Tobacco Control and Treatment for the Pediatric Clinician: Practice, Policy, and Research Updates.

Tobacco use is the leading cause of preventable death in the United States, and exposure to tobacco smoke harms children from conception forward. There is no safe level of tobacco exposure. Although overall smoking rates have declined, the advent of new products, such as electronic cigarettes, threatens to perpetuate nicotine addiction without clear health benefits.

Use of Gastroesophageal Reflux Medications in Premature Infants After NICU Discharge.

Objectives: To describe the epidemiology and management of gastroesophageal reflux (GER) medications started in the first year of life for premature infants.

Methods: Retrospective review of a cohort of infants ≤35 weeks' gestation presenting for care by 168 days of age to a 30-site network between 2005 and 2009 (n = 2217) and followed to 3 years of age. Medication frequency, types, and duration of use were assessed.

Initial testing (stage 1) of the curaxin CBL0137 by the pediatric preclinical testing program.

Background: CBL0137 is a novel drug that modulates FAcilitates Chromatin Transcription (FACT), resulting in simultaneous nuclear factor-κB suppression, heat shock factor 1 suppression and p53 activation. CBL0137 has demonstrated antitumor effects in animal models of several adult cancers and neuroblastoma.

Procedures: CBL0137 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations ranging from 1.

The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk Gene.

To identify genetic mechanisms involved in the interplay of risky sexual behaviors (RSBs) and alcohol dependence (AD), we conducted genome-wide gene-by-AD (GW-GxAD) analyses of RSB in 3924 alcohol-exposed and sexually experienced subjects. RSBs were defined as a score based on lifetime experiences of unprotected sex and multiple sexual partners. Diagnosis of lifetime AD was defined by DSM-IV criteria.

Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis.

Traditional approaches to evaluating antitumor agents using human tumor xenograft models have generally used cohorts of 8 to 10 mice against a limited panel of tumor models. An alternative approach is to use fewer animals per tumor line, allowing a greater number of models that capture greater molecular/genetic heterogeneity of the cancer type. We retrospectively analyzed 67 agents evaluated by the Pediatric Preclinical Testing Program to determine whether a single mouse, chosen randomly from each group of a study, predicted the median response for groups of mice using 83 xenograft models.

Initial Testing (Stage 1) of MK-8242-A Novel MDM2 Inhibitor-by the Pediatric Preclinical Testing Program.

Background: MK-8242 is an inhibitor of MDM2 that stabilizes the tumor suppressor TP53 and induces growth arrest or apoptosis downstream of TP53 induction.

Procedures: MK-8242 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0 nM to 10.

Immunogenicity of Human Papillomavirus Recombinant Vaccine in Children with CKD.

Background And Objectives: There is a disproportionate burden of human papillomavirus (HPV) -related genital tract disease in patients with CKD and kidney transplantation; therefore, the potential effect of the quadrivalent HPV vaccine (Gardasil; Merck GmbH, Darmstadt, Germany) is profound. Immune abnormalities associated with CKD and immunosuppression may prevent optimal vaccine response. Our objective was to determine antibody response to the HPV vaccine in adolescent girls with CKD.

Sex Differences in Outcomes Following Percutaneous Coronary Intervention According to Age.

Background: Women <50 years of age with coronary artery disease may represent a group at higher risk for recurrent ischemic events after percutaneous coronary intervention (PCI); however, no long-term, multicenter outcomes assessment exists in this population.

Methods And Results: Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated the association of sex and age on cardiovascular-related outcomes in 10,963 patients (3797 women, 394 <50 years) undergoing PCI and followed for 5 years. Death, myocardial infarction, coronary artery bypass graft surgery, and repeat PCI were primary outcomes comprising major adverse cardiovascular events.

Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program.

Background: NSC 750854 is a purine analog with an antitumor activity profile distinctive from that of other anticancer purines. It has shown significant activity against adult cancer preclinical models.

Procedure: NSC 750854 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.

Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia.

Objective: Friedreich ataxia (FRDA) is an inherited neurodegenerative disease characterized by ataxia and cardiomyopathy. Homozygous GAA trinucleotide repeat expansions in the first intron of FXN occur in 96% of affected individuals and reduce frataxin expression. Remaining individuals are compound heterozygous for a GAA expansion and a FXN point/insertion/deletion mutation.

Individuals With Traumatic Brain Injury and Their Significant Others' Perceptions of Information Given About the Nature and Possible Consequences of Brain Injury: Analysis of a National Survey.

Purpose Of The Study: An online survey was developed to assess how well individuals with brain injuries and family/friends of those with traumatic brain injury (TBI) (significant others) felt they were informed about the nature and consequences of brain injury.

Participants: A total of 117 significant others completed the survey. They were primarily female (84.

Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program.

Background: Selinexor (KPT-330) is an inhibitor of the major nuclear export receptor, exportin 1 (XPO1, also termed chromosome region maintenance 1, CRM1) that has demonstrated activity in preclinical models and clinical activity against several solid and hematological cancers.

Procedures: Selinexor was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0 nM to 10 μM and against the PPTP in vivo xenograft panels administered orally at a dose of 10 mg/kg thrice weekly for 4 weeks.

The Optical Biopsy: A Novel Technique for Rapid Intraoperative Diagnosis of Primary Pulmonary Adenocarcinomas.

Background: With increasing use of chest computed tomography scans, indeterminate pulmonary nodules are frequently detected as an incidental finding and present a diagnostic challenge. Tissue biopsy followed by histological review and immunohistochemistry is the gold standard to obtain a diagnosis and the most common malignant finding is a primary lung adenocarcinoma. Our objective was to determine whether an intraoperative optical biopsy (molecular imaging) may provide an alternative approach for determining if a pulmonary nodule is a primary lung adenocarcinoma.

Adherence to the 2012 American College of Rheumatology (ACR) Guidelines for Management of Gout: A Survey of Brazilian Rheumatologists.

Objective: To describe the current pharmacological approach to gout treatment reported by rheumatologists in Brazil.

Methods: We performed a cross-sectional survey study using an online questionnaire e-mailed to 395 rheumatologists, randomly selected, from among the members of the Brazilian Society of Rheumatology.

Results: Three hundred and nine rheumatologists (78.

Association between self-report adherence measures and oestrogen suppression among breast cancer survivors on aromatase inhibitors.

Purpose: Poor adherence to oral adjuvant hormonal therapy for breast cancer is a common problem, but little is known about the relationship between self-report adherence measures and hormonal suppression. We evaluated the relationship of three self-report measures of medication adherence and oestrogen among patients on aromatase inhibitors (AIs).

Materials And Methods: We recruited 235 women with breast cancer who were prescribed AI therapy.

Initial testing (stage 1) of the anti-microtubule agents cabazitaxel and docetaxel, by the pediatric preclinical testing program.

Background: Although microtubule-destabilizing agents (principally vincristine) are in common use in pediatric oncology, the microtubule-stabilizing taxanes are uncommonly used to treat childhood cancers. Cabazitaxel has been reported to have activity superior to that of docetaxel in preclinical models of multidrug-resistant adult cancers, and it was active in patients who had progressed on or after docetaxel. The PPTP conducted a comparison of these two agents against the PPTP in vitro panel and against a limited panel of solid tumor xenografts.

Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome.

Neuroblastoma in patients with congenital central hypoventilation syndrome (CCHS) as part of a neurocristopathy syndrome is a rare finding and has only been associated with paired-like homeobox 2b (PHOX2B) non-polyalanine-repeat-expansion mutations. To the best of our knowledge, we report the first case of a child with CCHS and Hirschsprung disease who had a PHOX2B polyalanine-repeat-expansion mutation (PARM) (genotype 20/33) and developed high-risk neuroblastoma. We further describe his treatment including chemotherapy and therapeutic I(131) -metaiodobenzylguanidine.

Eye color: A potential indicator of alcohol dependence risk in European Americans.

In archival samples of European-ancestry subjects, light-eyed individuals have been found to consume more alcohol than dark-eyed individuals. No published population-based studies have directly tested the association between alcohol dependence (AD) and eye color. We hypothesized that light-eyed individuals have a higher prevalence of AD than dark-eyed individuals.

Phase I/II study of (131)I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma.

Background: (131)I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan.

Synergistic activity of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric cancer models in the pediatric preclinical testing program.

Purpose: Inhibitors of PARP, an enzyme involved in base excision repair, have demonstrated single-agent activity against tumors deficient in homologous repair processes. Ewing sarcoma cells are also sensitive to PARP inhibitors, although the mechanism is not understood. Here, we evaluated the stereo-selective PARP inhibitor, talazoparib (BMN 673), combined with temozolomide or topotecan.

Genome-wide association study of copy number variations (CNVs) with opioid dependence.

Single-nucleotide polymorphisms that have been associated with opioid dependence (OD) altogether account for only a small proportion of the known heritability. Most of the genetic risk factors are unknown. Some of the 'missing heritability' might be explained by copy number variations (CNVs) in the human genome.

Serine catabolism regulates mitochondrial redox control during hypoxia.

Unlabelled: The de novo synthesis of the nonessential amino acid serine is often upregulated in cancer. In this study, we demonstrate that the serine catabolic enzyme, mitochondrial serine hydroxymethyltransferase (SHMT2), is induced when MYC-transformed cells are subjected to hypoxia. In mitochondria, SHMT2 can initiate the degradation of serine to CO2 and NH4+, resulting in net production of NADPH from NADP+.

Initial testing (Stage 1) of the antibody-maytansinoid conjugate, IMGN901 (Lorvotuzumab mertansine), by the pediatric preclinical testing program.

Background: IMGN901 (lorvotuzumab mertansine) is an antibody-drug conjugate composed of a humanized antibody that specifically binds to CD56 (NCAM, neural cell adhesion molecule) and that is conjugated to the maytansinoid, DM1 (a microtubule targeting agent).

Procedures: IMGN901 and DM1-SMe (unconjugated DM1 as a mixed disulfide with thiomethane to cap its sulfhydryl group) were tested in vitro at concentrations ranging from 0.01 nM to 0.