bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced functional echocardiographic imaging of the failing heart in children
Authors: Parthiban Anitha , Shirali Girish 
Published: September 2015

AbstractOver the past decade, new echocardiographic techniques such as three-dimensional echocardiography and the imaging of myocardial deformation (strain) have been developed, and are increasingly used in clinical practice. In this article, we describe the rationale and methodology, review available guidelines for practice, and discuss the advantages and limitations of each of these modalities. When available, we have also summarised the scientific evidence for the clinical application of these techniques to detect heart failure in children.
Heart Failure Summit Review: cardiac re-synchronisation therapy in the failing heart
Authors: Cohen Mitchell I. 
Published: September 2015

AbstractExtrapolating cardiac resynchronization therapy (CRT) to pediatric patients with heart failure has at times been difficult given the heterogeneity of pediatric cardiomyopathies, varying congenital heart disease (CHD) substrates, and the fact that most pediatric heart failure patients have right bundle branch block (RBBB) as opposed to LBBB. Yet, despite these limitations a number of multi-center retrospective studies in North America and Europe have identified some data to suggest that certain sub-populations tend to respond positively to CRT. In order to address some of the heterogeneity it is helpful to subdivide pediatric and young adult patients with CHD into four potential groups: (1) CRT for chronic RV pacing, (2) dilated cardiomyopathies, (3) pulmonary right ventricles, and (4) systemic right ventricles. The chronic RV paced group, especially long-standing RV apical pacing, with ventricular dyssynchrony has consistently shown to be the group that best responds to a proactive resynchronization course. CRT therapy in pulmonary right ventricles such as post-op tetralogy of Fallot have shown some promise and may be considered especially if there is evidence of concomitant left ventricular dysfunction with an electrical dyssynchrony. Patients with systemic right ventricles such as post-atrial baffle surgery or congenitally corrected transposition reportedly do well with CRT in the presence of both inter-ventricular and intra-ventricular dyssynchrony. There is little doubt that moving forward to best way to identify which pediatric patients with heart failure will respond to CRT, will require a collaborative effort between the electrophysiologist and the echocardiographer to identify appropriate candidates with electrical and mechanical dyssynchrony.
Lessons learned from the Pediatric Cardiomyopathy Registry (PCMR) Study Group
Authors: Wilkinson James D. , Westphal Joslyn A. , Bansal Neha , Czachor Jason D. , Razoky Hiedy , Lipshultz Steven E. 
Published: September 2015

AbstractCardiomyopathy is a rare disorder of the heart muscle, affecting 1.13 cases per 100,000 children, from birth to 18 years of age. Cardiomyopathy is the leading cause of heart transplantation in children over the age of 1. The Pediatric Cardiomyopathy Registry funded in 1994 by the National Heart, Lung, and Blood Institute was established to examine the epidemiology of the disease in children below 18 years of age. More than 3500 children across the United States and Canada have been enrolled in the Pediatric Cardiomyopathy Registry, which has followed-up these patients until death, heart transplantation, or loss to follow-up. The Pediatric Cardiomyopathy Registry has provided the most in-depth illustration of this disease regarding its aetiology, clinical course, associated risk factors, and patient outcomes. Data from the registry have helped in guiding the clinical management of cardiomyopathy in children under 18 years of age; however, questions still remain regarding the most clinically effective diagnostic and treatment approaches for these patients. Future directions of the registry include the use of next-generation whole-exome sequencing and cardiac biomarkers to identify aetiology-specific treatments and improve diagnostic strategies. This article provides a brief synopsis of the work carried out by the Pediatric Cardiomyopathy Registry since its inception, including the current knowledge on the aetiologies, outcomes, and treatments of cardiomyopathy in children.
Can linking databases answer questions about paediatric heart failure?
Authors: Pasquali Sara K. , Schumacher Kurt R. , Davies Ryan R. 
Published: September 2015

AbstractNumerous data sets collect information on patients with paediatric cardiovascular disease, including paediatric heart failure and transplant patients. This review discusses methodologies available for linking and integrating information across data sets, which may help facilitate answering important questions in the field of paediatric heart failure and transplant that cannot be answered with individual data sets or single-centre data alone.
Paediatric heart failure research: role of the National Heart, Lung, and Blood Institute
Authors: Burns Kristin M. 
Published: September 2015

AbstractThe National Heart, Lung, and Blood Institute, of the National Institutes of Health, is committed to supporting research in paediatric heart failure. The Institute’s support of paediatric heart failure research includes both investigator-initiated grants and Institute initiatives. There were 107 funded grants in paediatric heart failure over the past 20 years in basic, translational and clinical research, technology development, and support of registries. Such research includes a broad diversity of scientific topics and approaches. The Institute also supports several initiatives for paediatric heart failure, including the Pediatric Circulatory Support Program, the Pumps for Kids, Infants, and Neonates (PumpKIN) Program, PediMACS, and the Pediatric Heart Network. This review article describes the National Heart, Lung, and Blood Institute’s past, present, and future efforts to promote a better understanding of paediatric heart failure, with the ultimate goal of improving outcomes.
Introduction to the 2015 Supplement toCardiology in the Young: Proceedings of the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute
Authors: Jacobs Jeffrey P. 
Published: September 2015

AbstractIn the United States of America alone, ~14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve.The International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was held on 4 and 5 February, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children’s Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children’s Hospital Andrews/Daicoff Cardiovascular Program, the Johns Hopkins All Children’s Heart Institute International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary “think-tank”. Information about George R. Daicoff, MD, and Ed and Sarainne Andrews is provided in this introductory manuscript to the 2015 Supplement toCardiology in the Youngentitled: “Proceedings of the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute”. Dr Daicoff founded the All Children’s Hospital Pediatric Heart Surgery programme and directed this programme for over two decades. Sarainne Andrews made her generous bequest to All Children’s Hospital in honour of her husband Ed and his friendship with Dr Daicoff in order to support cardiovascular surgery research efforts.
Precision and Reliability of the Glasgow Coma Scale Score among a Cohort of Latin American Prehospital Emergency Care Providers
Authors: Báez Amado Alejandro , Giráldez Ediza M. , De Peña Julio M. 
Published: September 2015

AbstractIntroduction:The Glasgow Coma Scale (GCS) is the standard measure used to quantify the level of consciousness in patients with head injuries.Rapid and accurate GCS scoring is essential for adequate assessment and treatment of critically sick and injured patients. This study sought out to determine the precision and reliability of the GCS among a cohort of Latin American Critical Care Transport Providers.Methods:The study consisted of a cross-sectional design using an Internetbased examination. The evaluation consisted of four focused clinical scenarios with a classification based on severity. For measurement of intra-rater reliability the first and fourth cases were identical. Five minutes were allocated for each scenario. For categorical variables, chi-square testing and Fisher's exact testing were used to assess associations. For all tests, statistical significance was set at the 0.05 level.Results:A total of 62 providers participated, including 17 physicians and 45 advanced providers (nurses and paramedics). No statistically significant differences were observed between physicians and advanced providers in the correct classification of the individual scenarios. Five of the 17 physicians (29.4%) answered all cases correctly, while none of the 45 advanced providers did (p <0.001). When evaluating the duplicated cases (Cases 1 and 4), five physicians (29.4%) and 11 advanced providers (24.4%) correctly classified the cases. This difference was not statistically significant.Conclusions:This study demonstrated a poor precision and poor reliability in the use of the Glasgow Coma Scale within the study subjects.
Childhood ADHD & Comorbid Odd: Diagnosis & Contemporary Treatments
Authors: Donnelly Craig L. 
Published: September 2015

Marshall is a 6-year-old child who displayed significant symptoms of hyperactivity, impulsivity, defiance, and temper tantrums since 2 years of age. Marshall lives with his mother, a single parent, and two siblings, ages 4 and 1. His problematic behavior, defiance, and argumentativeness were significant problems at home for his mother, which often made her late to work in the morning. These behaviors were also problematic in the evenings at dinnertime and at bedtime not only for his mother but also for the whole family. Marshall was also having social problems at school including being increasingly shunned by other children because of his aggressiveness and impulsivity as well as being defiant and argumentative with his teachers.His mother initially sought out her pediatrician, who indicated that Marshall was too young for medication and that better discipline techniques were necessary. Medical workup at that point was unrevealing of any significant condition responsible for Marshall's behavior. Marshall's mother continued to pursue a psychiatric evaluation for Marshall, and a formal psychiatric evaluation revealed diagnoses of attention-deficit/hyperactivity disorder (ADHD), combined type, and oppositional defiant disorder (ODD). Paper and pencil instruments were used including the Swanson, Nolan, and Pelham (SNAP) form for assessing ADHD and ODD symptoms. On the form, both Marshall's mother and teacher indicated that he was significantly elevated in both ADHD and ODD symptom domains, and target symptoms were identified: hyperactivity, impulsivity, short attention span, difficulty with follow through, defiance, argumentativeness, tantrums, and the beginnings of aggressiveness.
Comprehensive Treatment of Three Patients with Comorbid OCPD and ADHD
Authors: Josephson Stephen C. , Hollander Eric , Sumner Jennifer 
Published: September 2015

ABSTRACTThree patients were seen in an outpatient setting with work difficulties involving disorganization and task completion.They were evaluated and found to have significant symptoms of both attention-deficit/hyperactivity disorder, inattentive subtype and obsessive-compulsive personality disorder and were then treated with a creative combined behavioral and medication treatment, which emphasized the use of external aides (eg, paraprofessionals). Significant symptom reduction was observed as a result of this combined intervention.
Migrationshintergrund als Risikofaktor für die Entwicklung Frühgeborener im Alter von zwei Jahren
Authors: Schoberer Anne , Dörr Regina , Schoberer Mark , Orlikowsky Thorsten , Häusler Martin , Hoberg Kathrin 
Published: September 2015

Zusammenfassung. Im Rahmen der Aachener Frühgeborenennachsorge wurden N = 199 Frühgeborene (< 32 SSW und/oder < 1500 g) der Geburtsjahrgänge 2007 bis 2011 im Alter von korrigiert zwei Jahren entwicklungsneurologisch nachuntersucht und ihr MDI mit dem Bayley II ermittelt. Die Daten wurden retrospektiv analysiert, um herauszufinden, ob der Migrationshintergrund die kognitive Leistungsfähigkeit zum Untersuchungszeitpunkt beeinflusst. Es zeigten sich keine Unterschiede hinsichtlich des Geschlechts, medizinischer Komplikationen und der Inanspruchnahme von Therapie zwischen Kindern mit (42 %) und ohne (58 %) Migrationshintergrund. In Übereinstimmung mit der Literatur lag die gesamte Aachener Stichprobe mit einem mittleren MDI von 83,3 (SD 17,4) eine Standardabweichung unter dem Durchschnitt der Referenzpopulation. Kinder mit Migrationshintergrund lagen im kognitiven Outcome 10 Punkte unter Kindern ohne diesen, was entscheidend durch das Vorliegen familiärer Risikofaktoren bedingt wurde. Im regressionsanalytischen Modell hatten familiäre Risikofaktoren und das Geburtsgewicht den größten Einfluss auf den kognitiven Outcome; aber auch das Vorliegen eines Migrationshintergrundes leistete einen zusätzlichen Beitrag zur Vorhersage. Frühgeborene mit Migrationshintergrund sollten daher als besondere Risikogruppe erkannt werden, insbesondere wenn sie zusätzlich familiäre Risikofaktoren aufweisen, um sie frühzeitig differenzierter fördern zu können.
Bone marrow-derived mesenchymal stem cells ameliorate chronic high glucose-induced β-cell injury through modulation of autophagy
Authors: Zhao K , Hao H , Liu J , Tong C , Cheng Y , Xie Z , Zang L , Mu Y , Han W 
Published: September 2015

AbstractChronic hyperglycemia causes a progressive decrease of β-cell function and mass in type 2 diabetic patients. Growing evidence suggests that augment of autophagy may be an effective approach to protect β cells against various extra-/intracellular stimuli. In this study, we thus investigated whether bone marrow-derived mesenchymal stem cells (BM-MSCs) could ameliorate chronic high glucose (HG)-induced β-cell injury through modulation of autophagy. Prolonged exposure to HG decreased cell viability, increased cell apoptosis and impaired basal insulin secretion and glucose-stimulated insulin secretion of INS-1 cells, but BM-MSC treatment significantly alleviated these glucotoxic alternations. In addition, western blotting displayed upregulated expression of Beclin1 and LC3-II in INS-1 cells co-cultured with BM-MSCs. Results from immunofluorescence staining and transmission electronic microscope analysis also revealed that BM-MSCs promoted autophagosomes and autolysosomes formation in HG-treated INS-1 cells. However, it should be noted that inhibition of autophagy significantly diminished the protective effects of BM-MSCs on HG-treated INS-1 cells, suggesting that the improvement of β-cell function and survival induced by BM-MSCs was mediated through autophagy. Furthermore, our results showed that BM-MSCs improved mitochondrial function and reduced reactive oxygen species production in HG-treated INS-1 cells, largely owing to autophagic clearance of impaired mitochondria. In vivo study was performed in rats with type 2 diabetes (T2D). BM-MSC infusion not only ameliorated hyperglycemia, but also promoted restoration of pancreatic β cells in T2D rats. Meanwhile, BM-MSC infusion upregulated LAMP2 expression and enhanced formation of autophagosomes and autolysosomes, combined with reduced β-cell apoptosis and increased number of insulin granules. These findings together indicated that BM-MSCs could protect β cells against chronic HG-induced injury through modulation of autophagy in vitro and in vivo. This study unveiled novel evidence of BM-MSCs as an ideal strategy to enhance autophagy for treatment of T2D mellitus.
SGK-1 protects kidney cells against apoptosis induced by ceramide and TNF-α
Authors: Pastore D , Della-Morte D , Coppola A , Capuani B , Lombardo M F , Pacifici F , Ferrelli F , Arriga R , Mammi C , Federici M , Bellia A , Di Daniele N , Tesauro M , Donadel G , Noto D , Sbraccia P , Sconocchia G , Lauro D 
Published: September 2015

AbstractCeramide regulates several different cellular responses including mechanisms leading to apoptosis. Serum- and glucocorticoid-inducible protein kinase (SGK)-1 is a serine threonine kinase, which activates survival pathways in response to stress stimuli. Recently, we demonstrated an anti-apoptotic role of SGK-1 in human umbilical endothelial cells treated with high glucose. In the present study, since ceramide induces apoptosis by multiple mechanisms in diabetes and its complication such as nephropathy, we aimed to investigate whether SGK-1 may protect even against apoptosis induced by ceramide in kidney cells. Human embryonic kidney (HEK)-293 cells stable transfected with SGK-1 wild type (SGK-1wt) and its dominant negative gene (SGK-1dn) have been used in this study. Apoptotic stimuli were induced by C2-ceramide and TNF-α to increase endogenous synthesis of ceramide. Upon activation with these stimuli, SGK-1wt transfected cells have a statistically significant reduction of apoptosis compared with SGK-1dn cells (P<0.001). This protection was dependent on activation of caspase-3 and Poly-ADP-ribose-polymerase-1 (PARP-1) cleavage. SGK-1 and AKT-1 two highly homologous kinases differently reacted to ceramide treatment, since SGK-1 increases in response to apoptotic stimulus while AKT-1 decreases. This enhancement of SGK-1 was dependent on p38-mitogen-activated-protein kinases (p38MAPK), cyclic-adenosine-monophosphate/protein kinase A (cAMP/PKA) and phosphoinositide-3-kinase (PI3K) pathways. Especially, by using selective LY294002 inhibitor, we demonstrated that the most involved pathway in the SGK-1 mediated process of protection was PI3K. Treatment with inhibitor of SGK-1 (GSK650394) significantly enhanced TNF-α-dependent apoptosis in HEK-293 cells overexpressing SGK-1wt. Caspase-3, -8 and -9 selective inhibitors confirmed that SGK-1 reduced the activation of caspase-dependent apoptosis, probably by both intrinsic and extrinsic pathways. In conclusion, we demonstrated that in kidney cells, overexpression of SGK-1 is protective against ceramide-induced apoptosis and the role of SGK-1 can be potentially explored as a therapeutic target in conditions like diabetes, where ceramide levels are increased.
Smac mimetic-induced upregulation of interferon-β sensitizes glioblastoma to temozolomide-induced cell death
Authors: Marschall V , Fulda S 
Published: September 2015

AbstractInhibitor of apoptosis (IAP) proteins are frequently expressed at high levels in cancer cells and represent attractive therapeutic targets. We previously reported that the Smac (second mitochondria-derived activator of caspases) mimetic BV6, which antagonizes IAP proteins, sensitizes glioblastoma cells to temozolomide (TMZ)-induced cell death in a nuclear factor-κB (NF-κB)-dependent manner. However, BV6-induced NF-κB target genes responsible for this synergistic interaction have remained elusive. Using whole-genome gene expression profiling, we here identify BV6-stimulated, NF-κB-dependent transcriptional upregulation of interferon-β (IFNβ) and IFN-mediated proapoptotic signaling as critical events that mediate BV6/TMZ-induced apoptosis. Knockdown of IFNβ significantly rescues cells from BV6/TMZ-induced cell death. Similarly, silencing of the corresponding receptor IFNα/β receptor (IFNAR) confers a significant protection against apoptosis, demonstrating that IFNβ and IFN signaling are required for BV6/TMZ-mediated cell death. Moreover, BV6 and TMZ cooperate to transcriptionally upregulate the proapoptotic B-cell lymphoma 2 family proteins Bax (Bcl-2-associated X protein) or Puma (p53-upregulated modulator of apoptosis). Knockdown of Bax or Puma significantly decreases BV6/TMZ-induced apoptosis, showing that both proteins are necessary for apoptosis. By identifying IFNβ as a key mediator of BV6/TMZ-induced apoptosis, our study provides novel insights into the underlying molecular mechanisms of Smac mimetic-mediated chemosensitization with important implications for the development of novel treatment strategies for glioblastoma.
Effects of mid-respiratory chain inhibition on mitochondrial function in vitro and in vivo
Authors: Broom Ashley J. , Ambroso Jeffrey , Brunori Gino , Burns Angie K. , Armitage James R. , Francis Ian , Gandhi Mitul , Peterson Richard A. , Gant Timothy W. , Boobis Alan R. , Lyon Jonathan J. 
Published: September 2015

Abstract
Relating the in vitro mitochondrial effects of drug candidates to likely in vivo outcomes remains challenging. Better understanding of this relationship, alongside improved methods to assess mitochondrial dysfunction in vivo, would both guide safer drug candidate selection and better support discovery programmes targeting mitochondria for pharmacological intervention. The aim of this study was to profile the in vivo effects of a compound with suspected complex III electron transport chain (ETC) inhibitory activity (GSK932121A) at doses associated with clinical signs, and relate findings back to in vitro data with the same compound. Control liver mitochondria or HepG2 cells were treated in vitro with GSK932121A to assess mitochondrial effects on both calcium retention capacity (CRC) and oxygen consumption rate (OCR) respectively. The same assessments were then performed on liver mitochondria isolated from Crl:CD(SD) rats, 5 hours following intraperitoneal (IP) administration of GSK932121A. Lactate/pyruvate assessment, hepatic microscopy, blood gas analysis, glutathione profiling and transcriptomics were used to characterise the acute toxicity. In vivo, GSK932121A caused hypothermia, increased levels of hepatocellular oxidative stress and a metabolic shift in energy production, resulting in an increased lactate/pyruvate ratio, liver steatosis and glycogen depletion, together with gene expression changes indicative of a fasted state. As would be expected of an ETC inhibitor, GSK932121A reduced the CRC of liver mitochondria isolated from naive control animals and the OCR of HepG2 cells when treated directly in vitro. In contrast, mitochondria isolated from animals treated with GSK932121A in vivo unexpectedly showed an increase in CRC and basal OCR. Whilst seemingly contradictory, these differences likely reflect an adapted state in vivo resulting from the initial insult in combination with compensatory changes made by the tissue to maintain energy production. Only the initial, unconfounded, response is observable in vitro. These findings improve current understanding of the toxicological and molecular consequences of ETC inhibition. Furthermore, this work highlights key differences in the way that mitochondrial perturbation is manifest in vivo versus in vitro in terms of functional endpoints and helps guide endpoint selection for future studies with potential mitochondrial toxicants or drugs designed to modulate mitochondrial function for therapeutic benefit.