morbidity. Full article

Women living with HIV face an increased burden of spontaneous preterm birth (sPTB); however, the underlying immunological mechanisms of sPTB and its association with HIV infection are poorly understood. Although the limited earlier literature implicates sphingosine-1-phosphate (S1P), a lysosphingolipid signaling molecule, in reproductive biology, the association of S1P signaling with HIV and sPTB has not been investigated. We examined whether two S1P signaling components, S1P receptors and sphingosine kinases, are expressed in the female reproductive tract and whether levels are associated with HIV status or spontaneous preterm birth. We quantified the mRNA expression of sphingosine-1-phosphate receptors 1 and 3 (S1PR1/S1PR3) and sphingosine kinases 1 and 2 (SPHK1/SPHK2) in 167 banked vaginal swab specimens collected between 14 and 26 weeks of gestation in a longitudinal pregnancy cohort in Lusaka, Zambia. We evaluated the expression of S1PR1, S1PR3, SPHK1, and SPHK2 by real-time quantitative reverse transcription PCR (RT-qPCR) in four groups (n = 41–42 each): women without HIV (WWoH) with term birth (≥37 weeks of gestation; TB), WWoH with spontaneous preterm birth (<37 weeks of gestation, sPTB), women with HIV (WWH) with TB, and WWH with sPTB. We found that S1P receptors and sphingosine kinases are expressed in the female reproductive tract. SPHK1 and SPHK2 mRNA expression were generally comparable among women independent of HIV status or birth outcome, though SPHK2 trended toward higher expression in women with HIV and women with sPTB. In contrast, S1PR1 mRNA trended toward higher expression in WWH vs. WWoH overall, as well as in WWH vs. WWoH among women with sPTB. Similarly, S1PR3 mRNA expression was greater in women with HIV than in women without HIV, and WWH, both with TB and sPTB, had higher S1PR3 mRNA expression than WWoH with TB. Perturbations in S1PR1 and S1PR3 mRNA expression may be associated with inflammation related to HIV infection and spontaneous preterm birth, suggesting that further studies of S1P signaling in pregnancy, especially among women with HIV, are warranted. Full article

Background: Staphylococcus pseudintermedius is a major opportunistic pathogen of dogs and the primary cause of canine pyoderma and other infections. The global emergence of methicillin-resistant S. pseudintermedius (MRSP) represents a significant challenge in veterinary medicine due to its frequent multidrug-resistant phenotype and limited therapeutic options. Methods: We describe the phenotypic and genomic characterization of an MRSP isolate recovered from a vaginal swab of an 11-year-old dog diagnosed with vulvovaginitis in southern Italy. Antimicrobial susceptibility testing was performed using broth microdilution according to CLSI VET01S guidelines. Whole-genome sequencing was conducted to determine sequence type and antimicrobial resistance determinants. Results: The isolate was identified as S. pseudintermedius by MALDI-TOF MS and confirmed by genomic analysis. Multilocus sequence typing assigned the strain to sequence type ST2333. Phenotypically, the isolate exhibited multidrug resistance, including resistance to β-lactams, macrolides, lincosamides, tetracyclines, aminoglycosides, fluoroquinolones, and trimethoprim–sulfamethoxazole, while remaining susceptible to amikacin, rifampicin, florfenicol, and vancomycin. Whole-genome sequencing confirmed the presence of mecA and additional resistance determinants consistent with the observed phenotype. Conclusions: This report suggests the possible occurrence of an MDR MRSP ST2333 lineage in southern Italy and highlights the importance of combined phenotypic and genomic surveillance to support antimicrobial stewardship in veterinary medicine within a One Health framework. Full article

The equine reproductive microbiota has emerged as an important factor influencing reproductive health and fertility in both mares and stallions. Traditionally, the equine uterus was considered sterile, and microbial presence was interpreted primarily in the context of infection. However, sequencing-based studies have demonstrated that the reproductive tract, including the uterus and semen, contains detectable microbial communities or microbial DNA signatures, challenging this traditional paradigm. In mares, the vaginal microbiota is consistently dominated by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, whereas the uterine environment represents a low-biomass niche in which interpretation is complicated by contamination risk and the inability of sequencing-based methods to distinguish viable from nonviable microorganisms. Culture-based studies consistently identify opportunistic pathogens such as Streptococcus equi subsp. zooepidemicus, Escherichia coli, and Pseudomonas aeruginosa in association with endometritis and persistent breeding-induced endometritis, while sequencing-based studies suggest broader community-level dysbiosis rather than simple pathogen presence. In stallions, semen is not sterile and commonly contains taxa such as Porphyromonas, Corynebacterium, Peptoniphilus, and other opportunistic bacteria that may influence sperm quality and microbial transmission to mares during breeding. However, most reported associations remain correlative, and direct longitudinal evidence for persistent stallion-to-mare microbial transmission is limited. This review synthesizes current evidence on microbial composition, hormonal influences, dysbiosis, and reproductive implications of the equine reproductive microbiota, integrating culture-based and sequencing-based findings while emphasizing methodological limitations associated with low-biomass samples. Improved understanding of these microbial ecosystems may support more evidence-based reproductive diagnostics and microbiome-informed fertility management in horses. Full article

Early-onset infection caused by Streptococcus agalactiae (Group B Streptococcus, GBS) may occur during gestation or delivery and can lead to severe neonatal sepsis, meningitis, or pneumonia. Discordant GBS infections in twin gestations are rare. We report a fatal case of early-onset GBS infection in dichorionic–diamniotic twins conceived via IVF and delivered by caesarean section at 32 weeks’ gestation due to discordant fetal growth and abnormal Doppler indices in Twin A (Umbilical Artery PI = 1.4; Middle Cerebral Artery PI = 1.5). Twin A had Apgar scores of 3, 5, and 5 and rapidly developed tachycardia, respiratory distress, and systemic infection, while Twin B, with Apgar scores of 7, 8, and 9, remained clinically stable. Both infants were admitted to the NICU and underwent routine blood, urine, and cerebrospinal fluid testing. Despite the prompt initiation of parenteral ceftriaxone and respiratory support, Twin A deteriorated rapidly and died within 28 h. GBS was isolated from Twin A’s blood culture, and maternal placental tissue and high vaginal samples collected before antibiotic administration also grew GBS, with all isolates demonstrating identical antimicrobial resistance profiles. Molecular analysis revealed matching rib1 and alp2/3 gene patterns in isolates from the mother and Twin A. Maternal anovaginal immunochromatography at delivery was positive, whereas screening cultures obtained at 29 weeks’ gestation were negative. This case highlights the limitations of culture-based GBS screening in high-risk pregnancies and preterm deliveries and underscores the potential value of molecular assays and point-of-care testing to improve detection of S. agalactiae throughout pregnancy and the peripartum period. Emerging preventive strategies, including modulation of the genital microbiome and maternal vaccination aligned with WHO recommendations, may further reduce the burden of neonatal GBS disease. Full article