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https://www.readbyqxmd.com/read/28434268/ubiquitin-c-terminal-hydrolase-l1-uch-l1-as-a-therapeutic-and-diagnostic-target-in-neurodegeneration-neurotrauma-and-neuro-injuries
#1
Kevin K Wang, Zhihui Yang, George Sarkis, Isabel Torres, Vijaya Raghavan
Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease...
April 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28430697/abusive-head-trauma-and-mortality-an-analysis-from-an-international-comparative-effectiveness-study-of-children-with-severe-traumatic-brain-injury
#2
Nikki Miller Ferguson, Ajit Sarnaik, Darryl Miles, Nadeem Shafi, Mark J Peters, Edward Truemper, Monica S Vavilala, Michael J Bell, Stephen R Wisniewski, James F Luther, Adam L Hartman, Patrick M Kochanek
OBJECTIVES: Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. DESIGN: First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial-a comparative effectiveness study using an observational, cohort study design...
April 20, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28429381/the-structural-connectome-of-children-with-traumatic-brain-injury
#3
Marsh Königs, L W Ernest van Heurn, Roel Bakx, R Jeroen Vermeulen, J Carel Goslings, Bwee Tien Poll-The, Marleen van der Wees, Coriene E Catsman-Berrevoets, Jaap Oosterlaan, Petra J W Pouwels
This study aimed to investigate the impact of mild to severe pediatric TBI on the structural connectome. Children aged 8-14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mild(RF+) , n = 20) or moderate/severe TBI (n = 16) at 2.8 years post-injury. Probabilistic tractography on diffusion tensor imaging data was used in combination with graph theory to study structural connectivity. Functional outcome was measured using neurocognitive tests and parent and teacher questionnaires for behavioral functioning...
April 21, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28425334/remifentanil-for-sedation-of-children-with-traumatic-brain-injury
#4
James L Hungerford, Nicole O'Brien, Melissa Moore-Clingenpeel, Eric A Sribnick, Cheryl Sargel, Mark Hall, Jeffrey R Leonard, Joseph D Tobias
OBJECTIVE: To determine whether remifentanil would provide adequate sedation while allowing frequent and reproducible neurologic assessments in children admitted to the pediatric intensive care unit (PICU) with traumatic brain injury (TBI) during mechanical ventilation. DESIGN: Retrospective review. SETTING: Tertiary care PICU. PATIENTS: Thirty-eight patients over a 30-month period. MEASUREMENTS AND MAIN RESULTS: Median age was 9 years (interquartile range [IQR] 2...
January 1, 2017: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/28406438/u-s-trends-of-ed-visits-for-pediatric-traumatic-brain-injuries-implications-for-clinical-trials
#5
Cheng Chen, Junxin Shi, Rachel M Stanley, Eric A Sribnick, Jonathan I Groner, Henry Xiang
Our goal in this paper was to use the 2006-2013 Nationwide Emergency Department Sample (NEDS) database to describe trends of annual patient number, patient demographics and hospital characteristics of pediatric traumatic brain injuries (TBI) treated in U.S. emergency departments (EDs); and to use the same database to estimate the available sample sizes for various clinical trials of pediatric TBI cases. National estimates of patient demographics and hospital characteristics were calculated for pediatric TBI...
April 13, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28405773/failure-and-fatigue-properties-of-immature-human-and-porcine-parasagittal-bridging-veins
#6
Stephanie A Pasquesi, Susan S Margulies
Tearing of the parasagittal bridging veins (BVs) is thought to be a source of extra-axial hemorrhage (EAH) associated with abusive traumatic brain injuries (TBIs) in children. However, the pediatric BV mechanical properties are unknown. We subjected porcine adult, porcine newborn, and human infant BVs to either a low rate pull to failure, a high rate pull to failure, or 30 s of cyclic loading followed by a pull to failure. An additional subset of human infant BVs was examined for viscoelastic recovery between two cycling episodes...
April 12, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28398160/should-young-children-with-tbi-be-compared-to-community-or-orthopedic-control-participants
#7
Miriam Helen Beauchamp, Catherine Landry-Roy, Jocelyn Gravel, Cindy Beaudoin, Annie Bernier
Pediatric traumatic brain injury (TBI) research depends on comparisons of profiles and outcome between brain injured individuals and groups consisting either of injured controls (e.g., orthopedic injuries, OI) or uninjured, typically developing children recruited from the community (community controls, CC). Children with OI are thought to provide optimal comparisons for individuals with TBI because they share injury-related experiences and pre-morbid characteristics; however, a study by Mathias and colleagues (2013) in adults has called into question the added value of injury control groups in TBI research...
April 11, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28396164/dose-escalation-of-total-marrow-irradiation-in-high-risk-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#8
Susanta Hui, Claudio Brunstein, Yutaka Takahashi, Todd DeFor, Shernan G Holtan, Veronika Bachanova, Christopher Wilke, Darren Zuro, Celalettin Ustun, Daniel Weisdorf, Kathryn Dusenbery, Michael R Verneris
Patients with refractory leukemia or minimal residual disease (MRD) at transplant have increased risk of relapse. Augmentation of irradiation, especially to sites of disease (i.e., bone marrow) is one potential strategy to overcome this risk. We studied the feasibility of radiation dose escalation in high risk patients using total marrow irradiation (TMI) in a phase I dose-escalation trial. Four pediatric and 8 adult patients received conditioning with cyclophosphamide and fludarabine in conjunction with image-guided radiation to the bone marrow at 15 Gy and 18 Gy (in 3 Gy/fractions), while maintaining the total body irradiation (TBI) dose to the vital organs (lungs, hearts, eyes, liver, kidneys) at <13...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28396162/phase-i-study-of-clofarabine-and-2-gy-total-body-irradiation-as-a-non-myeloablative-preparative-regimen-for-hematopoietic-stem-cell-transplantation-hsct-in-pediatric-patients-with-hematologic-malignancies-a-therapeutic-advances-in-childhood-leukemia-tacl-consortium
#9
Sandeep Soni, Hisham Abdel-Azim, Meghann McManus, Eneida Nemecek, Richard Sposto, Ann Woolfrey, Haydar Frangoul
Clofarabine is a purine nucleoside analog with immunosuppressive and anti-leukemic activity and its inclusion in reduced intensity regimens could potentially improve outcomes. We performed a prospective Phase I study of clofarabine combined with 2 Gy total body irradiation (TBI) as a non-myeloablative (NMA) preparative regimen for allogeneic stem cell transplantation in pediatric patients, who were considered at high risk of mortality from standard myeloablative regimens. The main goal of the study was to delineate the maximum feasible dose (MFD) of clofarabine in combination with 2 Gy TBI...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28387644/medical-necessity-of-routine-admission-of-children-with-mild-traumatic-brain-injury-to-the-intensive-care-unit
#10
Jared D Ament, Krista N Greenan, Patrick Tertulien, Joseph M Galante, Daniel K Nishijima, Marike Zwienenberg
OBJECTIVE Approximately 475,000 children are treated for traumatic brain injury (TBI) in the US each year; most are classified as mild TBI (Glasgow Coma Scale [GCS] Score 13-15). Patients with positive findings on head CT, defined as either intracranial hemorrhage or skull fracture, regardless of severity, are often transferred to tertiary care centers for intensive care unit (ICU) monitoring. This practice creates a significant burden on the health care system. The purpose of this investigation was to derive a clinical decision rule (CDR) to determine which children can safely avoid ICU care...
April 7, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28377126/vascular-impairment-as-a-pathological-mechanism-underlying-long-lasting-cognitive-dysfunction-after-pediatric-traumatic-brain-injury
#11
Ichkova Aleksandra, Beatriz Rodriguez-Grande, Claire Bar, Frederic Villega, Jan Pieter Konsman, Jerome Badaut
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults, pediatric TBI patients actually have worse outcome than adults for the same degree of injury severity. Acute trauma to the young brain likely interferes with the fine-tuned developmental processes and may give rise to long-lasting consequences on brain's function...
April 1, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28368380/risk-of-melanocytic-nevi-and-nonmelanoma-skin-cancer-in-children-after-allogeneic-hematopoietic-stem-cell-transplantation
#12
J S Song, W B London, E B Hawryluk, D Guo, M Sridharan, D E Fisher, L E Lehmann, C N Duncan, J T Huang
There is a known increased risk of skin cancer in the adult population after hematopoietic stem cell transplantation (HSCT). However, late dermatologic effects that children may experience after HSCT have not been well described. The primary objective of this study was to characterize nevi and skin cancers affecting children after allogeneic HSCT. A cross-sectional cohort study of 85 pediatric HSCT recipients and 85 controls matched for age, sex and skin phototype was performed at a single institution. All participants underwent a full skin examination...
April 3, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28365105/helmet-underutilization-by-children-during-equestrian-events-is-associated-with-increased-traumatic-brain-injury
#13
Scott S Short, Stephen J Fenton, Eric R Scaife, Brian T Bucher
PURPOSE: Awareness of equestrian related injury remains limited. Studies evaluating children after equestrian injury report underutilization of safety equipment and rates of operative intervention as high as 33%. METHODS: We hypothesized that helmets are underutilized during equestrian activity and lack of use is associated with increased traumatic brain injury. We queried the trauma database of a level one pediatric trauma center for all cases of equestrian and rodeo related injury from 2005 to 2015...
March 20, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28362667/implementation-strategies-in-pediatric-neurocritical-care
#14
Christopher Markham, Enola K Proctor, Jose A Pineda
PURPOSE OF REVIEW: Brain-directed critical care for children is a relatively new area of subspecialization in pediatric critical care. Pediatric neurocritical care teams combine the expertise of neurology, neurosurgery, and critical care medicine. The positive impact of delivering specialized care to pediatric patients with acute neurological illness is becoming more apparent, but the optimum way to implement and sustain the delivery of this is complicated and poorly understood. We aim to provide emerging evidence supporting that effective implementation of pediatric neurocritical care pathways can improve patient survival and outcomes...
March 30, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28359910/cost-effectiveness-of-defibrotide-in-the-prophylaxis-of-veno-occlusive-disease-after-pediatric-allogeneic-stem-cell-transplantation
#15
Herbert Pichler, Karolina Horner, Gernot Engstler, Ulrike Poetschger, Evgenia Glogova, Susanne Karlhuber, Manuel Martin, Werner Eibler, Volker Witt, Wolfgang Holter, Susanne Matthes-Martin
Veno-occlusive disease (VOD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prophylactic use of defibrotide (DF) might further reduce VOD rates but has no impact on the incidence of severe VOD or VOD-associated mortality. We investigated the cost-effectiveness of prophylactic DF according to the BCSH/BSBMT guidelines in 348 children who underwent transplantation between 2001 and 2013 in our hospital, 138 of whom were at risk for VOD. The VOD incidence was 7.4% for the total cohort...
March 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28355201/sex-and-age-differences-in-phenylephrine-mechanisms-and-outcomes-after-piglet-brain-injury
#16
Victor Curvello, Hugh Hekierski, John Riley, Monica Vavilala, William M Armstead
BACKGROUND: Traumatic brain injury (TBI) is the leading cause of injury related death in children, with boys and children under 4 having particularly poor outcomes. Cerebral autoregulation is often impaired after TBI, contributing to poor outcome. In prior studies of newborn pigs, phenylephrine (Phe) preferentially protected cerebral autoregulation in females but not males after TBI. We hypothesized that, in contrast to the newborn, Phe prevents impairment of autoregulation and tissue injury following TBI in both sexes of older pigs...
March 29, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28347845/global-assessment-of-oxidized-free-fatty-acids-in-brain-reveals-an-enzymatic-predominance-to-oxidative-signaling-after-trauma
#17
Tamil S Anthonymuthu, Elizabeth M Kenny, Andrew A Amoscato, Jesse Lewis, Patrick M Kochanek, Valerian E Kagan, Hülya Bayır
Traumatic brain injury (TBI) is a major health problem associated with significant morbidity and mortality. The pathophysiology of TBI is complex involving signaling through multiple cascades, including lipid peroxidation. Oxidized free fatty acids, a prominent product of lipid peroxidation, are potent cellular mediators involved in induction and resolution of inflammation and modulation of vasomotor tone. While previous studies have assessed lipid peroxidation after TBI, to our knowledge no studies have used a systematic approach to quantify the global oxidative changes in free fatty acids...
March 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28341799/use-of-traumatic-brain-injury-prediction-rules-with-clinical-decision-support
#18
Peter S Dayan, Dustin W Ballard, Eric Tham, Jeff M Hoffman, Marguerite Swietlik, Sara J Deakyne, Evaline A Alessandrini, Leah Tzimenatos, Lalit Bajaj, David R Vinson, Dustin G Mark, Steve R Offerman, Uli K Chettipally, Marilyn D Paterno, Molly H Schaeffer, Jun Wang, T Charles Casper, Howard S Goldberg, Robert W Grundmeier, Nathan Kuppermann
OBJECTIVES: We determined whether implementing the Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) prediction rules and providing risks of clinically important TBIs (ciTBIs) with computerized clinical decision support (CDS) reduces computed tomography (CT) use for children with minor head trauma. METHODS: Nonrandomized trial with concurrent controls at 5 pediatric emergency departments (PEDs) and 8 general EDs (GEDs) between November 2011 and June 2014...
March 24, 2017: Pediatrics
https://www.readbyqxmd.com/read/28329120/sleep-wake-disturbances-after-traumatic-brain-injury-synthesis-of-human-and-animal-studies
#19
Danielle K Sandsmark, Jonathan E Elliott, Miranda M Lim
Sleep-wake disturbances following traumatic brain injury (TBI) are increasingly recognized as a serious consequence following injury and as a barrier to recovery. Injury-induced sleep-wake disturbances can persist for years, often impairing quality of life. Recently, there has been a nearly exponential increase in the number of primary research articles published on the pathophysiology and mechanisms underlying sleep-wake disturbances after TBI, both in animal models and human subjects, including in the pediatric population...
March 17, 2017: Sleep
https://www.readbyqxmd.com/read/28323555/influence-of-dopamine-related-genes-on-neurobehavioral-recovery-after-traumatic-brain-injury-during-early-childhood
#20
Amery Treble-Barna, Shari L Wade, Lisa J Martin, Valentina Pilipenko, Keith Owen Yeates, H Gerry Taylor, Brad G Kurowski
The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3...
March 21, 2017: Journal of Neurotrauma
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