Cell-free DNA screening following severe fetal growth restriction leading to diagnosis of maternal mosaic Turner syndrome (45,X/46,XX) [Letter]
Sherer, David M; Hsieh, Vicky; Kheyman, Mila; Dryer, Alexandra M; Dalloul, Mudar
Current Perspectives of Prenatal Sonographic Diagnosis and Clinical Management Challenges of True Knot of the Umbilical Cord
Sherer, David M; Amoabeng, Opokua; Dryer, Alexandra M; Dalloul, Mudar
Umbilical cord accidents preceding labor are rare. Single and multiple nuchal cords, and true knot(s) of the umbilical cord, are often incidental findings noted at delivery of non-hypoxic non-acidotic newborns without any evidence of subsequent adverse neonatal outcome. In contrast to single nuchal cords, true knots of the umbilical cord, which occur in between 0.04% and 3% of all deliveries, have been associated with a reported 4 toÂ 10 fold increased risk of stillbirth. First reported with real-time ultrasound, current widespread application of color Doppler, power Doppler and three-dimension sonography, has enabled increasingly more accurate prenatal sonographic diagnoses of true knot(s) of the umbilical cord. Reflecting the inability to visualize the entire umbilical cord at prenatal ultrasound assessment, despite detailed second and third-trimester scanning, many occurrences of incidental true knot of the umbilical cord remain undetected and are noted only at delivery. Although prenatal sonographic diagnostic accuracy is increasing, false positive sonographic diagnosis of true knot of the umbilical cord cannot be ruled out with certainty, and must continue to be considered clinically. Notwithstanding the inability to diagnose all true knots, currently there is a clear absence of clinical management guidelines by governing bodies regarding patients in whom prenatal sonographic diagnosis of true knot(s) of the umbilical cord is / are suspected. As a result, in many prenatal ultrasound units, suspected sonographic findings suggestive of or consistent with true knot of the umbilical cord are often disregarded, not documented, and patients are not uniformly informed of this potentially life-threatening condition, which carries an associated considerable risk of stillbirth. This commentary will address current perspectives of prenatal sonographic diagnostic and management challenges associated with true knot(s) of the umbilical cord in singleton pregnancies.
Nondestructive evaluation of progressive neuronal changes in organotypic rat hippocampal slice cultures using ultrahigh-resolution optical coherence microscopy
Li, Fengqiang; Song, Yu; Dryer, Alexandra; Cogguillo, William; Berdichevsky, Yevgeny; Zhou, Chao
Three-dimensional tissue cultures have been used as effective models for studying different diseases, including epilepsy. High-throughput, nondestructive techniques are essential for rapid assessment of disease-related processes, such as progressive cell death. An ultrahigh-resolution optical coherence microscopy (UHR-OCM) system with [Formula: see text] axial resolution and [Formula: see text] transverse resolution was developed to evaluate seizure-induced neuronal injury in organotypic rat hippocampal cultures. The capability of UHR-OCM to visualize cells in neural tissue was confirmed by comparison of UHR-OCM images with confocal immunostained images of the same cultures. In order to evaluate the progression of neuronal injury, UHR-OCM images were obtained from cultures on 7, 14, 21, and 28 days in vitro (DIVs). In comparison to DIV 7, statistically significant reductions in three-dimensional cell count and culture thickness from UHR-OCM images were observed on subsequent time points. In cultures treated with kynurenic acid, significantly less reduction in cell count and culture thickness was observed compared to the control specimens. These results demonstrate the capability of UHR-OCM to perform rapid, label-free, and nondestructive evaluation of neuronal death in organotypic hippocampal cultures. UHR-OCM, in combination with three-dimensional tissue cultures, can potentially prove to be a promising tool for high-throughput screening of drugs targeting various disorders.
PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of post-traumatic epilepsy
Berdichevsky, Yevgeny; Dryer, Alexandra M; Saponjian, Yero; Mahoney, Mark M; Pimentel, Corrin A; Lucini, Corrina A; Usenovic, Marija; Staley, Kevin J
mTOR is activated in epilepsy, but the mechanisms of mTOR activation in post-traumatic epileptogenesis are unknown. It is also not clear whether mTOR inhibition has an anti-epileptogenic, or merely anticonvulsive effect. The rat hippocampal organotypic culture model of post-traumatic epilepsy was used to study the effects of long-term (four weeks) inhibition of signaling pathways that interact with mTOR. Ictal activity was quantified by measurement of lactate production and electrical recordings, and cell death was quantified with lactate dehydrogenase (LDH) release measurements and Nissl-stained neuron counts. Lactate and LDH measurements were well correlated with electrographic activity and neuron counts, respectively. Inhibition of PI3K and Akt prevented activation of mTOR, and was as effective as inhibition of mTOR in reducing ictal activity and cell death. A dual inhibitor of PI3K and mTOR, NVP-BEZ235, was also effective. Inhibition of mTOR with rapamycin reduced axon sprouting. Late start of rapamycin treatment was effective in reducing epileptic activity and cell death, while early termination of rapamycin treatment did not result in increased epileptic activity or cell death. The conclusions of the study are as follows: (1) the organotypic hippocampal culture model of post-traumatic epilepsy comprises a rapid assay of anti-epileptogenic and neuroprotective activities and, in this model (2) mTOR activation depends on PI3K-Akt signaling, and (3) transient inhibition of mTOR has sustained effects on epilepsy.