Non-invasive respiratory support for infants in low- and middle-income countries.

The overwhelming majority of neonatal deaths worldwide occur in low- and middle-income countries. Most of these deaths are attributable to respiratory illnesses and complications of preterm birth. The available data suggest that non-invasive continuous positive airway pressure (CPAP) is a safe and cost-effective therapy to reduce neonatal morbidity and mortality in these settings.

Relationship between obstructive sleep apnea cardiac complications and sleepiness in children with Down syndrome.

Objective/background: Children with Down syndrome (DS) have a high rate of pulmonary hypertension and sleepiness. They also have a high prevalence of obstructive sleep apnea syndrome (OSAS). We hypothesized that OSAS was associated with cardiovascular dysfunction and sleepiness in children with DS, and that this dysfunction was partly reversible.

Recombinant Adeno-Associated Virus Vector Genomes Take the Form of Long-Lived, Transcriptionally Competent Episomes in Human Muscle.

Gene augmentation therapy as a strategy to treat alpha-1 antitrypsin (AAT) deficiency has reached phase 2 clinical testing in humans. Sustained serum levels of AAT have been observed beyond one year after intramuscular administration of a recombinant adeno-associated virus (rAAV) vector expressing the AAT gene. In this study, sequential muscle biopsies obtained at 3 and 12 months after vector injection were examined for the presence of rAAV vector genomes.

Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia.

Osteonecrosis is a dose-limiting toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL). Prior studies on the genetics of osteonecrosis have focused on patients ≥10 years of age, leaving the genetic risk factors for the larger group of children <10 years incompletely understood. Here, we perform the first evaluation of genetic risk factors for osteonecrosis in children <10 years.

When has enough evidence accumulated to change neonatal practice?

Randomized clinical trials are the best method to assess the safety and efficacy of therapeutic interventions. However, it is not always clear how much evidence from randomized trials is required to change clinical practice. Throughout the history of neonatal medicine, some therapies were subject to excessive and unnecessary testing through replication of clinical trials.

Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on Respiratory Outcomes in Extremely Low-Birth-Weight Infants.

Importance: Extubation failure is common in extremely preterm infants. The current paucity of data on the adverse long-term respiratory outcomes associated with reinitiation of mechanical ventilation prevents assessment of the risks and benefits of a trial of extubation in this population.

Objective: To evaluate whether exposure to multiple courses of mechanical ventilation increases the risk of adverse respiratory outcomes before and after adjustment for the cumulative duration of mechanical ventilation.

Correlation of Clinical Outcomes With Multiplex Molecular Testing of Stool From Children Admitted to Hospital With Gastroenteritis in Botswana.

Background: Diarrheal disease is a leading cause of death for young children. Most pediatric gastroenteritis is caused by viral pathogens; consequently, current recommendations advocate against routine antibacterial therapy if children present without bloody stools.

Methods: In this prospective cohort study, we enrolled children with severe acute gastroenteritis admitted to hospital in Botswana.

The ethics of neonatal research: A trialists' perspective.

We are neonatal physicians who strive to practice evidence-based medicine. We conduct and promote randomized trials in preterm and critically ill infants to improve their care and outcomes. Controlled clinical trials are ethical and essential because randomization is the best strategy to minimize bias when evaluating therapies of uncertain benefit.

Mitochondrial synapses: intracellular communication and signal integration.

Communication is a central theme in biology. Consequently, specialized structures have evolved to permit rapid communication among cells, tissues, organs, and physiological systems, thus enhancing the overall function and adaptation of the organism. A prime example is the neuronal synapse.

The trajectory of life. Decreasing physiological network complexity through changing fractal patterns.

In this position paper, we submit a synthesis of theoretical models based on physiology, non-equilibrium thermodynamics, and non-linear time-series analysis. Based on an understanding of the human organism as a system of interconnected complex adaptive systems, we seek to examine the relationship between health, complexity, variability, and entropy production, as it might be useful to help understand aging, and improve care for patients. We observe the trajectory of life is characterized by the growth, plateauing and subsequent loss of adaptive function of organ systems, associated with loss of functioning and coordination of systems.

Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a MYCN independent mechanism.

Neuroblastoma, a childhood cancer with highly heterogeneous biology and clinical behavior, is characterized by genomic aberrations including amplification of MYCN. Hemizygous deletion of chromosome 11q is a well-established, independent marker of poor prognosis. While 11q22-q23 is the most frequently deleted region, the neuroblastoma tumor suppressor in this region remains to be identified.

Breastfeeding, co-sleeping and dental health advice.

Purpose: To identify dental health advice offered by healthcare providers (HCPs) to mothers that cosleep and breastfeed at night.

Study Design And Methods: Mothers were recruited via local contacts, e-mail, and support groups. In-person, digitally recorded interviews were conducted with 14 cosleeping, breastfeeding mothers with children from 6 months to 2 years.

Candidate genes that affect aging through protein homeostasis.

Because aging is a multifactorial, pleiotropic process where many interacting mechanisms contribute to the organismal decline, the candidate gene approach rarely provides a clear message. This chapter discusses some of the inherent complexity, focusing on aspects that impinge upon protein homeostasis and maintain a healthy proteome. We discuss candidate genes that operate in these pathways, and compare their actions in invertebrates, mice and humans.

Early Head CT Findings Are Associated With Outcomes After Pediatric Out-of-Hospital Cardiac Arrest.

Objectives: Head CT after out-of-hospital cardiac arrest is often obtained to evaluate intracranial pathology. Among children admitted to the PICU following pediatric out-of-hospital cardiac arrest, we hypothesized that loss of gray-white matter differentiation and basilar cistern and sulcal effacement are associated with mortality and unfavorable neurologic outcome.

Design: Retrospective, cohort study.

Genomic and functional comparison of mesenchymal stromal cells prepared using two isolation methods.

Background Aims: Mesenchymal stromal cells (MSCs) have been applied to patients in cell therapy for various diseases. Recently, we introduced a novel MSC separation filter device which could yield approximately 2.5-fold more MSCs from bone marrow in a closed system compared with the conventional open density gradient centrifugation method.

Detection of electrographic seizures by critical care providers using color density spectral array after cardiac arrest is feasible.

Objective: To determine the accuracy and reliability of electroencephalographic seizure detection by critical care providers using color density spectral array electroencephalography.

Design: Tutorial and questionnaire.

Subjects: Critical care providers (attending physicians, fellow trainees, and nurses).

ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura.

Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP.

Resilience to the effects of social stress: evidence from clinical and preclinical studies on the role of coping strategies.

The most common form of stress encountered by people stems from one's social environment and is perceived as more intense than other types of stressors. One feature that may be related to differential resilience or vulnerability to stress is the type of strategy used to cope with the stressor, either active or passive coping. This review focuses on models of social stress in which individual differences in coping strategies produce resilience or vulnerability to the effects of stress.

Reinstating aberrant mTORC1 activity in Huntington's disease mice improves disease phenotypes.

Huntington's disease (HD) is caused by a polyglutamine tract expansion in huntingtin (HTT). Despite HTTs ubiquitous expression, there is early and robust vulnerability in striatum, the cause of which is poorly understood. Here, we provide evidence that impaired striatal mTORC1 activity underlies varied metabolic and degenerative phenotypes in HD brain and show that introducing the constitutively active form of the mTORC1 regulator, Rheb, into HD mouse brain, alleviates mitochondrial dysfunction, aberrant cholesterol homeostasis, striatal atrophy, impaired dopamine signaling, and increases autophagy.

The changing nature of children's health development: new challenges require major policy solutions.

The epidemiology and social context of American childhood are rapidly changing. Adverse social, economic, and child-rearing conditions are loading children down with preventable illness, physical and behavioral disability, and dysfunction. This new epidemiology of childhood is swamping the capacity of the nation's health care system, schools, juvenile justice facilities, and child protective services to respond to the needs of those they serve.

Predictors of perioperative complications in higher risk children after adenotonsillectomy for obstructive sleep apnea: a prospective study.

Objective: Retrospective studies have limitations in predicting perioperative risk following adenotonsillectomy in children with obstructive sleep apnea syndrome (OSAS). Few prospective studies exist. We hypothesized that demographic and polysomnographic (PSG) variables would predict respiratory and general perioperative complications.