Visual pathway function and structure in Wolfram syndrome: patient age, variation and progression.

Background/aims: To report alterations in visual acuity and visual pathway structure over an interval of 1-3 years in a cohort of children, adolescents and young adults who have Wolfram syndrome (WFS) and to describe the range of disease severity evident in patients with WFS whose ages differed by as much as 20 years at first examination.

Methods: Annual, prospective ophthalmological examinations were performed in conjunction with retinal nerve fibre layer (RNFL) analysis. Diffusion tensor MRI-derived fractional anisotropy was used to assess the microstructural integrity of the optic radiations (OR FA).

The pediatric asthma yardstick: Practical recommendations for a sustained step-up in asthma therapy for children with inadequately controlled asthma.

Current asthma guidelines recommend a control-based approach to management involving assessment of impairment and risk followed by implementation of treatment strategies individualized according to the patient's needs and preferences. However, for children with asthma, achieving control can be elusive. Although tools are available to help children (and families) track and manage day-to-day symptoms, when and how to implement a longer-term step-up in care is less clear.

A Randomized Trial of a Multicomponent Intervention to Promote Medication Adherence: The Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT).

Background: Poor adherence to immunosuppressive medications is a major cause of premature graft loss among children and young adults. Multicomponent interventions have shown promise but have not been fully evaluated.

Study Design: Unblinded parallel-arm randomized trial to assess the efficacy of a clinic-based adherence-promoting intervention.

Fathers' Stress in the Neonatal Intensive Care Unit: A Systematic Review.

Background: Admission to the neonatal intensive care unit (NICU) is stressful for parents. Nurses often focus on maternal well-being and fail to acknowledge the stress of fathers. Research on fathers' psychological stress is limited.

Mutations in the thyroid transcription factor gene NKX2-1 result in decreased expression of SFTPB and SFTPC.

Background: Mutations in the NK2 homeobox 1 (NKX2-1) gene are associated with lung disease in infants and children. We hypothesize that disruption of normal surfactant gene expression with these mutations contributes to the respiratory phenotypes observed.

Methods: To assess transactivational activity, cotransfection of luciferase reporter vectors containing surfactant protein B or C (SFTPB or SFTPC) promoters with NKX2-1 plasmids was performed and luciferase activity was measured.

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

Background: Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited.

Non-immunologic allograft loss in pediatric kidney transplant recipients.

Non-immunologic risk factors are a major obstacle to realizing long-term improvements in kidney allograft survival. A standardized approach to assess donor quality has recently been introduced with the new kidney allocation system in the USA. Delayed graft function and surgical complications are important risk factors for both short- and long-term graft loss.

Infants with Atypical Presentations of Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins Who Underwent Bilateral Lung Transplantation.

Objective: To describe disease course, histopathology, and outcomes for infants with atypical presentations of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) who underwent bilateral lung transplantation.

Study Design: We reviewed clinical history, diagnostic studies, explant histology, genetic sequence results, and post-transplant course for 6 infants with atypical ACDMPV who underwent bilateral lung transplantation at St. Louis Children's Hospital.

The effects of disease-related symptoms on daily function in Wolfram Syndrome.

Objective: To investigate daily function among individuals with Wolfram Syndrome (WFS) and examine whether any limitations are related to disease-related symptoms.

Methods: WFS ( = 31), Type 1 diabetic (T1DM; = 25), and healthy control (HC; = 29) participants completed the Pediatric Quality of Life Questionnaire (PEDSQL) Self and Parent Report. PEDSQL domain scores were compared among these groups and between WFS patients with and without specific disease-related symptoms.

Prenatal and early-life triclosan and paraben exposure and allergic outcomes.

Background: In cross-sectional studies triclosan and parabens, ubiquitous ingredients in personal care and other products, are associated with allergic disease.

Objectives: We investigated the association between prenatal and early-life triclosan and paraben exposure and childhood allergic disease in a prospective longitudinal study.

Methods: Subjects were enrollees in the Vitamin D Antenatal Asthma Reduction Trial.

Gain-of-function HCN2 variants in genetic epilepsy.

Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes.

Pharmacogenomic Variability of Oral Baclofen Clearance and Clinical Response in Children With Cerebral Palsy.

Background: Pharmacogenomic variability can contribute to differences in pharmacokinetics and clinical responses. Pediatric patients with cerebral palsy with genetic variations have not been studied for these potential differences.

Objective: To determine the genetic sources of variation in oral baclofen clearance and clinical responses.

Survival among children with "Lethal" congenital contracture syndrome 11 caused by novel mutations in the gliomedin gene (GLDN).

Biallelic GLDN mutations have recently been identified among infants with lethal congenital contracture syndrome 11 (LCCS11). GLDN encodes gliomedin, a protein required for the formation of the nodes of Ranvier and development of the human peripheral nervous system. We report six infants and children from four unrelated families with biallelic GLDN mutations, four of whom survived beyond the neonatal period into infancy, childhood, and late adolescence with intensive care and chronic respiratory and nutritional support.

Severe Asthma in Children.

Severe asthma in children is associated with significant morbidity and is a highly heterogeneous disorder with multiple clinical phenotypes. Cluster analyses have been performed in several groups to explain some of the heterogeneity of pediatric severe asthma, which is reviewed in this article. The evaluation of a child with severe asthma includes a detailed diagnostic assessment and excluding other possible diagnoses and addressing poor control due to comorbidities, lack of adherence to asthma controller medications, poor technique, and other psychological and environmental factors.

A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses.

Background: Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear.

Methods: We conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis.

Effects of Participation in Sports Programs on Walking Ability and Endurance Over Time in Children With Cerebral Palsy.

Objective: Children with cerebral palsy may benefit from maintaining a high level of physical fitness similar to typically developing children especially in terms of long-term physical performance, although in practice this is often difficult. The purpose of this study was to determine the effect of participation in sports programs on walking ability and endurance over time.

Design: A retrospective cohort study included participants with cerebral palsy, aged 6 to 20 yrs, who attended a summer sports program from 2004 to 2012.

Intertumoral Heterogeneity within Medulloblastoma Subgroups.

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma.

Downregulation of transcription factor GATA4 sensitizes human hepatoblastoma cells to doxorubicin-induced apoptosis.

Hepatoblastoma, the most common type of pediatric liver cancer, is treated with a combination of surgery and chemotherapy. An essential drug in the treatment of hepatoblastoma is doxorubicin, which in high doses is cardiotoxic. This adverse effect is due to downregulation of cardiac expression of transcription factor GATA4, leading in turn to diminished levels of anti-apoptotic BCL2 (B-cell lymphoma 2) protein family members.

Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial.

Background: Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial.

Objective: We sought to study the effect of a vitamin D intervention in pregnancy between subjects of different races and the association between 25-hydroxyvitamin D (25[OH]D) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring.

Methods: The Vitamin D Antenatal Asthma Reduction Trial is a randomized trial of pregnant women at risk of having children with asthma randomized to 4400 international units/d vitamin D or placebo plus 400 international units/d vitamin D.

Outcomes of Lung Transplantation for Infants and Children with Genetic Disorders of Surfactant Metabolism.

Objective: To compare outcomes of infants and children who underwent lung transplantation for genetic disorders of surfactant metabolism (SFTPB, SFTPC, ABCA3, and NKX2-1) over 2 epochs (1993-2003 and 2004-2015) at St Louis Children's Hospital.

Study Design: We retrospectively reviewed clinical characteristics, mortality, and short- and long-term morbidities of infants (transplanted at <1 year; n = 28) and children (transplanted >1 year; n = 16) and compared outcomes by age at transplantation (infants vs children) and by epoch of transplantation.

Results: Infants underwent transplantation more frequently for surfactant protein-B deficiency, whereas children underwent transplantation more frequently for SFTPC mutations.