New Processes for Ionizing Nonvolatile Compounds in Mass Spectrometry: The Road of Discovery to Current State-of-the-Art.

This covers discovery and mechanistic aspects as well as initial applications of novel ionization processes for use in mass spectrometry that guided us in a series of subsequent discoveries, instrument developments, and commercialization. matrix-assisted ionization on an intermediate pressure matrix-assisted laser desorption/ionization source the use of a laser, high voltages, or any other added energy was simply unbelievable, at first. Individually and as a whole, the various discoveries and inventions started to paint, , an exciting new picture and outlook in mass spectrometry from which key developments grew that were at the time unimaginable, and continue to surprise us in its simplistic preeminence.

Growth capacity of a Wharton's Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets.

Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton's Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy.

Wharton's Jelly-Mesenchymal Stem Cell-Engineered Conduit for Pulmonary Artery Reconstruction in Growing Piglets.

Surgical treatment of congenital heart defects affecting the right ventricular outflow tract often requires complex reconstruction and multiple reoperations. With a randomized controlled trial, we compared a novel tissue-engineered small intestine submucosa-based graft for pulmonary artery reconstruction (seeded with mesenchymal stem cells derived from Wharton's Jelly) with conventional small intestine submucosa in growing piglets. Six months after implantation, seeded grafts showed integration with host tissues at cellular level and exhibited growth potential on transthoracic echocardiography and cardiovascular magnetic resonance.

Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes.

The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks.

Wharton's Jelly-Mesenchymal Stem Cell-Engineered Conduit for Pediatric Translation in Heart Defect.

The materials available for the right ventricular outflow tract (RVOT) reconstruction in patients with tetralogy of fallot (TOF)/pulmonary atresia come with the severe limitation of long-term degeneration and lack of growth potential, causing right ventricular dysfunction, aneurysm formation, and arrhythmias, thus necessitating several high-risk reoperations throughout patients' lives. In this study, we evaluated the capacity of mesenchymal stem cells (MSCs) derived from the Wharton's Jelly (WJ-MSCs), the gelatinous inner portion of the umbilical cord, to grow and recellularize an extracellular matrix (ECM) graft in our optimized xeno-free, good manufacturing practice-compliant culture system. WJ-MSCs were phenotypically and functionally characterized by flow cytometry and multilineage differentiation capacity, respectively.

A low threshold for neonatal intervention yields a high rate of biventricular outcomes in pulmonary atresia with intact ventricular septum.

Aims: Management strategies for pulmonary atresia with intact ventricular septum are variable and are based on right ventricular morphology and associated abnormalities. Catheter perforation of the pulmonary valve provides an alternative strategy to surgery in the neonatal period. We sought to assess the long-term outcome in terms of survival, re-intervention, and functional ventricular outcome in the setting of a 26-year single-centre experience of low threshold inclusion criteria for percutaneous valvotomy.

Visualization of coronary arteries in paediatric patients using whole-heart coronary magnetic resonance angiography: comparison of image-navigation and the standard approach for respiratory motion compensation.

Aims: To investigate the use of respiratory motion compensation using image-based navigation (iNAV) with constant respiratory efficiency using single end-expiratory thresholding (CRUISE) for coronary magnetic resonance angiography (CMRA), and compare it to the conventional diaphragmatic navigator (dNAV) in paediatric patients with congenital or suspected heart disease.

Methods: iNAV allowed direct tracking of the respiratory heart motion and was generated using balanced steady state free precession startup echoes. Respiratory gating was achieved using CRUISE with a fixed 50% efficiency.

Large Calibre Self-Expanding Stents for Pulmonary Stenosis After the Arterial Switch, a Low-Risk Solution to a Low-Flow Situation.

Branch pulmonary artery stenosis is one of the most common complications late after the arterial switch operation. The pathophysiology of stenosis in these circumstances is very different to that encountered in with normally related great vessels. The LeCompte manoeuvre leaves the pulmonary arteries straddled and stretched over the aortic root which contributing significantly to the degree of stenosis encountered.

Matrix-Assisted Ionization on a Portable Mass Spectrometer: Analysis Directly from Biological and Synthetic Materials.

Matrix-assisted ionization (MAI)-mass spectrometry (MS) eliminates the need for high voltage, a heat source, lasers, and compressed gases in the ionization process and uses minimal solvents in sample preparation, thus making MAI ideal for field-portable mass spectrometers. The broad applicability of MAI is demonstrated by simple, rapid, and robust positive and negative detection mode analyses of low and high mass compounds including some pesticides, dyes, drugs, lipids, and proteins (186 Da to 8.5 kDa) from various materials including urine, biological tissue sections, paper, and plant material on a low pumping capacity, single-quadrupole mass spectrometer.

Reproducibility and quantification of illicit drugs using matrix-assisted ionization (MAI) mass spectrometry.

Matrix-assisted ionization (MAI) mass spectrometry (MS) is a simple and sensitive method for analysis of low- and high-mass compounds, requiring only that the analyte in a suitable matrix be exposed to the inlet aperture of an atmospheric pressure ionization mass spectrometer. Here, we evaluate the reproducibility of MAI and its potential for quantification using six drug standards. Factors influencing reproducibility include the matrix compound used, temperature, and the method of sample introduction.

Second stage after initial hybrid palliation for hypoplastic left heart syndrome: Arterial or venous shunt?

Objective: Hybrid palliation for hypoplastic left heart syndrome has been developed as an alternative to neonatal Norwood surgery. At the second stage, a source of pulmonary blood flow has to be established. Options include an arterial modified Blalock-Taussig or a venous superior cavopulmonary shunt.

High-throughput characterization of small and large molecules using only a matrix and the vacuum of a mass spectrometer.

Matrix assisted ionization vacuum (MAIV) rapidly generates gas-phase analyte ions from subliming solid-phase matrix:analyte crystals for analysis by mass spectrometry (MS). Ionization from the solid-phase allows the use of a variety of surfaces for introducing matrix:analyte samples to the vacuum of a mass spectrometer, including common laboratory materials, such as disposable pipet tips, filter paper, tooth picks, and nylon mesh. MAIV is shown here to be capable of analyses as fast as 3 s per sample with achievable sensitivities in the low femtomole range.

Long-term follow-up is not indicated after routine interventional closure of persistent arterial ducts.

Background: Little is known about the necessity for long-term follow-up after interventional closure of persistent arterial duct (PDA). Potential side effects and complications include residual shunts, haemolysis, device embolization, and obstruction to flow in the adjoining vessels.

Methods: Single centre retrospective study of paediatric patients undergoing interventional PDA occlusion.

Anaesthetic management of previously non-diagnosed phaeochromocytoma: Clinical vigilance, the ultimate saviour of anaesthesiologist.

A 39-year-old male, post nephrectomy and adrenalectomy (right), was planned for adrenalectomy (left) and radiofrequency ablation of left renal mass. Clinical evaluation indicated a possibility of phaeochromocytoma, whereas biochemical parameters were found to be within normal limits. Intraoperatively, massive fluctuations in haemodynamic parameters were noticed while the tumour was being handled.

Amlodipine prevents apoptotic cell death by correction of elevated intracellular calcium in a primary neuronal model of Batten disease (CLN3 disease).

CLN3 disease (Spielmeyer-Vogt-Sjogren-Batten disease) is a severe pediatric neurodegenerative disorder for which there is currently no effective treatment. The disease is characterized by progressive neuronal death, which may be triggered by abnormal intracellular calcium levels leading to neuronal apoptosis. Previously, we demonstrated reversal of the calcium effect in a neuroblastoma cell line using amlodipine and other calcium channel antagonists.

Highlights of the 6th World Congress in Paediatric Cardiology and Cardiac Surgery.

The 6th World Congress in Paediatric Cardiology and Cardiac Surgery took place in Cape Town, South Africa, in February 2013. The congress is the largest meeting in the field of congenital and paediatric heart disease and attracts a global audience of specialists with the aim of sharing the latest multidisciplinary developments in research and clinical practice. The congress was commended as a huge success and this article aims to give a general flavor of the diverse meeting through detailing a few specific highlights from the various tracks.

Laparoscopic versus open pyeloplasty: comparison of two surgical approaches- a single centre experience of three years.

UPJO causes hydronephrosis and progressive renal impairment may ensue if left uncorrected. Open pyeloplasty remains the standard against which new technique must be compared. We analyzed the comparison of Laparoscopic and open pyeloplasty in a randomized prospective trial.

Diagnosis of a patient with a kinetic variant of medium and short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency by newborn screening.

Medium and short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is a rare cause of impaired mitochondrial fatty acid oxidation. We present a case report of a patient with hyperinsulinism and homozygosity for a novel mutation causing a kinetic variant of the enzyme. The diagnosis was initially inferred by abnormal newborn screening acylcarnitine analysis with elevated C4-hydroxyacylcarnitine.

Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways.

Proteins involved in mitochondrial metabolic pathways engage in functionally relevant multi-enzyme complexes. We previously described an interaction between short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) and glutamate dehydrogenase (GDH) explaining the clinical phenotype of hyperinsulinism in SCHAD-deficient patients and adding SCHAD to the list of mitochondrial proteins capable of forming functional, multi-pathway complexes. In this work, we provide evidence of SCHAD's involvement in additional interactions forming tissue-specific metabolic super complexes involving both membrane-associated and matrix-dwelling enzymes and spanning multiple metabolic pathways.

Flow injection tandem mass spectrometric measurement of ceramides of multiple chain lengths in biological samples.

A method is presented for the measurement of ceramide species in biological fluids using flow injection tandem mass spectrometry. Ceramides are important signaling compounds in a number of cell:cell interactions including apoptosis and neurodegeneration. Because of the large number of potential fatty acid constituent moieties on ceramide molecules, a method which accurately distinguishes different chain-length species was required.

Green tea polyphenols control dysregulated glutamate dehydrogenase in transgenic mice by hijacking the ADP activation site.

Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and, in animals, is extensively regulated by a number of metabolites. Gain of function mutations in GDH that abrogate GTP inhibition cause the hyperinsulinism/hyperammonemia syndrome (HHS), resulting in increased pancreatic β-cell responsiveness to leucine and susceptibility to hypoglycemia following high protein meals. We have previously shown that two of the polyphenols from green tea (epigallocatechin gallate (EGCG) and epicatechin gallate (ECG)) inhibit GDH in vitro and that EGCG blocks GDH-mediated insulin secretion in wild type rat islets.

Measurement of plasma amino acids by Ultraperformance® Liquid Chromatography.

Background: Since the early 1960s, quantitative amino acid analysis (AAA) has traditionally been performed using ion-exchange chromatography with post-column ninhydrin derivatization. This established technology has many advantages, including relatively low cost of operation and ease of use. However, analysis times of 120+ min and high maintenance requirements make this technology unsuitable for the modern clinical laboratories with a requirement for rapid turnaround times.