Pregnancy Outcomes in Non-Criteria Obstetric Antiphospholipid Syndrome: Analysis of a Cohort of 91 Patients.

: The clinical and laboratory features of patients with non-criteria obstetric antiphospholipid syndrome (NC-OAPS), as well as their pregnancy outcomes and ideal treatment are not clearly determined. The aim of this study is to describe the characteristics and outcomes of pregnancies in NC-OAPS and compare them with an obstetric APS (OAPS) cohort. : This is a retrospective study conducted on a cohort of women referred to a high-risk obstetric unit of a tertiary hospital.

Cardioprotection exerted by intravenous statin at index myocardial infarction event attenuates cardiac damage upon recurrent infarction.

Aims: Recurrent acute myocardial infarction (RE-AMI) is a frequent complication after STEMI, and its association with stent thrombosis can be life-threatening. Intravenous atorvastatin (IV-atorva) administration during AMI has been shown to limit infarct size and adverse cardiac remodeling. We determined by cardiac magnetic resonance (CMR) whether the cardioprotection exerted by IV-atorva at the index AMI event translates into a better prognosis upon RE-AMI in dyslipidemic pigs.

Circulating extracellular vesicles and neutrophil extracellular traps contribute to endothelial dysfunction in preeclampsia.

Background: Preeclampsia (PE) is a pregnancy complication characterized by hypertension, proteinuria, endothelial dysfunction, and complement dysregulation. Placenta-derived extracellular vesicles (EVs), necessary in maternal-fetal communication, might contribute to PE pathogenesis. Moreover, neutrophil extracellular traps (NETs) play a pathogenic role in other complement-mediated pathologies, and their contribution in PE remains unexplored.

Use of ctDNA in early breast cancer: analytical validity and clinical potential.

Circulating free tumor DNA (ctDNA) analysis is gaining popularity in precision oncology, particularly in metastatic breast cancer, as it provides non-invasive, real-time tumor information to complement tissue biopsies, allowing for tailored treatment strategies and improved patient selection in clinical trials. Its use in early breast cancer has been limited so far, due to the relatively low sensitivity of available techniques in a setting characterized by lower levels of ctDNA shedding. However, advances in sequencing and bioinformatics, as well as the use of methylome profiles, have led to an increasing interest in the application of ctDNA analysis in early breast cancer, from screening to curative treatment evaluation and minimal residual disease (MRD) detection.

Dearomative -Dihydroxylation of Naphthalenes with a Biomimetic Iron Catalyst.

Arenes are interesting feedstocks for organic synthesis because of their natural abundance. However, the stability conferred by aromaticity severely limits their reactivity, mostly to reactions where aromaticity is retained. Methods for oxidative dearomatization of unactivated arenes are exceedingly rare but particularly valuable because the introduction of Csp-O bonds transforms the flat aromatic ring in 3D skeletons and confers the oxygenated molecules with a very rich chemistry suitable for diversification.

An investigation of steric influence on the reactivity of Fe(O)(OH) tautomers in stereospecific C-H hydroxylation.

Two new tetradentate N4 ligands (LN4), LN4 = Me2,Me2PyzTACN (1-(2-(3,5-dimethyl-1-pyrazol-1-yl)ethyl)-4,7-dimethyl-1,4,7-triazacyclononane) and Me2,MeImTACN (1-((1-methyl-1-imidazol-1-yl)methyl)-4,7-dimethyl-1,4,7-triazacyclononane) have been synthesized and their corresponding Fe(II) complexes [Fe(Me2,Me2PyzTACN)(CFSO)], 1Pz, and [Fe(Me2,MeImTACN)(CFSO)], 1Im, have been prepared and characterized. Complexes 1Pz and 1Im catalyse the hydroxylation of C-H bonds of alkanes with excellent efficiencies, using hydrogen peroxide as oxidant. The high H/D kinetic isotope effect values for C-H hydroxylation, large normalized tertiary/secondary C-H (C3/C2) bond selectivities in adamantane oxidation, and high degrees of stereoretention in the oxidation of -1,2-dimethylcyclohexane are indicative of metal-based oxidation processes.

Effectiveness and Safety of Insulin Glargine 300 U/ml in Comparison with Insulin Degludec 100 U/ml Evaluated with Continuous Glucose Monitoring in Adults with Type 1 Diabetes and Suboptimal Glycemic Control in Routine Clinical Practice: The OneCARE Study.

Introduction: Data regarding efficacy of second-generation basal insulins (BI) using continuous glucose monitoring (CGM) come from clinical trials. We evaluated the effectiveness of insulin glargine 300 U/ml (Gla-300) compared to insulin degludec 100 U/ml (IDeg-100) in terms of percentage of time in range (TIR); 70-180 mg/dl was obtained from CGM in sub-optimally controlled patients with type 1 diabetes (T1D) in routine clinical practice.

Methods: This observational, multicenter, cross-sectional study included patients with T1D (> 3 years diabetes duration, HbA ≥ 7.

High rates of long-term progression in HIV-1-positive elite controllers.

Introduction: Elite controllers (EC) are a rare group of HIV-1-positive individuals who suppress viral loads (VL) to undetectable levels with elevated CD4 T-cell counts in the absence of ART. While rates of short- and mid-term progression have been described in these patients, few studies have focused on their long-term outcome This study aims to describe the virological and immunological behaviour in a cohort of elite controllers followed up for a median of 17 years in the University Hospital, and to identify factors that may be related to disease progression.

Methods: We conducted a descriptive, prospective and single-centre study of all HIV-positive adults recorded in the University Hospital database who met the definition criteria for EC.

Efficacy and safety of insulin glargine 300 U/mL (Gla-300) during hospitalization and therapy intensification at discharge in patients with insufficiently controlled type 2 diabetes: results of the phase IV COBALTA trial.

Introduction: This study assessed the efficacy and safety of insulin glargine 300 U/mL (Gla-300) during hospitalization and therapy intensification at discharge in insufficiently controlled people with type 2 diabetes.

Research Design And Methods: COBALTA (for its acronym in Spanish, COntrol Basal durante la hospitalizacion y al ALTA) was a multicenter, open-label, single-arm, phase IV trial including 112 evaluable inpatients with type 2 diabetes insufficiently controlled (glycosylated hemoglobin (HbA1c) 8%-10%) with basal insulin and/or non-insulin antidiabetic drugs. Patients were treated with a basal-bolus-correction insulin regimen with Gla-300 during the hospitalization and with Gla-300 and/or non-insulin antidiabetics for 6 months after discharge.

Clinical benefit and cost of breakthrough cancer drugs approved by the US Food and Drug Administration.

Background: The clinical benefit and pricing of breakthrough-designated cancer drugs are uncertain. This study compares the magnitude of the clinical benefit and monthly price of new and supplemental breakthrough-designated and non-breakthrough-designated cancer drug approvals.

Methods: A cross-sectional cohort comprised approvals of cancer drugs for solid tumors from July 2012 to December 2017.

Nickel-Catalyzed Decarbonylative Amination of Carboxylic Acid Esters.

The reaction of carboxylic acid derivatives with amines to form amide bonds has been the most widely used transformation in organic synthesis over the past century. Its utility is driven by the broad availability of the starting materials as well as the kinetic and thermodynamic driving force for amide bond formation. As such, the invention of new reactions between carboxylic acid derivatives and amines that strategically deviate from amide bond formation remains both a challenge and an opportunity for synthetic chemists.

Agency and responsibility over virtual movements controlled through different paradigms of brain-computer interface.

Key Points: Embodiment of a virtual body was induced and its movements were controlled by two different brain-computer interface (BCI) paradigms - one based on signals from sensorimotor versus one from visual cortical areas. BCI-control of movements engenders agency, but not equally for all paradigms. Cortical sensorimotor activation correlates with agency and responsibility.

Characterized cis-Fe(O)(OH) intermediate mimics enzymatic oxidations in the gas phase.

Fe(O)(OH) species have long been proposed to play a key role in a wide range of biomimetic and enzymatic oxidations, including as intermediates in arene dihydroxylation catalyzed by Rieske oxygenases. However, the inability to accumulate these intermediates in solution has thus far prevented their spectroscopic and chemical characterization. Thus, we use gas-phase ion spectroscopy and reactivity analysis to characterize the highly reactive [Fe(O)(OH)(tpa)] (3) complex.

Characterization of Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System for Controlled and Extended Release of Ranibizumab.

Purpose: To characterize a biodegradable microsphere-hydrogel drug delivery system (DDS) for controlled and extended release of ranibizumab.

Methods: The degradable microsphere-hydrogel DDSs were fabricated by suspending ranibizumab-loaded or blank poly(lactic-glycolic acid) microspheres within a poly(ethylene glycol)--(L-lactic-acid) diacrylate/N-isopropylacrylamide (PEG-PLLA-DA/NIPAAm) hydrogel. The thermal responsive behavior of various DDS formulations was characterized in terms of volume phase transition temperature (VPTT) and swelling ratios changes from 22°C to 42°C.

Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration Based on Single-Arm Trials.

This study uses the European Society of Medical Oncology Magnitude of Clinical Benefit Scale to evaluate the clinical benefit of anticancer drugs that gained approval by the US Food and Drug Administration based on single-arm rather than randomized clinical trials.

Microvasculature Recovery by Angiogenesis After Myocardial Infarction.

Advances in early reperfusion therapies focused on the revascularization of the ischemic tissues, in the last decades, lead to reduced mortality in acute myocardial infarction (MI) patients. However, a large proportion of patients show inadequate myocardial perfusion because of dysfunction of the microcirculation. The high prevalence of microvascular dysfunction after reperfusion therapies and the negative prognostic of this procedure justify the search for therapeutic strategies that aim to restore the microvascular network.

Silybum marianum provides cardioprotection and limits adverse remodeling post-myocardial infarction by mitigating oxidative stress and reactive fibrosis.

Aims: Milk thistle (Silybum marianum; SM) is an herb commonly used for hepatoprotection with antioxidant and antifibrotic properties. We investigated in pigs the cardiac effects of SM intake during the acute phase of myocardial infarction (MI) and remodeling period post-MI.

Methods: Study-1 tested the effect of SM use on the acute phase of MI.

Spectroscopic and DFT Characterization of a Highly Reactive Nonheme Fe-Oxo Intermediate.

The reaction of [(PyNMe)Fe(CFSO)], 1, with excess peracetic acid at -40 °C generates a highly reactive intermediate, 2b(PAA), that has the fastest rate to date for oxidizing cyclohexane by a nonheme iron species. It exhibits an intense 490 nm chromophore associated with an S = 1/2 EPR signal having g-values at 2.07, 2.

Mechanistically Driven Development of an Iron Catalyst for Selective Syn-Dihydroxylation of Alkenes with Aqueous Hydrogen Peroxide.

Product release is the rate-determining step in the arene syn-dihydroxylation reaction taking place at Rieske oxygenase enzymes and is regarded as a difficult problem to be resolved in the design of iron catalysts for olefin syn-dihydroxylation with potential utility in organic synthesis. Toward this end, in this work a novel catalyst bearing a sterically encumbered tetradentate ligand based in the tpa (tpa = tris(2-methylpyridyl)amine) scaffold, [Fe(CFSO)(tpa)], 1 has been designed. The steric demand of the ligand was envisioned as a key element to support a high catalytic activity by isolating the metal center, preventing bimolecular decomposition paths and facilitating product release.

Oxidation of alkane and alkene moieties with biologically inspired nonheme iron catalysts and hydrogen peroxide: from free radicals to stereoselective transformations.

The selective oxidation of hydrocarbons is a challenging reaction for synthetic chemists, but common in nature. Iron oxygenases activate the O-O bond of dioxygen to perform oxidation of alkane and alkenes moieties with outstanding levels of regio-, chemo- and stereoselectivity. Along a bioinspired approach, iron coordination complexes which mimic structural and reactivity aspects of the active sites of nonheme iron oxygenases have been explored as oxidation catalysts.

Pharmacodynamics assessment of Bemiparin after multiple prophylactic and single therapeutic doses in adult and elderly healthy volunteers and in subjects with varying degrees of renal impairment.

Introduction: Aging and renal impairment may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis.

Materials And Methods: Open, parallel study.

Genetic determinants of plasma β₂-glycoprotein I levels: a genome-wide association study in extended pedigrees from Spain.

Background: β2 -Glycoprotein I (β2 -GPI), also designated apolipoprotein H, is a 50-kDa protein that circulates in blood at high concentrations, playing important roles in autoimmune diseases, hemostasis, atherogenesis, and angiogenesis, as well as in host defense against bacteria and in protein/cellular waste removal. Plasma β2 -GPI levels have a significant genetic component (heritability of ~ 80%).

Objectives: To present the results of a genome-wide association study for plasma β2 -GPI levels in a set of extended pedigrees from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project.

A genome-wide association study identifies KNG1 as a genetic determinant of plasma factor XI Level and activated partial thromboplastin time.

Objective: Elevated plasma levels of coagulation factor XI (FXI) are implicated in the pathogenesis of venous thromboembolism and ischemic stroke, and polymorphisms in the F11 gene are associated both with risk of venous thromboembolism and an elevated plasma FXI level.

Methods And Results: Here, we report the first hypothesis-free genome-wide genetic analysis of plasma FXI levels. Two genome-wide significant loci were detected in the family-based Genetic Analysis of Idiopathic Thrombophilia 1 cohort: one located in the kininogen 1 gene (KNG1) (rs710446; P=7.