Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. The endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the artery-to-capillary-to-vein axis.

Seeing pulmonary hypertension through a paediatric lens: a viewpoint.

https://bit.ly/3TMm6bi

MicroRNA-34a-Dependent Attenuation of Angiogenesis in Right Ventricular Failure.

Background: The right ventricle (RV) is at risk in patients with complex congenital heart disease involving right-sided obstructive lesions. We have shown that capillary rarefaction occurs early in the pressure-loaded RV. Here we test the hypothesis that microRNA (miR)-34a, which is induced in RV hypertrophy and RV failure (RVF), blocks the hypoxia-inducible factor-1α-vascular endothelial growth factor (VEGF) axis, leading to the attenuated angiogenic response and increased susceptibility to RV failure.

Hyperoxia prevents the dynamic neonatal increases in lung mesenchymal cell diversity.

Rapid expansion of the pulmonary microvasculature through angiogenesis drives alveolarization, the final stage of lung development that occurs postnatally and dramatically increases lung gas-exchange surface area. Disruption of pulmonary angiogenesis induces long-term structural and physiologic lung abnormalities, including bronchopulmonary dysplasia, a disease characterized by compromised alveolarization. Although endothelial cells are primary determinants of pulmonary angiogenesis, mesenchymal cells (MC) play a critical and dual role in angiogenesis and alveolarization.

Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth.

Preterm birth affects ~10% of pregnancies in the US. Despite familial associations, identifying at-risk genetic loci has been challenging. We built deep learning and graphical models to score mutational effects at base resolution via integrating the pregnant myometrial epigenome and large-scale patient genomes with spontaneous preterm birth (sPTB) from European and African American cohorts.

Intravenous Calcium to Decrease Blood Loss During Intrapartum Cesarean Delivery: A Randomized Controlled Trial.

Objective: To evaluate whether prophylactic administration of 1 g of intravenous calcium chloride after cord clamping reduces blood loss from uterine atony during intrapartum cesarean delivery.

Methods: This single-center, block-randomized, placebo-controlled, double-blind superiority trial compared the effects of 1 g intravenous calcium chloride with those of saline placebo control on blood loss at cesarean delivery. Parturients at 34 or more weeks of gestation requiring intrapartum cesarean delivery after oxytocin exposure in labor were enrolled.

Loss of prolyl hydroxylase 1 and 2 in SM22α-expressing cells prevents Hypoxia-Induced pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a disease characterized by increased vasoconstriction and vascular remodeling. Pulmonary artery smooth muscle cells (PASMCs) highly express the transcription factor hypoxia-inducible factor-1α (HIF-1α), yet the role of PASMC HIF-1α in the development of PAH remains controversial. To study the role of SMC HIF-1α in the pulmonary vascular response to acute and chronic hypoxia, we used a gain-of-function strategy to stabilize HIF-1α in PASMC by generating mice lacking prolyl hydroxylase domain (PHD) 1 and 2 in SM22α-expressing cells.

Delivering a New Future for People With Cystic Fibrosis.

Treatment, prognosis, and quality of life for people with cystic fibrosis (CF) have improved steadily since the initial description of the disease, but most dramatically in the past decade. In 2021, the median predicted survival increased to 53 years, compared with 17 years in 1970. The recent improvement in outcomes is attributable to the advent of cystic fibrosis transmembrane regulator (CFTR) modulators, small molecules that enhance the function of defective CFTR protein.

Hypoxia-Inducible Factor-1α in SM22α-Expressing Cells Modulates Alveolarization.

Worldwide, the incidence of both preterm births and chronic lung disease of infancy, or bronchopulmonary dysplasia, remains high. Infants with bronchopulmonary dysplasia have larger and fewer alveoli, a lung pathology that can persist into adulthood. Although recent data point to a role for hypoxia-inducible factor-1α (HIF-1α) in mediating pulmonary angiogenesis and alveolarization, the cell-specific role of HIF-1α remains incompletely understood.

Fat Embolism Syndrome After Knee Arthroscopy in a Pediatric Patient.

Fat embolism syndrome describes a constellation of symptoms that follow an insult and that results in a triad of respiratory distress, neurologic symptoms, and petechia. The antecedent insult usually entails trauma or orthopedic procedure, most frequently involving long bone (especially the femur) and pelvic fractures. The underlying mechanism of injury remains unknown but entails biphasic vascular injury with vascular obstruction from fat emboli followed by an inflammatory response.

Developmental diversity and unique sensitivity to injury of lung endothelial subtypes during postnatal growth.

At birth, the lung is still immature, heightening susceptibility to injury but enhancing regenerative capacity. Angiogenesis drives postnatal lung development. Therefore, we profiled the transcriptional ontogeny and sensitivity to injury of pulmonary endothelial cells (EC) during early postnatal life.

SM22α cell-specific HIF stabilization mitigates hyperoxia-induced neonatal lung injury.

Though survival rates for preterm infants are improving, the incidence of chronic lung disease of infancy, or bronchopulmonary dysplasia (BPD), remains high. Histologically, BPD is characterized by larger and fewer alveoli. Hypoxia-inducible factors (HIFs) may be protective in the context of hyperoxia-induced lung injury, but the cell-specific effects of HIF expression in neonatal lung injury remain unknown.

A low-cost, highly functional, emergency use ventilator for the COVID-19 crisis.

Respiratory failure complicates most critically ill patients with COVID-19 and is characterized by heterogeneous pulmonary parenchymal involvement, profound hypoxemia and pulmonary vascular injury. The high incidence of COVID-19 related respiratory failure has exposed critical shortages in the supply of mechanical ventilators, and providers with the necessary skills to treat. Traditional mass-produced ventilators rely on an internal compressor and mixer to moderate and control the gas mixture delivered to a patient.

Coronavirus disease 2019 respiratory disease in children: clinical presentation and pathophysiology.

Purpose Of Review: Pediatric coronavirus disease 2019 (COVID-19) respiratory disease is a distinct entity from adult illness, most notable in its milder phenotype. This review summarizes the current knowledge of the clinical patterns, cellular pathophysiology, and epidemiology of COVID-19 respiratory disease in children with specific attention toward factors that account for the maturation-related differences in disease severity.

Recent Findings: Over the past 14 months, knowledge of the clinical presentation and pathophysiology of COVID-19 pneumonia has rapidly expanded.

Novel Prescriptions From Medical Schools for Physician-Scientist Training and Engagement in the Twenty-First Century.

Physicians engaged in biomedical research are well positioned to directly focus the discovery process on human biology. However, the relative proportion of investigators engaged in both caring for patients and conducting research is decreasing. To address the dwindling numbers of physician-scientists nationally, the Burroughs Wellcome Fund created the Physician-Scientist Institutional Awards Program by dedicating 25 million dollars to new initiatives at 10 degree granting, accredited medical schools in North America, awarded on the basis of institutions' proposals.