Subcutaneous Implantable Cardioverter Defibrillators in Pediatrics and Congenital Heart Disease.

Subcutaneous implantable cardioverter defibrillators (S-ICDs) are being used with increased frequency in children and patients with congenital heart disease. Vascular access complexities, intracardiac shunts, and specific anatomies make these devices particularly appealing for some of these patients. Alternative screening, implantation, and programming techniques should be considered based on patient size, body habitus, anatomy, procedural history, and preference.

Risk Stratification in Pediatric Wolff-Parkinson-White: Practice Variation Among Pediatric Cardiologists and Electrophysiologists.

Background: Published guidelines provide recommendations for risk stratification in pediatric Wolff-Parkinson-White (WPW). There are no data on provider concordance with these guidelines. We hypothesized that significant practice variation exists between pediatric cardiologists (PC) and electrophysiologists (EP).

Small-Molecule Mn Antioxidants in Caenorhabditis elegans and Deinococcus radiodurans Supplant MnSOD Enzymes during Aging and Irradiation.

Denham Harman's oxidative damage theory identifies superoxide (O) radicals as central agents of aging and radiation injury, with Mn-dependent superoxide dismutase (MnSOD) as the principal O-scavenger. However, in the radiation-resistant nematode Caenorhabditis elegans, the mitochondrial antioxidant enzyme MnSOD is dispensable for longevity, and in the model bacterium Deinococcus radiodurans, it is dispensable for radiation resistance. Many radiation-resistant organisms accumulate small-molecule Mn-antioxidant complexes well-known for their catalytic ability to scavenge O, along with MnSOD, as exemplified by D.

Cardiac Relapse of Acute Lymphoblastic Leukemia Following Hematopoietic Stem Cell Transplantation: A Case Report and Review of Literature.

Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) occurs in soft tissues and various organs outside the testis and central nervous system. Treatments such as hematopoietic stem cell transplantation and more novel modalities such as immunotherapy have eradicated ALL at extramedullary sites. In some instances, survival times for relapsed ALL at these sites are longer than those for relapsed disease involving only the bone marrow.

Sudden Death in the Young: Information for the Primary Care Provider.

There are multiple conditions that can make children prone to having a sudden cardiac arrest (SCA) or sudden cardiac death (SCD). Efforts have been made by multiple organizations to screen children for cardiac conditions, but the emphasis has been on screening before athletic competition. This article is an update of the previous American Academy of Pediatrics policy statement of 2012 that addresses prevention of SCA and SCD.

An Variant Affects Both Cardiac-Type (Na1.5) and Brain-Type (Na1.1) Sodium Currents and Contributes to Complex Concomitant Brain and Cardiac Disorders.

Voltage-gated sodium (Na) channels are transmembrane proteins that initiate and propagate neuronal and cardiac action potentials. Na channel β subunits have been widely studied due to their modulatory role. Mice null for , which encodes Na β1 and β1b subunits, have defects in neuronal development and excitability, spontaneous generalized seizures, cardiac arrhythmias, and early mortality.

Neonatal supraventricular tachycardia.

Supraventricular tachycardia (SVT) is one of the most common conditions requiring emergency cardiac care in neonates. Atrioventricular reentrant tachycardia utilizing an atrioventricular bypass tract is the most common form of SVT presenting in the neonatal period. There is high likelihood for spontaneous resolution for most of the common arrhythmia substrates in infancy.

Preincision Initiation of Dexmedetomidine Maximally Reduces the Risk of Junctional Ectopic Tachycardia in Children Undergoing Ventricular Septal Defect Repairs.

Objective: To evaluate whether initiation of dexmedetomidine (DEX) infusion before surgical incision and cardiopulmonary bypass (CPB) versus initiation after CPB had an impact on the incidence of junctional ectopic tachycardia (JET).

Design: Retrospective cohort study.

Setting: Single tertiary-care cardiac center.

Relationship between PCO2 and unfavorable outcome in infants with moderate-to-severe hypoxic ischemic encephalopathy.

Background: Abnormal PCO2 is common in infants with hypoxic ischemic encephalopathy (HIE). The objective was to determine whether hypocapnia was independently associated with unfavorable outcome (death or severe neurodevelopmental disability at 18 mo) in infants with moderate-to-severe HIE.

Methods: This was a post hoc analysis of the CoolCap Study in which infants were randomized to head cooling or standard care.

Cognitive impairments following cranial irradiation can be mitigated by treatment with a tropomyosin receptor kinase B agonist.

Brain radiotherapy is frequently used successfully to treat brain tumors. However, radiotherapy is often associated with declines in short-term and long-term memory, learning ability, and verbal fluency. We previously identified a downregulation of the brain-derived neurotrophic factor (BDNF) following cranial irradiation in experimental animals.

Diagnosis and Acute Management of Tachyarrhythmias in Children.

Tachyarrhythmias form a significant majority of the cardiac emergencies encountered in the pediatric age group. While the initial management often depends on the hemodynamic status of the patient at presentation, a systematic approach that follows the stabilization of the patient with the tools available at bedside, specifically the surface electrocardiogram often results in optimal treatment response that is tailored towards the mechanism and severity of the arrhythmia. The goal of this review is to provide the pediatric cardiologist with such an approach based on clinical history and analysis of the electrocardiogram (ECG).

Yeast Coq9 controls deamination of coenzyme Q intermediates that derive from para-aminobenzoic acid.

Coq9 is a polypeptide subunit in a mitochondrial multi-subunit complex, termed the CoQ-synthome, required for biosynthesis of coenzyme Q (ubiquinone or Q). Deletion of COQ9 results in dissociation of the CoQ-synthome, but over-expression of Coq8 putative kinase stabilizes the CoQ-synthome in the coq9 null mutant and leads to the accumulation of two nitrogen-containing Q intermediates, imino-demethoxy-Q6 (IDMQ6) and 3-hexaprenyl-4-aminophenol (4-AP) when para-aminobenzoic acid (pABA) is provided as a ring precursor. To investigate whether Coq9 is responsible for deamination steps in Q biosynthesis, we utilized the yeast coq5-5 point mutant.

Analysis of the transcriptome in hyperoxic lung injury and sex-specific alterations in gene expression.

Exposure to high concentration of oxygen (hyperoxia) leads to lung injury in experimental animal models and plays a role in the pathogenesis of diseases such as Acute Respiratory Distress Syndrome (ARDS) and Bronchopulmonary dysplasia (BPD) in humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. The major goal of this study was to characterize the changes in the pulmonary transcriptome following hyperoxia exposure and further elucidate the sex-specific changes.

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli.

Background: Studies with the nematode model Caenorhabditis elegans have identified conserved biochemical pathways that act to modulate life span. Life span can also be influenced by the composition of the intestinal microbiome, and C. elegans life span can be dramatically influenced by its diet of Escherichia coli.

Restoring de novo coenzyme Q biosynthesis in Caenorhabditis elegans coq-3 mutants yields profound rescue compared to exogenous coenzyme Q supplementation.

Coenzyme Q (ubiquinone or Q) is an essential lipid component of the mitochondrial electron transport chain. In Caenorhabditis elegans Q biosynthesis involves at least nine steps, including the hydroxylation of the hydroquinone ring by CLK-1 and two O-methylation steps mediated by COQ-3. We characterize two C.

Unincorporated iron pool is linked to oxidative stress and iron levels in Caenorhabditis elegans.

Free radicals or reactive oxygen species (ROS) are relatively short-lived and are difficult to measure directly; so indirect methods have been explored for measuring these transient species. One technique that has been developed using Escherichia coli and Saccharomyces cerevisiae systems, relies on a connection between elevated superoxide levels and the build-up of a high-spin form of iron (Fe(III)) that is detectable by electron paramagnetic resonance (EPR) spectroscopy at g = 4.3.

Limitations of standard echocardiographic methods for quantification of right ventricular size and function in children and young adults.

Objectives: The aim of this study was to evaluate correlation of 2-dimensional (2D) echocardiographic assessment of right ventricular (RV) and left ventricular (LV) size and function with magnetic resonance imaging (MRI) in children and young adults.

Methods: Patients with repaired tetralogy of Fallot (n = 23) and those who had normal RV volumes (n = 13) and a normal ejection fraction (EF) by MRI constituted the study groups. Echocardiographic indices including the end-diastolic area (EDa), end-systolic area (ESa), fractional area change (FAC), tricuspid annular motion (TAM), RV basal diameter, and RV basal shortening fraction were compared with MRI ventricular volumes and the EF.

Impact of staged palliation on somatic growth in patients with hypoplastic left heart syndrome.

Background: Somatic growth pattern in infants undergoing staged palliation for hypoplastic left heart syndrome (Norwood procedure [NP], stage 2 palliation [S2P], and Fontan procedure [FP]) during transition toward a more energy efficient series circulation is not well understood.

Objectives: We sought to determine growth pattern in these infants and factors influencing it.

Methods: Patients who underwent NP since 2001 and survived at least 1 year after S2P were followed until FP or death/heart transplantation (n = 46).

Standardized management improves outcomes after the Norwood procedure.

Background: In the past decade, many advances in the care of patients undergoing the Norwood procedure (NP) have been reported, but management remains nonstandardized at many institutions. We studied the impact of a standardized management protocol for neonates undergoing NP.

Methods: Care of NP patients has been protocol-driven at our institution since 2005, with routine use of regional low flow perfusion; near infrared spectroscopy; phenoxybenzamine with cardiopulmonary bypass; delayed sternal closure; peritoneal drainage; gastrostomy tubes; postoperative vocal cord assessment; and a home surveillance program of daily weight and oxygen saturation measurement.

Only one of a wide assortment of manganese-containing SOD mimicking compounds rescues the slow aerobic growth phenotypes of both Escherichia coli and Saccharomyces cerevisiae strains lacking superoxide dismutase enzymes.

A variety of manganese-containing coordination compounds, frequently termed superoxide dismutase (SOD) mimics, have been reported to have SOD activity in vitro and to be effective at improving conditions related to increased oxidative stress in multicellular organisms. We tested the effectiveness of several of these compounds in substituting for authentic SOD enzymes in two simple systems--the prokaryote Escherichia coli and the single-celled eukaryote, Saccharomyces cerevisiae--where strains are available that completely lack cytoplasmic SOD activity and are thus significantly impaired in their ability to grow aerobically. Most of the compounds tested, including Euk-8 and Euk-134, manganese salen derivatives developed by Eukarion; M40403, a manganese complex of a bis(cyclohexylpyridine)-substituted macrocyclic ligand developed by Metaphore; and several manganese porphyrin derivatives, were ineffective in both systems.

Measuring "free" iron levels in Caenorhabditis elegans using low-temperature Fe(III) electron paramagnetic resonance spectroscopy.

Oxidative stress, caused by free radicals within the body, has been associated with the process of aging and many human diseases. Because free radicals, in particular superoxide, are difficult to measure, an alternative indirect method for measuring oxidative stress levels has been used successfully in Escherichia coli and yeast. This method is based on a proposed connection between elevated superoxide levels and release of iron from solvent-exposed [4Fe-4S] enzyme clusters that eventually leads to an increase in hydroxyl radical production.

Manganous ion supplementation accelerates wild type development, enhances stress resistance, and rescues the life span of a short-lived Caenorhabditis elegans mutant.

Relative to iron and copper we know very little about the cellular roles of manganese. Some studies claim that manganese acts as a radical scavenger in unicellular organisms, while there have been other reports that manganese causes Parkinson's disease-like syndrome, DNA fragmentation, and interferes with cellular energy production. The goal of this study was to uncover if manganese has any free radical scavenging properties in the complex multicellular organism, Caenorhabditis elegans.

Exogenous manganous ion at millimolar levels rescues all known dioxygen-sensitive phenotypes of yeast lacking CuZnSOD.

Yeasts lacking copper-zinc superoxide dismutase (sod1Delta) exhibit a broad range of phenotypes, many of which can be rescued by growth in the presence of high levels of ionic manganese. We undertook a comprehensive survey of the effects of manganese on wild-type and sod1Delta yeasts and found that 5 mM Mn2+ rescued all known growth-related phenotypes, such as slow growth in air, temperature sensitivity, specific amino acid auxotrophies, no growth in high oxygen, poor growth in nonfermentable carbon sources, and decreased stationary-phase survival. Iron-related phenotypes-elevated electron paramagnetic resonance detectable ("free") iron, decreased aconitase activity, and fragmenting vacuoles-as well as zinc sensitivity were also rescued.

Competition between lithium and magnesium ions for the G-protein transducin in the guanosine 5'-diphosphate bound conformation.

Li(+) is the most effective drug used to treat bipolar disorder; however, its exact mechanism of action has yet to be elucidated. One hypothesis is that Li(+) competes with Mg2+ for the Mg2+ binding sites on guanine-nucleotide binding proteins (G-proteins). Using 7Li T1 relaxation measurements and fluorescence spectroscopy with the Mg2+ fluorophore furaptra, we detected Li(+)/Mg(2+) competition in three preparations: the purified G-protein transducin (Gt), stripped rod outer segment membranes (SROS), and SROS with purified Gt reattached (ROS-T).

Mutations in Saccharomyces cerevisiae iron-sulfur cluster assembly genes and oxidative stress relevant to Cu,Zn superoxide dismutase.

Saccharomyces cerevisiae lacking Cu,Zn superoxide dismutase (SOD1) show several metabolic defects including aerobic blockages in methionine and lysine biosynthesis. We have previously shown that mutations in genes implicated in the formation of iron-sulfur clusters, designated seo (suppressors of endogenous oxidation), reverse the oxygen-dependent methionine and lysine auxotrophies of a sod1Delta strain. We now report the surprising finding that seo mutants do not reduce oxidative damage as shown by the lack of reduction of EPR-detectable "free" iron, which is characteristic of sod1Delta mutants.