Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic

Synthesis, X-ray structure analysis and density functional study of an unusual anhydrous 5,6-dimethylbenzo-1,3-imidazolium(H3) chloride

The heteroaromatic base 5,6-dimethylbenzo-1,3-imidazole (DMBI) proved to be a Brönsted base in an anhydrous ethanol solution, which contained fac,trans-[Ru(CO)3Cl2]2 at 55 C in air when the DMBI:Ru molar ratio was 2:1. The reaction produced colorless anhydrous single crystals of {(HDMBI)+Cl}, C9H11ClN2, which were collected and analyzed using X-ray diffraction (XRD) techniques. A network of N–HCl hydrogen bond type interactions linking the protonated hetero-aromatic base to the chloride anions (bridging bases) stabilizes the crystal and mimics the N–HCl interactions that play important roles in CCl channel biological systems. The shortest NCl contact distance and corresponding N–HCl angle are 3.073(3) Å and 173(3), respectively. The packing is also assisted by weaker C–HCl hydrogen bond-type interactions and an extensive network of pp stacking interactions involving HDMBI+ cations. Density functional calculations at the B3LYP/6-31G⁄⁄ and /6-311++G⁄⁄ levels for models of fragments of the crystal structure allowed for the evaluation of geometric parameters, hydrogen bond-type interaction formation energies, and infrared parameters for {(HDMBI)+Cl} and {(HDMBI)+Cl(HDMBI)+}

Pathogenic Role of the Sphingosine 1-Phosphate (S1P) Pathway in Common Gynecologic Disorders (GDs): A Possible Novel Therapeutic Target

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid, noteworthy for its involvement both in the modulation of various biological processes and in the development of many diseases. S1P signaling can be either pro or anti-inflammatory, and the sphingosine kinase (SphK)-S1P-S1P receptor (S1PR) axis is a factor in accelerating the growth of several cells, including endometriotic cells and fibrosis. Gynecologic disorders, including endometriosis, adenomyosis, and uterine fibroids are characterized by inflammation and fibrosis. S1P signaling and metabolism have been shown to be dysregulated in those disorders and they are likely implicated in their pathogenesis and pathophysiology. Enzymes responsible for inactivating S1P are the most affected by the dysregulation of S1P balanced levels, thus causing accumulation of sphingolipids within these cells and tissues. The present review highlights the past and latest evidence on the role played by the S1P pathways in common gynecologic disorders (GDs). Furthermore, it discusses potential future approaches in the regulation of this signaling pathway that could represent an innovative and promising therapeutical target, also for ovarian cancer treatment

Hypovitaminosis D and "small burden" uterine fibroids: Opportunity for a vitamin D supplementation

The aim of this study was to evaluate the effect of vitamin D supplementation in women with hypovitaminosis D and "small burden" uterine fibroids.This study focused on 208 women diagnosed with uterine fibroids and concomitant hypovitaminosis D, from January to December 2014. One hundred eight women of the initial study population were diagnosed with "small burden" uterine fibroids. Among them, those who underwent a proper vitamin D supplementation constituted the "study group" (n = 53), while women who spontaneously refused the therapy or did not perform it properly, constituted the "control group" (n = 55). The characteristics of uterine fibroids, the fibroid-related symptoms, and the vitamin D serum levels were evaluated 12 months after the initial diagnosis.In women with uterine fibroids, a negative correlation emerged between the baseline 25-hydroxy-cholecalciferol (25-OH-D3) concentration and both the volume of the largest fibroid (r = -0.18, P = 0.01) and the total volume of fibroids (r = -0.19, P = 0.01). No correlation was found between the baseline 25-OH-D3 levels and the number of fibroids per patient (r = -0.10, P = 0.16). In women of the "study group," a significant increase in the 25-OH-D3 serum level was observed after 12 months of supplementation, and a lower rate of surgical or medical treatment due to the "progression to extensive disease" was reported (13.2% vs 30.9%, P = 0.05).Supplementation therapy with 25-OH-D3 restores normal vitamin D serum levels in women with "small burden" fibroids. In these women, vitamin D supplementation seems to reduce the progression to an extensive disease, and thus the need of conventional surgical or medical therapy

Ru(CO)x-core complexes with selected azoles: Synthesis, X-ray structure, spectroscopy, DFT analysis and evaluation of cytotoxic activity against human cancer cells

The reaction of [RuII(CO) Cl ], 1, in methanol with azoles affords complexes that contain the fac-{RuII 262 (CO)3}2+-core. The complexes presented in this paper have the general formula fac-[RuII(CO)3Cl2L], with a molecule L of imidazole (IM), 2, or N-methyl-imidazole (MIM), 3, as a ligand in the pseudo-octahedral coor- dination sphere that is completed by two chlorido ligands cis to each other. The compounds show an appre- ciable solubility in water (up to ca 1 g/L) at 25 °C, and are well soluble in other solvents, such as alcohol, acetone, dicholoromethane, dimethylsulfoxide, and in mixtures of solvents. In the case where water is pres- ent in the medium (10% v/v or higher), significant dissociation of the Ru–N bond that is trans to a carbonyl ligand occurs, and a series of substitutions and other types of reactions may take place afterwards, depend- ing on the reactants and the applied experimental conditions. The synthesis and isolation of single crystals of 2 was performed by reacting the starting dimer 1 with 1-acetylimidazole in alcohol medium. DFT structure simulations/optimizations were carried out at Becke3lyp level of theory by using several basis sets up to 6-311++G⁄⁄ for C, H, Cl, N and O atoms, and the Lanl2DZ pseudo-potential for Ru. In vitro cytotoxicity tests for 2, 3 and fac-[RuII(CO)3Cl2(THZ)] (THZ = 1,3-thiazole), 4, showed IC50 values mostly in the range 100–200 lM in CH1 (ovarian carcinoma) and SW480 (colon carcinoma) cell lines. ESI-MS studies revealed the ability of these complexes to link the model proteins Lysozyme and Cytochrome c and similar binding patterns are highlighted; interestingly, protein binding is accompanied by a partial release of the original ligands. Fragments of the type [RuII(CO)2]2+ or [RuII(CO)]2+ are found associated to the proteins

{Ru(CO)x}-core complexes with selected azoles: Synthesis, X-ray structure, spectroscopy, DFT analysis and evaluation of cytotoxic activity against human cancer cells

The reaction of [RuII2(CO)6Cl2], 1, in methanol with azoles affords complexes that contain the fac-{RuII (CO)3}2+-core. The complexes presented in this paper have the general formula fac-[RuII(CO)3Cl2L], with a molecule L of imidazole (IM), 2, or N-methyl-imidazole (MIM), 3, as a ligand in the pseudo-octahedral coordination sphere that is completed by two chlorido ligands cis to each other. The compounds show an appreciable solubility in water (up to ca 1 g/L) at 25 C, and are well soluble in other solvents, such as alcohol, acetone, dicholoromethane, dimethylsulfoxide, and in mixtures of solvents. In the case where water is present in the medium (10% v/v or higher), significant dissociation of the Ru–N bond that is trans to a carbonyl ligand occurs, and a series of substitutions and other types of reactions may take place afterwards, depending on the reactants and the applied experimental conditions. The synthesis and isolation of single crystals of 2 was performed by reacting the starting dimer 1 with 1-acetylimidazole in alcohol medium. DFT structure simulations/optimizations were carried out at Becke3lyp level of theory by using several basis sets up to 6-311++G⁄⁄ for C, H, Cl, N and O atoms, and the Lanl2DZ pseudo-potential for Ru. In vitro cytotoxicity tests for 2, 3 and fac-[RuII(CO)3Cl2(THZ)] (THZ = 1,3-thiazole), 4, showed IC50 values mostly in the range 100–200 lM in CH1 (ovarian carcinoma) and SW480 (colon carcinoma) cell lines. ESI-MS studies revealed the ability of these complexes to link the model proteins Lysozyme and Cytochrome c and similar binding patterns are highlighted; interestingly, protein binding is accompanied by a partial release of the original ligands. Fragments of the type [RuII(CO)2]2+ or [RuII(CO)]2+ are found associated to the proteins

Middle alternatives revisited: How the neither/nor response acts as a 'face-saving' way of saying 'I don't know'

A persistent problem in the design of bipolar attitude questions is whether or not to include a middle response alternative. On the one hand, it is reasonable to assume that people might hold opinions which are 'neutral' with regard to issues of public controversy. On the other, question designers suspect that offering a mid-point may attract respondents with no opinion, or those who lean to one side of an issue but do not wish to incur the cognitive costs required to determine a directional response. Existing research into the effects of offering a middle response alternative has predominantly used a split-ballot design, in which respondents are assigned to conditions which offer or omit a midpoint. While this body of work has been useful in demonstrating that offering or excluding a mid-point substantially influences the answers respondents provide, it does not offer any clear resolution to the question of which format yields more accurate data. In this paper, we use a different approach. We use follow-up probes administered to respondents who initially select the mid-point to determine whether they selected this alternative in order to indicate opinion neutrality, or to indicate that they do not have an opinion on the issue. We find the vast majority of responses turn out to be what we term 'face-saving don't knows' and that reallocating these responses from the mid-point to the don't know category significantly alters descriptive and multivariate inferences. Counter to the survey-satisficing perspective, we find that those with this tendency is greatest amongst those who express more interest in the topic area