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BACKGROUND: Desmopressin, a synthetic analogue of the natural hormone vasopressin, stimulates endogenous haemostasis and exerts a powerful myometrial and vasoconstrictor action in a variety of pharmacological preparations. Both mechanisms of action may have therapeutic value for the treatment of intrauterine device (IUD)-related menorrhagia, which is believed to be caused not only by altered local haemostasis but also--according to a new hypothesis--by decreased vascular uterine resistance. The aim of this prospective study was to evaluate the effect of vasopressin drug on menstrual blood loss and on changes, if any, in uterine flow impedance. Mefenamic acid, which is commonly used to treat IUD-related menorrhagia, was administered as a comparison. METHODS: Twenty-four women with IUD-induced menorrhagia were recruited and randomly allocated to treatment with either desmopressin or mefenamic acid. Menstrual blood loss (measured by pictorial blood loss assessment chart) and uterine artery resistance (measured with transvaginal colour Doppler) performed in two pretreatment periods were compared with 3-month treatment periods. RESULTS: Menstrual blood loss was significantly reduced in both treatment groups. In the desmopressin group, the effect was clinically useful in all subjects, but in the mefenamic group menstrual blood loss was consistently menorrhagic in two patients. No significant differences were observed in the uterine artery pulsatility index before and during treatment. CONCLUSIONS: Desmopressin may be a useful therapeutic tool for many women with IUD-related menorrhagia. Its mechanism of action lies in an ability to enhance local haemostasis, without affecting uterine blood flow. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ovarian failure is a frequent complication occurring after haematopoietic stem cell transplantion (SCT), which is generally ascribed to radiation treatment and antiblastic alkylating agents. METHODS: Ovarian morphology and function were studied in reproductive age women 12-24 months after allogeneic SCT (n = 23) received from an HLA identical sibling, or autologous SCT (n = 22). Thirteen allo-transplanted women were suffering from chronic graft-versus-host disease (cGVHD). RESULTS: Menstrual cycles recovered in two and four women in the allo- and auto-SCT groups respectively, being associated with younger age and longer period elapsed from transplant. There was no difference in previous use of alkylating agents between allo- and auto-transplantation, while corticosteroid treatment was longer and more recent in the allo-SCT group. Significantly higher gonadotrophin levels and lower estradiol were seen in the combined group of patients than in controls. In allo-transplanted women, androgens were also significantly lower than in controls. Ovarian and uterine volumes were lower in patients than in controls, and in the allo- than in the auto-transplanted women. Within the allo-SCT group, endocrine function and ovarian and uterine volumes were significantly lower in the patients suffering from cGVHD. CONCLUSIONS: Ovarian failure in SCT recipients is likely to be caused principally by myelo-ablative treatments, but the condition of gonadal and androgen insufficiency can be worsened by an altered immunomodulation in allogeneic setting. [ABSTRACT FROM AUTHOR]

Objective: The incidence of caesarean sections (CSs) has increased significantly in recent years, especially in developed countries. This study aimed to identify the factors that most influence the length of hospital stay (LOS) after a CS, using data from 9,900 women who underwent CS at the "Federico II" University Hospital of Naples between 2014 and 2021., Methods: Various artificial intelligence models were employed to analyze the relationships between the LOS and a set of independent variables, including maternal and foetal characteristics. The analysis focused on identifying the model with the best predictive performance and specific comorbidities impacting LOS., Results: A multiple linear regression model determined the highest R-value (0.815), indicating a strong correlation between the identified variables and LOS. Significant predictors of LOS included abnormal foetuses, cardiovascular disease, respiratory disorders, hypertension, haemorrhage, multiple births, preeclampsia, previous delivery complications, surgical complications, and preoperative LOS. In terms of classification models, the decision tree yielded the highest accuracy (75%)., Conclusions: The study concluded that certain comorbidities, such as cardiovascular disease and preeclampsia, significantly impact LOS following a CS. These findings can assist hospital management in optimizing resource allocation and reducing costs by focusing on the most influential factors., Competing Interests: Declarations. Ethics approval and consent to participate: In compliance with the Declaration of Helsinki and with the Italian Legislative Decree 211/2003, Implementation of the 2001/20/CE directive, since no patients/children were involved in the study, the signed informed consent form and ethical approval are not mandatory for these types of studies. Furthermore, in compliance with the regulations of the Italian National Institute of Health, our study is not reported among those needing assessment by the Ethical Committee of the Italian National Institute of Health. Consent for publication: Not applicable. Consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cortisol and DHEA(S) are markers of allostatic load and resilience; as such, they may be added to the definition of performance measures alongside immunocompetence. We aimed at studying the potential carryover effects of management practices on growth performances and the interrelationship between the hypothalamic-pituitary-adrenal (HPA) axis, immunocompetence and performances during the preweaning period in dairy calves. This study consisted of first a retrospective cohort study and second a prospective study. Calves had their growth performances and disease occurrence recorded, and their hair steroids (T1 at 20.03 ± 0.39 and T2 at 50.83 ± 0.41 days from birth) and plasmatic and colostral immunoglobulin G (IgG) was measured by immunoassays. The occurrence of preweaning diseases and the duration of individual housing negatively correlated to body weight (BW) at 60 days and the hair cortisol-to-DHEA(S) ratio (HC/HDHEA(S)) (T2) was negatively correlated to the daily weight gain (DWG) (-0.36; p < 0.05), plasmatic IgG (plaIgG) and the apparent efficiency of absorption (AEA) (-0.41; p < 0.01). Our results confirmed that the occurrence of diseases during the preweaning period and individual housing duration are pivotal for calves' growth. This prospective study highlighted a detrimental effect of allostatic load on immunocompetence and described a link between resilience and growth performances.

Based on the established neuroprotective properties of indole-based compounds and their significant potential as multi-targeted therapeutic agents, a series of synthetic indole-phenolic compounds was evaluated as multifunctional neuroprotectors. Each compound demonstrated metal-chelating properties, particularly in sequestering copper ions, with quantitative analysis revealing approximately 40% chelating activity across all the compounds. In cellular models, these hybrid compounds exhibited strong antioxidant and cytoprotective effects, countering reactive oxygen species (ROS) generated by the Aβ(25-35) peptide and its oxidative byproduct, hydrogen peroxide, as demonstrated by quantitative analysis showing on average a 25% increase in cell viability and a reduction in ROS levels to basal states. Further analysis using thioflavin T fluorescence assays, circular dichroism, and computational studies indicated that the synthesized derivatives effectively promoted the self-disaggregation of the Aβ(25-35) fragment. Taken together, these findings suggest a unique profile of neuroprotective actions for indole-phenolic derivatives, combining chelating, antioxidant, and anti-aggregation properties, which position them as promising compounds for the development of multifunctional agents in Alzheimer's disease therapy. The methods used provide reliable in vitro data, although further in vivo validation and assessment of blood-brain barrier penetration are needed to confirm therapeutic efficacy and safety.

To report a rare case of a right interstitial pregnancy spontaneously occurring in a patient who had previously undergone homolateral salpingo-oophorectomy, and to propose possible explanations for the mechanisms involved in the genesis of this rare scenario. A 32-year-old G3P1 female presented to our emergency room with symptoms related to a suspected ectopic interstitial pregnancy managed in another hospital using a conservative pharmacological approach. After discussing the risks, firstly she underwent a transvaginal ultrasound examination, then a diagnostic hysteroscopy to clarify the unclear ultrasound finding, followed by a successful robot-assisted laparoscopic cornual resection. Hysteroscopy demonstrated an empty uterine cavity, confirming the suspect of pregnancy localization into the interstitial portion of the tubal stump. Through the robot-assisted laparoscopic approach, all the trophoblastic tissue was removed without causing significant damage to the surrounding myometrium and preserving the patient's fertility. No post-operative complications were recorded. The robotic approach successfully allowed the cornual resection, with minimal blood loss and optimal suturing of the uterine defect. Although our knowledge is still limited, it is possible that the pregnancy nested in the tubal residue after being properly fertilized into the intact tube. However, it cannot be ruled out that there have been remodeling phenomena of the tubal residue so that it has acquired the ability to intercept the oocyte., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ascione, Della Corte, D’Angelo, Palumbo, Watrowski, Di Spiezio Sardo and Bifulco.)

Introduction: Minimally invasive surgery is considered the gold standard for the treatment of gynecological diseases. Our study aims to assess the effectiveness of the new concept of ultra-low-impact laparoscopy as a combination of low-impact laparoscopy, consisting in the use of miniaturized instruments through 3-5mm ports and low-pressure pneumoperitoneum, with regional anesthesia to evaluate the perioperative outcomes., Methods: A cross-sectional study was performed from May 2023 to December 2023, to enroll 26 women affected by benign gynecological disease and threated by mini-invasive surgical approach. The surgical procedures were performed following the low-impact laparoscopy protocol and the regional anesthesia protocol. The postoperative pain, nausea, and vomiting and the antiemetic/analgesic intake were evaluated. Postoperative surgical and anesthesiological variables were analyzed., Results: Operative time was within 90 min (41.1 ± 17.1 mean ± standard deviation (SD)) and no conversion to laparotomy or general anesthesia was required. According to VAS score, the postoperative pain during the whole observation time was less than 3 (mean). Faster resumption of bowel motility (6.5 ± 2.1 mean ± SD) and women's mobilization (3.1 ± 0.7 mean ± SD) were observed as well as low incidence of post-operative nausea and vomit. Early discharge and patient's approval were recorded. Intraoperatively pain score was assessed on Likert scale during all stages., Conclusion: Ultra-low-impact laparoscopy showed to provide a satisfying recovery experience for patients in terms of short hospital stays, cosmetic result, and pain relief, without compromising surgical outcomes. The encouraging results lead us to recruit a greater number of patients to validate our technique as a future well-established produce., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The antiapoptotic BAG3 protein plays a crucial role in cellular proteostasis and it is involved in several signalling pathways governing cell proliferation and survival. Owing to its multimodular structure, it possesses an extensive interactome including the molecular chaperone HSP70 and other specific cellular partners, which make it an eminent factor in several pathologies, particularly in cancer. Despite its potential as a therapeutic target, very few BAG3 modulators have been disclosed so far. Here we describe the identification of a promising BAG3 modulator able to bind the BAG domain of the protein featuring an imidazopyridine scaffold and obtained through the application of the Groebke-Blackburn-Bienaymé chemical synthesis procedure. The disclosed compound 10 showed a relevant cytotoxic activity, and in line with the biological profile of BAG3 disruption, it induced the activation of caspase 3 and 9.

Objective: This study aimed to evaluate the efficacy of a new biomarker, termed SIR-En, in identifying patients at risk of endometrial carcinoma among those presenting with abnormal uterine bleeding during menopause., Material and Methods: A retrospective case-control analysis was conducted on 242 women with menopausal abnormal uterine bleeding and endometrial thickness ≥ 4 mm. Peripheral blood samples were collected within 7 days before histological diagnosis. systemic inflammatory reaction (SIR) indices were calculated, including NLR, MLR, PLR, and SII. SIR-En was derived by multiplying SII and endometrial thickness. Statistical analyses, including multivariate linear regression and ROC curve analysis, were performed to assess the diagnostic capability of SIR-En., Results: Patients were categorized into endometrial hyperplasia (50 patients) and endometrial cancer (192 patients) groups. The SIR-En index was significantly higher in the carcinoma group (8710 vs. 6420; p = 0.003). The ROC curve for SIR-En had an AUC of 0.6351 (95% CI: 0.5579-0.7121). Using Youden's method, the optimal SIR-En cutoff was 13,806, showing a specificity of 0.940 and a positive predictive value of 0.957., Conclusions: Combining systemic inflammatory indices with endometrial thickness, the SIR-En index can effectively distinguish between endometrial hyperplasia and carcinoma in menopausal women with abnormal uterine bleeding. Despite the retrospective design, the identified cutoff's high specificity and positive predictive value support its potential utility in clinical practice. Further prospective studies are required to validate these findings and optimize clinical application.

The common bean ( Phaseolus vulgaris L.) is one of the oldest food crops in the world. In this study, the ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-MS/MS) technique was used to characterize the polar lipid composition and polyphenolic fraction of five bean varieties commonly consumed in Italy: Cannellino (PVCA), Controne (PVCO), Borlotti (PVBO), Stregoni (PVST), and Vellutina (PVVE). Lipid content represents a minor fraction of the whole metabolome in dry beans, and little is known about their polar lipids, which could be potentially bioactive components. Thirty-three compounds were detected through UHPLC-MS/MS, including oxylipins, phospholipids, N-acyl glycerolipids, and several fatty acids. The dichloromethane extracts were subjected to principal component analysis (PCA), with the results showing greater differentiation for the Borlotti variety. Moreover, 27 components belonging to different polyphenol classes, such as phenolic acids, flavonoids, catechins, anthocyanins and their glycosides, and some saponins, were identified in the hydroalcoholic seed extracts. In addition, the mineral content of the beans was determined. Considering the high number of compounds in the five apolar seed extracts, all samples were examined to determine their in vitro inhibitory activity against the enzyme cyclooxygenase-2 (COX-2), which is inducible in inflammatory cells and mediates inflammatory responses. Only PVCO showed the best inhibition of the COX-2 enzyme with an IC 50 = 31.15 ± 2.16 µg/mL. In light of these results, the potential anti-inflammatory properties of PVCO were evaluated in the LPS-stimulated murine macrophage cell line J774A.1. Herein, we demonstrate, for the first time, that PVCO at 30 µg/mL can significantly reduce the release of TNF-α, with a less significant anti-inflammatory effect being observed in terms of IL-6 release.

Notwithstanding its acknowledged pivotal role for cardiovascular prevention, cardiac rehabilitation (CR) is still largely under prescribed, in almost 25% of patients owing an indication for. In addition, when considering differences concerning the two sexes, female individuals are underrepresented in CR programmes with lower referral rates, participation, and completion as compared to male counterpart. This picture becomes even more tangled with reference to gender, a complex socio-cultural construct characterized by four domains (gender identity, relation, role, and institutionalized gender). Indeed, each of them reveals several obstacles that considerably penalize CR adherence for different categories of people, especially those who are not identifiable with a non-binary gender. Aim of the present review is to identify the sex- (i.e. biological) and gender- (i.e. socio-cultural) specific obstacles to CR related to biological sex and sociocultural gender and then envision a likely viable solution through tailored treatments towards patients' well-being., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

A 3D structure-based pharmacophore model built for bromodomain-containing protein 4 (BRD4) is reported here, specifically developed for investigating and identifying the key structural features of the (+)-JQ1 known inhibitor within the BRD4 binding site. Using this pharmacophore model, 273 synthesized and purchased compounds previously considered for other targets but yielding poor results were screened in a drug repositioning campaign. Subsequently, only six compounds showed potential as BRD4 binders and were subjected to further biophysical and biochemical assays. Compounds 2 , 5 , and 6 showed high affinity for BRD4, with IC 50 values of 0.60 ± 0.25 µM, 3.46 ± 1.22 µM, and 4.66 ± 0.52 µM, respectively. Additionally, these compounds were tested against two other bromodomains, BRD3 and BRD9, and two of them showed high selectivity for BRD4. The reported 3D structure-based pharmacophore model proves to be a straightforward and useful tool for selecting novel BRD4 ligands.

Laurus nobilis L. is commonly used in folk medicine in the form of infusion or decoction to treat gastrointestinal diseases and flatulence as a carminative, antiseptic, and anti-inflammatory agent. In this study, the essential oil (EO) composition of wild-grown L. nobilis L. leaves collected from seven different altitudinal locations in the Molise region and adjacent regions (Abruzzo and Campania) was investigated. EOs from the leaves were obtained by hydrodistillation and analyzed by GC-FID and GC/MS, and 78 compounds were identified. The major oil components were 1,8-cineol (43.52-31.31%), methyl-eugenol (14.96-4.07%), α-terpinyl acetate (13.00-8.51%), linalool (11.72-1.08%), sabinene (10.57-4.85%), α-pinene (7.41-3.61%), eugenol (4.12-1.97%), and terpinen-4-ol (2.33-1.25%). Chemometric techniques have been applied to compare the chemical composition. To shed light on the nutraceutical properties of the main hydrophobic secondary metabolites (≥1.0%) of laurel EOs, we assessed the in vitro antioxidant activities based on 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging activity and the reducing antioxidant power by using a ferric reducing power (FRAP) assay. Furthermore, we highlighted the anti-inflammatory effects of seven EOs able to interfere with the enzyme soluble epoxide hydrolase (sEH), a key enzyme in the arachidonic acid cascade, in concentrations ranging from 16.5 ± 4.3 to 8062.3 ± 580.9 mg/mL. Thanks to in silico studies, we investigated and rationalized the observed anti-inflammatory properties, ascribing the inhibitory activity toward the disclosed target to the most abundant volatile phytochemicals (≥1.0%) of seven EOs.

We have developed a biopsy technique aimed at preoperative evaluating the extent of Paget's vulvar disease in order to plan subsequent radical vulvar surgery. The aim is to find all possible lesion sites that are not visible macroscopically, to obtain a clear evaluation of the disease spread and to tailor the radical surgical procedure to remove even microscopic lesions, avoiding recurrences and excessively destructive surgery, adopting as conservative an approach as possible. We used this procedure for the first time to establish the radicality of the surgical intervention in a 68-year-old patient initially suffering from a single invasive vulvar Paget's lesion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Della Corte, Ascione and Bifulco.)

The cheese wine pairing is a beloved combination subject to a certain subjectivity due to sensorial, psychological, chemical, and cultural factors. This work represents a first attempt to explore the in vitro interactions between cheese, wine, and saliva to objectively measure the pairing. Two experimental red wines obtained from the same grape cultivar and four different cheeses were studied for their composition. Binding reactions between wine and cheese were carried out in three simulated tasting trials and, after precipitation, the wine phenolic content, Saliva Precipitation Index (SPI), and total proteins were evaluated. The optimal pairing (OP) was calculated considering the decrease in salivary and cheese proteins by wine, defined as the cleansing effect; the decrease in astringency due to the cheese, measured by the SPI, and the coating fat which would remain in mouth after eating a piece of cheese. Based on obtained results, the semi-hard cheese was identified as the best pairing option for the two experimental red wines. The differences in the phenolic content between the two wines were instead not enough to show a significant influence on the OP. The in vitro cheese wine pairing can contribute to understanding of wine tasting but it is only a part of the puzzle. However, this first contribution paves the way for additional studies on the molecular and chemical interactions involved in aroma and textural perception in simulated trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

This research focuses on the target deconvolution of the natural compound myrianthic acid, a triterpenoid characterized by an ursane skeleton isolated from the roots of Myrianthus arboreus and from Oenothera maritima Nutt. (Onagraceae), using MS-based chemical proteomic techniques. Application of drug affinity responsive target stability (DARTS) and targeted-limited proteolysis coupled to mass spectrometry (t-LiP-MS) led to the identification of the enzyme fatty acid synthase (FAS) as an interesting macromolecular counterpart of myrianthic acid. This result, confirmed by comparison with the natural ursolic acid, was thoroughly investigated and validated in silico by molecular docking, which gave a precise picture of the interactions in the MA/FAS complex. Moreover, biological assays showcased the inhibitory activity of myrianthic acid against the FAS enzyme, most likely related to its antiproliferative activity towards tumor cells. Given the significance of FAS in specific pathologies, especially cancer, the myrianthic acid structural moieties could serve as a promising reference point to start the potential development of innovative approaches in therapy.

Vulvar carcinoma is a rare cancer affecting the genital tract, constituting 4% of gynecological tumors. Vulvar squamous cell carcinoma (VSCC) is the most common type. Diagnosis relies on biopsy during vulvoscopy, plus imaging such as ultrasonography (USG), magnetic resonance imaging (MRI) and positron emission tomography (PET). This review aims to lay out a thorough overview as to the current preoperative management of VSCC, both in case of vulvar and lymph node involvement. The data research was conducted using the following databases: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library from 2010 to 2024. The selection criteria included only original articles. Seventeen studies were assessed for eligibility. A concordance rate of 62.3% for vHSIL and 65.2% for carcinoma at vulvoscopy, with a sensitivity of 98%, specificity of 40%, PPV (Positive Predictive Value) of 37% and NPV (Negative Predictive Value) of 98% in identifying malignant lesions was found. Regarding the reliability of PET for staging and assessing lymph node involvement, a mean SUV (Standardized Uptake Value) for malignant vulvar lesions of 8.4 (range 2.5-14.7) was reported. In the case of MRI, useful for the evaluation of loco-regional infiltration and lymph node involvement, the ratio of the short-to-long-axis diameter and the reader's diagnostic confidence for the presence of lymph node metastasis yielded accuracy of 84.8% and 86.9%, sensitivity of 86.7% and 87.5%, specificity of 81.3% and 86.2%, PPV of 89.7% and 87.5% and NPV of 76.5% and 86.2%, respectively. A long lymph node axis >10 mm and a short diameter >5.8 mm were found to be predictors of malignancy. At USG, instead, the two main characteristics of potentially malignant lymph nodes are cortical thickness and short axis length; the combination of these ultrasound parameters yielded the highest accuracy in distinguishing between negative and positive lymph nodes. Despite the heterogeneity of the included studies and the lack of randomized clinical trials, this review provides a broad overview of the three imaging tools used for the presurgical management of VSCC. Nowadays, although MRI and PET represent the gold standard, ultrasound evaluation is taking on a growing role, as long as it is carried out by expert sonographer. The management of this rare disease should be always performed by a multidisciplinary team in order to precisely stage the tumor and determine the most suitable treatment approach.

The development of BRD9 inhibitors involves the design and synthesis of molecules that can specifically bind the BRD9 protein, interfering with the function of the chromatin-remodeling complex ncBAF, with the main advantage of modulating gene expression and controlling cellular processes. Here, we summarize the work conducted over the past 10 years to find new BRD9 binders, with an emphasis on their structure-activity relationships, efficacies, and selectivities in preliminary studies. BRD9 is expressed in a variety of cancer forms, hence, its inhibition holds particular significance in cancer research. However, it is crucial to note that the expanding research in the field, particularly in the development of new degraders, may uncover new therapeutic potentials.

The clinical implementation of liquid biopsy has dramatically modified the analytical paradigm for several solid tumors. To date, however, only circulating free DNA (cfDNA) has been approved in clinical practice to select targeted treatments for patients with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and breast cancer (BC). Interestingly, emerging liquid biopsy analytes in peripheral blood, including circulating tumor cells (CTC), miRNA, and extracellular vesicles (EVs), have been shown to play a crucial role in the clinical management of solid tumor patients. Here, we review how these blood-based biomarkers may positively impact early diagnosis, prognosis, and treatment response in ovarian cancer (OC) patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs) are rare uterine mesenchymal neoplasms with uncertain biological potential. These tumors, which affect both premenopausal and postmenopausal women, usually have a benign clinical course. Nevertheless, local recurrences and distant metastases have been described. By analyzing 511 cases retrieved from individual reports and cases series, we provide here the most comprehensive overview of UTROSCT cases available in the literature, supplemented by two new cases of UTROSCTs. Case 1 was an asymptomatic 31-year-old woman who underwent a laparoscopic resection of a presumed leiomyoma. Case 2 was a 58-year-old postmenopausal woman with abnormal vaginal bleeding who underwent an outpatient hysteroscopic biopsy of a suspicious endometrial area. In both cases, immunohistochemical positivity for Calretinin and Inhibin was noted, typical for a sex cord differentiation. In both cases, total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed. In light of the available literature, no pathognomonic clinical or imaging finding can be attributed to UTROSCT. Patients usually present with abnormal uterine bleeding or pelvic discomfort, but 20% of them are asymptomatic. In most cases, a simple hysterectomy appears to be the appropriate treatment, but for women who wish to become pregnant, uterus-preserving approaches should be discussed after excluding risk factors. Age, tumor size, lymphovascular space invasion, nuclear atypia, and cervical involvement are not reliable prognostic factors in UTROSCT. The current research suggests that aggressive cases (with extrauterine spread or recurrence) can be identified based on a distinct genetic and immunohistochemical phenotype. For instance, UTROSCTs characterized by GREB1::NCOA1-3 fusions and PD-L1 molecule expression appear to be predisposed to more aggressive behaviors and recurrence, with GREB1::NCOA2 being the most common gene fusion in recurrent tumors. Hence, redefining the criteria for UTROSCTs may allow a better selection of women suitable for fertility-sparing treatments or requiring more aggressive treatments in the future.

The metabolite fingerprinting of four Italian commercial bean seed cultivars, i.e., Phaseolus Cannellino (PCANN), Controne (PCON), Vellutina (PVEL), and Occhio Nero (PON), were investigated by Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate data analysis. The hydroalcoholic and organic extract analysis disclosed more than 32 metabolites from various classes, i.e., carbohydrates, amino acids, organic acids, nucleosides, alkaloids, and fatty acids. PVEL, PCON, and PCANN varieties displayed similar chemical profiles, albeit with somewhat different quantitative results. The PON metabolite composition was slightly different from the others; it lacked GABA and pipecolic acid, featured a higher percentage of malic acid than the other samples, and showed quantitative variations of several metabolites. The lipophilic extracts from all four cultivars demonstrated the presence of omega-3 and omega-6 unsaturated fatty acids. After the determination of the total phenolic, flavonoids, and condensed tannins content, in vitro antioxidant activity was then assessed using the DPPH scavenging activity, the ABTS scavenging assay, and ferric-reducing antioxidant power (FRAP). Compared to non-dark seeds (PCON, PCANN), brown seeds (PVEL, PON) featured a higher antioxidant capacity. Lastly, only PON extract showed in vitro antifungal activity against the sclerotia growth of S. rolfsii , by inhibiting halo growth by 75%.

Mass spectrometry-based chemical proteomic approaches using limited proteolysis have become a powerful tool for the identification and analysis of the interactions between a small molecule (SM) and its protein target(s). Gracilioether A (GeA) is a polyketide isolated from a marine sponge, for which we aimed to trace the interactome using this strategy. DARTS (Drug Affinity Responsive Target Stability) and t-LiP-MS (targeted-Limited Proteolysis-Mass Spectrometry) represented the main techniques used in this study. DARTS was applied on HeLa cell lysate for the identification of the GeA target proteins, and t-LiP-MS was employed to investigate the protein's regions involved in the binding with GeA. The results were complemented through the use of binding studies using Surface Plasmon Resonance (SPR) and in silico molecular docking experiments. Ubiquitin carboxyl-terminal hydrolase 5 (USP5) was identified as a promising target of GeA, and the interaction profile of the USP5-GeA complex was explained. USP5 is an enzyme involved in the pathway of protein metabolism through the disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. This activity is connected to different cellular functions concerning the maintenance of chromatin structure and receptors and the degradation of abnormal proteins and cancerogenic progression. On this basis, this structural information opens the way to following studies focused on the definition of the biological potential of Gracilioether A and the rational development of novel USP5 inhibitors based on a new structural skeleton., Competing Interests: The authors declare no conflicts of interest.

Purpose: Uterine leiomyomas are benign uterine tumors. The choice of surgical treatment is guided by patient's age, desire to preserve fertility or avoid "radical" surgical interventions such as hysterectomy. In laparotomy, the issue of extracting the fibroid from the cavity does not arise. However, in laparoscopy and robotic surgery, this becomes a challenge. The aim of the present study was to determine the optimal surgical approach for fibroid extraction following laparoscopic or robotic myomectomy in terms of postoperative pain, extraction time, overall surgical time, scar size, and patient satisfaction., Methods: A total of 51 patients met the inclusion criteria and were considered in our analysis: 33 patients who had undergone the "ExCITE technique" (Group A), and 18 patients a minilaparotomy procedure (Group B), after either simple myomectomy, multiple myomectomy, supracervical hysterectomy, or total hysterectomy. The diagnosis of myoma was histologically confirmed in all cases., Results: Regarding the postoperative pain evaluation, at 6 h, patients reported 4 [3-4] vs 6 [5.3-7] on the VAS in Group A and B, as well as at 12 h, 2 [0-2] vs 3.5 [2.3-4] in Group A and B, respectively: both differences were statistically significant (p < 0.001). No statistically significant difference at 24 h from surgery was found. All patients in Group A were satisfied with the ExCITE technique, while in Group B only 67% of them. The length of the hospital stay was significantly shorter in Group A as compared to Group B (p = 0.007). In terms of the operative time for the extraction of the surgical specimen, overall operative time, and the scar size after the surgery, there was a statistically significant difference for those in Group A., Conclusion: The ExCITE technique does not require specific training and allows the surgeon to offer a minimally invasive surgical option for patients, with also an aesthetic result. It is a safe and standardized approach that ensures tissue extraction without the need for mechanical morcellation., (© 2023. The Author(s).)

Despite the existing body of evidence, there is still limited knowledge about the impact of SARS-CoV-2 positivity on delivery outcomes. We aimed to assess the impact of SARS-CoV-2 infection in women who gave birth at the University Hospital "Federico II" of Naples, Italy, between 2020 and 2021. We conducted a retrospective single-center population-based observational study to assess the differences in the caesarean section and preterm labor rates and the length of stay between women who tested positive for SARS-CoV-2 and those who tested negative at the time of labor. We further stratified the analyses considering the time period, dividing them into three-month intervals, and changes in SARS-CoV-2 as the most prevalent variant. The study included 5236 women with 353 positive cases. After vaccination availability, only 4% had undergone a complete vaccination cycle. The Obstetric Comorbidity Index was higher than 0 in 41% of the sample. When compared with negative women, positive ones had 80% increased odds of caesarean section, and it was confirmed by adjusting for the SARS-CoV-2 variant. No significant differences were found in preterm birth risks. The length of stay was 11% higher in positive cases but was not significant after adjusting for the SARS-CoV-2 variant. When considering only positive women in the seventh study period (July-September 2021), they had a 61% decrease in the odds of receiving a caesarean section compared to the fourth (October-December 2020). Guidelines should be implemented to improve the safety and efficiency of the delivery process, considering the transition of SARS-CoV-2 from pandemic to endemic. Furthermore, these guidelines should aim to improve the management of airborne infections in pregnant women.

Cervical cancer (CC) is the fourth most common cancer among women worldwide. The aim of this study is to focus on the state of the art of CC prevention, early diagnosis, and treatment and, within the latter, the role of surgery in the various stages of the disease with a focus on the impact of the LACC study (Laparoscopic Approach to Cervical Cancer trial) on the scientific debate and clinical practice. We have discussed the controversial application of minimally invasive surgery (MIS) for tumors < 2 cm and the possibility of fertility-sparing surgery on young women desirous of pregnancy. This analysis provides support for surgeons in the choice of better management, including patients with a desire for offspring and the need for sentinel node biopsy (SNB) rather than pelvic lymphadenectomy for tumors < 4 cm, and without suspicious lymph nodes' involvement on imaging. Vaccines and early diagnosis of pre-cancerous lesions are the most effective public health tool to tackle cervical cancer worldwide.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis, and it holds promise as a therapeutic strategy, but its role remains elusive. The aim of this study was to assess the existing evidence for the use or not of HIPEC in primary debulking surgery (PDS), interval debulking surgery (IDS), and recurrent ovarian cancer (ROC), evaluated in terms of survival rates and post-surgical morbidity., Methods: Medline, Pubmed, Cochrane, and Medscape were systematically searched for any article comparing the use of HIPEC treatment with any other therapy in patients with ovarian cancer in PDS, IDS, and ROC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. We only considered English-language published studies., Results: We included 14 studies, including two RCTs with a total of 1813 women, published between 2003 and 2023 with a recruitment period between 1998 and 2020. In PDS, there were no differences in progression-free survival (PFS) between HIPEC and controls [MD -5.53 months [95% CI -19.91 to 8.84 months]; I 2 = 96%]. Conversely, in patients treated with NACT, pooled results showed a significant survival advantage in terms of progression-free survival (PFS) and overall survival (OS) in the combined HIPEC plus IDS group rather than surgery alone [PFS: MD 4.68 months (95% CI 3.49 to 5.86 months, I 2 = 95%); OS: MD 11.81 months (95% CI 9.34 to 14.27 months); I 2 = 97%]. Concerning ROC patients, pooled MD did not show either a significant PFS difference between intervention and controls [MD 2.68 months (95% CI 433 to 9.70 months); I 2 = 95%], and OS significant difference (MD 6.69 months [95% CI -9.09 to 22.47 months]; I 2 = 98%). Severe post-operative complications (≥grade 3) were available in 10 studies, accounting for 1108 women. Overall, there was a slightly but significantly increased risk with the combined approach compared to controls [RR 1.26 (95% CI 1.02 to 1.55); I 2 = 0%]., Conclusions: The combination of HIPEC with cytoreductive surgery prolongs OS and PFS in advanced epithelial ovarian cancer after NACT with acceptable morbidity. However, additional trials are still needed to determine the effectiveness of HIPEC in primary and recurrence settings. In the era of personalized medicine, the correlation between the efficacy of HIPEC and biological and molecular findings represents a challenge for the future of ovarian cancer.

Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation promotes the expression of antioxidant enzymes in response to rising oxidative stress, resulting in reactive oxygen species (ROS) detoxification and playing a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Moreover, the biological effects of Nrf2 pathway activation contribute to reducing apoptosis and enhancing cell survival. The activity of Nrf2 is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). Prompted by the recent results reporting the impact of xanthone metabolites on oxidative stress, cancer, and inflammation, the antioxidant properties of xanthones isolated from Garcinia mangostana (γ-mangostin, α-mangostin, 8-deoxygartanin, demethylcalabaxanthone, garcinone D) were assessed. In particular, the capability of these natural products to disrupt the interaction between Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), triggering the activation of the Nrf2-mediated pathway, was evaluated using molecular docking experiments and in vitro tests. The modulation of some key Nrf2-related mediators like glutathione (GSH) and lactate dehydrogenase (LDH) to highlight a possible direct antioxidant effect was investigated. Among the tested compounds, demethylcalabaxanthone showed an indirect antioxidant effect, as corroborated by a Western blot assay, displaying a significant increase in the translocated protein upon its administration.