Preconditioning of skeletal myoblast-based engineered tissue constructs enables functional coupling to myocardium in vivo.

Objective: Skeletal myoblasts fuse to form functional syncytial myotubes as an integral part of the skeletal muscle. During this differentiation process, expression of proteins for mechanical and electrical integration is seized, which is a major drawback for the application of skeletal myoblasts in cardiac regenerative cell therapy, because global heart function depends on intercellular communication.

Methods: Mechanically preconditioned engineered tissue constructs containing neonatal mouse skeletal myoblasts were transplanted epicardially.

Independent contribution of individual white matter pathways to language function in pediatric epilepsy patients.

Background And Purpose: Patients with epilepsy and malformations of cortical development (MCDs) are at high risk for language and other cognitive impairment. Specific impairments, however, are not well correlated with the extent and locale of dysplastic cortex; such findings highlight the relevance of aberrant cortico-cortical interactions, or connectivity, to the clinical phenotype. The goal of this study was to determine the independent contribution of well-described white matter pathways to language function in a cohort of pediatric patients with epilepsy.

STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models.

Chronic inflammation is a well-recognized pathogenic factor in tumor initiation and progression. Mice lacking the pro-oncogenic transcription factor STAT3 were shown to be protected from both colitis-associated and epidermal cancers induced by the AOM/DSS and DMBA/TPA protocols, respectively. However, these murine models did not distinguish between the two STAT3 isoforms, the full-length STAT3α, believed to exert most pro-oncogenic functions attributed to STAT3, and the shorter STAT3β, often referred to as a dominant-negative, but possessing specific transcriptional activities.

ALK-dependent control of hypoxia-inducible factors mediates tumor growth and metastasis.

Rearrangements involving the anaplastic lymphoma kinase (ALK) gene are defining events in several tumors, including anaplastic large-cell lymphoma (ALCL) and non-small cell lung carcinoma (NSCLC). In such cancers, the oncogenic activity of ALK stimulates signaling pathways that induce cell transformation and promote tumor growth. In search for common pathways activated by oncogenic ALK across different tumors types, we found that hypoxia pathways were significantly enriched in ALK-rearranged ALCL and NSCLC, as compared with other types of T-cell lymphoma or EGFR- and K-RAS-mutated NSCLC, respectively.

Technical performance score is associated with outcomes after the Norwood procedure.

Objectives: The technical performance score (TPS) has been reported in a single center study to predict the outcomes after congenital cardiac surgery. We sought to determine the association of the TPS with outcomes in patients undergoing the Norwood procedure in the Single Ventricle Reconstruction trial.

Methods: We calculated the TPS (class 1, optimal; class 2, adequate; class 3, inadequate) according to the predischarge echocardiograms analyzed in a core laboratory and unplanned reinterventions that occurred before discharge from the Norwood hospitalization.

Dysregulation of system xc(-) expression induced by mutant huntingtin in a striatal neuronal cell line and in R6/2 mice.

Oxidative stress has been implicated in the pathogenesis of Huntington's disease (HD), however, the origin of the oxidative stress is unknown. System xc(-) plays a role in the import of cystine to synthesize the antioxidant glutathione. We found in the STHdh(Q7/Q7) and STHdh(Q111/Q111) striatal cell lines, derived from neuronal precursor cells isolated from knock-in mice containing 7 or 111 CAG repeats in the huntingtin gene, that there is a decrease in system xc(-) function.

Longitudinal assessment of growth in hypoplastic left heart syndrome: results from the single ventricle reconstruction trial.

Background: We sought to characterize growth between birth and age 3 years in infants with hypoplastic left heart syndrome who underwent the Norwood procedure.

Methods And Results: We performed a secondary analysis using the Single Ventricle Reconstruction Trial database after excluding patients <37 weeks gestation (N=498). We determined length-for-age z score (LAZ) and weight-for-age z score (WAZ) at birth and age 3 years and change in WAZ over 4 clinically relevant time periods.

Greater surgical precision of a flexible carbon dioxide laser fiber compared to monopolar electrosurgery in porcine myometrium.

The objective of this experimental animal study was to compare the surgical precision of a flexible CO2 laser fiber with that of monopolar electrosurgery in porcine myometrium. The subjects were 6 live adult non-pregnant female pigs. Linear injury to the uterine horns was created using a flexible CO2 laser fiber at 5W, 10W, and 15W and with monopolar electrosurgery at 10W, 20W, 30W, and 40W in both cut and coagulation modes.

Phosphorylation of Shox2 is required for its function to control sinoatrial node formation.

Background: Inactivation of Shox2, a member of the short-stature homeobox gene family, leads to defective development of multiple organs and embryonic lethality as a result of cardiovascular defects, including bradycardia and severe hypoplastic sinoatrial node (SAN) and sinus valves, in mice. It has been demonstrated that Shox2 regulates a genetic network through the repression of Nkx2.5 to maintain the fate of the SAN cells.

Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro.

Current in vitro hematopoiesis models fail to demonstrate the cellular diversity and complex functions of living bone marrow; hence, most translational studies relevant to the hematologic system are conducted in live animals. Here we describe a method for fabricating 'bone marrow-on-a-chip' that permits culture of living marrow with a functional hematopoietic niche in vitro by first engineering new bone in vivo, removing it whole and perfusing it with culture medium in a microfluidic device. The engineered bone marrow (eBM) retains hematopoietic stem and progenitor cells in normal in vivo-like proportions for at least 1 week in culture.

Sleep duration affects risk for ulcerative colitis: a prospective cohort study.

Background & Aims: Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined.

Repeatability of quantitative metrics derived from MR diffusion tractography in paediatric patients with epilepsy.

Objective: To quantify the test-retest repeatability of mean diffusivity (MD) and fractional anisotropy (FA) derived from diffusion tensor imaging (DTI) tractography in a cohort of paediatric patients with localization-related epilepsy.

Methods: 30 patients underwent 2 DTI acquisitions [repetition time/echo time (ms), 7000/90; flip, 90°; b-value, 1000 s mm(-2); voxel (mm), 2 × 2 × 2]. Two observers used Diffusion Toolkit and TrackVis ( www.

Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease.

Background And Purpose: Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively.

Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development.

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants.

Brain volume and neurobehavior in newborns with complex congenital heart defects.

Objective: To investigate the relationship between tissue-specific alterations in brain volume and neurobehavioral status in newborns with complex congenital heart defects preoperatively.

Study Design: Three-dimensional volumetric magnetic resonance imaging was used to calculate tissue-specific brain volumes and a standardized neurobehavioral assessment was performed to assess neurobehavioral status in 35 full-term newborns admitted to the hospital before cardiopulmonary bypass surgery. Multiple linear regression models were performed to evaluate relationships between neurobehavioral status and brain volumes.

Leaning in to the power of the possible: the crucial role of women scientists on preventing Haemophilus influenzae type b disease.

Beginning in an era when female scientists were a lonely minority, women have made major contributions to our understanding of Haemophilus influenzae type b (Hib) as a pathogen, its treatment and its prevention. The individual scientific and public health contributions, and their collective impact, are reviewed in the context of the development and successful implementation of highly efficacious Hib vaccines that are now being deployed to nearly every country worldwide for the prevention of life-threatening pediatric Hib disease.

AMPA receptor antagonist NBQX attenuates later-life epileptic seizures and autistic-like social deficits following neonatal seizures.

Purpose: To determine whether AMPA receptor (AMPAR) antagonist NBQX can prevent early mammalian target of rapamycin (mTOR) pathway activation and long-term sequelae following neonatal seizures in rats, including later-life spontaneous recurrent seizures, CA3 mossy fiber sprouting, and autistic-like social deficits.

Methods: Long-Evans rats experienced hypoxia-induced neonatal seizures (HS) at postnatal day (P)10. NBQX (20 mg/kg) was administered immediately following HS (every 12 h × 4 doses).

Cardiac output assessed by non-invasive monitoring is associated with ECG changes in children with critical asthma.

The primary aim of this study was to determine changes in CI and SI, if any, in children hospitalized with status asthmatics during the course of treatment as measured by non-invasive EC monitoring. The secondary aim was to determine if there is an association between Abnormal CI (defined as <5 or >95 % tile adjusted for age) and Abnormal ECG (defined as ST waves changes) Non-invasive cardiac output (CO) recordings were obtained daily from admission (Initial) to discharge (Final). Changes in CI and SI measurements were compared using paired t tests or 1-way ANOVA.

Effects of exercise and lifestyle modification on fitness, insulin resistance, skeletal muscle oxidative phosphorylation and intramyocellular lipid content in obese children and adolescents.

Background: Obesity is associated with poor fitness and adverse metabolic consequences in children.

Objective: To investigate how exercise and lifestyle modification may improve fitness and insulin sensitivity in this population.

Design And Subjects: Randomized controlled trial, 21 obese (body mass index ≥ 95% percentile) subjects, ages 10 to 17 years.

Pulmonary artery conduit in vivo dimensional requirements in a growing ovine model: comparisons with the ascending aorta.

Background And Aim Of The Study: The pulmonary trunk (PT) structure and function are abnormal in multiple congenital cardiovascular diseases. Existing surgical treatments of congenital malformations of the right ventricular outflow tract and PT do not provide a long-term replacement that can adapt to normal growth. Although there is strong interest in developing tissue-engineered approaches for PT conduit replacement, there remains an absence of any complete investigation of the native geometric growth patterns of the PT to serve as a necessary benchmark.

Neuropsychological outcomes in fatty acid oxidation disorders: 85 cases detected by newborn screening.

Mitochondrial fatty acid oxidation disorders include conditions in which the transport of activated acyl-Coenzyme A (CoA) into the mitochondria or utilization of these substrates is disrupted or blocked. This results in a deficit in the conversion of fat into energy. Most patients with fatty acid oxidation defects are now identified through newborn screening by tandem mass spectrometry.

Factor structure of the children's depression inventory in a multisite sample of children and adolescents with chronic pain.

Unlabelled: This study examined the factor structure of the Children's Depression Inventory (CDI) among children and adolescents with chronic pain using exploratory and confirmatory factor analysis in a large, multisite sample of treatment-seeking youth. Participants included 1,043 children and adolescents (ages 8-18) with a range of chronic pain complaints who presented for initial evaluation at 1 of 3 tertiary care pediatric chronic pain clinics across the United States. They completed the CDI and reported on pain intensity and functional disability.