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Objective: The Italian healthcare jurisdiction promotes patient mobility, which is a major determinant of practice variation, thus being related to the equity of access to health services. We aimed to explore how travel times, waiting times, and other efficiency- and quality-related hospital attributes influenced the hospital choice of women needing pelvic organ prolapse (POP) surgery in Tuscany, Italy., Methods: We obtained the study population from Hospital Discharge Records. We duplicated individual observations (n = 2533) for the number of Tuscan hospitals that provided more than 30 POP interventions from 2017 to 2019 (n = 22) and merged them with the hospitals' list. We generated the dichotomous variable "hospital choice" assuming the value one when hospitals where patients underwent surgery coincided with one of the 22 hospitals. We performed mixed logit models to explore between-hospital patient choice, gradually adding the women's features as interactions., Results: Patient choice was influenced by travel more than waiting times. A general preference for hospitals delivering higher volumes of interventions emerged. Interaction analyses showed that poorly educated women were less likely to choose distant hospitals and hospitals providing greater volumes of interventions compared to their counterpart. Women with multiple comorbidities more frequently chose hospitals with shorter average length of stay., Conclusion: Travel times were the main determinants of hospital choice. Other quality- and efficiency-related hospital attributes influenced hospital choice as well. However, the effect depended on the socioeconomic and clinical background of women. Managers and policymakers should consider these findings to understand how women behave in choosing providers and thus mitigate equity gaps., (© 2023. The Author(s).)

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG's role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (<50 µM) did not have an antiproliferative effect over A-431 cells; however, EGCG inhibited clonogenic cell capability. Furthermore, EGCG (<50 µM) improved MAL-PDT cytotoxicity, increasing PpIX and ROS levels, exerting a positive influence on PpIX synthesis, decreasing intracellular iron concentration and modifying HGS enzyme gene expression such as PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: When adopting new methods, surgeons may experience a period of complexity and longer operation times because of their inexperience. This period is known as the "learning curve." This study was aimed at systematically reviewing the current literature on functional urology learning curves., Methods: A comprehensive search was conducted across multiple databases from inception to July 2023 with no language restrictions. All original studies on urogynecological and functional urological procedures, including cross-sectional, cohort, and clinical trials, were eligible for inclusion. Relevant data were extracted, and methodological quality was appraised using standardized Joanna Briggs Institute critical appraisal tools. To quantitatively investigate learning curves, a mixed-effects generalized linear regression analysis was conducted on studies employing cumulative summation methods., Results: From the 7,104 records, 68 studies met the inclusion criteria. The majority of studies were observational and the most common outcome measures were surgical duration, blood loss, and hospital stay. The learning curves varied by procedure type-for incontinence surgeries, 15-80 cases were required; for pelvic organ prolapse surgeries, 18-47 cases; for laparoscopic procedures, 10-105 cases; and for robotic procedures, 5-84 cases. The analysis showed that the number of cases required to surpass the learning curve decreased over time, likely reflecting technological advancements and increased surgical experience., Conclusion: The learning curve for surgical procedures varies significantly. It varies between 5 cases for robotic supratrigonal cystectomy to 75 cases for robot-assisted ventral mesh rectopexy or robotic sacrocolpopexy surgery in 84 cases. These variable learning curves highlight the need for structured training programs and ongoing assessment., Competing Interests: Declarations. Ethical Approval and Registration: This project was approved by the Ethics Committee of Tabriz University of Medical Sciences (code: IR.TBZMED.REC.1401.668). Conflicts of Interest: None., (© 2025. The International Urogynecological Association.)

Background: Estetrol (E4) is a natural estrogen produced by the fetal liver during pregnancy. Due to its favorable safety profile, E4 was recently approved as estrogenic component of a new combined oral contraceptive. E4 is a selective ligand of estrogen receptor (ER)α and ERβ, but its binding to the G Protein-Coupled Estrogen Receptor (GPER) has not been described to date. Therefore, we aimed to explore E4 action in GPER-positive Triple-Negative Breast Cancer (TNBC) cells. Methods: The potential interaction between E4 and GPER was investigated by molecular modeling and binding assays. The whole transcriptomic modulation triggered by E4 in TNBC cells via GPER was explored through high-throughput RNA sequencing analyses. Gene and protein expression evaluations as well as migration and invasion assays allowed us to explore the involvement of the GPER-mediated induction of the plasminogen activator inhibitor type 2 (SERPINB2) in the biological responses triggered by E4 in TNBC cells. Furthermore, bioinformatics analysis was aimed at recognizing the biological significance of SERPINB2 in ER-negative breast cancer patients. Results: After the molecular characterization of the E4 binding capacity to GPER, RNA-seq analysis revealed that the plasminogen activator inhibitor type 2 (SERPINB2) is one of the most up-regulated genes by E4 in a GPER-dependent manner. Worthy, we demonstrated that the GPER-mediated increase of SERPINB2 is engaged in the anti-migratory and anti-invasive effects elicited by E4 in TNBC cells. In accordance with these findings, a correlation between SERPINB2 levels and a good clinical outcome was found in ER-negative breast cancer patients. Conclusions: Overall, our results provide new insights into the mechanisms through which E4 can halt migratory and invasive features of TNBC cells. [ABSTRACT FROM AUTHOR]

Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E4) is a weak estrogen that recently has been approved for contraception. We evaluated the effect of E4 on the growth of endometriotic-like lesions and the expression of TNF-α, estrogen receptors (ERs), and progesterone receptors (PRs) in an in vivo murine model. Endometriosis was induced surgically in female C57BL/6 mice. E4 was delivered via Alzet pump (3 mg/kg/day) from the 15th postoperative day for 4 weeks. E4 significantly reduced the volume (p < 0.001) and weight (p < 0.05) of ectopic lesions. Histologically, E4 did not affect cell proliferation (PCNA immunohistochemistry) but it did increase cell apoptosis (TUNEL assay) (p < 0.05). Furthermore, it modulated oxidative stress (SOD, CAT, and GPX activity, p < 0.05) and increased lipid peroxidation (TBARS/MDA, p < 0.01). Molecular analysis showed mRNA (RT-qPCR) and protein (ELISA) expression of TNF-α decreased (p < 0.05) and mRNA expression of Esr2 reduced (p < 0.05), in contrast with the increased expression of Esr1 (p < 0.01) and Pgr (p < 0.05). The present study demonstrates for the first time that E4 limited the development and progression of endometriosis in vivo. [ABSTRACT FROM AUTHOR]

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Trocar site hernia is a rare, serious operation-related complication after robotic gynecologic surgery. Here, we present two 8-mm port-site hernia cases after three-port robotic myomectomy with a review of reported previous cases. In the first case, small bowel obstruction was found postoperatively due to herniation at the left mid-axillary line 8-mm trocar site. Small bowel herniation through the same site as the first case was found in the second case. Emergency exploration was performed in both cases by extending the left trocar site. There was no sign of bowel ischemia, and successful bowel reduction and hernia repair were done. Unlike previously reported cases, these cases occurred in a normal body mass index (BMI) patient (first case 20.28 kg/m2, second case BMI 24.80 kg/m2) and were pelvic drain insertion sites. These sites were the weak points of the abdominal muscle coverage. Therefore, the closure of 8-mm trocar sites should be considered. [ABSTRACT FROM AUTHOR]

Aim: Periodontitis is a potential risk factor for preterm birth (PTB) in women; however, the causal relationship or the exact mechanism remain unknown. This study aimed to compare the oral microbiome features of mothers with full-term birth (FTB) with those who had preterm delivery., Methods: This study prospectively enrolled 60 women (30 mothers with PTB and 30 mothers with FTB), and subgingival plaque samples were collected and analysed by metagenomic 16S rDNA sequencing. Clinical measurements, including periodontal probing depth, clinical attachment level, modified gingival index (mGI) and plaque index, were performed to determine the periodontal state of the participants. Medical and obstetric data were collected as well., Results: Among the periodontal measurements, mGI score, reflecting the level of gingival inflammation, exhibited a statistically significant association with PTB (adjusted odds ratio 2.705, 95% confidence interval 1.074-6.811, p = .035). When subgroup analysis was conducted based on mean mGI scores (mGI ≥ 2, high inflammation [HI] versus mGI < 2, low inflammation [LI]), microbiome analysis revealed clear distinctions in microbial compositions between PTB and FTB mothers in both the HI and LI groups. Especially in the HI group, alpha diversity exhibited a decreasing trend in PTB mothers compared to FTB mothers. Beta diversity also revealed significant differences between the two groups. In Linear Discriminant Analysis Effect Size analysis, certain anaerobic taxa, including the genera Spirochaetes, Treponema and Porphyromonas, were relatively abundant in the FTB/HI group, whereas the PTB/HI group showed a high abundance of the order Actinomycetales. Network analysis showed that the FTB/HI had relatively stronger connectivity in microbial composition than the PTB/HI group. Dysbiosis ratio of plaque microbiome, in terms of periodontitis, was significantly lower in PTB/HI group compared to FTB/HI group., Conclusion: The compositions of maternal subgingival microbiomes differed between PTB and FTB mothers in both the high and low levels of gingival inflammation groups. In the presence of high level of gingival inflammation, dysbiosis in plaque microbiome, in terms of periodontitis, was decreased in PTB mothers compared to FTB mothers., (© 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

We evaluated the association between gestational age at threatened preterm birth (TPTB) diagnosis and preterm birth (PTB) incidence using a nationwide birth cohort. Data of 94,236 women with singleton deliveries from the Japan Environment and Children's Study (enrolled between 2011 and 2014) were analysed. Participants were divided based on parity and gestational age at TPTB diagnosis (22–24, 25–27, 28–30, 31–33, and 34–36 weeks). Multivariable logistic regression models were used to calculate the odds ratios (ORs) for PTB before 37 and 34 weeks in women from all groups, using participants without TPTB as the reference. The adjusted ORs for PTB before 37 weeks were the highest in the latest gestational age group in nulliparous and multiparous women without previous PTB, while those before 34 weeks were the highest in the earliest and latest gestational age group in multiparous women without previous PTB and in the earliest gestational age group in multiparous women with previous PTB. The association between gestational age at TPTB diagnosis and PTB incidence varies based on maternal parity and PTB before 37 or 34 weeks. Further studies with detailed clinical data and a unified TPTB diagnosis protocol are necessary to clarify this association. [ABSTRACT FROM AUTHOR]

Background: Robotic surgery has gained popularity for the reconstruction of pelvic floor defects. Nonetheless, there is no evidence that robot-assisted reconstructive surgery is either appropriate or superior to standard laparoscopy for the performance of pelvic floor reconstructive procedures or that it is sustainable. The aim of this project was to address the proper role of robotic pelvic floor reconstructive procedures using expert opinion. Methods: We set up an international, multidisciplinary group of 26 experts to participate in a Delphi process on robotics as applied to pelvic floor reconstructive surgery. The group comprised urogynecologists, urologists, and colorectal surgeons with long-term experience in the performance of pelvic floor reconstructive procedures and with the use of the robot, who were identified primarily based on peer-reviewed publications. Two rounds of the Delphi process were conducted. The first included 63 statements pertaining to surgeons' characteristics, general questions, indications, surgical technique, and future-oriented questions. A second round including 20 statements was used to reassess those statements where borderline agreement was obtained during the first round. The final step consisted of a face-to-face meeting with all participants to present and discuss the results of the analysis. Results: The 26 experts agreed that robotics is a suitable indication for pelvic floor reconstructive surgery because of the significant technical advantages that it confers relative to standard laparoscopy. Experts considered these advantages particularly important for the execution of complex reconstructive procedures, although the benefits can be found also during less challenging cases. The experts considered the robot safe and effective for pelvic floor reconstruction and generally thought that the additional costs are offset by the increased surgical efficacy. Conclusion: Robotics is a suitable choice for pelvic reconstruction, but this Delphi initiative calls for more research to objectively assess the specific settings where robotic surgery would provide the most benefit. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the results of patients with laparoscopic lateral suspension (LLS) and sacrospinous fixation (SSF). Methods: This prospective observational study included 52 patients who underwent LLS and 53 patients who underwent SSF due to pelvic organ prolapse. The pelvic organ prolapse's anatomical cure and the frequency of recurrence have been recorded. Female Sexual Function Index, Pelvic Organ Prolapse Symptom Score, and complications were evaluated preoperatively and at the postoperative 24th month. Results: In the LLS group, the subjective treatment rate was 88.4% and the anatomical cure rate for apical prolapse was 96.1%. In the SSF group, the subjective treatment rate was 83.0% and the anatomical cure rate for apical prolapse was 90.5%. There was a significant difference between the groups regarding Clavien-Dindo classification and reoperation (p < 0.05). Female Sexual Function Index, and the Pelvic Organ Prolapse Symptom Score were different between the groups (p < 0.05). Conclusions: This study showed that there is no difference between two surgical techniques in apical prolapse cure rates. However, the LLS seem preferable in terms of the Female Sexual Function Index, Pelvic Organ Prolapse Symptom Score, reoperation, and complications. We need larger sample size studies in terms of incidence of complications and reoperation. [ABSTRACT FROM AUTHOR]

Estrogen is an important hormone that plays a role in regulating follicle development and oocyte maturation. Transzonal projections (TZPs) act as communication bridges between follicle somatic cells and oocytes, and their dynamic changes are critical for oocyte development and maturation. However, the roles and mechanisms of estrogen in regulating TZPs during follicular development are not yet understood. We found that the proportion of oocytes spontaneously resuming meiosis increases as the follicle grows, which is accompanied by rising estrogen levels in follicles and decreasing TZPs in cumulus-oocyte complex. To further explore the effect of elevated estrogen levels on TZP assembly, additional estrogen was added to the culture system. The increased estrogen level significantly decreased the mRNA and protein expression levels of TZP assembly-related genes. Subsequent research revealed that TZP regulation by estrogen was mediated by the membrane receptor GPER and downstream ERK1/2 signaling pathway. In summary, our study suggests that estrogen may regulate goat oocyte meiosis arrest by decreasing TZP numbers via estrogen-mediated GPER activation during follicle development., (© 2024 Wiley Periodicals LLC.)

Introduction and hypothesis: The aim of this video is to show a step-by-step approach to robotically assisted laparoscopic lateral suspension for pelvic organ prolapse aiming to standardize this procedure. Methods: This video shows a robotically assisted laparoscopic approach to a POP-Q stage 3 prolapse with a combined anterior and apical defect. First, the trocars are positioned, with one 8-mm trocar, two lateral trocars 5 cm above the anterior–superior iliac spine, and a 10-mm assistant trocar either paraumbilically or suprapubically. Second, the uterovesical pouch is dissected up to 2 cm above the level of the bladder neck. The mesh is then fixed to the vesicovaginal fascia and to the isthmus uteri. Next, a laparoscopic forceps is inserted retroperitoneally through the lateral trocars and the lateral arms of the mesh are pulled retroperitoneally. The peritoneum of the uterovesical fold is sutured, including round ligament plication. Finally, the lateral arms of the peritoneum are fixed to the peritoneum of the abdominal wall. Conclusions: Robotically assisted laparoscopic lateral suspension is a safe alternative to laparoscopic and robotically assisted laparoscopic sacropexy and very well suited for uterine-preserving POP surgery. This video contributes to the standardization of this procedure, and we believe our video to be useful in helping urogynecologists to perform this innovative procedure. [ABSTRACT FROM AUTHOR]

During the first year of life, development and balance of newborn gut microbiota are strongly influenced by external factors such as delivery mode, breastfeeding, duration of pregnancy, mother diet and lifestyle, siblings and pets, environment, and antibiotics administration. Gut microbiota colonization starts with facultative anaerobes and continues with the establishment of anaerobic genera of which Bifidobacteria are the gold standard of a healthy gut neonatal microbiota. Scientific literature traditionally describes the fetus as sterile in the womb and identifies the membranes rupture as the beginning of microbial colonization. Vaginal delivery is an important source for the onset of infant colonization which will then continue with the transfer of a new selection of intestinal bacteria with breastfeeding. During cesarean delivery a direct contact of the mouth of newborn with the vaginal and intestinal microbiota is absent, and environmental bacteria play an important role for infants intestinal colonization. Nature has ensured that newborns receive other specific maternal bacteria, through a subsequent method of transfer: breastfeeding. We present a brief and comprehensive state-of-the-art in order to encourage natural childbirth and breastfeeding whenever possible and discuss innovative directions for develop new ad hoc personalized treatments in order to restore physiological microbiota. [ABSTRACT FROM AUTHOR]