Accessing and utilizing clinical and genomic data from an electronic health record data warehouse.

Electronic health records (EHRs) and linked biobanks have tremendous potential to advance biomedical research and ultimately improve the health of future generations. Repurposing EHR data for research is not without challenges, however. In this paper, we describe the processes and considerations necessary to successfully access and utilize a data warehouse for research.

Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine.

Can Placental Corticotropin-Releasing Hormone Inform Timing of Antenatal Corticosteroid Administration?

Context: Antenatal corticosteroids are commonly administered to pregnant women at risk for delivering between 23 and 34 gestational weeks; they provide crucial benefits to fetal lung maturation and reduce risk for neonatal morbidity and mortality. Corticosteroids are maximally efficacious for lung maturation when administered within 2 to 7 days of delivery. Accurately identifying the timing of preterm delivery is thus critical to ensure that antenatal corticosteroids are administered within a week of delivery and to avoid unnecessary administration to women who will deliver at term.

Association of Cerebrospinal Fluid Biomarkers of Central Nervous System Injury With Neurocognitive and Brain Imaging Outcomes in Children Receiving Chemotherapy for Acute Lymphoblastic Leukemia.

Importance: Little is known about treatment-related neurotoxic mechanisms in children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only.

Objective: To examine concentration of cerebrospinal fluid (CSF) biomarkers of brain injury at ALL diagnosis and during cancer therapy and to evaluate associations with long-term neurocognitive and neuroimaging outcomes and relevant genetic polymorphisms.

Design, Setting, And Participants: This prospective cohort study included 235 patients with ALL who received a chemotherapy-only protocol.

Uric Acid and Neurocognitive Function in Survivors of Childhood Acute Lymphoblastic Leukemia Treated with Chemotherapy Only.

Background: Hyperuricemia is implicated in cardiovascular and cerebrovascular diseases. This study evaluated associations between uric acid (UA), cardiovascular health, and neurocognitive function in adolescent and adult survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only.

Methods: 126 adolescent [mean (SD) age 14.

Neurocognitive and Patient-Reported Outcomes in Adult Survivors of Childhood Osteosarcoma.

Importance: This study provides the first objective data documenting neurocognitive impairment in long-term survivors of childhood osteosarcoma.

Objective: To examine neurocognitive, neurobehavioral, emotional, and quality-of-life outcomes in long-term survivors of childhood osteosarcoma.

Design, Setting, And Participants: Cross-sectional cohort study at an academic research hospital, with prospective treatment and chronic health predictors.

Regional brain glucose metabolism and neurocognitive function in adult survivors of childhood cancer treated with cranial radiation.

Unlabelled: The objective of this study was to examine associations between regional brain metabolism, as measured by (18)F-FDG PET, and neurocognitive outcomes in adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation.

Method: Thirty-eight adult survivors of ALL were randomly selected from a large cohort treated with cranial radiation therapy (19 with 18 Gy and 19 with 24 Gy of exposure). At a mean age of 26.

Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia.

Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.

Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia.

The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment.

Dexamethasone exposure and memory function in adult survivors of childhood acute lymphoblastic leukemia: A report from the SJLIFE cohort.

Background: Dexamethasone is used in acute lymphoblastic leukemia (ALL) treatment, though long-term impact on central nervous system (CNS) function is unclear. As glucocorticoids influence hippocampal function, we investigated memory networks in survivors of childhood ALL treated with dexamethasone or prednisone.

Procedure: Neurocognitive assessment and functional magnetic resonance imaging (fMRI) were conducted in 38 adult survivors randomly recruited from cohorts treated on one of two standard treatment protocols, which differed primarily in the glucocorticoid administered during continuation therapy (dexamethasone [n = 18] vs.

Maternal touch moderates sex differences in juvenile social play behavior.

Additional somatosensory contact of preterm human infants improves a variety of developmental assessment scores, but less is known about its lasting consequences. In rodents, maternal contact may influence the programming of juvenile social play behavior. Therefore, we used a paradigm where we can control the levels of somatosensory contact associated with maternal care.

Epigenetic impact of simulated maternal grooming on estrogen receptor alpha within the developing amygdala.

Variations in maternal care alter the developmental programming of some genes by creating lasting differences in DNA methylation patterns, such as the estrogen receptor alpha (ERα) promoter region. Interestingly, mother rats preferentially lick and groom their male offspring more than females; therefore, we questioned whether the somatosensory stimuli associated with maternal grooming influences potential sex differences in DNA methylation patterns within the developing amygdala, an area important for socioemotional processing. We report a sex difference in the DNA methylation pattern of specific CpG sites of the ERα promoter region within the developing amygdala.

Epigenetic organization of brain sex differences and juvenile social play behavior.

The study of epigenetic mechanisms is important for elucidating how gene-by-environment interactions can have lasting outcomes on brain function and behavior. In general, studies of epigenetic processes mainly focus on the methylation status of DNA. While methylation of DNA alone can interfere with gene transcription, it is the binding of methyl-CpG binding proteins to methylated DNA, and subsequent recruitment of nuclear corepressors and histone deacetylases, that results in more efficient gene repression.

Altered dopamine signaling in naturally occurring maternal neglect.

Background: Child neglect is the most common form of child maltreatment, yet the biological basis of maternal neglect is poorly understood and a rodent model is lacking.

Methodology/principal Findings: The current study characterizes a population of mice (MaD1) which naturally exhibit maternal neglect (little or no care of offspring) at an average rate of 17% per generation. We identified a set of risk factors that can predict future neglect of offspring, including decreased self-grooming and elevated activity.

Neuronal nitric oxide synthase and calbindin delineate sex differences in the developing hypothalamus and preoptic area.

Throughout the hypothalamus there are several regions known to contain sex differences in specific cellular, neurochemical, or cell grouping characteristics. The current study examined the potential origin of sex differences in calbindin expression in the preoptic area and hypothalamus as related to sources of nitric oxide. Specific cell populations were defined by immunoreactive (ir) calbindin and neuronal nitric oxide synthase (nNOS) in the preoptic area/anterior hypothalamus (POA/AH), anteroventral periventricular nucleus (AVPv), and ventromedial nucleus of the hypothalamus (VMN).