OMX: A NOVEL OXYGEN DELIVERY BIOTHERAPEUTIC IMPROVES OUTCOMES IN AN OVINE MODEL OF CONTROLLED HEMORRHAGIC SHOCK.

Hemorrhagic shock is a major source of morbidity and mortality worldwide. While whole blood or blood product transfusion is a first-line treatment, maintaining robust supplies presents significant logistical challenges, particularly in austere environments. OMX is a novel nonhemoglobin (Hb)-based oxygen carrier derived from the H-NOX (heme-nitric oxide/oxygen binding) protein family.

The effect of fertility treatment and socioeconomic status on neonatal and post-neonatal mortality in the United States.

Objective: To determine the association between fertility treatment, socioeconomic status (SES), and neonatal and post-neonatal mortality.

Study Design: Retrospective cohort study of all births (19,350,344) and infant deaths from 2014-2018 in the United States. The exposure was mode of conception-spontaneous vs fertility treatment.

Effect of Clemastine on Neurophysiological Outcomes in an Ovine Model of Neonatal Hypoxic-Ischemic Encephalopathy.

Originally approved by the U.S. Food and Drug Administration (FDA) for its antihistamine properties, clemastine can also promote white matter integrity and has shown promise in the treatment of demyelinating diseases such as multiple sclerosis.

Perinatal Azithromycin Provides Limited Neuroprotection in an Ovine Model of Neonatal Hypoxic-Ischemic Encephalopathy.

Background: Hypoxic-ischemic brain injury/encephalopathy affects about 1.15 million neonates per year, 96% of whom are born in low- and middle-income countries. Therapeutic hypothermia is not effective in this setting, possibly because injury occurs significantly before birth.

Fertility treatment increases the risk of preterm birth independent of multiple gestations.

Objective: To investigate the complex interplay between fertility treatment, multiple gestations, and prematurity.

Design: Retrospective cohort study linking the national Center for Disease Control and Prevention infant birth and death data from 2014 to 2018.

Setting: National database from Center of Disease Control and Prevention.

Comparing the efficacy in reducing brain injury of different neuroprotective agents following neonatal hypoxia-ischemia in newborn rats: a multi-drug randomized controlled screening trial.

Intrapartum hypoxia-ischemia leading to neonatal encephalopathy (NE) results in significant neonatal mortality and morbidity worldwide, with > 85% of cases occurring in low- and middle-income countries (LMIC). Therapeutic hypothermia (HT) is currently the only available safe and effective treatment of HIE in high-income countries (HIC); however, it has shown limited safety or efficacy in LMIC. Therefore, other therapies are urgently required.

Placental pathology is necessary to understand common pregnancy complications and achieve an improved taxonomy of obstetrical disease.

The importance of a fully functioning placenta for a good pregnancy outcome is unquestioned. Loss of function can lead to pregnancy complications and is often detected by a thorough placental pathologic examination. Placental pathology has advanced the science and practice of obstetrics and neonatal-perinatal medicine by classifying diseases according to underlying biology and specific patterns of injury.

Defining Longer-Term Outcomes in an Ovine Model of Moderate Perinatal Hypoxia-Ischemia.

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 1 million infants born with HIE each year survive with cerebral palsy and/or serious cognitive disabilities. While infants born with mild and severe HIE frequently result in predictable outcomes, infants born with moderate HIE exhibit variable outcomes that are highly unpredictable.

Outcomes of Very Preterm Infants Conceived with Assisted Reproductive Technologies.

Objective: To compare mortality and early respiratory outcomes of very preterm infants conceived via assisted reproductive technology (ART) vs spontaneously.

Study Design: We identified inborn infants (July 2014-July 2019) with gestational age <32 weeks (n = 439); 54 cases were ART conceived. Spontaneously conceived controls (n = 103) were matched by multiple gestation status and gestational age.

Monitoring deep-tissue oxygenation with a millimeter-scale ultrasonic implant.

Vascular complications following solid organ transplantation may lead to graft ischemia, dysfunction or loss. Imaging approaches can provide intermittent assessments of graft perfusion, but require highly skilled practitioners and do not directly assess graft oxygenation. Existing systems for monitoring tissue oxygenation are limited by the need for wired connections, the inability to provide real-time data or operation restricted to surface tissues.

HIF-1α promotes cellular growth in lymphatic endothelial cells exposed to chronically elevated pulmonary lymph flow.

Normal growth and development of lymphatic structures depends on mechanical forces created by accumulating interstitial fluid. However, prolonged exposure to pathologic mechanical stimuli generated by chronically elevated lymph flow results in lymphatic dysfunction. The mechanisms that transduce these mechanical forces are not fully understood.

Effect of culture conditions and method of conception on mouse live birth rate.

Objective: To understand in a mouse model whether there are differences in the decidua and live birth rate after transfer of blastocysts generated by in vitro fertilization (IVF) or by superovulation with spontaneous mating into unstimulated recipients.

Design: Animal experiment.

Setting: University-affiliated tertiary hospital.

Sex-specific epigenetic profile of inner cell mass of mice conceived in vivo or by IVF.

The preimplantation stage of development is exquisitely sensitive to environmental stresses, and changes occurring during this developmental phase may have long-term health effects. Animal studies indicate that IVF offspring display metabolic alterations, including hypertension, glucose intolerance and cardiac hypertrophy, often in a sexual dimorphic fashion. The detailed nature of epigenetic changes following in-vitro culture is, however, unknown.

Defining the ATPome reveals cross-optimization of metabolic pathways.

Disrupted energy metabolism drives cell dysfunction and disease, but approaches to increase or preserve ATP are lacking. To generate a comprehensive metabolic map of genes and pathways that regulate cellular ATP-the ATPome-we conducted a genome-wide CRISPR interference/activation screen integrated with an ATP biosensor. We show that ATP level is modulated by distinct mechanisms that promote energy production or inhibit consumption.

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.

The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to the lysosome for enzymatic degradation and recycling of metabolic precursors. Autophagy is a major cellular defense against oxidative stress, or related conditions that cause accumulation of damaged proteins or organelles. Selective forms of autophagy can maintain organelle populations or remove aggregated proteins.

Human placental trophoblast progenitor cells (hTPCs) promote angiogenesis and neurogenesis after focal cerebral ischemia in rats.

Introduction: Reduction of blood flow below a threshold value in brain regions locally or globally is called cerebral ischemia and proper treatment requires either the restoration of normal blood flow and/or the administration of neuroprotective therapies. Human trophoblast progenitor cells (hTPCs) give rise to the placenta and are responsible for the invasion and vascular remodeling of the maternal vessels within the uterus. Here, we tested whether hTPCs promoted to differentiate along neural lineages may exhibit therapeutic properties in the setting of cerebral ischemia .

Mechanical forces alter endothelin-1 signaling: comparative ovine models of congenital heart disease.

The risk and progression of pulmonary vascular disease in patients with congenital heart disease is dependent on the hemodynamics associated with different lesions. However, the underlying mechanisms are not understood. Endothelin-1 is a potent vasoconstrictor that plays a key role in the pathology of pulmonary vascular disease.

Outcomes of pulmonary vascular disease in infants conceived with non-IVF fertility treatment and assisted reproductive technologies at 1 year of age.

Background: Assisted reproductive technologies (ARTs) have been associated with the development of endothelial dysfunction.

Objective: To determine potential differences in outcomes associated with pulmonary vascular disease in infants born to mothers receiving any infertility treatment including ART and non-IVF fertility treatments (NIFTs).

Design/methods: The sample was derived from an administrative database containing detailed information on infant and maternal characteristics for live-born infants in California (2007-2012) with gestational age (GA) 22 to 44 weeks.

Pulmonary Endothelial Mechanical Sensing and Signaling, a Story of Focal Adhesions and Integrins in Ventilator Induced Lung Injury.

Patients with critical illness such as acute lung injury often undergo mechanical ventilation in the intensive care unit. Though lifesaving in many instances, mechanical ventilation often results in ventilator induced lung injury (VILI), characterized by overdistension of lung tissue leading to release of edemagenic agents, which further damage the lung and contribute to the mortality and progression of pulmonary inflammation. The endothelium is particularly sensitive, as VILI associated mechanical stress results in endothelial cytoskeletal rearrangement, stress fiber formation, and integrity loss.

The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification.

Peg10 (paternally expressed gene 10) is an imprinted gene that is essential for placental development. It is thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag and Pol-like domains. Here we show that the Gag domain of PEG10 can promote vesicle budding similar to the HIV p24 Gag protein.

Murine trophoblast-derived and pregnancy-associated exosome-enriched extracellular vesicle microRNAs: Implications for placenta driven effects on maternal physiology.

The role of extracellular vesicles (EVs), specifically exosomes, in intercellular communication likely plays a key role in placental orchestration of pregnancy and maternal immune sensing of the fetus. While murine models are powerful tools to study pregnancy and maternal-fetal immune interactions, in contrast to human placental exosomes, the content of murine placental and pregnancy exosomes remains largely understudied. Using a recently developed in vitro culture technique, murine trophoblast stem cells derived from B6 mice were differentiated into syncytial-like cells.

Correction: Preservation of myocardial contractility during acute hypoxia with OMX-CV, a novel oxygen delivery biotherapeutic.

[This corrects the article DOI: 10.1371/journal.pbio.

Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease.

Oxidative stress in the cell is characterized by excessive generation of reactive oxygen species (ROS). Superoxide (O) and hydrogen peroxide (HO) are the main ROS involved in the regulation of cellular metabolism. As our fundamental understanding of the underlying causes of lung disease has increased it has become evident that oxidative stress plays a critical role.