Pollution and endometriosis: A deep dive into the environmental impacts on women's health.

BACKGROUND: The interaction between pollution and endometriosis is a pressing issue that demands immediate attention. The impact of pollution, particularly air and water pollution, or occupational hazards, on hormonal disruption and the initiation of endometriosis remains a major issue. OBJECTIVES: This narrative review aims to delve into the intricate connection between pollution and endometriosis, shedding light on how environmental factors contribute to the onset and severity of this disease and, thus, the possible public health policy implications. DISCUSSION: Endocrine-disrupting chemicals (EDCs) in pollutants dysregulate the hormonal balance, contributing to the progression of this major gynaecological disorder. Air pollution, specifically PM2.5 and PAHs, has been associated with an increased risk of endometriosis by enhancing chronic inflammation, oxidative stress, and hormonal imbalances. Chemical contaminants in water and work exposures, including heavy metals, dioxins, and PCBs, disrupt the hormonal regulation and potentially contribute to endometriosis. Mitigating the environmental impact of pollution is required to safeguard women's reproductive health. This requires a comprehensive approach involving stringent environmental regulations, sustainable practices, responsible waste management, research and innovation, public awareness, and collaboration among stakeholders. CONCLUSION: Public health policies have a major role in addressing the interaction between pollution and endometriosis in a long-term commitment.

Clinical impact of low-volume lymph node metastases in early-stage cervical cancer: A comprehensive meta-analysis.

OBJECTIVE: In order to define the clinical significance of low-volume metastasis, a comprehensive meta-analysis of published data and individual data obtained from articles mentioning micrometastases (MIC) and isolated tumor cells (ITC) in cervical cancer was performed, with a follow up of at least 3 years. METHODS: We performed a systematic literature review and meta-analysis, following Cochrane's review methods guide and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was the disease-free survival (DFS), and the secondary outcome was the overall survival (OS). The hazard ratio (HR) was taken as the measure of the association between the low-volume metastases (MIC+ITC and MIC alone) and DFS or OS; it quantified the hazard of an event in the MIC (+/- ITC) group compared to the hazard in node-negative (N0) patients. A random-effect meta-analysis model using the inverse variance method was selected for pooling. Forest plots were used to display the HRs and risk differences within individual trials and overall. RESULTS: Eleven articles were finally retained for the meta-analysis. In the analysis of DFS in patients with low-volume metastasis (MIC + ITC), the HR was increased to 2.60 (1.55-4.34) in the case of low-volume metastasis vs. N0. The presence of MICs had a negative prognostic impact, with an HR of 4.10 (2.71-6.20) compared to N0. Moreover, this impact was worse than that of MIC pooled with ITCs. Concerning OS, the meta-analysis shows an HR of 5.65 (2.81-11.39) in the case of low-volume metastases vs. N0. The presence of MICs alone had a negative effect, with an HR of 6.94 (2.56-18.81). CONCLUSIONS: In conclusion, the presence of MIC seems to be associated with a negative impact on both the DFS and OS and should be treated as MAC.

A new titanium-covered transobturator tape for surgical treatment of stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To assess the long-term satisfaction, cure rate and safety of a new titanium-covered transobturator tape compared to polypropylene tape for the treatment of stress urinary incontinence (SUI). METHODS: A prospective study was conducted with 151 patients. Seventy patients underwent transobturator sling surgery with titanium tape from 2011 to 2019, and a historical control group (CG) of 81 patients was treated with a noncoated tape and underwent incontinence surgery from 1999 to 2009. We compared patient-reported outcome measures (PROMs) with the incontinence outcome questionnaire (IOQ). RESULTS: The median follow-up was 2½ years in both groups. Based on responses to the IOQ, a statistically significantly shorter time of recovery (IOQ 15: 21.3 ± 26.4 [TG], 40.2 ± 38.5 [CG], p = 0.02), improvement of sex life (IOQ 13: 34.1 ± 29.4 [TG] vs. 65.3 ± 35.6 [CG], p = 0.01) and less voiding dysfunction (IOQ 19: 30.9 ± 28.1 [CG], 9.3 ± 18.6 [TG], p = 0.01) were observed in the TG. Objectively, no postoperative urinary retention was observed in the TG, but four cases were described in the CG. Ten patients needed a reoperation for SUI in the CG compared to three in the TG (p = 0.03). CONCLUSION: The titanium-covered transobturator sling had superior recovery time, improved sexual function and reduced reoperation rate compared to a historical polypropylene group.

Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro.

Induced pluripotent stem cell secretome (iPSC-CM) mitigate organ injury and help in repair. Macrophages play a critical role in tissue repair and regeneration and can be directed to promote tissue repair by iPSC-CM, although the exact mechanisms are not known. In the current investigative study, we evaluated the possible mechanism by which iPSC-CM regulates the phenotype and secretory pattern of macrophages in vitro. Macrophages were obtained from human peripheral blood mononuclear cells and differentiated to various subpopulations and treated with either iPSC-CM or control media in vitro. Macrophage phenotype was assessed by flow cytometry, gene expression changes by qRT PCR and secretory pattern by multiplex protein analysis. The protein and gene interaction network revealed the involvement of Amyloid precursor protein (APP) and ELAV-like protein 1 (ELAVL-1) both present in the iPSC-CM to play an important role in regulating the macrophage phenotype and their secretory pattern. This exploratory study reveals, in part, the possible mechanism and identifies two potential targets by which iPSC-CM regulate macrophages and help in repair and regeneration.

Domains of genome-wide gene expression dysregulation in Down's syndrome.

Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.

Generation of an alveolar epithelial type II cell line from induced pluripotent stem cells.

Differentiation of primary alveolar type II epithelial cells (AEC II) to AEC type I in culture is a major barrier in the study of the alveolar epithelium in vitro. The establishment of an AEC II cell line derived from induced pluripotent stem cells (iPSC) represents a novel opportunity to study alveolar epithelial cell biology, for instance, in the context of lung injury, fibrosis, and repair. In the present study, we generated long-lasting AEC II from iPSC (LL-iPSC-AEC II). LL-iPSC-AEC II displayed morphological characteristics of AEC II, including growth in a cobblestone monolayer, the presence of lamellar bodies, and microvilli, as shown by electron microscopy. Also, LL-iPSC-AEC II expressed AEC type II proteins, such as cytokeratin, surfactant protein C, and LysoTracker DND 26 (a marker for lamellar bodies). Furthermore, the LL-iPSC-AEC II exhibited functional properties of AEC II by an increase of transepithelial electrical resistance over time, secretion of inflammatory mediators in biologically relevant quantities (IL-6 and IL-8), and efficient in vitro alveolar epithelial wound repair. Consistent with the AEC II phenotype, the cell line showed the ability to uptake and release surfactant protein B, to secrete phospholipids, and to differentiate into AEC type I. In summary, we established a long-lasting, but finite AEC type II cell line derived from iPSC as a novel cellular model to study alveolar epithelial cell biology in lung health and disease.

Postmenopausal endometriosis: a challenging condition beyond menopause.

IMPORTANCE AND OBJECTIVE: Postmenopausal endometriosis is a complex condition that challenges the conventional belief that endometriosis resolves with menopause. Despite the cessation of menstruation, a subset of women continues to experience or develop endometriosis-related symptoms during the postmenopausal period. Thus, this review aimed to shed light on postmenopausal endometriosis, exploring its clinical features, diagnostic considerations, management approaches, and the potential impact on women's health. METHODS: PubMed/Medline, Scopus, and Web of Science databases were used for the research, with only articles in English language, using the following terms: "postmenopausal endometriosis," "menopause," "management," "treatment," and "quality of life," from inception to 2023. DISCUSSION AND CONCLUSION: The clinical features of postmenopausal endometriosis include persistent or recurrent pelvic pain, dyspareunia, bowel, or urinary symptoms and, occasionally, abnormal vaginal bleeding. The absence of menstrual cycles presents a diagnostic challenge, as the traditional diagnostic criteria for endometriosis rely on menstrual patterns. Visual cues may be less evident, and the symptoms often overlap with other gynecological conditions, necessitating a thorough evaluation to differentiate postmenopausal endometriosis from other potential causes. Management approaches for postmenopausal endometriosis encompass surgical intervention, hormonal therapies, pain management, and individualized care. Postmenopausal endometriosis significantly impacts the quality of life, sexual health, and long-term well-being of women. Understanding the clinical features, diagnostic challenges, and management approaches of postmenopausal endometriosis is crucial for healthcare professionals to provide effective care and to improve the quality of life of women affected by this condition.

The Impact of Conservative Surgical Treatment of Adenomyosis on Fertility and Perinatal Outcomes.

Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients trying to conceive. The PubMed and Medline databases were searched using the keywords: "adenomyosis", "surgery", "radiofrequency", "infertility", "pregnancy", "sterility", "conception", "miscarriage", and "endometrial receptivity". Abstracts were screened, and relevant articles were selected for review. This review reveals that surgery appears to improve fertility outcomes with or without medical therapy; however, the risk of uterine rupture remains high and the best technique to reduce this risk is still not known. More studies are needed to formulate the best surgical approach for preserving fertility in treating adenomyosis and to establish standardized guidelines.

External beam radiotherapy boost versus surgical debulking followed by radiotherapy for the treatment of metastatic lymph nodes in cervical cancer: A systematic review and meta-analysis.

OBJECTIVE: We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. METHODS: We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). RESULTS: We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade≥3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). CONCLUSION: No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments.

Endometriosis in transgender men: recognizing the missing pieces.

Endometriosis, traditionally associated with cisgender women, should be recognized as a significant issue for transgender men. This perspective highlights the need to address the unique experiences and challenges faced by transgender men with endometriosis. Diagnostic difficulties arise due to hormone therapy and surgical interventions, which can alter symptoms. Limited research in transgender men undergoing hysterectomy further complicates the understanding of endometriosis in this population. Healthcare providers must be aware of these challenges and adapt the diagnostic approaches accordingly. Education and inclusive care are essential to ensure timely and appropriate management of endometriosis in transgender men, ultimately improving their quality of life.

Antenatal, Intrapartum and Postpartum Interventions for Preventing Postpartum Urinary and Faecal Incontinence: An Umbrella Overview of Cochrane Systematic Reviews.

Post-partum, women can suffer from urinary and faecal incontinence. It is important to assess interventions to prevent this problem. Cochrane systematic reviews summarize the data available from systematic reviews of randomized trials assessing interventions. We conducted an umbrella overview of Cochrane systematic reviews encompassing antenatal, intrapartum and postpartum interventions for preventing postpartum urinary and faecal incontinence. We searched the Cochrane Database of Systematic Reviews on the 9 May 2023. Results: Our search identified nine Cochrane reviews providing results. Data for urinary and faecal incontinence were available from 77 (72%) trials and included 51,113 women. The reviews assessed antenatal digital perineal massage, pelvic floor muscle training, techniques for repairing anal sphincter tears, routine use of episiotomy, use of endoanal ultrasound prior to repairing perineal tears, caesarean versus vaginal delivery (overall, for breech and for twins), and vaginal delivery with forceps or vacuum. Only the use of a vacuum instead of forceps if an assisted vaginal delivery is needed, the use of an endo-anal ultrasound prior to repairing perineal tears and postpartum pelvic floor muscle training suggest a reduction in postpartum incontinence. Due to the small number of relevant reviews, a consequence of the relatively small number of primary studies, the effect of almost all the tested interventions was found to be imprecise.

Ovarian Follicular Response Is Altered by Salpingectomy in Assisted Reproductive Technology: A Pre- and Postoperative Case-Control Study.

Objectives: The goal of this study was to assess the effect of unilateral salpingectomy on the number of mature follicles in the ipsilateral ovary during an assisted reproductive technology (ART) stimulation cycle, as compared to the contralateral ovary. Methods: This was a retrospective, single-center, case-control cohort study conducted from 2017 to 2022. Patients from 18 to 43 years old who underwent at least one ART cycle before and after a unilateral salpingectomy were included. The number of recruited follicles, including mature (≥16 mm) and intermediate follicles (13-15.5 mm), on the salpingectomy side (case) were compared to those present on the contralateral ovary (control) during an ART attempt. To take into account the inter-ovarian variability, the comparison was performed on two ART cycles, performed before then after the salpingectomy. Results: Overall, 24 patients were included in our study. While the number of mature follicles was similar in both ovaries before surgery, the mean number of mature follicles was significantly reduced after salpingectomy in the operated side, as compared to the control side, being, respectively 3.00 vs. 5.08 (p = 0.048). There was no significant difference between the intermediate and total recruited follicles. Conclusions: Our study suggests that salpingectomy may impact the follicle recruitment on the ipsilateral side by altering the vascularization during mesosalpinx coagulation. Gynecologists should be mindful of this concept and accurately set surgical indications. Beyond the indication, this emphasizes the critical role of having infertility surgeons sensitive to fertility preservation for optimal management of ART patients. Further studies with larger patient populations are required to confirm these results.

Adenomyosis: An Updated Review on Diagnosis and Classification.

Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths and limitations.

Radiofrequency Ablation for Adenomyosis.

Adenomyosis is a common benign gynecologic condition characterized by ectopic endometrial glands and stroma in the myometrium causing pain (dysmenorrhea) and abnormal uterine bleeding. New interventional techniques have been introduced over recent years. This study evaluates the treatment success and side effects of radiofrequency ablation. An electronic literature search in the PubMed, Scopus, and ScienceDirect databases was carried out on the outcomes of pain reduction and, secondarily, on abnormal uterine bleeding, reintervention, reproductive outcome, imaging outcome, and complications. There was a mean decrease in dysmenorrhea pain scores by -63.4 ± 9.0% at 12 months. Data on other outcome parameters were sparse. No major complications were reported. Radiofrequency ablation represents a promising minimally invasive and organ-preserving treatment in patients with symptomatic adenomyosis. It is associated with clinically meaningful improvement of adenomyosis-related pain in the short term.

The Present and the Future of Medical Therapies for Adenomyosis: A Narrative Review.

Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.

Does Endometriosis Impact the Composition of Follicular Fluid in IL6 and AMH? A Case-Control Study.

OBJECTIVE: The aim of this study was to compare follicular liquid levels of IL6 and AMH in women with and without endometriosis and to evaluate their potential impact on ICSI outcomes. MATERIALS AND METHODS: It is a prospective case-control study conducted on 25 women with proven endometriosis and 50 patients diagnosed with other causes of infertility. All these patients were candidates for ICSI cycles. Their follicular fluid was collected at the time of oocyte retrieval and used to evaluate IL-6 and AMH titers by electro-chemiluminescent immunoassay (Cobas e411-Roche). RESULTS: The IL-6 levels in follicular fluid were higher in the endometriosis group than in the control group (152.3 vs. 19.9 pg/mL; p = 0.02). The median level for AMH was 2.2 ± 1.88 ng/mL with no statistical difference between the two groups (2.2 vs. 2.7 ng/mL, p = 0.41). No significant correlation between the follicular IL6 and AMH levels was observed. CONCLUSIONS: The oocyte quality seems to be preserved in patients with endometriosis with the adequate response to ovarian stimulation. High levels of follicular IL6 are in accordance with the inflammatory phenomenon of the disease; however, this increase has no impact on ICSI outcomes.

The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity.

Neuronal disorders, like Huntington's disease (HD), are difficult to study, due to limited cell accessibility, late onset manifestations, and low availability of material. The establishment of an in vitro model that recapitulates features of the disease may help understanding the cellular and molecular events that trigger disease manifestations. Here, we describe the generation and characterization of a series of induced pluripotent stem (iPS) cells derived from patients with HD, including two rare homozygous genotypes and one heterozygous genotype. We used lentiviral technology to transfer key genes for inducing reprogramming. To confirm pluripotency and differentiation of iPS cells, we used PCR amplification and immunocytochemistry to measure the expression of marker genes in embryoid bodies and neurons. We also analyzed teratomas that formed in iPS cell-injected mice. We found that the length of the pathological CAG repeat did not increase during reprogramming, after long term growth in vitro, and after differentiation into neurons. In addition, we observed no differences between normal and mutant genotypes in reprogramming, growth rate, caspase activation or neuronal differentiation. However, we observed a significant increase in lysosomal activity in HD-iPS cells compared to control iPS cells, both during self-renewal and in iPS-derived neurons. In conclusion, we have established stable HD-iPS cell lines that can be used for investigating disease mechanisms that underlie HD. The CAG stability and lysosomal activity represent novel observations in HD-iPS cells. In the future, these cells may provide the basis for a powerful platform for drug screening and target identification in HD.

Ruptured ectopic pregnancy as complete hydatidiform mole: Case report and review of the literature.

Usually, a hydatidiform mole (HM) develops inside the uterus. The occurrence of HM in ruptured tubal pregnancy is exceptional. Cases reported in the literature are scarce. In this article, a case of haemoperitoneum secondary to a ruptured fallopian tube by a complete mole is reported. A 50-year-old gravida 2, para 1 was admitted to the emergency department for acute abdominal pain. After the clinical examination, an abdominal sonography and CT scan were done, revealing the presence of an adnexal left mass associated with an important haemoperitoneum. A urine pregnancy test was done and was positive, indicating an immediate laparoscopic exploration. The laparoscopy revealed a haemoperitoneum secondary to a ruptured tubal mass. The pathological exam concluded a complete hydatidiform mole (CHM) invading the wall of the fallopian tube. Any acute abdominal pain in a potentially pregnant woman imposes first the routine realization of a pregnancy test. The occurrence of CHM in a ruptured fallopian tube is particularly rare and has exceptionally been diagnosed before the laparoscopic exploration.