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Objective: Examine the influence of household income on health‐related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). Design: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. Exposure: Household income was self‐reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. Outcome: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. Result: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2–20.2). Seven percent of enrolled patients presented with high acuity (ICU‐level care in the first 72 h), and 16% had high toxicity (any ICU‐level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. Conclusions: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research. [ABSTRACT FROM AUTHOR]

Summary: Low light intensities affect the outbreak of plant diseases. However, the underlying molecular mechanisms remain poorly understood.High‐performance liquid chromatography analysis of tomato (Solanum lycopersicum) revealed that apoplastic glucose (Glc) levels decreased in response to low light. Conversely, low‐light‐induced susceptibility to Pseudomonas syringae pv tomato (Pst) DC3000 was significantly alleviated by exogenous Glc treatment. Using cell‐based biolayer interferometry assays, we found that Glc specifically binds to the tomato regulator of G protein signaling 1 (RGS1). Laser scanning confocal microscopy imaging revealed that Glc triggers RGS1 endocytosis, which influences the uncoupling of the RGS1‐Gα (GPA1) and GPA1‐Gβ (SlGB1) proteins, in a dose‑ and duration‐dependent manner.Analysis of G protein single and double mutants revealed that RGS1 negatively regulates disease resistance under low light and is required for Glc‐enhanced defense. Downstream of RGS1‐Glc binding, GPA1 negatively mediates the light‐intensity‐regulated defense, whereas SlGB1 positively regulates this process.These results reveal a novel light‐intensity‐responsive defense system that is mediated by a Glc–RGS1–G protein signaling pathway. This information will be critical for future investigations of how plant cells sense extracellular sugars and adjust defense under different environments, as well as for genetic engineering approaches to improve stress resilience. [ABSTRACT FROM AUTHOR]

Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug‐resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient‐matched tumor cells obtained at diagnosis. Electron microscopy identified reduced ER–mitochondria‐associated membranes (MAMs; ER–mitochondria contacts, ERMCs) in therapy‐resistant cells, and genetically or biochemically reducing MAMs in therapy‐sensitive tumors phenocopied resistance. MAMs serve as platforms to transfer Ca2+ and bioactive lipids to mitochondria. Reduced Ca2+ transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ER–mitochondria‐associated membranes as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance. Synopsis: Longitudinal analysis of patient‐derived tumor cell lines identifies reduced levels of ER–mitochondria‐associated membranes (MAMs; ER–mitochondria contacts, ERMCs) as a novel contributor to multidrug resistance in childhood neuroblastoma. Mitochondria from drug‐resistant neuroblastoma cells exhibit attenuated apoptotic signal transduction, cytochrome c release, and MAMs.Transfer of Ca2+ from MAMs to mitochondria is not required for reduced apoptosis in therapy‐resistant cells.Disruption of ceramide biosynthesis at MAMs and of lipid transfer to the outer mitochondrial membrane decreases apoptotic signaling and enhances multidrug resistance in relapsed cells. [ABSTRACT FROM AUTHOR]

Previous data suggest that patients enrolled on clinical trials for treatment of cancer have better overall survival than patients who do not enroll; however, short-term outcomes relative to trial enrollment and corresponding mediators have not been assessed. A cohort of pediatric patients with newly-diagnosed acute myeloid leukemia was assembled from the Pediatric Health Information System. We evaluated whether patients not enrolled onto Children's Oncology Group trial AAML0531 had greater intensive care unit ( ICU)-level requirements than enrolled patients and whether early discharge after chemotherapy administration mediated this association. Patients not enrolled on AAML0531 were more likely to be discharged early ( aOR = 1.40, 95% confidence interval [ CI]: 1.02, 1.90) and to require ICU-level care ( aOR = 2.00, 95% CI: 1.06, 3.78) than enrolled patients, but early discharge explained only a small proportion (12.3%) of the absolute difference in ICU-level care risk. The direct effect of nonenrollment on the need for ICU-level care was significant ( aOR = 1.89, 95% CI: 1.00, 3.94), whereas the indirect effect mediated through early discharge was not ( aOR = 1.07, 95% CI: 0.95, 1.19). Factors other than postchemotherapy discharge strategy drive the difference in ICU utilization by trial enrollment status. [ABSTRACT FROM AUTHOR]

In addition to dichotomous measures of abstinence, smoking studies may use daily cigarette consumption as an outcome variable. These counts hold the promise of more efficient and detailed analyses than dichotomous measures, but present serious quality issues - measurement error and heaping - if obtained by retrospective recall. A doubly-coded dataset with a retrospective recall measurement (timeline followback, TLFB) and a more precise instantaneous measurement (ecological momentary assessment, EMA) serves as a calibration dataset, allowing us to predict EMA given TLFB and baseline factors. We apply this model to multiply impute precise cigarette counts for a randomized, placebo-controlled trial of bupropion with only TLFB measurements available. To account for repeated measurements on a subject, we induce correlation in the imputed counts. Finally, we analyze the imputed data in a longitudinal model that accommodates random subject effects and zero inflation. Both raw and imputed data show a significant drug effect for reducing the odds of non-abstinence and the number of cigarettes smoked among non-abstainers, but the imputed data provide efficiency gains. This method permits the analysis of daily cigarette consumption data previously deemed suspect due to reporting error and is applicable to other self-reported count data sets for which calibration samples are available. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Comparisons of early discharge and outpatient postchemotherapy supportive care in pediatric acute myeloid leukemia ( AML) patients are limited. We used data from the Pediatric Health Information System on a cohort of children treated for newly diagnosed AML to compare course-specific mortality and resource utilization in patients who were discharged after chemotherapy to outpatient management during neutropenia relative to patients who remained hospitalized. Patients were categorized at each course as early or standard discharge. Discharges within 3 days after chemotherapy completion were considered 'early'. Resource utilization was determined based on daily billing data and reported as days of use per 1000 hospital days. Inpatient mortality, occurrence of intensive care unit ( ICU)-level care, and duration of hospitalization were compared using logistic, log-binomial and linear regression methods, respectively. Poisson regression with inpatient days as offset was used to compare resource use by discharge status. The study population included 996 patients contributing 2358 treatment courses. Fewer patients were discharged early following Induction I (7%) than subsequent courses (22-24%). Across courses, patients discharged early experienced high readmission rates (69-84%), yet 9-12 fewer inpatient days (all P < 0.001). Inpatient mortality was low across courses and did not differ significantly by discharge status. The overall risk for ICU-level care was 116% higher for early compared to standard discharge patients (adjusted risk ratio: 2.16, 95% confidence interval: 1.50, 3.11). Rates of antibiotic, vasopressor, and supplemental oxygen use were consistently elevated for early discharge patients. Despite similar inpatient mortality to standard discharge patients, early discharge patients may be at greater risk for life-threatening chemotherapy-related complications, including infections. [ABSTRACT FROM AUTHOR]

Establishing the normative range of age-dependent fluorodeoxyglucose (FDG) uptake in the developing brain is necessary for understanding regional quantitative analysis of positron emission tomography (PET) brain images in children and also to provide functional information on brain development. We analyzed head sections of FDG PET/computed tomography (CT) images for 115 patients (5 months to 23 years) without central nervous system disease before treatment, as PET studies are not performed on healthy children owing to ethical considerations and the risk of radiation exposure. We investigated the changes in FDG uptake and established age-associated normative ranges of cerebral FDG. Head sections of FDG PET/CT images were registered to a population-based probabilistic atlas of human cortical structures. Gray matter of 56 brain structures was defined on normalized PET images according to the atlas. To avoid individual and experimental confounding factors, the relative standardized uptake value (SUV) over the cerebellum of each structure was calculated. Relative SUVs were analyzed by ANOVA and modeled using generalized estimating equalization analysis with false discovery rate control. Age and structure were significant factors affecting SUVs. Anatomic proximity had little effect on FDG uptake. Linear and quadratic developmental trajectories were observed on absolute and relative SUVs, respectively. An increase from posterior-to-anterior and superior-to-inferior pattern was observed in both absolute SUV increase rate and relative SUV peak age. The SUV of each structure was modeled with respect to age, and these models can serve as baselines for the quantitative analysis of cerebral FDG-PET images of children. Hum Brain Mapp 35:2297-2309, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]