Assessing the Clinical Utility of Liquid Biopsies Across 5 Potential Indications From Therapy Selection to Population Screening: A Review.

Importance: There has been great enthusiasm for the emerging technology of molecular-based tests to detect and quantify tumor DNA circulating in the bloodstream, colloquially known as a liquid biopsy. However, less attention has been given to how their clinical utility depends on the indication for testing, which includes a range of clinical situations, each presenting unique challenges.

Observations: Five indications for circulating tumor DNA (ctDNA) blood testing were considered.

Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes.

Introduction: Placental vascularity may be important in the development of fetal growth restriction (FGR). The overnourished adolescent ewe is a robust model of the condition, with ∼50% of offspring demonstrating FGR (birthweight >2 standard deviations below optimally-fed control mean). We studied whether placental vascularity, angiogenesis and glucose transport reflect FGR severity.

Peri- and Postnatal Effects of Prenatal Adenoviral VEGF Gene Therapy in Growth-Restricted Sheep.

Uterine artery (UtA) adenovirus (Ad) vector-mediated overexpression of vascular endothelial growth factor (VEGF) enhances uterine blood flow in normal sheep pregnancy and increases fetal growth in the overnourished adolescent sheep model of fetal growth restriction (FGR). Herein, we examined its impact on gestation length, neonatal survival, early postnatal growth and metabolism. Singleton-bearing ewes were evenly allocated to receive Ad.

The safety of obstetric acupuncture: forbidden points revisited.

Background/aim: Although the safety of acupuncture per se in pregnancy is reasonably well accepted, there remains debate regarding needling at points historically considered to be 'forbidden' during pregnancy. This article reviews the scientific literature on this topic.

Main Findings: There is no objective evidence of harm following needling at forbidden points, summarised by the following four lines of evidence.

VEGF Gene Transfer to the Utero-Placental Circulation of Pregnant Sheep to Enhance Fetal Growth.

In this chapter, we describe a safe and effective approach to achieve local VEGF gene transfer to the uterine arteries in pregnant sheep using direct injection of viral vectors into the uterine arteries. This approach resulted in improved fetal growth in growth-restricted pregnancies. Adenoviral vectors encoding VEGF-A165 or a reporter gene β-galactosidase were dissolved in 10 mL normal saline shortly before administration.

VEGF Gene Transfer to the Utero-Placental Circulation of Pregnant Guinea Pigs to Enhance Fetal Growth.

In this chapter, we describe a novel method of adenoviral gene transfer to the uterine and radial arteries of pregnant guinea pigs to improve fetal growth. Adenoviruses encoding VEGF-A165 or a reporter gene β-galactosidase were reconstituted in pluronic gel and applied topically to the exposed uterine and radial arteries following laparotomy. Pluronic gel is a thermosensitive gel that is liquid at 4 °C, but becomes solid as soon as it comes in contact with body temperature.

The arc mutants of Arabidopsis with fewer large chloroplasts have a lower mesophyll conductance.

Photosynthetic cells of most land plant lineages have numerous small chloroplasts even though most algae, and even the early diverging land plant group the hornworts, tend to have one or a few large chloroplasts. One constraint that small chloroplasts could improve is the resistance to CO2 diffusion from the atmosphere to the chloroplast stroma. We examined the mesophyll conductance (inverse of the diffusion resistance) of mutant Arabidopsis thaliana plants with one or only a few large chloroplasts per cell.

Uteroplacental adenovirus vascular endothelial growth factor gene therapy increases fetal growth velocity in growth-restricted sheep pregnancies.

Fetal growth restriction (FGR) occurs in ∼8% of pregnancies and is a major cause of perinatal mortality and morbidity. There is no effective treatment. FGR is characterized by reduced uterine blood flow (UBF).

Fetoplacental biometry and umbilical artery Doppler velocimetry in the overnourished adolescent model of fetal growth restriction.

Objective: The purpose of this study was to evaluate ultrasonographically fetal growth trajectories, placental biometry, and umbilical artery (UA) Doppler indices in growth-restricted pregnancies of overnourished adolescent ewes and normally developing pregnancies of control-fed ewes.

Study Design: Singleton pregnancies were established using embryo transfer in 42 adolescent ewes that were overnourished (n = 27) or control-fed (n = 15) and were scanned at weekly intervals from 83-126 days' gestation and necropsied at 131 days' gestation (term = 145 days).

Results: Ultrasonographic placental measurements were reduced and UA Doppler indices were increased from 83 days' gestation; measurements of fetal abdominal circumference and femur length, renal volume and tibia length, and biparietal diameter were reduced from 98, 105, and 112 days' gestation, respectively, in overnourished vs control-intake pregnancies.

Engineering starch accumulation by manipulation of phosphate metabolism of starch.

A new understanding of leaf starch degradation has emerged in the last 10 years. It has been shown that starch phosphorylation and dephosphorylation are critical components of this process. Glucan, water dikinase (GWD) (and phosphoglucan, water dikinase) adds phosphate to starch, and phosphoglucan phosphatase (SEX4) removes these phosphates.

Ultrasonographic assessment of growth and estimation of birthweight in late gestation fetal sheep.

Our aim was to identify which ultrasound parameters can be most accurately measured and best predict ovine fetal weight in late gestation. Singleton pregnancies were established using embryo transfer in 32 adolescent ewes, which were subsequently overnourished to produce fetuses of variable size (1720-6260 g). Ultrasound measurements at 126-133 days gestation were compared with fetal weight/biometry at late-gestation necropsy (n = 19) or term delivery (n = 13).

Fluorescent bio-barcode DNA assay for the detection of Salmonella enterica serovar Enteritidis.

Salmonella enterica serovar Enteritidis is one of the most frequently reported causes of foodborne illness. It is a major threat to the food safety chain and public health. A highly amplified bio-barcode DNA assay for the rapid detection of the insertion element (Iel) gene of Salmonella Enteritidis is reported in this paper.

Prediction of hemodialysis sorbent cartridge urea nitrogen capacity and sodium release from in vitro tests.

In sorbent-based hemodialysis, factors limiting a treatment session are urea conversion capacity and sodium release from the cartridge. In vitro experiments were performed to model typical treatment scenarios using various dialyzers and 4 types of SORB sorbent cartridges. The experiments were continued to the point of column saturation with ammonium.

Sorbent suspensions vs. sorbent columns for extracorporeal detoxification in hepatic failure.

Hepatic failure is a significant medical problem which has been unsuccessfully treated by hemodialysis. However, similar therapies using recirculated dialysate regenerated by sorbents in place of single-pass dialysate have been beneficial in treating acute-on-chronic liver failure. The advantages of sorbent-based treatments include some selectivity of toxin removal and improved removal of protein-bound toxins.

Predicting dialysate sodium composition in sorbent dialysis using single point and multiple-dilution conductivity measurement.

This research establishes the ability to predict the sodium composition in dialysate from a single conductivity measurement over the wide range of concentrations of chloride, bicarbonate, and acetate that occur during sorbent dialysis. The ranges explored in mEq/L were sodium 100-180, chloride 76-143, bicarbonate 16-31, and acetate 4-11. Through mathematical optimization using a pattern search method, a single point measurement technique was shown to predict the total sodium concentration within approximately +/- 4.

Treatment of severe tricyclic antidepressant overdose with extracorporeal sorbent detoxification.

Tricyclic overdose can be a medical emergency, and therapy with intravenous bicarbonate is not always successful in preventing cardiac toxicity or coma. Mortality in patients developing these complications is from 1% to 15%. Extracorporeal detoxification with sorbents has been used in treatment of patients with very high drug levels and declining clinical condition.