VP39.04: Early/late‐IUGR treated with NO donors transdermal patches: prognostic and predictive value of maternal hemodynamic assessment at the onset of therapy

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VP39.01: Maternal hemodynamics and umbilical vein flow in fetal growth restriction

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Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer

In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa

Maternal cardiovascular dysfunction is associated with hypoxic cerebral and umbilical doppler changes

We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as z-scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI; the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (z-score 97, p = 0.02) and PVR higher (z-score 2.88, p = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention

C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition

Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring

H19-Dependent Transcriptional Regulation of \u3b23 and \u3b24 Integrins Upon Estrogen and Hypoxia Favors Metastatic Potential in Prostate Cancer.

Estrogen and hypoxia promote an aggressive phenotype in prostate cancer (PCa), driving transcription of progression-associated genes. Here, we molecularly dissect the contribution of long non-coding RNA H19 to PCa metastatic potential under combined stimuli, a topic largely uncovered. The effects of estrogen and hypoxia on H19 and cell adhesion molecules' expression were investigated in PCa cells and PCa-derived organotypic slice cultures (OSCs) by qPCR and Western blot. The molecular mechanism was addressed by chromatin immunoprecipitations, overexpression, and silencing assays. PCa cells' metastatic potential was analyzed by in vitro cell-cell adhesion, motility test, and trans-well invasion assay. We found that combined treatment caused a significant H19 down-regulation as compared with hypoxia. In turn, H19 acts as a transcriptional repressor of cell adhesion molecules, as revealed by up-regulation of both \u3b23 and \u3b24 integrins and E-cadherin upon H19 silencing or combined treatment. Importantly, H19 down-regulation and \u3b2 integrins induction were also observed in treated OSCs. Combined treatment increased both cell motility and invasion of PCa cells. Lastly, reduction of \u3b2 integrins and invasion was achieved through epigenetic modulation of H19-dependent transcription. Our study revealed that estrogen and hypoxia transcriptionally regulate, via H19, cell adhesion molecules redirecting metastatic dissemination from EMT to a \u3b2 integrin-mediated invasion

The correlation between exaggerated fluid in lumbar facet joints and degenerative spondylolisthesis: prospective study of 52 patients

Magnetic resonance imaging (MRI) is often used to evaluate low back pain; however, MRI in the supine position does not always reveal degenerative spondylolisthesis. The existence of a linear correlation between increased fluid in the facet joints seen on the supine axial T2 MRI of the lumbosacral spine and lumbar instability seen on standing lateral flexion-extension lumbosacral radiographs has recently been reported. The objective of this prospective study was to determine the incidence of increased fluid in the lumbar facet joints seen on the supine axial T2 MRI, and to evaluate the correlation of this finding with radiographic evidence of lumbar instability

Vaccination against SARS-CoV-2 in pregnancy during the Omicron wave: the prospective cohort study of the Italian obstetric surveillance system

Objectives: Evidence on the effects of the SARS-CoV-2 Omicron variant on vaccinated and unvaccinated pregnant women is sparse. This study aimed to compare maternal and perinatal outcomes of women infected with SARS-CoV-2 during the Omicron wave in Italy, according to their vaccine protection.Methods: This national prospective cohort study enrolled pregnant women with a positive SARS-CoV-2 nasopharyngeal swab within 7 days of hospital admission between 1 January and 31 May, 2022. Women who received at least one dose of vaccine during pregnancy and those who completed the vaccine cycle with the first booster were considered protected against moderate or severe COVID-19 (MSCD). A multivariable logistic regression model evaluated the association between vaccine protection and disease severity. Maternal age, educational level, citizenship, area of birth, previous comorbidities, and obesity were analysed as potential risk factors. Results: MSCD was rare (41/2147, 1.9%; 95% CI, 1.4-2.6), and the odds of developing it were significantly higher among unprotected women (OR, 2.78; 95% CI, 1.39-5.57). Compared with protected women (n = 1069), the unprotected (n = 1078) were more often younger, with lower educational degrees, and foreigners. A higher probability of MSCD was found among women with previous comorbidities (OR, 2.86; 95% CI, 1.34-6.12) and those born in Asian countries (OR, 3.05; 95% CI, 1.23-7.56). The percentage of preterm birth was higher among women with MSCD compared with milder cases (32.0% [8/25] versus 8.4% [161/1917], p < 0.001) as well as the percentage of caesarean section (52.0% [13/25] versus 31.6% [606/1919], p 0.029). Discussion: Although severe maternal and perinatal outcomes were rare, their prevalence was significantly higher among women without vaccine protection. Vaccination during pregnancy has the potential to protect both the mother and the baby, and it is therefore strongly recommended. Edoardo Corsi Decenti, Clin Microbiol Infect 2023;29:772 (c) 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved