Development of a Promising Method for Producing Oligomeric Mixture of Branched Alkylene Guanidines to Improve Substance Quality and Evaluate Their Antiviral Activity against SARS-CoV-2.

This paper reports the synthesis of branched alkylene guanidines using microfluidic technologies. We describe the preparation of guanidine derivatives at lower temperatures, and with significantly less time than that required in the previously applicable method. Furthermore, the use of microfluidics allows the attainment of high-purity products with a low residual monomer content, which can expand the range of applications of this class of compounds.

A new thiol-independent mechanism of epithelial host defense against Pseudomonas aeruginosa: iNOS/NO sabotage of theft-ferroptosis.

Ferroptosis is a redox-driven type of regulated cell death program arising from maladaptation of three metabolic pathways: glutathione homeostasis, iron handling and lipid peroxidation. Though GSH/Gpx4 is the predominant system detoxifying phospholipid hydroperoxides (PLOOH) in mammalian cells, recently Gpx4-independent regulators of ferroptosis like ferroptosis suppressor protein 1 (FSP1) in resistant cancer lines and iNOS/NO in M1 macrophages have been discovered. We previously reported that Pseudomonas aeruginosa (PA) utilizes its 15- lipoxygenase (pLoxA) to trigger ferroptotic death in epithelial cells by oxidizing the host arachidonoyl-phosphatidylethanolamine (ETE-PE) into pro-ferroptotic 15-hydroperoxy- arachidonyl-PE (15-HpETE-PE).

[Peptide inhibitors of the interaction of the SARS-CoV-2 receptor-binding domain with the ACE2 cell receptor].

Computer simulation has been used to identify peptides that mimic the natural target of the SARS-CoV-2 coronavirus spike (S) protein, the angiotensin converting enzyme type 2 (ACE2) cell receptor. Based on the structure of the complex of the protein S receptor-binding domain (RBD) and ACE2, the design of chimeric molecules consisting of two 22-23-mer peptides linked to each other by disulfide bonds was carried out. The chimeric molecule X1 was a disulfide dimer, in which edge cysteine residues in the precursor molecules h1 and h2 were connected by the S-S bond.

Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial.

Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.

Prediction of delivery after 40 weeks by antepartum ultrasound in singleton multiparous women: a prospective cohort study.

Objective: Universal elective induction of labor (IOL) in singleton parous pregnancies has been advocated to reduce the rate of cesarean section (CD), without impacting on maternal outcome. However, about 50% of women deliver after 40 weeks; therefore, an accurate estimation of the time of delivery might avoid unnecessary early IOL. The aim of this study was to test the diagnostic accuracy of ultrasound in predicting delivery ≥40 weeks of gestation in singleton parous women.

Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV-Related Liver Cancer.

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. A possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, but also those not infected with HCV.

NO Represses the Oxygenation of Arachidonoyl PE by 15LOX/PEBP1: Mechanism and Role in Ferroptosis.

We recently discovered an anti-ferroptotic mechanism inherent to M1 macrophages whereby high levels of NO suppressed ferroptosis via inhibition of hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) production by 15-lipoxygenase (15LOX) complexed with PE-binding protein 1 (PEBP1). However, the mechanism of NO interference with 15LOX/PEBP1 activity remained unclear. Here, we use a biochemical model of recombinant 15LOX-2 complexed with PEBP1, LC-MS redox lipidomics, and structure-based modeling and simulations to uncover the mechanism through which NO suppresses ETE-PE oxidation.

Hydroxychloroquine in obstetric antiphospholipid syndrome: rationale and results of an observational study of refractory cases.

Background: The current recommended therapy of obstetric antiphospholipid syndrome (APS) is a long-term anticoagulant therapy that affects the final event, namely, when the thrombosis has already occurred. Unfortunately, this schedule is not always effective and fails despite the correct risk stratification and an adequate adjusted dose.

Materials And Methods: From 2013 to 2020 we observed 217 women with antiphospholipid antibodies and obstetric morbidities who were treated with conventional treatment protocol (aspirin low doses ± LMWH).

Previous and First Detected Cardiovascular Diseases in Patients with New Coronavirus Pneumonia: Possible Mechanisms and Place in a Unified Prognostic Model.

Purpose: The aim of this study is to evaluate the frequency of cardiac involvement in patients with coronavirus disease 2019 (COVID-19), possible immune mechanisms of myocardial injury, and the place of cardiovascular pathology among other prognostic factors.

Methods: The study included 86 patients (48 male, 60.2 ± 16.

SARS-CoV-2 Vaccine and Thrombosis: An Expert Consensus on Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Historically, the vaccination strategies developed in the second half of the 20th century have facilitated the eradication of infectious diseases. From the onset of COVID-19 pandemic to the end of April 2021, more than 150 million cases and 3 million deaths were documented worldwide with disruption of the economic and social activity, and with devastating material, physical, and psychological consequences. Reports of unusual and severe thrombotic events, including cerebral and splanchnic venous thrombosis and other autoimmune adverse reactions, such as immune thrombocytopenia or thrombotic microangiopathies in connection with some of the SARS-CoV-2 vaccines, have caused a great deal of concern within the population and the medical community.

Phenoxazine nucleoside derivatives with a multiple activity against RNA and DNA viruses.

Emerging and re-emerging viruses periodically cause outbreaks and epidemics all over the world, eventually leading to global events such as the current pandemic of the novel SARS-CoV-2 coronavirus infection COVID-19. Therefore, an urgent need for novel antivirals is crystal clear. Here we present the synthesis and evaluation of an antiviral activity of phenoxazine-based nucleoside analogs divided into three groups: (1) 8-alkoxy-substituted, (2) acyclic, and (3) carbocyclic.

Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1.

Ferroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown.

Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation.

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation.

Women perception of SARS-CoV-2 vaccination during pregnancy and subsequent maternal anxiety: a prospective observational study.

Objective: The use of Coronavirus 2 (SARS-CoV-2) vaccine in pregnant women is controversial and still not performed in Italy. Our objective was to evaluate the propensity of a population of Italian women to receive the vaccine and its psychological impact.

Methods: A prospective, observational study was performed on pregnant women attending Ospedale Cristo Re Università Roma TorVergata.

Using the Method of "Optical Biopsy" of Prostatic Tissue to Diagnose Prostate Cancer.

The possibilities of using optical spectroscopy methods in the differential diagnosis of prostate cancer were investigated. Analytical discrimination models of Raman spectra of prostate tissue were constructed by using the projections onto latent structures data analysis(PLS-DA) method for different wavelengths of exciting radiation-532 and 785 nm. These models allowed us to divide the Raman spectra of prostate cancer and the spectra of hyperplasia sites for validation datasets with the accuracy of 70-80%, depending on the specificity value.

Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study.

Introduction: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction.

Material And Methods: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria.

Counseling in maternal-fetal medicine: SARS-CoV-2 infection in pregnancy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic coronavirus that crossed species to infect humans, causing coronavirus disease 2019 (COVID-19). Despite a potentially higher risk of pregnant women acquiring SARS-CoV-2 infection compared with the non-pregnant population (particularly in some ethnic minorities), no additional specific recommendations to avoid exposure are needed in pregnancy. The most common clinical symptoms and laboratory signs of SARS-CoV-2 infection in pregnancy are fever, cough, lymphopenia and elevated C-reactive protein levels.

Effect of SARS-CoV-2 infection during the second half of pregnancy on fetal growth and hemodynamics: A prospective study.

Introduction: Our objective was to compare the fetal growth velocity and fetal hemodynamics in pregnancies complicated and in those not complicated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Material And Methods: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. The z scores of head circumference, abdominal circumference, femur length, and estimated fetal weight were compared between the two groups.