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https://www.readbyqxmd.com/read/29676680/midline-central-fluid-percussion-model-of-traumatic-brain-injury-in-pediatric-and-adolescent-rats
#1
Rachel K Rowe, Jordan L Harrison, Timothy W Ellis, P David Adelson, Jonathan Lifshitz
OBJECTIVE Experimental traumatic brain injury (TBI) models hold significant validity to the human condition, with each model replicating a subset of clinical features and symptoms. TBI is the leading cause of mortality and morbidity in children and teenagers; thus, it is critical to develop preclinical models of these ages to test emerging treatments. Midline fluid percussion injury (FPI) might best represent mild and diffuse clinical brain injury because of the acute behavioral deficits, the late onset of behavioral morbidities, and the absence of gross histopathology...
April 20, 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/29675639/pharmacokinetic-pharmacodynamic-modeling-in-pediatric-drug-development-and-the-importance-of-standardized-scaling-of-clearance
#2
REVIEW
Eva Germovsek, Charlotte I S Barker, Mike Sharland, Joseph F Standing
Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects...
April 19, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29674994/a-cross-sectional-study-on-cerebral-hemodynamics-after-mild-traumatic-brain-injury-in-a-pediatric-population
#3
Corey M Thibeault, Samuel Thorpe, Michael J O'Brien, Nicolas Canac, Mina Ranjbaran, Ilyas Patanam, Artin Sarraf, James LeVangie, Fabien Scalzo, Seth J Wilk, Ramon Diaz-Arrastia, Robert B Hamilton
The microvasculature is prominently affected by traumatic brain injury (TBI), including mild TBI (concussion). Assessment of cerebral hemodynamics shows promise as biomarkers of TBI, and may help inform development of therapies aimed at promoting neurologic recovery. The objective of this study was to assess the evolution in cerebral hemodynamics observable with transcranial Doppler (TCD) ultrasound in subjects suffering from a concussion at different intervals during recovery. Pediatric subjects between the ages of 14 and 19 years clinically diagnosed with a concussion were observed at different points post-injury...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29670611/advances-in-biomarker-guided-therapy-for-pediatric-and-adult-onset-neuroinflammatory-disorders-targeting-chemokines-cytokines
#4
REVIEW
Michael R Pranzatelli
The concept and recognized components of "neuroinflammation" are expanding at the intersection of neurobiology and immunobiology. Chemokines (CKs), no longer merely necessary for immune cell trafficking and positioning, have multiple physiologic, developmental, and modulatory functionalities in the central nervous system (CNS) through neuron-glia interactions and other mechanisms affecting neurotransmission. They issue the "help me" cry of neurons and astrocytes in response to CNS injury, engaging invading lymphoid cells (T cells and B cells) and myeloid cells (dendritic cells, monocytes, and neutrophils) (adaptive immunity), as well as microglia and macrophages (innate immunity), in a cascade of events, some beneficial (reparative), others destructive (excitotoxic)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669823/recurrent-patterns-of-protein-expression-signatures-in-pediatric-acute-lymphoblastic-leukemia-recognition-and-therapeutic-guidance
#5
Fieke W Hoff, Chenyue W Hu, Yihua Qiu, Andrew Ligeralde, Suk-Young Yoo, Eveline Sjm De Bont, Amina A Qutub, Terzah M Horton, Steven M Kornblau
Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, and the second leading cause of pediatric cancer death in developed countries. While the cure rate for newly-diagnosed ALL is excellent, the genetic heterogeneity and chemoresistance of leukemia cells at relapse makes individualized curative treatment plans difficult. We hypothesize that genetic events would coalesce into a finite number of protein signatures that could guide the design of individualized therapy. Custom Reverse Phase Protein Arrays were produced from pediatric ALL (n=73) and normal CD34+ (n=10) samples with 194 validated antibodies...
April 18, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29669821/recognition-of-recurrent-protein-expression-patterns-in-pediatric-acute-myeloid-leukemia-identified-new-therapeutic-targets
#6
Fieke W Hoff, Chenyue W Hu, Yihua Qiu, Andrew Ligeralde, Suk-Young Yoo, Hasan Mahmud, Eveline Sjm De Bont, Amina A Qutub, Terzah M Horton, Steven M Kornblau
Heterogeneity in the genetic landscape of pediatric acute myeloid leukemia (AML) makes personalized medicine challenging. As genetic events are mediated by the expression and function of proteins, recognition of recurrent protein patterns could enable classification of pediatric AML patients and could reveal crucial protein dependencies. This could help to rationally select combinations of therapeutic targets. To determine if protein expression levels could be clustered into functionally relevant groups, custom Reverse Phase Protein Arrays (RPPA) were performed on pediatric AML (n=95) and CD34+ normal bone marrow (n=10) clinical specimens using 194 validated antibodies...
April 18, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29669714/cannabidiol-inhibits-endocannabinoid-signaling-in-autaptic-hippocampal-neurons
#7
Alex Straiker, Michaela Dvorakova, Anaelle Zimmowitch, Ken P Mackie
Δ9-THC and cannabidiol (CBD) are two main cannabinoid constituents of marijuana and hashish. The pharmacology of Δ9-THC has been extensively studied, while our understanding of the pharmacology of CBD has remained limited, despite excitement in CBD's potential role in treating certain pediatric epilepsies and its reputation for attenuating some Δ9-THC-induced effects. It was established early on that CBD binds poorly to the orthosteric site of CB1 or CB2 cannabinoid receptors and its actions were commonly attributed to other non-cannabinoid receptor mechanisms...
April 18, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29668479/mobile-application-neurogame-for-assessment-the-attention-focus-and-concentration
#8
Mario Loleski, Sofija Loleska, Nada Pop-Jordanova
Smartphones are ubiquitous, but it is still unknown what physiological functions can be monitored at clinical quality. In medicine their use is cited in many fields (cardiology, pulmology, endocrinology, rheumatology, pediatrics as well as in the field of mental health). The aim of this paper is to explain how the use of mobile application can help clients to improve the index of their focus, concentration and motor skills. Our original developed application on Android operating system, named "neurogame" is based on an open source platform to enable assessment and therapeutic stimulation, focus and concentration with the ability to monitor the progress of the results obtained in a larger number of participants (normal subjects as well as patients with different disorders) over a period of time...
December 1, 2017: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/29667952/useful-pharmacodynamic-endpoints-in-children-selection-measurement-and-next-steps
#9
REVIEW
Lauren E Kelly, Yashwant Sinha, Charlotte I S Barker, Joseph F Standing, Martin Offringa
Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools...
April 18, 2018: Pediatric Research
https://www.readbyqxmd.com/read/29667338/variation-in-the-tek-gene-is-not-associated-with-asthma-but-with-allergic-conjunctivitis
#10
L E Fodor, A Gézsi, Z Gál, A Nagy, A Kiss, A Bikov, C Szalai
The Tie2 receptor is an important player in angiogenesis. The Tie2 mRNA and protein are abundantly expressed in the lungs and the associated pathway also has an important role in the development and function of the eye. Tie2 is encoded by the TEK gene in humans. Recently, variations in the TEK gene have been found associated with asthma. The objective of the present study was to investigate whether variations in the TEK gene influenced the susceptibility to pediatric asthma and/or associated phenotypes like GINA status, viral- or exercise-induced asthma, allergic asthma, indoor, outdoor, inhalative allergies, IgE and eosonophil levels, allergic rhinitis and allergic conjunctivitis...
April 18, 2018: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/29663971/proliferative-periostitis-in-a-pediatric-patient
#11
Ivan Lima Oliveira-Filho, Cristiane Tomaz Rocha, Alinne Késsia Almeida de Menezes, Marcelo Ferraro Bezerra, Beatriz Gonçalves Neves
Proliferative periostitis is a rare condition that can affect children and adolescents. It is characterized by the successive deposition of layers of bone caused by low-virulence infection or chronic inflammatory stimulation. The purpose of this paper is to report a case of proliferative periostitis in a pediatric patient, emphasizing the clinical and radiographic aspects as well as the therapeutic management.
January 15, 2018: Journal of Dentistry for Children
https://www.readbyqxmd.com/read/29663421/population-pharmacokinetic-analysis-of-busulfan-in-japanese-pediatric-and-adult-hct-patients
#12
Atsuko Kawazoe, Tomoo Funaki, Seongryul Kim
Busulfan is the most common chemotherapy agent used in allogeneic hematopoietic cell transplant (HCT) conditioning regimens. As narrow therapeutic index and interpatient variability exists in the effectiveness and toxicity of conditioning regimens, personalizing intravenous busulfan therapy is desirable. Population pharmacokinetic-based approaches have been applied to therapeutic drug monitoring for the purpose of personalizing therapy. A population pharmacokinetic analysis with the objective of personalizing therapy in Japanese patients was conducted by integrating pediatric patient data with adult patient data...
April 17, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29662633/tracking-cellular-and-molecular-changes-in-a-species-specific-manner-during-experimental-tumor-progression-in-vivo
#13
Emilie Indersie, Katarzyna B Hooks, Caroline Capdevielle, Monique Fabre, Nathalie Dugot-Senant, Angélique Desplat, Sébastien Lepreux, Aksam Merched, Christophe F Grosset, Martin Hagedorn
Hepatoblastoma (HBL) is a pediatric liver cancer with defined molecular alterations driving its progression. Here, we describe an animal model for HBL on the chick chorioallantoic membrane (CAM), which recapitulates relevant features of HBL in patients. Expression of classic tumor-associated proteins such as β-catenin, EpCAM and CK19 was maintained in acini-like organized tumors on CAM, as was synthesis of AFP, a tumor marker used for monitoring patient response. RNA sequencing revealed an unexpected molecular evolution of HBL cells on the CAM, with significant deregulation of more than 6,000 genes including more than half of all HOX genes...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662050/does-vitamin-d-affect-chronic-renal-allograft-function-in-pediatric-transplant-patients
#14
Brooke Wile, Elisa Yoo, Ana Catalina Alvarez Elias, Lakshmimathy Subramanian, Kathryn Eager, Ajay Parkesh Sharma, Guido Filler
BACKGROUND Correction of hypovitaminosis D is simple, but it is unclear whether it is associated with an accelerated decline of renal allograft function in pediatric renal transplantation patients. This retrospective single center cohort study aimed at analyzing the effect of vitamin D and covariates on the slope of 1/creatinine after the first year. MATERIAL AND METHODS After ethics committee approval, 37 (14 male) pediatric renal transplant recipients on mycophenolate mofetil, who were followed between 2006 and 2014, were included in this study...
April 17, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29660042/pediatric-irritable-bowel-syndrome-perspectives-on-pain-and-adolescent-social-functioning
#15
Elizabeth Donovan, Sarah R Martin, Kirsten Lung, Subhadra Evans, Laura C Seidman, Tara M Cousineau, Elizabeth Cook, Lonnie K Zeltzer
Objective: The goal of the study was to describe the experiences of adolescents with irritable bowel syndrome (IBS) from the perspective of adolescents, their parents, and health care providers who treat adolescents who have IBS. Design: The study consisted of semistructured interviews. Setting: Participants were recruited from multidisciplinary pain clinics. Subjects: Thirty-six people participated in the study: 12 adolescents, 12 parents, and 12 health care providers...
April 5, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29659473/external-validation-of-a-5-variable-clinical-prediction-rule-for-identifying-children-at-very-low-risk-for-intra-abdominal-injury-following-blunt-abdominal-trauma
#16
Chase A Arbra, Adam M Vogel, Leah Plumblee, Jingwen Zhang, Patrick D Mauldin, Melvin S Dassinger, Robert T Russell, Martin L Blakely, Christian J Streck
BACKGROUND: A clinical prediction rule was previously developed by the Pediatric Surgery Research Collaborative (PedSRC) to identify patients at very low risk for intra-abdominal injury (IAI) and intra-abdominal injury receiving an acute intervention (IAI-I) who could safely avoid abdominal computed tomography (CT) scans following blunt abdominal trauma (BAT). Our objective was to externally validate the rule. METHODS: The public use dataset was obtained from the Pediatric Emergency Care Applied Research Network (PECARN) Intra-abdominal Injury Study...
April 13, 2018: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29659360/-development-of-a-product-anti-shiga-toxin-for-prevention-of-the-hemolytic-uremic-syndrome
#17
Yanina Hiriart, Romina Pardo, Lucas Bukata, Constanza Lauché, Luciana Muñoz, Mariana Colonna, Fernando Goldbaum, Santiago Sanguineti, Vanesa Zylberman
The typical hemolytic uremic syndrome (HUS) is an orphan disease caused by Shiga toxin(Stx) producing Escherichia coli strains and characterized by acute kidney damage, microangiopathic hemolytic anemia and low platelet count. It is endemic in Argentina, the country with the highest incidence of HUS in the world. Stx is essential for its development and therefore, HUS is considered a toxemic non-bacteremic disorder, which could be treated with antibodies. Herein we describe the development of a new treatment capable of neutralizing the toxic effect of Stx and its variants...
2018: Medicina
https://www.readbyqxmd.com/read/29652968/-therapeutic-monitoring-of-antimicrobial-agents-in-pediatrics-review-based-on-latin-american-experiences
#18
Brenda Zylbersztajn, Marlon Barraza, Juan P Torres, Jorge Morales
This review summarizes recommendations of therapeutic monitoring of three antimicrobials based in regional data: vancomycin, amikacin and voriconazole in pediatric population. Regional evidence agrees with international literature regarding the requirement of higher daily doses than 40 mg/kg/day of vancomycin, as well as with the possibility of use one daily doses of amikacin and to recommend higher doses of voriconazole compared to the initially recommended doses of 8 mg/kg/day. Local data on the pharmacokinetic/pharmacodynamic behavior of various antimicrobials in pediatrics are of great value for dosing adjustment in our pediatric population...
2018: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/29652858/oncosuppressors-and-oncogenes-role-in-haemangioma-genesis-and-potential-for-therapeutic-targeting
#19
REVIEW
Peace Mabeta
Genetic lesions in proto-oncogenes result in the perturbation of angiogenesis, the formation of neovessels from a pre-existing microvasculature. Similarly, the subversion of tumor suppressor genes promotes tumor vascularization. Excessive neovessel formation is associated with various neoplasms such as infantile hemangiomas (IH). Hemangiomas are the most common tumors in pediatric patients and at present have no definitive treatment. The pathogenesis of IH is not well understood; however, both vasculogenesis and angiogenesis are associated with hemangioma genesis...
April 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29652753/hybrid-extracorporeal-therapies-as-a-bridge-to-pediatric-liver-transplantation
#20
Ayse Akcan Arikan, Poyyapakkam Srivaths, Ryan W Himes, Naile Tufan Pekkucuksen, Fong Lam, Trung Nguyen, Tamir Miloh, Michael Braun, John Goss, Moreshwar S Desai
OBJECTIVES: Standard intensive care treatment is inadequate to keep children with liver failure alive without catastrophic complications to ensure successful transplant, as accumulation of endogenous protein-bound toxins often lead to hepatic encephalopathy, hepatorenal syndrome, cardiovascular instability, and multiple organ failure. Given paucity of proven treatment modalities for liver failure, blood purification using different extracorporeal treatments as a bridge to transplantation is used, but studies evaluating the safety and efficacy of combination of these therapies, especially in pediatric liver failure, are lacking...
April 12, 2018: Pediatric Critical Care Medicine
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