TFAP2C is a key regulator of intrauterine trophoblast cell invasion and deep hemochorial placentation.

Transcription factor AP-2 gamma ( ) has been identified as a key regulator of the trophoblast cell lineage and hemochorial placentation. The rat possesses deep placentation characterized by extensive intrauterine trophoblast cell invasion, which resembles human placentation. expressed in multiple trophoblast cell lineages, including invasive trophoblast cells situated within the uterine-placental interface of the rat placentation site.

Conditionally mutant animal model for investigating the invasive trophoblast cell lineage.

Placental development involves coordinated expansion and differentiation of trophoblast cell lineages possessing specialized functions. Among the differentiated trophoblast cell lineages are invasive trophoblast cells, which exit the placenta and invade the uterus, where they restructure the uterine parenchyma and facilitate remodeling of uterine spiral arteries. The rat exhibits deep intrauterine trophoblast cell invasion, a feature shared with human placentation, and is also amenable to gene manipulation using genome-editing techniques.

Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.

Importance: Patients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. β-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality.

Objectives: To assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support.

biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial.

Aim: To describe the protocol for a multi-centre randomised controlled trial to determine whether treatment protocols monitoring daily CRP (C-reactive protein) or PCT (procalcitonin) safely allow a reduction in duration of antibiotic therapy in hospitalised adult patients with sepsis.

Design: Multicentre three-arm randomised controlled trial.

Setting: UK NHS hospitals.

CONDITIONALLY MUTANT ANIMAL MODEL FOR INVESTIGATING THE INVASIVE TROPHOBLAST CELL LINEAGE.

Placental development involves coordinated expansion and differentiation of trophoblast cell lineages possessing specialized functions. Among the differentiated trophoblast cell lineages are invasive trophoblast cells, which exit the placenta and invade into the uterus where they restructure the uterine parenchyma and facilitate remodeling of uterine spiral arteries. The rat exhibits deep intrauterine trophoblast cell invasion, a feature shared with human placentation, and is also amenable to gene manipulation using genome editing techniques.

CORE CONSERVED TRANSCRIPTIONAL REGULATORY NETWORKS DEFINE THE INVASIVE TROPHOBLAST CELL LINEAGE.

The invasive trophoblast cell lineage in rat and human share crucial responsibilities in establishing the uterine-placental interface of the hemochorial placenta. These observations have led to the rat becoming an especially useful animal model to study hemochorial placentation. However, our understanding of similarities or differences between regulatory mechanisms governing rat and human invasive trophoblast cell populations is limited.

The AKT1-FOXO4 axis reciprocally regulates hemochorial placentation.

Hemochorial placentation involves the differentiation of invasive trophoblast cells, specialized cells that possess the capacity to exit the placenta and invade into the uterus where they restructure the vasculature. Invasive trophoblast cells arise from a well-defined compartment within the placenta, referred to as the junctional zone in rat and the extravillous trophoblast cell column in human. In this study, we investigated roles for AKT1, a serine/threonine kinase, in placental development using a genome-edited/loss-of-function rat model.

Conservation at the uterine-placental interface.

The hemochorial placentation site is characterized by a dynamic interplay between trophoblast cells and maternal cells. These cells cooperate to establish an interface required for nutrient delivery to promote fetal growth. In the human, trophoblast cells penetrate deep into the uterus.

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies.

Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure.

Intersection of regulatory pathways controlling hemostasis and hemochorial placentation.

Hemochorial placentation is characterized by the development of trophoblast cells specialized to interact with the uterine vascular bed. We utilized trophoblast stem (TS) cell and mutant rat models to investigate regulatory mechanisms controlling trophoblast cell development. TS cell differentiation was characterized by acquisition of transcript signatures indicative of an endothelial cell-like phenotype, which was highlighted by the expression of anticoagulation factors including tissue factor pathway inhibitor (TFPI).

PCB126 induced toxic actions on liver energy metabolism is mediated by AhR in rats.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in the regulation of biological responses to more planar aromatic hydrocarbons, like TCDD. We previously described the sequence of events following exposure of male rats to a dioxin-like polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), that binds avidly to the AhR and causes various types of toxicity including metabolic syndrome, fatty liver, and disruption of energy homeostasis. The purpose of this study was, to investigate the role of AhR to mediate those toxic manifestations following sub-acute exposure to PCB126 and to examine possible sex differences in effects.

The impact of the Queensland Government's Tackling Alcohol-Fuelled Violence Policy on live music performances in Fortitude Valley, Brisbane, Australia.

Introduction: The Queensland Government's Tackling Alcohol-Fuelled Violence (TAFV) Policy was met with concern from live music venue owners who feared decreased patronage and associated revenue. This study investigates the impact of the TAFV Policy on live music venues and performances in Fortitude Valley, an inner-city suburb of Brisbane, Australia recognised as a hub of live music performances.

Methods: Data relating to live music venues and performances in Fortitude Valley for the 2000-2018 financial years were obtained from the Australasian Performing Right Association (APRA AMCOS), who maintains an online data portal allowing artists to enter performance details to collect royalty payments.

Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT.

Background: Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes.

Objectives: The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use.

Design: This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation.

ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development.

Invasive trophoblast cells are critical to spiral artery remodeling in hemochorial placentation. Insufficient trophoblast cell invasion and vascular remodeling can lead to pregnancy disorders including preeclampsia, preterm birth, and intrauterine growth restriction. Previous studies in mice identified achaete-scute homolog 2 (ASCL2) as essential to extraembryonic development.

Long term outcomes of participants in the PARAMEDIC2 randomised trial of adrenaline in out-of-hospital cardiac arrest.

Aims: We recently reported early outcomes in patients enrolled in a randomised trial of adrenaline in out-of-hospital cardiac arrest: the PARAMEDIC2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest) trial. The purpose of the present paper is to report long-term survival, quality of life, functional and cognitive outcomes at 3, 6 and 12-months.

Methods: PARAMEDIC2 was a pragmatic, individually randomised, double blind, controlled trial with an economic evaluation.

Protective role of IL33 signaling in negative pregnancy outcomes associated with lipopolysaccharide exposure.

Interleukin 33 (IL33) signaling has been implicated in the establishment and maintenance of pregnancy and in pregnancy disorders. The goal of this project was to evaluate the role of IL33 signaling in rat pregnancy. The rat possesses hemochorial placentation with deep intrauterine trophoblast invasion; features also characteristic of human placentation.

Mechanical versus manual chest compressions in the treatment of in-hospital cardiac arrest patients in a non-shockable rhythm: A multi-centre feasibility randomised controlled trial (COMPRESS-RCT).

Background: Mechanical chest compression devices deliver high-quality chest compressions. Early data suggests that mechanical devices may be superior to manual chest compressions in adults following an in-hospital cardiac arrest patients. To determine the feasibility of undertaking an effectiveness trial in this population, we undertook a feasibility randomised controlled trial.

RECOVERY- Respiratory Support: Respiratory Strategies for patients with suspected or proven COVID-19 respiratory failure; Continuous Positive Airway Pressure, High-flow Nasal Oxygen, and standard care: A structured summary of a study protocol for a randomised controlled trial.

Objective: The trial objective is to determine if Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) is clinically effective compared to standard oxygen therapy in patients with confirmed or suspected COVID-19.

Trial Design: Adaptive (group-sequential), parallel group, pragmatic, superiority randomised controlled, open-label, multi-centre, effectiveness trial.

Participants: The trial is being conducted across approximately 60 hospitals across England, Wales, Scotland, and Northern Ireland.

Poorly controlled diabetes mellitus alters placental structure, efficiency, and plasticity.

Introduction: The hemochorial placenta provides a critical barrier at the maternal-fetal interface to modulate maternal immune tolerance and enable gas and nutrient exchange between mother and conceptus. Pregnancy outcomes are adversely affected by diabetes mellitus; however, the effects of poorly controlled diabetes on placental formation, and subsequently fetal development, are not fully understood.

Research Design And Methods: Streptozotocin was used to induce hyperglycemia in pregnant rats for the purpose of investigating the impact of poorly controlled diabetes on placental formation and fetal development.

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.

Background: Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine whether the use of epinephrine is safe and effective in such patients.

Methods: In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days.