Animals exposed to brief periods of moderate hypoxia (8% to 10% oxygen for 3 hours) are protected against cerebral and cardiac ischemia between 1 and 2 days later. This hypoxia preconditioning requires new RNA and protein synthesis. The mechanism of this hypoxia-induced tolerance correlates with the induction of the hypoxia-inducible factor (HIF), a transcription factor heterodimeric complex composed of inducible HIF-1alpha and constitutive HIF-1beta proteins that bind to the hypoxia response elements in a number of HIF target genes. Our recent studies show that HIF-1alpha correlates with hypoxia induced tolerance in neonatal rat brain. HIF target genes, also induced following hypoxia-induced tolerance, include vascular endothelial growth factor, erythropoietin, glucose transporters, glycolytic enzymes, and many other genes. Some or all of these genes may contribute to hypoxia-induced protection against ischemia. HIF induction of the glycolytic enzymes accounts in part for the Pasteur effect in brain and other tissues. Hypoxia-induced tolerance is not likely to be equivalent to treatment with a single HIF target gene protein since other transcription factors including Egr-1 (NGFI-A) have been implicated in hypoxia regulation of gene expression. Understanding the mechanisms and genes involved in hypoxic tolerance may provide new therapeutic targets to treat ischemic injury and enhance recovery.
BACKGROUND AND OBJECTIVE: Children and adolescents with minor blunt head trauma and isolated skull fractures are often admitted to the hospital. The objective of this study was to describe the injury circumstances and frequency of clinically important neurologic complications among children with minor blunt head trauma and isolated linear skull fractures.
Animals exposed to brief periods of moderate hypoxia (8% to 10% oxygen for 3 hours) are protected against cerebral and cardiac ischemia between 1 and 2 days later. This hypoxia preconditioning requires new RNA and protein synthesis. The mechanism of this hypoxia-induced tolerance correlates with the induction of the hypoxia-inducible factor (HIF), a transcription factor heterodimeric complex composed of inducible HIF-1␣ and constitutive HIF-1 proteins that bind to the hypoxia response elements in a number of HIF target genes. Our recent studies show that HIF-1␣ correlates with hypoxia induced tolerance in neonatal rat brain. HIF target genes, also induced following hypoxia-induced tolerance, include vascular endothelial growth factor, erythropoietin, glucose transporters, glycolytic enzymes, and many other genes. Some or all of these genes may contribute to hypoxia-induced protection against ischemia. HIF induction of the glycolytic enzymes accounts in part for the Pasteur effect in brain and other tissues. Hypoxiainduced tolerance is not likely to be equivalent to treatment with a single HIF target gene protein since other transcription factors including Egr-1 (NGFI-A) have been implicated in hypoxia regulation of gene expression. Understanding the mechanisms and genes involved in hypoxic tolerance may provide new therapeutic targets to treat ischemic injury and enhance recovery.
Objective: Children with minor head trauma frequently present to emergency departments (EDs). Identifying those with traumatic brain injuries (TBIs) can be difficult, and it is unknown whether clinical prediction rules outperform clinician suspicion. Our primary objective was to compare the test characteristics of the Pediatric Emergency Care Applied Research Network (PECARN) TBI prediction rules to clinician suspicion for identifying children with clinically important TBIs (ciTBIs) after minor blunt head trauma. Our secondary objective was to determine the reasons for obtaining computed tomography (CT) scans when clinical suspicion of ciTBI was low.Methods: This was a planned secondary analysis of a previously conducted observational cohort study conducted in PECARN to derive and validate clinical prediction rules for ciTBI among children with minor blunt head trauma in 25 PECARN EDs. Clinicians recorded their suspicion of ciTBI before CT as <1, 1-5, 6-10, 11-50, or >50%. We defined ciTBI as 1) death from TBI, 2) neurosurgery, 3) intubation for
Children with minor blunt head trauma presenting to the emergency department with isolated LOC are at very low risk for ciTBI and do not routinely require computed tomographic evaluation.
Physicians at a branch of the emergency department at Cincinnati Children's Hospital Medical Center complained that their schedules were too erratic because of the multitude of operating requirements, regulatory constraints, physician preferences, and holiday requests. We addressed this issue by using integer programming to build cyclic schedules that can be repeated throughout the year. These schedules are flexible enough to handle incorporating holidays, work assignments, and vacation requests ex post. After we rolled out the calendar-year-based cyclic schedule, we captured statistics to assess the viability and the quality of the yearly schedule generated. Surveys of the physicians and the scheduler after implementation showed that the new schedule provides predictability and well-balanced work patterns.
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