A single institution anesthetic experience with catheterization of pediatric pulmonary hypertension patients.

Cardiac catheterization remains the gold standard for the diagnosis and management of pediatric pulmonary hypertension (PH). There is lack of consensus regarding optimal anesthetic and airway regimen. This retrospective study describes the anesthetic/airway experience of our single center cohort of pediatric PH patients undergoing catheterization, in which obtaining hemodynamic data during spontaneous breathing is preferential. A total of 448 catheterizations were performed in 232 patients. Of the 379 cases that began with a natural airway, 274 (72%) completed the procedure without an invasive airway, 90 (24%) received a planned invasive airway, and 15 (4%) required an unplanned invasive airway. Median age was 3.4 years (interquartile range [IQR] 0.7-9.7); the majority were either Nice Classification Group 1 (48%) or Group 3 (42%). Vasoactive medications and cardiopulmonary resuscitation were required in 14 (3.7%) and eight (2.1%) cases, respectively; there was one death. Characteristics associated with use of an invasive airway included age <1 year, Group 3, congenital heart disease, trisomy 21, prematurity, bronchopulmonary dysplasia, WHO functional class III/IV, no PH therapy at time of case, preoperative respiratory support, and having had an intervention (p < 0.05). A composite predictor of age <1 year, Group 3, prematurity, and any preoperative respiratory support was significantly associated with unplanned airway escalation (26.7% vs. 6.9%, odds ratio: 4.9, confidence interval: 1.4-17.0). This approach appears safe, with serious adverse event rates similar to previous reports despite the predominant use of natural airways. However, research is needed to further investigate the optimal anesthetic regimen and respiratory support for pediatric PH patients undergoing cardiac catheterization.

Electrochemical Impedance Spectroscopy as a Tool for Monitoring Cell Differentiation from Floor Plate Progenitors to Midbrain Neurons in Real Time.

Here shows that electrical impedance spectroscopy can be used as a non-invasive and real time tool to probe cell adhesion and differentiation from midbrain floor plate progenitors into midbrain neurons on Au electrodes coated with human laminin. The electrical data and equivalent circuit modeling are consistent with standard microscopy analysis and reveal that within the first 6 hours progenitor cells sediment and attach to the electrode within 40 hours. Between 40 and 120 hours, midbrain progenitor cells differentiate into midbrain neurons, followed by an electrochemically stable maturation phase. The ability to sense and characterize non-invasively and in real time cell differentiation opens up unprecedented avenues for implantable therapies and differentiation strategies.

The Canonical Wnt Pathway as a Key Regulator in Liver Development, Differentiation and Homeostatic Renewal.

The canonical Wnt (Wnt/ß-catenin) signalling pathway is highly conserved and plays a critical role in regulating cellular processes both during development and in adult tissue homeostasis. The Wnt/ß-catenin signalling pathway is vital for correct body patterning and is involved in fate specification of the gut tube, the primitive precursor of liver. In adults, the Wnt/ß-catenin pathway is increasingly recognised as an important regulator of metabolic zonation, homeostatic renewal and regeneration in response to injury throughout the liver. Herein, we review recent developments relating to the key role of the pathway in the patterning and fate specification of the liver, in the directed differentiation of pluripotent stem cells into hepatocytes and in governing proliferation and zonation in the adult liver. We pay particular attention to recent contributions to the controversy surrounding homeostatic renewal and proliferation in response to injury. Furthermore, we discuss how crosstalk between the Wnt/ß-catenin and Hedgehog (Hh) and hypoxia inducible factor (HIF) pathways works to maintain liver homeostasis. Advancing our understanding of this pathway will benefit our ability to model disease, screen drugs and generate tissue and organ replacements for regenerative medicine.

Next generation in vitro liver model design: Combining a permeable polystyrene membrane with a transdifferentiated cell line.

Herein we describe the manufacture and characterisation of biocompatible, porous polystyrene membranes, suitable for cell culture. Though widely used in traditional cell culture, polystyrene has not been used as a hollow fibre membrane due to its hydrophobicity and non-porous structure. Here, we use microcrystalline sodium chloride (4.7 ±â€¯1.3 µm) to control the porosity of polystyrene membranes and oxygen plasma surface treatment to reduce hydrophobicity. Increased porogen concentration correlates to increased surface pore density, macrovoid formation, gas permeability and mean pore size, but a decrease in mechanical strength. For tissue engineering applications, membranes spun from casting solutions containing 40% (w/w) sodium chloride represent a compromise between strength and permeability, having surface pore density of 208.2 ±â€¯29.7 pores/mm2, mean surface pore size of 2.3 ±â€¯0.7 µm, and Young's modulus of 115.0 ±â€¯8.2 MPa. We demonstrate the biocompatibility of the material with an exciting cell line-media combination: transdifferentiation of the AR42J-B13 pancreatic cell line to hepatocyte-like cells. Treatment of AR42J-B13 with dexamethasone/oncostatin-M over 14 days induces transdifferentiation towards a hepatic phenotype. There was a distinct loss of the pancreatic phenotype, shown through loss of expression of the pancreatic marker amylase, and gain of the hepatic phenotype, shown through induction of expression of the hepatic markers transferrin, carbamoylphosphate synthetase and glutamine synthetase. The combination of this membrane fabrication method and demonstration of biocompatibility of the transdifferentiated hepatocytes provides a novel, superior, alternative design for in vitro liver models and bioartificial liver devices.

Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions.

Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1, a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3. Here we show that while most siRNAs silence GNG12-AS1 post-transcriptionally, siRNA complementary to exon 1 of GNG12-AS1 suppresses its transcription by recruiting Argonaute 2 and inhibiting RNA polymerase II binding. Transcriptional, but not post-transcriptional, silencing of GNG12-AS1 causes concomitant upregulation of DIRAS3, indicating a function in transcriptional interference. This change in DIRAS3 expression is sufficient to impair cell cycle progression. In addition, the reduction in GNG12-AS1 transcripts alters MET signalling and cell migration, but these are independent of DIRAS3. Thus, differential siRNA targeting of a lncRNA allows dissection of the functions related to the process and products of its transcription.

Awake craniotomy in a patient with ejection fraction of 10%: considerations of cerebrovascular and cardiovascular physiology.

A 37-year-old man with nonischemic 4-chamber dilated cardiomyopathy and low-output cardiac failure (estimated ejection fraction of 10%) underwent awake craniotomy for a low-grade oligodendroglioma resection under monitored anesthesia care. The cerebrovascular and cardiovascular physiologic challenges and our management of this patient are discussed.