Mechanisms of exercise-related neurocardiogenic syncope and the relationship between resting and dynamic cardiac testing.

Objective: Syncope is common among pediatric patients and is rarely pathologic. The mechanisms for symptoms during exercise are less well understood than the resting mechanisms. Additionally, inert gas rebreathing analysis, a non-invasive examination of haemodynamics including cardiac output, has not previously been studied in youth with neurocardiogenic syncope.

Anomalous Left Coronary Artery from the Pulmonary Artery in Three Patients with MYRF-Associated Cardiac-Urogenital Syndrome.

Cardiac-Urogenital Syndrome (CUGS) is a recently identified genetic disease characterized by urogenital, diaphragmatic, ophthalmic, and cardiac abnormalities caused by heterozygous pathogenic variants in the Myelin Regulatory Factor (MYRF) gene. The complete spectrum of disease characteristics and prevalence is not yet defined. This report documents the first known cases of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in MYRF-associated Cardiac-Urogenital Syndrome (MYRF-CUGS).

Age-related changes in left ventricular vortex and energy loss patterns: from newborns to adults.

Left ventricular vortex formation optimizes the effective transport of blood volume while minimizing energy loss (EL). Vector flow mapping (VFM)-derived EL patterns have not been described in children, especially in those less than 1 yr of age. A prospective cohort of 66 (0 days-22 yr, 14 patients ≤ 2 mo) cardiovascularly normal children was used to determine left ventricular (LV) vortex number, size (mm), strength (m/s), and energy loss (mW/m/m) in systole and diastole and compared across age groups.

Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements.

Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE-ACS) event. First, non-targeted microRNA concentrations and PR were compared in a case (N = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial.

Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review.

Importance: Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature regarding obesity's effect on drug safety, pharmacokinetics, and dosing in obese children is unknown.

Objective: To perform a systematic literature review describing the current evidence of the effect of obesity on drug disposition in children.

Necrotizing enterocolitis in infants with ductal-dependent congenital heart disease.

Objective: Infants with congenital heart disease (CHD) receiving prostaglandins (PGEs) may be at an increased risk for necrotizing enterocolitis (NEC). Enteral feeding may further increase the risk of NEC in these patients. We evaluated the incidence of NEC and its association with enteral feeding in infants with ductal-dependent CHD.

Use of the complete blood cell count in late-onset neonatal sepsis.

Background: Late-onset sepsis is an important cause of morbidity and mortality in infants. Diagnosis of late-onset sepsis can be challenging. The complete blood cell count and differential have been previously evaluated as diagnostic tools for late-onset sepsis in small, single-center reports.

Use of the complete blood cell count in early-onset neonatal sepsis.

Background: Early-onset sepsis (EOS) is an important cause of morbidity and mortality in neonates, and its diagnosis remains challenging. The complete blood cell count and differential have been previously evaluated as diagnostic tools for EOS in small, single-center reports. We evaluated the diagnostic accuracy of the complete blood cell count and differential in EOS in a large, multicenter population of neonates admitted to the neonatal intensive care unit.

Factor IXa as a target for pharmacologic inhibition in acute coronary syndrome.

Anticoagulant therapy, combined with platelet-directed inhibitors, represents a standard-of-care in the management of patients with acute coronary syndrome, particularly those who require percutaneous coronary interventions. While a vast clinical experience, coupled with large clinical trials have collectively provided guidance, an optimal anticoagulant drug and applied strategy, defined as one that reduces thrombotic and hemorrhagic events consistently, with minimal off-target effects and active control of systemic anticoagulation according to patient and clinical-setting specific need, remains at large. An advancing knowledge of coagulation, hemostasis, and thrombosis suggests that factor IXa, a protease that governs thrombin generation in common thrombotic disorders may represent a prime target for pharmacologic inhibition.

Reciprocal regulation of 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression by dexamethasone inhibits human coronary artery smooth muscle cell proliferation in vitro.

The actions of glucocorticoids are mediated, in part, by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which amplifies their effects at the pre-receptor level by converting cortisone to cortisol. Glucocorticoids, such as dexamethasone, inhibit vascular smooth muscle cell proliferation; however, the role of 11β-HSD1 in this response remains unknown. Accordingly, we treated human coronary artery smooth muscle cells (HCSMC) with dexamethasone (10(-9)-10(-6) mol/l) and found that after 72 h dexamethasone increased 11β-HSD1 expression (14.

Antidote-controlled antithrombotic therapy targeting factor IXa and von Willebrand factor.

Thrombotic disorders and their common clinical phenotypes of acute myocardial infarction, ischemic stroke, and venous thromboembolism are the proximate cause of substantial morbidity, mortality, and health care expenditures worldwide. Accordingly, therapies designed to attenuate thrombus initiation and propagation, reflecting integrated platelet-mediated and coagulation protease-mediated events, respectively, represent a standard of care. Unfortunately, there are numerous inherent limitations of existing therapies that include target nonselectivity, variable onset and offset of pharmacodynamic effects, a narrow efficacy-safety profile, and the absence of a safe and reliable platform for either accurate titration, based on existing patient-specific, disease-specific, and clinical conditions, or active reversibility.

Factor IXa inhibitors as novel anticoagulants.

Currently available anticoagulants are limited by modest therapeutic benefits, narrow clinical applications, increased bleeding risk, and drug-induced thrombophilia. Because factor IX plays a pivotal role in tissue factor (TF)-mediated thrombin generation, it may represent a promising target for drug development. Several methods of attenuating factor IX activity, including monoclonal antibodies, synthetic active site-blocked competitive inhibitors, oral inhibitors, and RNA aptamers, have undergone investigation.

Nucleic acid aptamers as adjuncts to vaccine development.

Nucleic acid 'aptamers', a term derived from the Latin word aptus, 'to fit', are RNA or DNA oligonucleotides that conform to the three-dimensional structure of a selected protein, peptide or small molecules' functional moiety. The 'lock and key' relationship between aptamers and their binding partner permits distinction between closely related but non-identical members of a protein family, or between different functional or conformational states of the same protein. This, along with other properties, separates aptamers from antibodies--the most popular class of molecular recognition tool for the past three decades.

The effect of temperature variation in vitro on platelet-leukocyte interactions and individual prothrombotic potential.

Background: Temperature variation within human atheromatous plaques, a finding which supports inflammatory cell-mediated thermogenesis, predicts clinical events among patients with coronary artery disease.

Purpose: Our study was designed to investigate the effect of ambient temperature in vitro on platelet-leukocyte interactions, monocyte tissue factor expression and platelet-dependent thrombin generation.

Methods/results: Whole blood samples obtained from healthy volunteers were incubated at 37 degrees, 38 degrees and 39 degrees C for three hours.