Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant.

Importance: Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain.

Objective: To investigate the safety of a standardized perioperative DOAC management strategy.

Design, Setting, And Participants: The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018.

Hemodynamic factors associated with fetal cardiac remodeling in late fetal growth restriction: a prospective study.

Background Altered cardiac geometry affects a proportion of fetuses with growth restriction (FGR). The aim of this study was to explore the hemodynamic factors associated with cardiac remodeling in late FGR. Methods This was a prospective study of singleton pregnancies complicated by late-onset FGR undergoing assessment of left (LV) and right (RV) ventricular sphericity-index (SI).

Role of first-trimester umbilical vein blood flow in predicting large-for-gestational age at birth.

Objectives: To describe umbilical vein (UV) hemodynamics at 11 + 0 to 13 + 6 weeks of gestation in pregnancies delivering a large-for-gestational-age (LGA) neonate, and to build a multiparametric model, including pregnancy and ultrasound characteristics in the first trimester, that is able to predict LGA at birth.

Methods: This was a matched case-control study, of singleton pregnancies that underwent ultrasound examination at 11 + 0 to 13 + 6 weeks for aneuploidy screening, at a single center over a 4-year period. Cases were women who delivered a neonate with birth weight (BW) > 90 centile for gestational age and sex, according to local birth-weight standards, while controls were those who delivered a neonate with BW ranging between the 10 and 90 centiles, matched for maternal and gestational age, at a ratio of 1:3.

Role of Doppler ultrasound at time of diagnosis of late-onset fetal growth restriction in predicting adverse perinatal outcome: prospective cohort study.

Objective: Pregnancies complicated by late-onset fetal growth restriction (FGR) are at increased risk of short- and long-term morbidities. Despite this, identification of cases at higher risk of adverse perinatal outcome, at the time of FGR diagnosis, is challenging. The aims of this study were to elucidate the strength of association between fetoplacental Doppler indices at the time of diagnosis of late-onset FGR and adverse perinatal outcome, and to determine their predictive accuracy.

Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis.

Objectives: To determine the rate of a first recurrent venous thromboembolism (VTE) event after discontinuation of anticoagulant treatment in patients with a first episode of unprovoked VTE, and the cumulative incidence for recurrent VTE up to 10 years.

Design: Systematic review and meta-analysis.

Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials (from inception to 15 March 2019).

The use of a hybrid mannequin for the modern high-fidelity simulation in the labor ward: the Italian experience of the Ecografia Gestione Emergenze Ostetriche (EGEO) group.

Regular training in the management of intrapartum emergencies has been demonstrated to yield measurable benefits in terms of maternal and perinatal outcomes. Thanks to technologic advances, computerized, full-body mannequins have been created and made available for high-fidelity simulation in obstetrics. The technical skills subjected to training are conventionally represented by classical manual maneuvers, which are recommended in the case of instrumental vaginal delivery, shoulder dystocia, or postpartum hemorrhage.

Bioactive Oxylipins in Infants and Children With Congenital Heart Disease Undergoing Pediatric Cardiopulmonary Bypass.

Objectives: To determine the production of 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid during cardiopulmonary bypass in infants and children undergoing cardiac surgery, evaluate their relationship with increase in cell-free plasma hemoglobin, provide evidence of bioactivity through markers of inflammation and vasoactivity (WBC count, milrinone use, vasoactive-inotropic score), and examine their association with overall clinical burden (ICU/hospital length of stay and mechanical ventilation duration).

Design: Prospective observational study.

Setting: Twelve-bed cardiac ICU in a university-affiliated children's hospital.

Post-partum pelvic floor dysfunction assessed on 3D rotational ultrasound: a prospective study on women with first- and second-degree perineal tears and episiotomy.

To evaluate the morphology and biometry of pelvic floor structures 3 months after birth in women experiencing first- or second-degree perineal tears or undergoing episiotomy during labor. Prospective observational study including nulliparous women delivering at term with a clinical diagnosis of first- or second-degree perineal tears after birth or undergoing episiotomy. The role of Kristeller maneuver during labor in affecting pelvic structure and function is also explored.

Unusual thrombosis or pregnancy complications associated to ovarian cancers: two clinical cases.

Aim: Using illustrative cases of two patients with ovarian cancer who developed unusual thrombosis in pregnancy, to describe the difficulties in diagnosing and managing such patients.

Methods: We present the analysis of two cases of thrombosis of unusual localization (central artery of the retina and transverse and sigmoid sinus thrombosis) during pregnancy in women with hidden ovarian cancer.

Results: In both cases, the symptomatic of unususal thrombosis was interpreted as a manifestation of eclampsia, leading to a choice of non-optimal obstetric tactics on a background of hidden ovarian cancer, which in both cases were diagnosed only postpartum.

Women's compliance with ultrasound in labor: a prospective observational study.

Objective: To explore women's compliance with ultrasound evaluation (UE) during labor compared with standard vaginal examination (VE).

Methods: This is a prospective observational cohort study including uncomplicated singleton pregnancies with the fetus in vertex presentation from 37 weeks of gestation. Labor progress was assessed by both VE and UE.

Dendrigraft of Poly-l-lysine as a Promising Candidate To Reverse Heparin-based Anticoagulants in Clinical Settings.

By using a combination of experimental and computational experiments, we demonstrated that a second-generation dendrigraft of poly-l-lysine neutralizes the anticoagulant activity of unfractionated heparin, low-molecular-weight heparin, and fondaparinux more efficiently than protamine does in human plasma, making this synthetic polymer a promising surrogate of this problematic protein in clinical settings.

Interrogating Parkinson's disease associated redox targets: Potential application of CRISPR editing.

Loss of dopaminergic neurons in the substantia nigra is one of the pathogenic hallmarks of Parkinson's disease, yet the underlying molecular mechanisms remain enigmatic. While aberrant redox metabolism strongly associated with iron dysregulation and accumulation of dysfunctional mitochondria is considered as one of the major contributors to neurodegeneration and death of dopaminergic cells, the specific anomalies in the molecular machinery and pathways leading to the PD development and progression have not been identified. The high efficiency and relative simplicity of a new genome editing tool, CRISPR/Cas9, make its applications attractive for deciphering molecular changes driving PD-related impairments of redox metabolism and lipid peroxidation in relation to mishandling of iron, aggregation and oligomerization of alpha-synuclein and mitochondrial injury as well as in mechanisms of mitophagy and programs of regulated cell death (apoptosis and ferroptosis).

SENS-U: clinical evaluation of a full-bladder notification - a pilot study.

Introduction: Urinary incontinence is one of the most commonly treated disorders in children at school age. Recently, a new, wearable bladder sensor became available, the SENS-U Bladder Sensor. The SENS-U is a small, wireless ultrasonic sensor, which continuously monitors the bladder filling and provides a personalized notification when it is time to go to the toilet.

Aids to management of headache disorders in primary care (2nd edition) : on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache.

The Aids to Management are a product of the Global Campaign against Headache, a worldwide programme of action conducted in official relations with the World Health Organization. Developed in partnership with the European Headache Federation, they update the first edition published 11 years ago.The common headache disorders (migraine, tension-type headache and medication-overuse headache) are major causes of ill health.

Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury.

Spinal cord injury (SCI) is an incurable disorder with an unmet need of an effective treatment. Recently, autologous human bone marrow-derived stem cells have shown to promote functional improvement, due to their anti-inflammatory and regenerative/apocrine properties. In this study, the primary objective was to test whether a single intrathecal injection with a 100 μL suspension of 400,000 fresh human bone marrow-derived CD34 and an equal number of CD105 stem cells (Neuro-Cells (NC)), one day after balloon-compression of the spinal cord, improves motor function and reduces secondary damage in immunodeficient rats.

[Small Molecular Inhibitors of DNA Double Strand Break Repair Pathways Increase the ANTI-HBV Activity of CRISPR/Cas9].

The CRISPR/Cas9 nuclease system can effectively suppress the replication of the hepatitis B virus (HBV), while covalently closed circular DNA (cccDNA), a highly resistant form of the virus, persists in the nuclei of infected cells. The most common outcome of DNA double-strand breaks (DSBs) in cccDNA caused by CRISPR/Cas9 is double-strand break repair by nonhomologous end-joining, which results in insertion/deletion mutations. Modulation of the DNA double-strand break repair pathways by small molecules was shown to stimulate CRISPR/Cas9 activity and may potentially be utilized to enhance the elimination of HBV cccDNA.

[The need for specific toothpaste in patients receiving occlusal splint therapy].

The aim of the study is to determine the optimal properties of toothpaste for patients receiving occlusal splint therapy. The study comprised 50 people with full dentition (21 male and 29 female) divided into two groups. The main group included 25 individuals receiving occlusal splint therapy while 25 people who did not use splints were recruited as controls.

Redox (phospho)lipidomics of signaling in inflammation and programmed cell death.

In addition to the known prominent role of polyunsaturated (phospho)lipids as structural blocks of biomembranes, there is an emerging understanding of another important function of these molecules as a highly diversified signaling language utilized for intra- and extracellular communications. Technological developments in high-resolution mass spectrometry facilitated the development of a new branch of metabolomics, redox lipidomics. Analysis of lipid peroxidation reactions has already identified specific enzymatic mechanisms responsible for the biosynthesis of several unique signals in response to inflammation and regulated cell death programs.

Fatty acid transport protein 2 reprograms neutrophils in cancer.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are pathologically activated neutrophils that are crucial for the regulation of immune responses in cancer. These cells contribute to the failure of cancer therapies and are associated with poor clinical outcomes. Despite recent advances in the understanding of PMN-MDSC biology, the mechanisms responsible for the pathological activation of neutrophils are not well defined, and this limits the selective targeting of these cells.

"Redox lipidomics technology: Looking for a needle in a haystack".

Aerobic life is based on numerous metabolic oxidation reactions as well as biosynthesis of oxygenated signaling compounds. Among the latter are the myriads of oxygenated lipids including a well-studied group of polyunsaturated fatty acids (PUFA) - octadecanoids, eicosanoids, and docosanoids. During the last two decades, remarkable progress in liquid-chromatography-mass spectrometry has led to significant progress in the characterization of oxygenated PUFA-containing phospholipids, thus designating the emergence of a new field of lipidomics, redox lipidomics.

Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics.

The peroxidation of cardiolipins by reactive oxygen species, which is regulated and enhanced by cytochrome c (cyt c), is a critical signaling event in mitochondrial apoptosis. We probe the molecular underpinnings of this mitochondrial death signal through structural and functional studies of horse heart cyt c binding to mixed-lipid membranes containing cardiolipin with mono- and polyunsaturated acyl chains. Lipidomics reveal the selective oxidation of polyunsaturated fatty acid (PUFA) cardiolipin (CL), while multidimensional solid-state NMR probes the structure and dynamics of the membrane and the peripherally bound protein.

Lipidomics Detection of Brain Cardiolipins in Plasma Is Associated With Outcome After Cardiac Arrest.

Objectives: Brain mitochondrial dysfunction limits neurologic recovery after cardiac arrest. Brain polyunsaturated cardiolipins, mitochondria-unique and functionally essential phospholipids, have unprecedented diversification. Since brain cardiolipins are not present in plasma normally, we hypothesized their appearance would correlate with brain injury severity early after cardiac arrest and return of spontaneous circulation.

Ferroptotic cell death and TLR4/Trif signaling initiate neutrophil recruitment after heart transplantation.

Non-apoptotic forms of cell death can trigger sterile inflammation through the release of danger-associated molecular patterns, which are recognized by innate immune receptors. However, despite years of investigation the mechanisms which initiate inflammatory responses after heart transplantation remain elusive. Here, we demonstrate that ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, decreases the level of pro-ferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamine, reduces cardiomyocyte cell death and blocks neutrophil recruitment following heart transplantation.

[Possibilities of application of the liquid transport medium for capture of pathological material at laboratory diagnosis of a diphtheria infection.].

The main objective of laboratory diagnosis of a diphtheria is identification of the causative agent by means of the minimum quantity of diagnostic tests for obtaining the authentic answer in the most short time. One of the major stages is capture and delivery of pathological material on which the efficiency of carrying out and timeliness of issue of the final answer depends. Considering emergence in the market of commercial liquid transport mediums, assessment of their efficiency for diagnosis of diphtheria is advisable.

Characterization of Differential Dynamics, Specificity, and Allostery of Lipoxygenase Family Members.

Accurate modeling of structural dynamics of proteins and their differentiation across different species can help us understand generic mechanisms of function shared by family members and the molecular basis of the specificity of individual members. We focused here on the family of lipoxygenases, enzymes that catalyze lipid oxidation, the mammalian and bacterial structures of which have been elucidated. We present a systematic method of approach for characterizing the sequence, structure, dynamics, and allosteric signaling properties of these enzymes using a combination of structure-based models and methods and bioinformatics tools applied to a data set of 88 structures.