Microglia ameliorate delirium-like phenotypes in a murine model of acute ventilator-induced lung injury.

Background: Delirium affects 50-85% of patients on mechanical ventilation and is associated with increased mortality, prolonged hospitalization, and a three-fold higher risk of dementia. Microglia, the resident immune cells of the brain, exhibit both neuroprotective and neurotoxic functions; however, their effects in mechanical ventilation-induced acute lung injury (VILI) are unknown. We hypothesize that in a model of short-term VILI, microglia play a neuroprotective role to ameliorate delirium-like phenotypes.

Real-world evidence for the utility of serum soluble fms-like tyrosine kinase 1/placental growth factor test for routine clinical evaluation of hospitalized women with hypertensive disorders of pregnancy.

Background: An imbalance of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, and proangiogenic factor, placental growth factor, in the circulation is a reliable predictor for the development of preeclampsia with severe features and related adverse outcomes. In 2023, the US Food and Drug Administration approved a serum soluble fms-like tyrosine kinase-1/placental growth factor test at a cutoff of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy for the progression to preeclampsia with severe features between 23 and 35 weeks.

Objective: This study aimed to generate real-world evidence for clinical utility for serum soluble fms-like tyrosine kinase-1/placental growth factor test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within 2 weeks of testing among hospitalized patients with hypertensive disorders of pregnancy.

Data-driven prediction of continuous renal replacement therapy survival.

Continuous renal replacement therapy (CRRT) is a form of dialysis prescribed to severely ill patients who cannot tolerate regular hemodialysis. However, as the patients are typically very ill to begin with, there is always uncertainty whether they will survive during or after CRRT treatment. Because of outcome uncertainty, a large percentage of patients treated with CRRT do not survive, utilizing scarce resources and raising false hope in patients and their families.

Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 weeks of testing.

Background: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform.

Objective: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features.

Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes.

Reduced insulin sensitivity (insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM). We conducted transcriptomic profiling of 434 human placentas and identified a positive association between insulin-like growth factor binding protein 1 gene (IGFBP1) expression in the placenta and insulin sensitivity at ~26 weeks gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which, together with high gene expression levels in our placenta samples, suggests a placental or decidual source.

Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study.

Rationale & Objective: Hemoglobin A (HbA) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown.

Prior Exposure to Experimental Preeclampsia Increases Atherosclerotic Plaque Inflammation in Atherogenic Mice-Brief Report.

Background: Women with a history of preeclampsia have evidence of premature atherosclerosis and increased risk of myocardial infarction and stroke compared with women who had a normotensive pregnancy. Whether this is due to common risk factors or a direct impact of prior preeclampsia exposure has never been tested in a mouse atherosclerosis model.

Methods: Pregnant LDLR-KO (low-density lipoprotein receptor knockout; n=35) female mice were randomized in midgestation to sFlt1 (soluble fms-like tyrosine kinase 1)-expressing adenovirus or identical control adenovirus.

Lipid droplets in the endothelium: The missing link between metabolic syndrome and cardiovascular disease?

The physiology of lipid droplets (LDs) has been most extensively characterized in adipocytes, but LDs also accumulate in endothelial cells lining blood vessels in response to changing levels of triglycerides. In recent issues of the JCI, two independent papers highlight a direct role of endothelial LDs in the genesis of hypertension and atherosclerosis in rodent models. Kim et al.

Translation of mechanistic advances in preeclampsia to the clinic: Long and winding road.

As one of the leading causes of premature birth and maternal and infant mortality worldwide, preeclampsia remains a major unmet public health challenge. Preeclampsia and related hypertensive disorders of pregnancy are estimated to cause >75 000 maternal and 500 000 infant deaths globally each year. Because of rising rates of risk factors such as obesity, in vitro fertilization and advanced maternal age, the incidence of preeclampsia is going up with rates ranging from 5% to 10% of all pregnancies worldwide.

Strikingly High Activity of 15-Lipoxygenase Towards Di-Polyunsaturated Arachidonoyl/Adrenoyl-Phosphatidylethanolamines Generates Peroxidation Signals of Ferroptotic Cell Death.

The vast majority of membrane phospholipids (PLs) include two asymmetrically positioned fatty acyls: oxidizable polyunsaturated fatty acids (PUFA) attached predominantly at the sn2 position, and non-oxidizable saturated/monounsaturated acids (SFA/MUFA) localized at the sn1 position. The peroxidation of PUFA-PLs, particularly sn2-arachidonoyl(AA)- and sn2-adrenoyl(AdA)-containing phosphatidylethanolamines (PE), has been associated with the execution of ferroptosis, a program of regulated cell death. There is a minor subpopulation (≈1-2 mol %) of doubly PUFA-acylated phospholipids (di-PUFA-PLs) whose role in ferroptosis remains enigmatic.

Data-driven prediction of continuous renal replacement therapy survival.

Continuous renal replacement therapy (CRRT) is a form of dialysis prescribed to severely ill patients who cannot tolerate regular hemodialysis. However, as the patients are typically very ill to begin with, there is always uncertainty as to whether they will survive during or after CRRT treatment. Because of outcome uncertainty, a large percentage of patients treated with CRRT do not survive, utilizing scarce resources and raising false hope in patients and their families.

Agaricus Subrufescens ameliorates ovarian dysfunction and regulates altered biochemical parameters in rats with Letrozole induced polycystic ovarian syndrome.

Objective: The objective of this study is to investigate the effects of an ethanolic extract derived from Agaricus subrufescens on rat models exhibiting Polycystic Ovarian Syndrome (PCOS) induced by Letrozole.

Methods: A total of thirty female Wistar rats were divided into five groups, each consisting of six rats. The negative control group was administered a volume of 1 mL of a 0.

Placental RNA sequencing implicates IGFBP1 in insulin sensitivity during pregnancy and in gestational diabetes.

Reduced insulin sensitivity (or greater insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM) pathophysiology. We conducted transcriptomic profiling of 434 human placentas and identified a strong positive association between insulin-like growth factor binding protein 1 gene () expression in the placenta and insulin sensitivity at ~ 26 weeks' gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which together with high placental gene expression levels, suggests a placental source.

Higher Maternal Body Mass Index Is Associated With Lower Placental Expression of EPYC: A Genome-Wide Transcriptomic Study.

Context: Elevated body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. The placental transcriptome may elucidate molecular mechanisms underlying these associations.

Objective: We examined the association of first-trimester maternal BMI with the placental transcriptome in the Gen3G prospective cohort.

Hypoxia-inducible factor 1 signaling drives placental aging and can provoke preterm labor.

Most cases of preterm labor have unknown cause, and the burden of preterm birth is immense. Placental aging has been proposed to promote labor onset, but specific mechanisms remain elusive. We report findings stemming from unbiased transcriptomic analysis of mouse placenta, which revealed that hypoxia-inducible factor 1 (HIF-1) stabilization is a hallmark of advanced gestational timepoints, accompanied by mitochondrial dysregulation and cellular senescence; we detected similar effects in aging human placenta.