Search Results (41)

Background: Cervical dysplasia is a pre-malignant condition of the uterine cervix and is highly prevalent in Sub-Saharan Africa; especially affecting HIV-infected Black women. The anti-dysplastic effect of vitamin D hormones in cervical dysplasia is poorly understood. Therefore, we conducted a cross-sectional case–control observational study to assess the relationship between serum 25-hydroxycholecalciferol (25(OH)D) and cervical dysplasia, amongst Black women with and without HIV infection. Methods: The study participants attended a gynaecologic oncology clinic at an academic hospital in Pretoria, South Africa (n = 109). Patient clinical data were obtained during consultation. Cervical dysplasia was identified by cytology (PAP smear) which classified the case group as high-grade squamous epithelial lesions (HSILs), and the control group as <HSIL. Serum biochemistry measured 25(OH)D and its covariate biochemical variables. The data were statistically modelled to adjust for clinical and biochemical covariates, identify a significant relationship (p ≤ 0.05) between 25(OH)D and cervical dysplasia, and analyse subgroup interaction between HIV status and cervical dysplasia. Results: The data showed high levels of vitamin D insufficiency and deficiency in Black women with and without HIV infection. After covariate adjustment, 25(OH)D demonstrated an inverse relationship with HSIL in HIV-uninfected Black women. Furthermore, an interaction effect between women with and without HIV infection was observed. Conclusions: The role of 25(OH)D in the primary prevention of cervical dysplasia in Black women without HIV infection is promising, and dosing strategies require investigation. Also, future studies exploring the immunomodulatory role of 25(OH)D in cervical dysplasia in HIV-infected women is warranted. Full article

Treating endometritis is one of the major challenges faced by veterinarians. The effect of post-insemination intrauterine infusion Wharton’s jelly mesenchymal stromal/stem cell-derived conditioned medium (WJ-MSC-CM) on the uterine response and pregnancy outcomes in problem mares was evaluated in this study. The cycles of 12 problem mares were treated seven/eight hours after insemination with intrauterine infusion of 20 mL of WJ-MSC-CM (TRT) or non-conditioned Ringer’s lactate solution (CTR). Before (PRE) and 12 h after (POST) treatment, an ultrasonographic examination and a low-volume flush (LVF) for efflux clarity evaluation and bacteriological and cytological analysis were made. Pregnancy diagnosis was performed at 14 days and confirmed at 60 days after ovulation. A decrease (p < 0.05) in polymorphonuclear neutrophils infiltration and a trend toward significance in LVF efflux clarity (p < 0.1) were observed in TRT cycles. The TRT (50%) had a higher pregnancy rate (p < 0.05) than CTR group (0%) at first cycle. Only a trend toward significance was observed comparing pregnancy frequencies between the two groups (CTR 12.5% vs. TRT 54.5%), the pregnancy rate of TRT cycles was comparable to that of normal mares (p > 0.05) and higher (p < 0.05) than that reported for problem mares in the literature. Post-insemination uterine infusion of WJ-MSC-CM in mares restores pregnancy rates to normal levels, by its anti-inflammatory effect. Full article

Following the U.S. Food and Drug Administration’s warning against power morcellators due to potential cell dissemination of occult malignancy, there has been a shift away from minimally invasive approaches. This concern also overshadows the well-documented advantages of minimally invasive surgery in benign gynecology. Objectives: To evaluate whether intraperitoneal cell dissemination during laparoscopic surgery for uterine fibroids can be reduced by (i) the choice of morcellation method and/or (ii) copious irrigation after the procedure. Methods: This prospective multicenter comparative pilot study included 72 women undergoing laparoscopic myomectomy (LM) or total laparoscopic hysterectomy (TLH) for benign conditions. Women were divided into four groups in order to compare different types of morcellation, including a reference group without morcellation: (i) LM with power morcellation (n = 21, Group A), (ii) TLH with en-bloc transvaginal tissue removal without morcellation (n = 17, Group B), (iii) TLH with manual vaginal morcellation (n = 19, Group C), and (iv) TLH with contained manual vaginal morcellation (n = 15, Group D). Patients receiving cold knife morcellation were randomized into Groups C or D. In order to assess cell spread before surgery, after surgery but before morcellation, after morcellation, and after abdominal irrigation with a total of 3000 mL saline solution, peritoneal washings were collected at six timepoints. Results: After specimen removal (TP3), cell spread was significantly higher in cases with power morcellation [13/19 (68%) in Group A] compared to transvaginal cold knife morcellation, both contained and uncontained [Group C 1/14 (7%) and Group D 1/19 (9%)] (p < 0.001), or to TLH with en bloc removal [Group B 1/17 (6%)]. Saline irrigation reduced the positive cytologies. After 3000 mL (TP6), the difference between Group A and the TLH groups was not significant [4/18 (22%) vs. 3/45 (7%), p = 0.079]. Conclusions: Our study shows that (i) transvaginal cold knife morcellation results in significantly less peritoneal cell dissemination than power morcellation, and (ii) peritoneal irrigation with 3000 mL of saline significantly reduces residual cell presence. These findings could support maintaining minimally invasive approaches while addressing safety concerns. Full article

Uterine health is paramount to fertility in broodmares and for the success of a breeding project, and the Lusitano breed is no exception. This study aimed to characterize the mare uterine microbiota using practical clinical evaluation methods. Mares were examined by transrectal palpation and ultrasonography, followed by the collection of samples by one of three different techniques: uterine lavage, biopsy, or swab. The results of cytology, histology, microbiology, and antimicrobial susceptibility testing were recorded, and statistical analyses were performed. Inflammation was present in 42.2% of the mares and positive culture in 65.4%. Escherichia coli and Streptococcus spp. were the most isolated microorganisms. The most efficient antimicrobials were gentamicin, trimethoprim-sulfamethoxazole, and enrofloxacin and resistance was detected mainly for doxycycline, penicillin, and ceftiofur. The phase of the cycle was significantly associated with the presence of inflammation (p = 0.0308). The isolation of Gram-positive or Gram-negative bacteria correlated to the microbiological isolation by primoculture/enrichment processes (p = 0.0183). This was a routine standard breeding evaluation of broodmares in the management of a stud farm, hence displaying the characteristics of a field study. The antimicrobial resistance findings reinforce the importance of performing microbiology and susceptibility tests, even under field conditions, to maximize targeted antimicrobial therapy efficiency and minimize the worldwide problem of antimicrobial resistance, promoting antimicrobial stewardship. Full article

A 10-month-old pygmy goat was examined at the Royal (Dick) School of Veterinary Studies at the University of Edinburgh in January 2022, having been referred with a suspected diagnosis of a disorder of sexual development (DSD). The animal displayed a predominantly female phenotype (vulva with enlarged clitoris and vagina) but some male external characteristics such as a beard, larger body size, and larger horns. It also typically exhibits male behaviours such as mounting, aggression, and flehmen response. Computed tomography (CT) detected a bicornuated tubular fluid-filled structure connected to bulbous soft tissue masses. Subsequent exploratory laparotomy and reproductive tract removal identified underdeveloped uterine horns connected to ductus deferens and gonads, which were confirmed as testicles by histological examination. No spermatogenesis was detected, and no ovarian tissue was apparent. Blood levels of testosterone showed a marked decrease post-surgery (2.10 nmol/L to <0.03 nmol/L). Whole genome sequencing suggested that the patient may have an XY male karyotype, although cytological analysis was not possible to confirm the XY karyotype. Full article

Introduction: Among uterine tumors resembling ovarian sex cord tumors (UTROSCTs), it has been suggested that GREB1-rearranged cases are biologically distinct from ESR1-rearranged cases and might be considered as a separate entity. Objectives: The aim of this systematic review was to assess the difference between GREB1- and ESR1-rearranged UTROSCTs with regard to several clinico-pathological parameters. Methods: Three electronic databases were searched from their inception to February 2025 for all studies assessing the presence of GREB1 and ESR1 rearrangements in UTROSCTs. Exclusion criteria comprised overlapping patient data, case reports, and reviews. Statistical analysis was performed to compare clinicopathological variables between GREB1- and ESR1-rearranged UTROSCTs. Dichotomous variables were compared by using Fisher’s exact test; continuous variables were compared by using Student’s t-test. A p-value < 0.05 was considered significant. Results: Six studies with 88 molecularly classified UTROSCTs were included. A total of 36 cases were GREB1-rearranged, and 52 cases were ESR1-rearranged. GREB1-rearranged UTROSCTs showed a significantly older age (p < 0.001), larger tumor size (p = 0.002), less common submucosal/polypoid growth (p = 0.005), higher mitotic index (p = 0.010), more common LVSI (p = 0.049), and higher likelihood to undergo hysterectomy (p = 0.008) compared to ESR1-rearranged cases. No significant differences were detected with regard to margins, cytological atypia, necrosis, retiform pattern, and rhabdoid cells. No significant differences were found in the immunohistochemical expression of any of the assessed markers (wide-spectrum cytokeratins, α-inhibin, calretinin, WT1, CD10, CD56, CD99, smooth muscle actin, desmin, h-caldesmon, Melan-A/MART1, SF1, or Ki67). GREB1-rearranged UTROSCTs showed significantly lower disease-free survival compared to ESR1-rearranged UTROSTCs (p = 0.049). Conclusions: In conclusion, GREB1-rearranged UTROSCTs occur at an older age, are less likely to display a submucosal/polypoid growth, and exhibit larger size, a higher mitotic index, more common lymphovascular space invasion, and lower disease-free survival compared to ESR1-rearranged UTROSCTs. Nonetheless, the similar immunophenotype suggests that they belong to the same tumor family. Further studies are necessary to confirm this point. Full article

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are among the rarest types of uterine tumors. Diagnosis of a UTROSCT is often challenging. Imaging techniques such as ultrasound and MRI are limited in distinguishing UTROSCTs as their appearance is usually suggestive of uterine leiomyoma or adenomyosis. Additionally, the value of a preoperative biopsy remains uncertain due to the heterogeneous composition of the tumor and the inadequacy of limited samplings. We present a rare case of UTROSCT in a 59-year-old woman and we have performed a narrative review of the literature on PubMed, Scopus, and Web of Science from 2000 to June 2024, identifying 133 cases. According to our review, at histological exam UTROSCTs are mainly composed of cells resembling ovarian sex-cord elements which are arranged in cords or trabeculae, typically with a mild cytologic atypia. The most expressed sex-cord differentiation markers include inhibin, calretinin, melan A, CD56, CD99, SF1, WT1, CD10, and FOXL2. For women who have completed their reproductive plans, a total hysterectomy with adnexectomy is an adequate treatment for tumors confined to the uterus. For younger patients who wish to preserve fertility, tumorectomy via hysteroscopy or laparoscopy is the preferred treatment option and the recurrence rates range from 5% to 30%. Treatments for recurrent disease include surgery, chemotherapy, and radiation therapy, often used in combination. Advancements in molecular profiling and immunohistochemistry will improve our ability to diagnose and manage this tumor. Such investigations will enhance prognostic stratification, facilitating more accurate predictions of biological behavior and recurrence risk. Full article

Olive cake was incorporated at a low inclusion rate (3.7%) into the rations of dairy cows through partial substitution of maize, and its effects on milk production, general health, and fertility traits were investigated. Multiparous purebred Holstein dairy cows (n = 148) were divided into two groups: a treated group (n = 86) and a control group (n = 62). The control ration (group C) was modified by replacing 1 kg of maize with an equal quantity of olive cake (group T). The experiment lasted from 60 days prepartum to 150 days postpartum. Electronic aids were utilized to quantify daily milk yield and detect estrus expression, while clinical and uterine examinations were performed weekly. Blood samples, uterine epithelial cells, and endometrial tissue samples were collected from a subgroup of healthy animals in both groups at specific time points. Blood samples were examined to determine the β-hydroxybutyric acid (BHBA), acute phase proteins (haptoglobin [Hpt] and serum amyloid A [SAA]), progesterone, and pregnancy-associated glycoproteins concentrations. Uterine epithelial cells were assessed for polymorphonuclear neutrophil (PMN) counts, and the expression of nine genes encoding inflammatory cytokines and immune system activation was analyzed in uterine biopsy tissue. No significant differences (p > 0.05) were observed between groups in milk yield, general morbidity, clinical endometritis, or conception rates. However, animals in group T came to estrus approximately 6 days earlier (p = 0.013) than those in group C; progesterone concentrations on day 7 of the subsequent cycle tended (p = 0.07) to be higher in group T. On day 21, BHBA concentrations were higher in group C than in group T (p < 0.05). Throughout the experiment, Hpt levels in group T were consistently lower (p < 0.001), while SAA was lower on day 7 compared to group C. From days 21 to 42 postpartum, there was a significant reduction in PMN numbers (group C p = 0.02; group T p < 0.0001), with a tendency for a greater reduction rate in group T (p = 0.08). Among the genes studied, a significant difference was revealed in the expression of the ILA1 gene, with strong correlations of gene expression in group C and weak to moderate correlations in group T. In conclusion, under the conditions of this experiment, the inclusion of olive cake into dairy cows’ rations did not affect milk production but improved certain health and fertility parameters, making olive cake a suitable alternative feedstuff for high-producing animals. Full article

Endometriosis is a chronic inflammatory, estrogenic disorder caused by endometrial tissue growth places other than uterine lumen, resulting in infertility and severe pelvic pain. Thymol, an extract of Thymus vulgaris, processes diverse biological properties, including anti-inflammatory, local anesthetic, decongestant, and antiseptic effects. However, the efficacy of thymol in treating endometriosis has still not been explored. Herein, this research aimed to investigate the role of thymol in the treatment of endometriosis using a murine model and Ishikawa cells. Thirty C57BL/6 mice were administered 17β-E2 (100 ng/mouse) subcutaneously for three consecutive days to induce synchronous estrus. On the last day of injection, the mice underwent surgical induction of endometriosis. After that, the mice were divided into three groups, i.e., Control (CTRL), Thymol 30 mg/kg and Thymol 60 mg/kg, receiving oral administration of either saline or thymol (30 mg/kg/d or 60 mg/kg/d, as 0.1 mL/kg/d, respectively) for a three-week duration. Each group consisted of ten mice and was evenly divided into estrus and diestrus according to the vaginal cytology on the last day of treatment. Thymol significantly (p < 0.05) reduced the weight and volume of ectopic tissue, hindered cell proliferation, and stimulated apoptosis compared to the CTRL group. Additionally, in the thymol-treated group, the levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, as well as the numbers of neutrophils and macrophages, were significantly (p < 0.05) decreased. Moreover, a novel role of thymol in rebalancing estrogen and progesterone (E₂-P₄) signaling was explored, and it was distributed in the ectopic endometrium. Next, the role of thymol on Ishikawa cells was determined. The results demonstrated that thymol significantly (p < 0.05) suppressed the E₂-induced proliferation of Ishikawa cells. Furthermore, molecular docking analyses suggested that thymol potentially binds to ESR1-like estrogens, indicating its antagonistic activity against estrogens. The estrogen receptor 1 (ESR1) and its target gene expression exhibited significant (p < 0.05) downregulation, while progesterone receptor (PGR) and target genes were markedly (p < 0.05) upregulated following thymol treatment in the ectopic endometrium. Most importantly, our data revealed the minimal impact of thymol treatment on the eutopic endometrium and its crucial role in supporting pregnancy, thus indicating the safety of thymol in treating endometriosis. Overall, our study suggests that thymol holds promising therapeutic implications for endometriosis by virtue of its anti-inflammatory properties and ability to antagonize estrogen activity. Full article

The risk of infection transmission from mother to fetus depends on the pathogen. TORCH agents cause some neuroinfections, including Toxoplasmosis, rubella, Cytomegalovirus, herpes simplex 1 and 2, and others (Varicella Zoster, Parvovirus B-19, Epstein–Barr virus, and Zika virus). The consequences can be stillbirth, prematurity, uterine growth restriction, and congenital malformations. The detection of DNA/RNA from CSF by molecular methods is a marker of the involvement of congenital infection in the central nervous system. This study aimed to identify the frequency of these pathogens in CSF samples from newborns (1 to 28 days old) at a tertiary hospital, using PCR, and determine the clinical consequences. Methods: This was a prospective descriptive study involving the molecular analysis of 151 CSF samples from neonates, collected for cytological and biochemical diagnosis from 2017 to 2021. After the results and consent from the participants’ caregivers were obtained, the leftover material was sent to the University’s Virology Laboratory and submitted for DNA/RNA extraction and Nested-PCR/RT-PCR. A review of the patients’ medical records and descriptive statistics was performed. This work was approved by the Ethics Committee (CAAE: 86760218.3.0000.5404). Results: A total of 151 CSF samples were obtained, 16 of which were positive (10.6% [95% CI%: 6.18–16.63%]). Two of these were PCR-positive for HSV-1 (1.3%), four for VZV (2.6%), one for CMV (0.67%), two for Toxoplasmosis (1.3%), four for Parvovirus B-19 (2.6%), and four for Zika (2.6%). The proportion of positive PCR results was higher in the group that presented with malformations (25.0% vs. 8.4%, p = 0.040). Conclusions: The pathogens identified by PCR were mostly Zika virus, VZV, and B-19, and these were mainly found in newborns with malformations. Full article

Human Papillomavirus (HPV) infection represents a global health concern. HPV infects the mucosa, particularly in the uterine cervix, where it may establish a persistent infection, exposing women to a risk of developing cancer. The available treatments include surgery or topic solutions, while a systemic treatment is still unavailable. In recent years, natural molecules such as epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12, and hyaluronic acid (HA) gained importance as innovative therapies for HPV. We enrolled 163 women with a positive HPV DNA test or previous history of HPV infections, and a PAP test indicating LSIL/AGUS/ASCUS cytology. The patients in the treatment group (n = 86) received an oral combination of EGCG 200 mg, FA 400 µg, vitamin B12 1 mg, and HA 50 mg (1 cps/day) for 3 months (T1), while the control group (n = 77) underwent standard clinical surveillance. Both groups repeated a PAP test and an HPV DNA test after 3 (T1) months, and another PAP test after 6 months (T2) as a follow up. The treatment group experienced a significant reduction in HPV positivity at T1 compared to the control group. Moreover, the treatment group exhibited an improvement in cervical lesions either at T1 (p < 0.0001) or T2 (p < 0.00001). Full article

The data from the literature show that women undergoing a LEEP due to CIN3 have a greater risk of having subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue, and they show mixed results. This study aimed to investigate the incidence of high-grade or severe VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease and illustrate the treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent a laparoscopic hysterectomy due to high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and a diagnosis of high-grade VaIN was 18 months. Results: High-grade or severe VaIN was found in eight patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized due to CIN3 showed an eight-fold greater risk than women hysterectomized due to benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized due to benign disease. The risk of developing VaIN is greater in women with viral persistence. Conclusion: All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing. Full article

HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of proto-oncogenes and the silencing of tumor suppressor genes; some of these are proteins with PDZ domains involved in homeostasis and cell polarity. Through a bioinformatics approach based on interaction networks, a group of proteins associated with HPV 16 infection, PDZ domains, and direct physical interaction with E6 and related to different hallmarks of cancer were identified. MAGI-1 was selected to evaluate the expression profile and subcellular localization changes in premalignant lesions and ISCC with HPV 16 in an integrated state in cervical cytology; the profile expression of MAGI-1 diminished according to lesion grade. Surprisingly, in cell lines CaSki and SiHa, the protein localization was cytoplasmic and nuclear. In contrast, in histological samples, a change in subcellular localization from the cytoplasm in low-grade squamous intraepithelial lesions (LSIL) to the nucleus in the high-grade squamous intraepithelial lesion (HSIL) was observed; in in situ carcinomas and ISCC, MAGI-1 expression was absent. In conclusion, MAGI-1 expression could be a potential biomarker for distinguishing those cells with normal morphology but with HPV 16 integrated from those showing morphology-related uterine cervical lesions associated with tumor progression. Full article

A Lactococcus (L.) lactis strain producing antimicrobial and anti-inflammatory biomolecules (mainly 1,4-Diaza-2,5-dioxobicyclo[4.3.0]nonanes and pyrazine-derivatives) was tested for its capacity to cure clinical endometritis in buffaloes compared to conventional antibiotic-based treatment. Clinical endometritis-diagnosed buffaloes (n = 16/group) were infused intrauterine with four doses of 10⁹ CFU-free (FLC group) or nanoencapsulated L. lactis (NLC group) and compared to those that received three doses of saline + a single dose of 500 mg cephapirin benzathin (AB group) or four doses of saline (control, C group) every other day. Endometrium samples were analyzed for cytological (polymorphonuclear cells, PMN), bacteriological, and proinflammatory mRNA expression. Uterine wash and blood samples were collected to determine proinflammatory cytokine concentrations and metabolites in the blood samples. The reproductive performance of buffaloes was assessed. Compared to the C group, the AB and NLC groups had the lowest percentage of PMN, followed by those in the FLC group (p < 0.05). All treated buffaloes had significantly lower numbers of pathogens than the control buffaloes. Compared to control, all treatments significantly down-regulated endometrial proinflammatory encoding mRNA expression. The concentrations of IL1B, TNFAIP7, and leukocyte esterase activity in the uterine washings were significantly decreased in the AB and NLC groups compared to the C and FLC groups. All treatments significantly decreased concentrations of serum proinflammatory cytokines compared to control. Both the AB and NLC groups had significantly lower concentrations of serum NEFA than the C and FLC groups. The percentage of control buffaloes having an echogenic uterus and PVD score > 2 was significantly higher than those in the treated buffaloes with higher numbers of corpora lutea, higher conception rates, and shorter days open than control buffaloes (p < 0.05). In conclusion, L. lactis-producing antimicrobial and anti-inflammatory metabolites reduce uterine inflammatory responses and improve fertility in buffaloes. Full article

(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL. Full article