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Vulvovaginal candidosis (VVC) is a frequently occurring infection of the lower female genital tract, mostly affecting immuno-competent women at childbearing age. Candida albicans is the most prevalent pathogenic yeast—apart from other non-albicans species—related to this fungal infection. Different virulence factors of C. albicans have been identified, which increase the risk of developing VVC. To initiate treatment and positively influence the disease course, fast and reliable diagnosis is crucial. In this narrative review, we cover the existing state of understanding of the epidemiology, pathogenesis and diagnosis of VVC. However, treatment recommendations should follow current guidelines.

This study aimed to evaluate the potential of oral probiotics to eradicate vaginal GBS colonization during the third trimester of pregnancy. We screened 1058 women for GBS colonization at 33–37 gestational weeks using a combination of vaginal-to-rectal swab and culture-based methods. Women who tested GBS positive were randomized to either the verum group, receiving a dietary probiotic supplement of four viable strains of Lactobacillus twice-daily for 14 days, or to the placebo group. Women underwent follow-up smears, whereat GBS colonization upon follow-up was considered the primary endpoint. We found that 215 women (20.3%) were positive for GBS upon screening, of which 82 (38.1%) were eligible for study inclusion; 41 (50%) of these were randomized to the verum and placebo groups each. After treatment, 21/33 (63.6%) members of the verum group, and 21/27 (77.8%) of the placebo group were still GBS positive ( p  = 0.24). Four (9.8%) women in the verum group and one (2.4%) in the placebo group experienced preterm birth ( p  = 0.20); smokers showed significantly higher rates of preterm birth ( p  = 0.03). Hence, the findings did not support the hypothesis that oral probiotics can eradicate GBS during pregnancy, although we observed a trend toward reduced GBS persistence after probiotic intake.

Preeclampsia (PE) is a complex disease with unclear etiology. It is the most dangerous human pregnancy disease, causing morbidity and mortality in thousands of women and newborns worldwide. The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is currently the best and only predictive biomarker. The higher the ratio, the more likely the pregnant women will develop PE. The molecular mechanism underlying the increased sFlt-1/PlGF ratio is not known. Here, we show that amino acid transporter LAT1 ( SLC7A5 ) and transcription factor NRF2 regulate this ratio via a previously unknown mechanism to produce sFlt-1 and PlGF in an anti-angiogenic ratio as observed in PE. In addition, we show that PE-associated oxidative stress, whose origin was unknown, is a secondary phenomenon caused by reduced NRF2 and LAT1 activity. The interdependence of the involved proteins, including also ATF4, Flt-1 and Akt, indicates that any disruption of the interaction would ultimately lead to a PE-like phenotype. Reduced placental angiogenesis is suspected to cause preeclampsia. Using placental in vitro models and an in vivo model, the authors uncover the key role of an amino acid transporter and related molecular interactions that together induce an anti-angiogenic state, as observed in preeclampsia.

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients. Therefore, samples from 20 premenopausal women with BV and treated with metronidazole were analyzed. Vaginal swabs, menstrual cup, and endocervical cytobrush samples were collected before treatment, weekly for four weeks, and at 2, 4, and 6 months for Nugent scoring, immune cell populations and cytokine analysis. Of 105 study intervals, 27 (25.7%) showed improvement in Nugent category, 61 (58.1%) remained unchanged, and 17 (16.2%) worsened. Improvement correlated with decreased monocytes ( p  = 0.005), while worsening was linked to increased monocytes ( p  < 0.001) and dendritic cells ( p  = 0.02). B cells ( p  = 0.02) and IFN-γ-induced chemokines - IP-10 ( p  = 0.007), MIG ( p  = 0.049), and ITAC ( p  = 0.005) - were associated with improvement. In conclusion, although the T-cell-associated chemokines IP-10, ITAC, and MIG were strongly associated with improvements in Nugent category, our findings indicate that antigen-presenting cells, particularly monocytes, show the most dynamic response to shifts in the vaginal microbiota in patients with BV.

Cervical insufficiency is one of the main risk factors for preterm birth. It has been suggested that a more diverse vaginal microbial colonization might lead to cervical insufficiency and subsequently further increase the risk for preterm birth. To date, the microbial colonization in women with cervical insufficiency has not been sufficiently categorized. Therefore, this study is aimed at describing the vaginal microbial colonization in this high-risk collective and exploring a possible association with preterm birth. All women treated for cervical insufficiency from June 2021 until March 2024 at the Division for Obstetrics and Feto-Maternal Medicine of the Medical University of Vienna were evaluated for inclusion. Vaginal bacterial/fungal culture results during pregnancy were used for the characterization of the vaginal microbial colonization and categorized in 17 predefined microbial groups. We included 118 women with cervical insufficiency with available vaginal culture results, of whom 58.5% experienced preterm birth. spp., coagulase-negative staphylococci, spp. and spp. were the most frequently detected microorganisms. Further, we conducted a secondary exploratory analysis of the association of each individual microbial group with preterm birth, which found an absence of lactobacilli ( = 0.047) and the presence of a more diverse microbial composition with Gram-negative anaerobes, spp. and spp. to be more frequent in PTB. Cervical insufficiency is associated with a diverse vaginal microbial colonization. Especially colonization with coagulase-negative staphylococci, spp., and spp. seems to play an important role in cervical insufficiency. spp. absence was associated with subsequent preterm birth.

Background and Objectives: Peripheral blood mononuclear cells (PBMCs) and urine‐derived epithelial cells have both emerged as valuable sources for induced pluripotent stem cell (iPSC) generation, each presenting unique advantages in terms of accessibility and reprograming efficiency. This study aimed to assess and compare the potential of PBMC‐derived iPSCs (PiPSCs) and urine‐derived iPSCs (UiPSCs) in generating functional endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), which are critical for vascular tissue engineering and disease modeling. Phenotypic characteristics, differentiation efficacy, and functional properties of iPSC‐derived ECs and VSMCs from these distinct sources were investigated to reveal variations attributed to cellular origin. Methods and Results: PiPSCs and UiPSCs both successfully differentiated into functional ECs and VSMCs. EC differentiation efficiency was similar, yielding about 45% mature ECs with characteristic morphology, marker expression, and tube formation abilities, showing no significant differences between cell types. Transcriptomic analysis revealed upregulation of key endothelial markers (platelet endothelial cell adhesion molecule 1 [PECAM1], cadherin 5 [CDH5], and melanoma cell adhesion molecule [MCAM]) and downregulation of lymphatic markers (Fms‐related tyrosine kinase 4 [FLT4], prospero homeobox protein 1 [PROX1], and podoplanin [PDPN]), confirming blood EC identity. The upregulation of collagen type IV alpha 1 chain (COL4A1) and collagen type I alpha 1 chain (COL1A1) indicated a mature endothelial state with enhanced extracellular matrix (ECM) production. VSMC differentiation resulted in high percentages of α ‐smooth muscle actin ( α ‐SMA) positive cells for both PiPSCs (96%) and UiPSCs (94%). These VSMCs exhibited typical spindle‐shaped morphology, expressed VSMC markers, and responded to carbachol. Transcriptomic analysis showed significant upregulation of VSMC markers (actin alpha 2 [ACTA2], caldesmon 1 [CALD1], calponin 1 [CNN1], transgelin [TAGLN], tropomyosin 2 [TPM2]), with concurrent downregulation of ACTA1 and upregulation of ACTA2, confirming their vascular smooth muscle phenotype. The upregulation of COL6A1 in VSMCs indicated a mature phenotype with enhanced ECM production, crucial for vascular tissue integrity and function. Gene set enrichment analysis highlighted the upregulation of multiple hallmark pathways, delineating a distinctive transcriptional profile. Conclusions: This study presents a comprehensive comparative analysis of functionally differentiated ECs and VSMCs derived from PiPSCs and UiPSCs, providing critical insights into the expression patterns and phenotypic transitions during differentiation. Our findings enhance the understanding of distinct molecular signatures in iPSCs from different sources and their progeny.

Humans are the only species with a commensal Lactobacillus -dominant vaginal microbiota. Reproductive tract microbes have been linked to fertility outcomes, as has intrauterine inflammation, suggesting immune response may mediate adverse outcomes. In this pilot study, we compared vaginal microbiota composition and immune marker concentrations between patients with unexplained or male factor infertility (MFI), as a control. We applied a supervised machine learning algorithm that integrated microbiome and inflammation data to predict pregnancy outcomes. Twenty-eight participants provided vaginal swabs at three IVF cycle time points; 18 achieved pregnancy. Pregnant participants had lower microbial diversity and inflammation. Among them, MFI cases had higher diversity but lower inflammation than those with unexplained infertility. Our model showed the highest prediction accuracy at time point 2 of the IVF cycle. These findings suggest that vaginal microbiota and inflammation jointly impact fertility and can inform predictive tools in reproductive medicine.

Current treatments for bacterial vaginosis (BV) often result in recurrent disease. Gardnerella , a key player in BV pathogenesis, forms biofilms on vaginal epithelial cells. Recombinant endolysins have shown to specifically kill Gardnerella , but not commensal lactobacilli, in vitro. This study evaluated the pharmacodynamics of BNT331-endolysin (BNT331-EL) on vaginal samples from 49 women with BV (Nugent score ≥7, Amsel criteria, and clue cells). Whole genome sequencing confirmed BV-associated community state types IV-B and III, with Gardnerella dominating in 53% of samples and present in 86%. Ex vivo treatment with BNT331-EL reduced viable Gardnerella by ≥94% at 20–50 µg/mL over 19 h. L. iners was reduced by an average of 92% across samples, while L. crispatus proliferated where present in substantial amounts. Endolysin treatment effectively disrupted Gardnerella biofilms and reduced viable bacterial load in a time- and concentration-dependent manner. These results informed the definition of the treatment dose for a first-in-human trial with BNT331-EL.

Pregnant women have an increased risk of vulvovaginal candidosis. Recurrent candidosis is under debate as a contributor to preterm birth, and vertical transmission may cause diaper dermatitis and oral thrush in the newborn. Apart from cultural methods, the gold standard for diagnosing candidosis is Gram staining, which is time-consuming and requires laboratory facilities. The objective of this prospective study was to validate a point-of-care vaginal yeast detection assay (SavvyCheck™ Vaginal Yeast Test) and to evaluate it in asymptomatic pregnant women. We enrolled 200 participants, 100 of whom had vulvovaginal candidosis according to Gram stain (study group) and 100 were healthy pregnant controls (control group). Of these, 22 participants (11%) had invalid test results. The point-of-care test of the remaining 85 and 93 study participants in the study and control groups, respectively, showed a sensitivity of 94.1%, specificity of 98.9%, positive predictive value of 90.3%, and negative predictive value of 99.4% when compared with Gram stain. In conclusion, we found a high correlation between the SavvyCheck™ Vaginal Yeast Test and Gram-stained smears during pregnancy. This suggests a potential role of this point-of-care test as a screening tool for asymptomatic pregnant women in early gestation.

Introduction Gender disparities exist in the OBGYN discipline. This study investigates, for the first time, whether gender impacts on the confidence of practical and surgical skills among OBGYN residents, and of being prepared to work as a specialist. Methods The gynecological societies of Austria, Germany, and Switzerland established a web-based survey of 30 questions that was sent to all registered OBGYN members-in-training from August to September 2020. Data collection, controlling and analysis were performed by the Swiss Federal Institute of Technology in Zurich (ETH). Results A total of 422 participants took part in the survey, of which 375 (88.9%) were female, 46 (10.9%) were male, and one (0.2%) was divers. The diverse participant was excluded from further analyses. The gender distribution was comparable in all three countries. Multiple regression analyses showed that gender is an independent variable significantly impacting on the confidence levels in performing standard gynaecological ( p  = 0.03) and obstetric ( p  < 0.001) procedures. Similarly, the feeling of confidence in being prepared for working as a specialist in a clinic showed to be gender-dependent ( p  < 0.001), however, not the feeling of being prepared for working as specialist in an outpatient setting ( p  = 0.37). The “female factor” significantly decreases the confidence rating for surgical and practical skills and for working in a hospital. Covariates including year of training, country, workload, receiving regular feedback, and implemented simulation training were included in all analyses. Discussion Improvements of residency programs to promote female doctors to overcome factors reducing their confidence in their own OBGYN skills are highly warranted.