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Find video protocols related to scientific articles indexed in Pubmed.
Trait positive affect is associated with hippocampal volume and change in caudate volume across adolescence.
Cogn Affect Behav Neurosci
PUBLISHED: 09-19-2014
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Trait positive affect (PA) in childhood confers both risk and resilience to psychological and behavioral difficulties in adolescence, although explanations for this association are lacking. Neurodevelopment in key areas associated with positive affect is ongoing throughout adolescence, and is likely to be related to the increased incidence of disorders of positive affect during this period of development. The aim of this study was to prospectively explore the relationship between trait indices of PA and brain development in subcortical reward regions during early to mid-adolescence in a community sample of adolescents. A total of 89 (46 male, 43 female) adolescents participated in magnetic resonance imaging assessments during both early and mid-adolescence (mean age at baseline = 12.6 years, SD = 0.45; mean follow-up period = 3.78 years, SD = 0.21) and also completed self-report measures of trait positive and negative affect (at baseline). To examine the specificity of these effects, the relation between negative affect and brain development was also examined. The degree of volume reduction in the right caudate over time was predicted by PA. Independent of time, larger hippocampal volumes were associated with higher PA, and negative affect was associated with smaller left amygdala volume. The moderating effect of negative affect on the development of the left caudate varied as a function of lifetime psychiatric history. These findings suggest that early to mid-adolescence is an important period whereby neurodevelopmental processes may underlie key phenotypes conferring both risk and resilience for emotional and behavioral difficulties later in life.
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Nanoparticles Containing a Liver X Receptor Agonist Inhibit Inflammation and Atherosclerosis.
Adv Healthc Mater
PUBLISHED: 08-22-2014
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Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism.
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Mycobacterium simiae Infection in Two Unrelated Patients with Different Forms of Inherited IFN-?R2 Deficiency.
J. Clin. Immunol.
PUBLISHED: 08-19-2014
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Interferon-? receptor 2 (IFN-?R2) deficiency is a rare primary immunodeficiency characterized by predisposition to infections with weakly virulent mycobacteria, such as environmental mycobacteria and BCG vaccines. We describe here two children with IFN-?R2 deficiency, from unrelated, consanguineous kindreds of Arab and Israeli descent. The first patient was a boy who died at the age of 4.5 years, from recurrent, disseminated disease caused by Mycobacterium simiae. His IFN-?R2 defect was autosomal recessive and complete. The second patient was a girl with multiple disseminated mycobacterial infections, including infection with M. simiae. She died at the age of 5 years, a short time after the transplantation of umbilical cord blood cells from an unrelated donor. Her IFN-?R2 defect was autosomal recessive and partial. Autosomal recessive IFN-?R2 deficiency is life-threatening, even in its partial form, and genetic diagnosis and familial counseling are therefore particularly important for this condition. These two cases are the first of IFN-?R2 deficiency associated with M. simiae infection to be described.
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Long-term effects of controllability or the lack of it on coping abilities and stress resilience in the rat.
Stress
PUBLISHED: 08-11-2014
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Findings suggest that stress-induced impaired learning and coping abilities may be attributed more to the psychological nature of the stressor, rather than its physical properties. It has been proposed that establishing controllability over stressors can ameliorate some of its effects on cognition and behavior. Gaining controllability was suggested to be associated with the development of stress resilience. Based on repeated exposure to the two-way shuttle avoidance task, we previously developed and validated a behavioral task that leads to a strict dissociation between gaining controllability (to the level that the associated fear is significantly reduced) and a fearful state of uncontrollability. Employing this protocol, we investigated here the impact of gaining or failing to gain emotional controllability on indices of anxiety and depression and on subsequent abilities to cope with positively or negatively reinforcing learning experiences. In agreement with previous studies, rats exposed to the uncontrollable protocol demonstrated high concentration of sera corticosterone, increased immobility, reduced duration of struggling in the forced swim test and impaired ability to acquire subsequent learning tasks. Achieving emotional controllability resulted in resilience to stress as was indicated by longer duration of struggling in the forced swim test, and enhanced learning abilities. Our prolonged training protocol, with the demonstrated ability of rats to gain emotional controllability, is proposed as a useful tool to study the neurobiological mechanisms of stress resilience.
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Genetic prion disease: no role for the immune system in disease pathogenesis?
Hum. Mol. Genet.
PUBLISHED: 03-25-2014
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Prion diseases, which can manifest by transmissible, sporadic or genetic etiologies, share several common features, such as a fatal neurodegenerative outcome and the aberrant accumulation of proteinase K (PK)-resistant PrP forms in the CNS. In infectious prion diseases, such as scrapie in mice, prions first replicate in immune organs, then invade the CNS via ascending peripheral tracts, finally causing death. Accelerated neuroinvasion and death occurs when activated prion-infected immune cells infiltrate into the CNS, as is the case for scrapie-infected mice induced for experimental autoimmune encephalomyelitis (EAE), a CNS inflammatory insult. To establish whether the immune system plays such a central role also in genetic prion diseases, we induced EAE in TgMHu2ME199K mice, a line mimicking for late onset genetic Creutzfeldt Jacob disease (gCJD), a human prion disease. We show here that EAE induction of TgMHu2ME199K mice neither accelerated nor aggravated prion disease manifestation. Concomitantly, we present evidence that PK-resistant PrP forms were absent from CNS immune infiltrates, and most surprisingly also from lymph nodes and spleens of TgMHu2ME199K mice at all ages and stages of disease. These results imply that the mechanism of genetic prion disease differs widely from that of the infectious presentation, and that the conversion of mutant PrPs into PK resistant forms occurs mostly/only in the CNS. If the absence of pathogenic PrP forms form immune organs is also true for gCJD patients, it may suggest their blood is devoid of prion infectivity.
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Stress modulation of hippocampal activity--spotlight on the dentate gyrus.
Neurobiol Learn Mem
PUBLISHED: 03-17-2014
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The effects of stress on learning and memory are diverse, ranging from impairment to facilitation. Many studies emphasize the major role of the hippocampus, mainly its CA1 and CA3 areas, in the process of memory formation under emotional and stressful conditions. In the current review, we summarize work which suggests that the dentate gyrus (DG) of the hippocampus is likely to play a pivotal role in defining the impact of stress on hippocampal functioning. We describethe effects of stress on long term potentiation (LTP) and local circuit activity in the DG and the role of the amygdala in mediating these effects. As one of the brain regions known to have a high rate of adult neurogenesis, the effects of stress on DG neurogenesis will also be reviewed. Finally, we discuss exposure to stress during juvenility and its influence on the adult DG. The DG is a dynamic structure which is susceptible to stress. Under stressful conditions, its response is variable and complex, much like the behavioral outcomes of such circumstances. It is likely to significantly contribute to the diverse effects of stress on memory formation.
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Structural brain development and depression onset during adolescence: a prospective longitudinal study.
Am J Psychiatry
PUBLISHED: 03-01-2014
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The authors sought to investigate whether the structural development of limbic, striatal, and prefrontal regions that are critically implicated in the pathophysiology of depression is associated with adolescent-onset depression.
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Development of therapeutic polymeric nanoparticles for the resolution of inflammation.
Adv Healthc Mater
PUBLISHED: 02-19-2014
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Liver X receptors (LXRs) attenuate inflammation by modulating the expression of key inflammatory genes, making LXRs and their ligands particularly attractive candidates for therapeutic intervention in cardiovascular, metabolic, and/or inflammatory diseases. Herein, enhanced proresolving activity of polymeric nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (LXR-NPs) is demonstrated, developed from a combinatorial library of more than 70 formulations with variations in critical physicochemical parameters. In vitro studies on peritoneal macrophages confirm that LXR-NPs are significantly more effective than the free agonist at downregulating pro-inflammatory mediators (MCP-1 and TNF?), as well as inducing the expression of LXR target genes (ABCA1 and SREBP1c). Through a zymosan-induced acute peritonitis in vivo model, LXR-NPs are found to be more efficient than free GW3965 at limiting the recruitment of polymononuclear neutrophils (50% vs 17%), suppressing the gene expression and secretion of pro-inflammatory factors MCP-1 and TNF? in peritoneal macrophages, and decreasing the resolution interval up to 4 h. Furthermore, LXR-NPs suppress the secretion of MCP-1 and TNF? by monocytes and macrophages more efficiently than the commercial drug dexamethasone. Overall, these findings demonstrate that LXR-NPs are capable of promoting resolution of inflammation and highlight the prospect of LXR-based nanotherapeutics for inflammatory diseases.
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Reduction in maternal polycomb levels contributes to transgenerational inheritance of a response to toxic stress in flies.
J. Physiol. (Lond.)
PUBLISHED: 02-17-2014
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Transgenerational persistence of parental responses to environmental stimuli has been reported in various organisms, but the underlying mechanisms remain underexplored. In one of these reported examples, we have shown that exposure of fly larvae to G418 antibiotic leads to non-Mendelian inheritance of ectopic induction of certain developmental genes. Here we investigate if this inheritance involves changes in mRNA composition within the early, maternal-stage offspring embryos of exposed flies. Exposure to G418 in F1 modified the maternal RNA levels of many genes in their early (F2) embryos. This includes reduction of maternal Polycomb group genes which persisted in the following generation of embryos (F3). To investigate the functional meaning of this reduction, we compared genetically normal embryos of Polycomb mutant females to normal embryos of normal females. Analysis with two different alleles of Polycomb, Pc1 and Pc3, revealed that maternal reduction in Polycomb gene dosage has a positive influence on the inheritance of induced expression. Together, this shows that exposure to G418 stress reduces the maternal levels of Polycomb in the offspring embryos and this reduction contributes to the inheritance of induced expression.
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Long-term motor and cognitive outcome of acute encephalitis.
Pediatrics
PUBLISHED: 02-17-2014
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To examine the long-term motor and neurocognitive outcome of children with acute encephalitis and to look at possible prognostic factors.
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Firing pattern characteristics of tonically active neurons in rat striatum: context dependent or species divergent?
J. Neurosci.
PUBLISHED: 02-07-2014
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Tonically active neurons (TANs)--presumably, striatal cholinergic interneurons--exert a strong influence on striatal information processing. Primate studies often describe a characteristic TAN response comprising suppressed activity followed by rebound firing that occasionally is preceded by a brief activation. By contrast, studies in behaving rats report pronounced excitation during movement. These differences in firing patterns may be due to variations in behavioral conditions or could stem from the fact that TANs in rodents use different neuronal mechanisms. If similar/different task conditions yield similar/different activity patterns, then the two species may share neuronal mechanisms; however, if similar task conditions yield different activity patterns, then the two species use different neuronal mechanisms. To evaluate these possibilities, we recorded TAN activity in the ventral and dorsolateral striatal regions in rats performing a simple instrumental task similar in concept to one used in primate studies. We demonstrate that TAN activity is substantially influenced by event context; yet, under identical task conditions, primate and rat TANs display similar activity patterns, whereas under different conditions they do not. Our results suggest that the observed differences in firing patterns likely reflect dissimilarities in task attributes rather than species-dependent neuronal mechanisms and call for re-evaluation of the excitatory response in primate research.
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Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD.
Nanomedicine
PUBLISHED: 02-06-2014
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Neurodegenerative diseases generate the accumulation of specific misfolded proteins, such as PrP(Sc) prions or A-beta in Alzheimer's diseases, and share common pathological features, like neuronal death and oxidative damage. To test whether reduced oxidation alters disease manifestation, we treated TgMHu2ME199K mice, modeling for genetic prion disease, with Nano-PSO, a nanodroplet formulation of pomegranate seed oil (PSO). PSO comprises large concentrations of a unique polyunsaturated fatty acid, Punicic acid, among the strongest natural antioxidants. Nano-PSO significantly delayed disease presentation when administered to asymptomatic TgMHu2ME199K mice and postponed disease aggravation in already sick mice. Analysis of brain samples revealed that Nano-PSO treatment did not decrease PrP(Sc) accumulation, but rather reduced lipid oxidation and neuronal loss, indicating a strong neuroprotective effect. We propose that Nano-PSO and alike formulations may be both beneficial and safe enough to be administered for long years to subjects at risk or to those already affected by neurodegenerative conditions.
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Retrospective follow up of gross motor development in children using propranolol for treatment of infantile haemangioma at Sydney Children's Hospital.
Australas. J. Dermatol.
PUBLISHED: 01-31-2014
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Questions have been raised as to whether propranolol, which crosses the blood-brain barrier, when used early in life may have an adverse effect on gross motor development. A retrospective survey asking questions about gross motor development was sent to the families of children who had been prescribed oral propranolol for infantile haemangioma at Sydney Children's Hospital between 2008 and 2013. It was found that of the 84 patients surveyed, four were delayed in walking unassisted. There was a statistically significant influence if the child was taking other medications which included prednisolone, vincristine, omeprazole, ranitidine, salbutamol, Flixotide, Timoptol and antibiotics. This was not further analysed in this study because of the low numbers involved. There was no statistically significant influence of gestational age, birth weight or length of time on propranolol. This study adds to the retrospective data available; however large-scale prospective studies are needed to identify unexpected long-term side-effects.
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Extended-spectrum ?-lactamase-producing bacteria causing community-acquired urinary tract infections in children.
Pediatr. Nephrol.
PUBLISHED: 01-08-2014
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Extended-spectrum ?-lactamase (ESBL)-producing bacteria are infrequent pathogens of community-acquired (CA) urinary tract infections (UTIs) in children. The aim of this study was to assess the frequency of and identify risk factors for CA-UTIs due to ESBL-producing microorganisms (CA-ESBL-UTI).
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eIF4EBP3L acts as a gatekeeper of TORC1 in activity-dependent muscle growth by specifically regulating Mef2ca translational initiation.
PLoS Biol.
PUBLISHED: 10-01-2013
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Muscle fiber size is activity-dependent and clinically important in ageing, bed-rest, and cachexia, where muscle weakening leads to disability, prolonged recovery times, and increased costs. Inactivity causes muscle wasting by triggering protein degradation and may simultaneously prevent protein synthesis. During development, muscle tissue grows by several mechanisms, including hypertrophy of existing fibers. As in other tissues, the TOR pathway plays a key role in promoting muscle protein synthesis by inhibition of eIF4EBPs (eukaryotic Initiation Factor 4E Binding Proteins), regulators of the translational initiation. Here, we tested the role of TOR-eIF4EBP in a novel zebrafish muscle inactivity model. Inactivity triggered up-regulation of eIF4EBP3L (a zebrafish homolog of eIF4EBP3) and diminished myosin and actin content, myofibrilogenesis, and fiber growth. The changes were accompanied by preferential reduction of the muscle transcription factor Mef2c, relative to Myod and Vinculin. Polysomal fractionation showed that Mef2c decrease was due to reduced translation of mef2ca mRNA. Loss of Mef2ca function reduced normal muscle growth and diminished the reduction in growth caused by inactivity. We identify eIF4EBP3L as a key regulator of Mef2c translation and protein level following inactivity; blocking eIF4EBP3L function increased Mef2ca translation. Such blockade also prevented the decline in mef2ca translation and level of Mef2c and slow myosin heavy chain proteins caused by inactivity. Conversely, overexpression of active eIF4EBP3L mimicked inactivity by decreasing the proportion of mef2ca mRNA in polysomes, the levels of Mef2c and slow myosin heavy chain, and myofibril content. Inhibiting the TOR pathway without the increase in eIF4EBP3L had a lesser effect on myofibrilogenesis and muscle size. These findings identify eIF4EBP3L as a key TOR-dependent regulator of muscle fiber size in response to activity. We suggest that by selectively inhibiting translational initiation of mef2ca and other mRNAs, eIF4EBP3L reprograms the translational profile of muscle, enabling it to adjust to new environmental conditions.
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Hypothalamic-pituitary-adrenal axis recovery following prolonged prednisolone therapy in infants.
J. Clin. Endocrinol. Metab.
PUBLISHED: 09-30-2013
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Context: The duration of hypothalamic-pituitary-adrenal (HPA) axis suppression after glucocorticoid treatment is uncertain. Objective: We aimed to determine the duration of HPA axis suppression in prednisolone-treated infants and the age at which circadian variation in salivary cortisol is established in healthy infants. Design, Setting, and Participants: Before the adoption of propranolol treatment by the Vascular Birthmarks Clinic, 12 infants with infantile hemangioma received high-dose prednisolone for 12 to 25 weeks duration, weaned over 4 to 6 weeks, and ceased at age 21 to 31 weeks. Parents collected serial salivary samples at two time points per day (before first and last feed) until circadian variation in salivary cortisol (measured by radioimmunoassay) was observed, when a confirmatory 1 ?g Synacthen test was performed. Ten healthy control infants had serial salivary cortisol measurements to determine the age at which circadian variation is established. Main Outcome Measure: We defined circadian variation as evening salivary cortisol <50% of the early morning level on two consecutive sampling weeks. Results: Circadian variation appeared within 6 weeks (median 2.7, range 1.4-5.4) of prednisolone cessation. All confirmatory Synacthen tests were normal (peak serum cortisol >600 nmol/L) and were performed within 12 weeks of prednisolone cessation. Healthy controls developed circadian variation at median 16 weeks of age (range 8-24). Conclusion: HPA recovery occurred within 6 to 12 weeks, shorter than empirical recommendations, to give stress cover for 6 to 12 months. Reduced duration of stress-cover precautions may reduce parental anxiety and side effects from unnecessary glucocorticoid use. Healthy control infants established circadian variation in salivary cortisol between 2 and 6 months of age.
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Adjuvanted influenza vaccines.
Expert Rev Vaccines
PUBLISHED: 09-24-2013
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Influenza is one of the most common causes of human morbidity and mortality that is preventable by vaccination. Immunization with available vaccines provides incomplete protection against illness caused by influenza virus, especially in high-risk groups such as the elderly and young children. Thus, more efficacious vaccines are needed for the entire population, and all the more so for high-risk groups. One way to improve immune responses and protection is to formulate the vaccine with antigen carriers and/or adjuvants, which can play an important role in improving immune responses and delivery to antigen-presenting cells, especially for a vaccine like influenza that is based on protein antigens usually administered without a carrier or adjuvant. In this review, the authors present an overview of available vaccines, focusing on research and development of new adjuvants used in influenza vaccines, as well as adjuvanted influenza vaccines aimed to improve immune responses, protection and breadth of coverage for influenza.
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Gradenigos syndrome: Is fusobacterium different? Two cases and review of the literature.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 09-17-2013
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Gradenigos syndrome is a rare but life threatening complication of acute otitis media (AOM), which includes a classic triad of otitis media, deep facial pain and ipsilateral abducens nerve paralysis. The incidence of Fusobacterium necrophorum infections has increased in recent years. We describe two cases of Gradenigos syndrome caused by F. necrophorum. Additional four cases were identified in a review of the literature. Gradenigos syndrome as well as other neurologic complications should be considered in cases of complicated acute otitis media. F. necrophorum should be empirically treated while awaiting culture results.
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Function and distribution of apolipoprotein A1 in the artery wall are markedly distinct from those in plasma.
Circulation
PUBLISHED: 08-22-2013
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Prior studies show that apolipoprotein A1 (apoA1) recovered from human atherosclerotic lesions is highly oxidized. Ex vivo oxidation of apoA1 or high-density lipoprotein (HDL) cross-links apoA1 and impairs lipid binding, cholesterol efflux, and lecithin-cholesterol acyltransferase activities of the lipoprotein. Remarkably, no studies to date directly quantify either the function or HDL particle distribution of apoA1 recovered from the human artery wall.
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Staphylococcus aureus urinary tract infections in children are associated with urinary tract abnormalities and vesico-ureteral reflux.
Pediatr. Nephrol.
PUBLISHED: 08-18-2013
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Staphylococcus aureus is an uncommon cause of pediatric urinary tract infection (UTI). Data regarding urinary tract malformations in children with S. aureus UTI is limited.
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Congenital Cardiac, Aortic Arch, and Vascular Bed Anomalies in PHACE Syndrome (from the International PHACE Syndrome Registry).
Am. J. Cardiol.
PUBLISHED: 06-26-2013
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PHACE syndrome represents the association of large infantile hemangiomas of the head and neck with brain, cerebrovascular, cardiac, ocular, and ventral or midline defects. Cardiac and cerebrovascular anomalies are the most common extracutaneous features of PHACE, and they also constitute the greatest source of potential morbidity. Congenital heart disease in PHACE is incompletely described, and this study was conducted to better characterize its features. This study of the International PHACE Syndrome Registry represents the largest central review of clinical, radiologic, and histopathologic data for cardiovascular anomalies in patients with PHACE to date. Sixty-two (41%) of 150 subjects had intracardiac, aortic arch, or brachiocephalic vessel anomalies. Aberrant origin of a subclavian artery was the most common cardiovascular anomaly (present in 31 (21%) of 150 subjects). Coarctation was the second most common anomaly, identified in 28 (19%) of 150 subjects, and can be missed clinically in patients with PHACE because of the frequent association of arch obstruction with aberrant subclavian origin. Twenty-three (37%) of 62 subjects with cardiovascular anomalies required procedural intervention. A greater percentage of hemangiomas were located on the left side of the head and neck in patients with coarctation (46% vs 39%); however, hemangioma distribution did not predict the presence of cardiovascular anomalies overall. In conclusion, PHACE is associated with a high risk of congenital heart disease. Cardiac and aortic arch imaging with detailed assessment of arch patency and brachiocephalic origins is essential for any patient suspected of having PHACE. Longitudinal investigation is needed to determine the long-term outcomes of cardiovascular anomalies in PHACE.
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Differences in prevalence of parasites in stool samples between three distinct ethnic pediatric populations in southern Israel, 2007-2011.
Parasitol. Int.
PUBLISHED: 05-23-2013
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Intestinal parasites cause significant morbidity worldwide, particularly in developing populations. At least three pediatric populations reside in southern Israel: the Bedouin population, the general Jewish population and Jewish children of Ethiopian origin. Our aim was to compare intestinal parasite prevalence between the three pediatric populations in southern Israel. This is a retrospective, laboratory, population-based surveillance. Most ova and parasite (O&P) tests in southern Israel (hospital and community obtained) are performed by the hospital parasitology laboratory. All pediatric stool O&P tests examined by the hospital laboratory between 2007 and 2011 were included. Overall, 45,978 samples were examined; 27,354, 16,969 and 1655 from Bedouin, non-Ethiopian Jewish and Ethiopian children, respectively. 16,317 parasites were identified in 12,325 (26.8%) positive samples. Total prevalences were 36%, 11% and 46% for Bedouin, non-Ethiopian Jewish and Ethiopian children, respectively. Blastocystis hominis, Giardia lamblia and Entamoeba species were the most common parasites identified, constituting ?80% of positive samples in all groups. Hymenolepis nana was rarely identified in non-Ethiopian Jewish children (0.04% of isolates compared with 2.6% and 0.5% in Bedouin and Ethiopian children, respectively). Other helminths, excluding H. nana and Enterobius vermicularis, were identified almost exclusively in Ethiopian children ?5years of age. In conclusion, the Bedouin and Ethiopian children were characterized by higher parasite prevalence in stool, compared with the non-Ethiopian Jewish children, probably reflecting higher intestinal parasitic disease rates. Certain helminthic infections were identified almost exclusively in the Ethiopian children. These differences may be associated with lifestyle differences between the three populations.
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The complex fate in plasma of gadolinium incorporated into high-density lipoproteins used for magnetic imaging of atherosclerotic plaques.
Bioconjug. Chem.
PUBLISHED: 05-10-2013
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We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL, and VLDL particles containing Gd chelated to phosphatidyl ethanolamine (DTPA-DMPE) and a lipidic fluorophore were used to demonstrate the transfer of Gd-phospholipids among plasma lipoproteins in vitro and in vivo. To determine the basis of this transfer, the roles of phospholipid transfer protein (PLTP) and lipoprotein lipase (LpL) in mediating the migration of Gd-DTPA-DMPE among lipoproteins were investigated. The results indicated that neither was an important factor, suggesting that spontaneous transfer of Gd-DTPA-DMPE was the most probable mechanism. Finally, two independent mouse models were used to quantify the relative contributions of HDL and LDL reconstituted with Gd-DTPA-DMPE to plaque imaging enhancement by MR. Both sets of results suggested that Gd-DTPA-DMPE originally associated with LDL was about twice as effective as that injected in the form of Gd-HDL, and that some of Gd-HDLs effectiveness in vivo is indirect through transfer of the imaging agent to LDL. In conclusion, the fate of Gd-DTPA-DMPE associated with a particular type of lipoprotein is complex, and includes its transfer to other lipoprotein species that are then cleared from the plasma into tissues.
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RCT of timolol maleate gel for superficial infantile hemangiomas in 5- to 24-week-olds.
Pediatrics
PUBLISHED: 05-06-2013
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Timolol maleate 0.5% gel is a safe and effective medication for treating superficial infantile hemangiomas (IHs) in infants with a median age of 9 weeks.
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Positive parenting predicts the development of adolescent brain structure: A longitudinal study.
Dev Cogn Neurosci
PUBLISHED: 04-18-2013
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Little work has been conducted that examines the effects of positive environmental experiences on brain development to date. The aim of this study was to prospectively investigate the effects of positive (warm and supportive) maternal behavior on structural brain development during adolescence, using longitudinal structural MRI. Participants were 188 (92 female) adolescents, who were part of a longitudinal adolescent development study that involved mother-adolescent interactions and MRI scans at approximately 12 years old, and follow-up MRI scans approximately 4 years later. FreeSurfer software was used to estimate the volume of limbic-striatal regions (amygdala, hippocampus, caudate, putamen, pallidum, and nucleus accumbens) and the thickness of prefrontal regions (anterior cingulate and orbitofrontal cortices) across both time points. Higher frequency of positive maternal behavior during the interactions predicted attenuated volumetric growth in the right amygdala, and accelerated cortical thinning in the right anterior cingulate (males only) and left and right orbitofrontal cortices, between baseline and follow up. These results have implications for understanding the biological mediators of risk and protective factors for mental disorders that have onset during adolescence.
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Estrogens and hyperglycemic modulation of mRNAs expressions involved in bone metabolism: an overshadowed association?
Connect. Tissue Res.
PUBLISHED: 04-15-2013
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Human bone cell line (SaOS2) express different mRNAs involved in bone biology and physiology such as estrogen receptor ? (ER?), estrogen receptor ? (ER?), vitamin D receptor (VDR), 1?, 25 hydroxy vitamin D(3) hydroxylase (1OHase) as well as 12 and 15 lipoxygenases (12LO and 15LO). These mRNAs are modulated by estrogenic compounds. Since the skeletal protective effects of estrogens are not discernible in diabetic women, we tested whether the expression of the parameters measured here and their modulations by estrogens, in SaOS2 cells grown in growth medium containing high glucose (HG; 9.0 g/L; 44 mM) compared to normal glucose (NG; 4.5 g/L; 22 mM). High Glucose (HG) significantly increased DNA synthesis and creatine kinase (CK) specific activity in SaOS2 cells. Stimulations of DNA but not of CK by E(2), by 4, 4, 4-[4-propyl-(1H)-pyrazol-1, 3, 5- triyl] tris-phenol (PPT, ER? specific agonist), or by 2, 3-bis (4-hydroxyphenyl)-propionitrile (DPN, ER? specific agonist), were abolished by HG. HG itself upregulated the expression of mRNA of 12LO and 15LO and upregulated to much less extent of ER? and VDR, but had no effect on the expression of mRNA of ER? and 1OHase. The different hormonal treatments modulated the expressions of 12LO and 15LO mRNAs which was reduced in HG, whereas the induction of their products 12HETE and 15HETE was only slightly affected by HG. The exact mechanism of HG effects on bone cell responses is yet to be investigated and its relationship to human bone physiology is not yet clear.
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RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.
Hum. Mutat.
PUBLISHED: 03-17-2013
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Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n = 100), common CM(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the "second-hit" hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up.
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Inducible clindamycin resistance in ?-hemolytic streptococci and Streptococcus pneumoniae.
Isr. Med. Assoc. J.
PUBLISHED: 03-15-2013
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Resistance to macrolides in beta-hemolytic streptococci and Streptococcus pneumoniae arises primarily due to Erm(B) or Mef(A). Erm(B) typically confers high level resistance to macrolides, lincosamides and streptogramin B (MLSB phenotype), whereas Mef(A) confers low level resistance to macrolides only (M phenotype).
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Estrogens and Hyperglycemic Modulation of mRNAs Expressions Involved in Bone Metabolism: An Overshadowed Association?
Connect. Tissue Res.
PUBLISHED: 02-07-2013
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Human bone cell line (SaOS2) express different mRNAs involved in bone biology and physiology such as estrogen receptor ? (ER?), estrogen receptor ? (ER?), vitamin D receptor (VDR), 1?, 25 hydroxy vitamin D(3) hydroxylase (1OHase) as well as 12 and 15 lipoxygenases (12LO and 15LO). These mRNAs are modulated by estrogenic compounds. Since the skeletal protective effects of estrogens are not discernible in diabetic women, we tested whether the expression of the parameters measured here, and their modulations by estrogens, in SaOS2 cells grown in growth medium containing high glucose (HG; 9.0g/L; 44mM) compared to normal glucose (NG; 4.5g/L; 22mM). HG significantly increased DNA synthesis (DNA) and creatine kinase specific activity (CK) in SaOS2 cells. Stimulations of DNA but not of CK by E(2), by 4, 4, 4"-[4-propyl-(1H)-pyrazol-1, 3, 5- triyl] tris-phenol (PPT; ER? specific agonist), or by 2, 3-bis (4-hydroxyphenyl)-propionitrile (DPN; ER? specific agonist), were abolished by HG. HG Itself up regulated the expression of mRNA of 12LO and 15LO and up regulated to much less extent ER? and VDR, but had no effect on the expression of mRNA of ER? and 1OHase. The different hormonal treatments modulated the expressions of 12LO and 15LO mRNAs which was reduced in HG, whereas the induction of their products 12 and 15HETE was only slightly affected by HG. The exact mechanism of HG effects on bone cell responses is yet to be investigated and its relationship to human bone physiology is not yet clear.
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[Prognosis of acute pancreatitis by PANC 3 score].
Arq Bras Cir Dig
PUBLISHED: 02-05-2013
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Acute pancreatitis is a disease of great importance in clinical practice, defined as an inflammatory process of the pancreas that may involve local tissues or affect other organs in a systemic manner, requiring, in such cases, an intensive care.
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Lymphomatoid papulosis with associated cerebellar lesion of similar histology and T-cell clonality.
Australas. J. Dermatol.
PUBLISHED: 01-19-2013
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A 9-year old boy presented with a 4-month history of a truncal monomorphic eruption with self-healing papulonecrotic lesions. A skin biopsy revealed a dermal infiltrate of CD4, CD8 and CD30-positive T-cells, consistent with lymphomatoid papulosis. He responded to 4 months of treatment with narrowband UVB phototherapy (311?nm) which stabilised his disease. Five years later he presented with an acute onset of nausea and vomiting, dizziness, headache and ataxia. Magnetic resonance imaging of the brain revealed a lesion in the cerebellum and stereotactic resection was undertaken. Histology showed CD4, CD8 and CD30-positive T-cells similar to his skin lesions, with a monoclonal T-cell receptor (TCR) gamma gene rearrangement. Subsequent analysis of the skin detected a monoclonal band of the same size as the cerebellar lesion. Treatment was initiated for a primary central nervous system (CNS) lymphoma but ceased after one course of high-dose methotrexate. Opinion on the pathology was divided as to whether the cerebellar lesion represented an atypical reactive T-cell lymphoproliferative response or a T-cell lymphoma. On follow-up 2 years later, the patient remains clinically and radiologically clear, making CNS lymphoma unlikely.
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Proliferative nodules of undifferentiated spindle cells arising in a large congenital melanocytic naevus.
Australas. J. Dermatol.
PUBLISHED: 01-18-2013
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Proliferative nodules (PN) are benign lesions that arise in large congenital melanocytic naevi (LCMN). Clinically and histologically they can be difficult to differentiate from malignancies, which are also associated with LCMN. The PN in this case consisted of undifferentiated spindle cells and exhibited unusual histological features including negative stains for melanocytic markers (S100, HMB45 and MelA), negative stain for c-Kit, high mitotic index and unusual morphology of the lesional cells. As a result, a firm histological classification could not be made, which posed a challenge for the clinical management.
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Maternal parenting behaviors and adolescent depression: the mediating role of rumination.
J Clin Child Adolesc Psychol
PUBLISHED: 01-16-2013
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Substantial evidence suggests that rumination is an important vulnerability factor for adolescent depression. Despite this, few studies have examined environmental risk factors that might lead to rumination and, subsequently, depression in adolescence. This study examined the hypothesis that an adverse family environment is a risk factor for rumination, such that the tendency to ruminate mediates the longitudinal association between a negative family environment and adolescent depressive symptoms. It also investigated adolescent gender as a moderator of the relationship between family environment and adolescent rumination. Participants were 163 mother-adolescent dyads. Adolescents provided self-reports of depressive symptoms and rumination across three waves of data collection (approximately at ages 12, 15, and 17 years). Family environment was measured via observational assessment of the frequency of positive and aggressive parenting behaviors during laboratory-based interactions completed by mother-adolescent dyads, collected during the first wave. A bootstrap analysis revealed a significant indirect effect of low levels of positive maternal behavior on adolescent depressive symptoms via adolescent rumination, suggesting that rumination might mediate the relationship between low levels of positive maternal behavior and depressive symptoms for girls. This study highlights the importance of positive parenting behaviors as a possible protective factor against the development of adolescent rumination and, subsequently, depressive symptoms. One effective preventive approach to improving adolescent mental health may be providing parents with psychoeducation concerning the importance of pleasant and affirming interactions with their children.
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Rivaroxaban, a direct inhibitor of the coagulation factor Xa interferes with hormonal-induced physiological modulations in human female osteoblastic cell line SaSO2.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 01-06-2013
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The use of anticoagulants has been associated with systemic osteoporosis and increased risk for poor fracture healing but is inevitable following major orthopedic surgery of lower limbs. Rivaroxaban A (R) is an anticoagulant recently introduced in the clinical setting, which is a specific factor Xa inhibitor. We reported previously that R significantly inhibited cell growth, energy metabolism and alkaline phosphatase activity in human osteoblastic cell line SaOS2, with no effect on mineralization, indicating transient inhibition of bone formation. We now investigated the effects of R on SaOS2 response to osteoblast-modulating hormones. At sub-confluence cells were treated with: estradiol-17? (E2), the phytoestrogens daidzein (D) and biochainin A (BA), the carboxy-pytoestrogenic derivative carboxy-D (cD), the estrogen receptor ? (ER?) agonist PPT, the estrogen receptor ? (ER?) agonist DPN, parathyroid hormone (PTH) and several vitamin D metabolites and analogs with/without R for 24h. All hormones tested stimulated significantly DNA synthesis (DNA), creatine kinase (CK) and alkaline phosphatase (ALP) specific activities, but all these stimulations were totally inhibited when given together with R. R had no effect on mRNA expression of ER?, ER? and 25 Hydroxy-vitamin D3-1? hydroxylase (1OHase), but inhibited hormonal modulations of mRNA expressions. In conclusion R inhibited significantly hormonal stimulation of different parameters indicating inhibition of not only the early stages of bone formation, but also the stimulatory effects of bone modulating hormones with a yet unclear mechanism. The relevance of these findings to human bone physiology is yet to be investigated.
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PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.
PLoS ONE
PUBLISHED: 01-01-2013
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While the conversion of PrP(C) into PrP(Sc) in the transmissible form of prion disease requires a preexisting PrP(Sc) seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST)), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST) as in TgMHu2ME199K mice, and "classical" PrP(Sc) as in infectious prion diseases, coincide in the patients post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.
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Purulent pericarditis in children: is pericardiotomy needed?
Pediatr Emerg Care
PUBLISHED: 12-14-2011
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This study aimed to describe our experience with pediatric bacterial pericarditis and review the optimal therapy for this entity.
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A prospective study of infantile hemangiomas with a focus on incidence and risk factors.
Pediatr Dermatol
PUBLISHED: 10-13-2011
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Infantile hemangiomas (IHs) are the most common tumor of infancy and have been estimated to occur in 4% of infants. Only two previous incidence studies of IH in a healthy population have been published, and both of these were performed in the first week of life. The objective was to identify the incidence of IH in an Australian neonatal population and characterize the risk factors. All women who presented to the postnatal ward in a 200-bed maternity hospital were asked to complete a questionnaire. Details of maternal history and birth details were recorded. Two follow-up emails 3 and 6 weeks after discharge were sent to all mothers who consented, asking if their baby had developed an IH. Babies reported to have an IH were seen in clinic to confirm the diagnosis. Details were collected from 1,034 mothers of 1,065 babies; 28 (2.6%) of the infants developed IH. Babies that developed IH were more likely to be female (p < 0.001), have a low birth weight (p = 0.020), be born at a gestational age of <37 weeks (p = 0.005), and be conceived through in vitro fertilization (IVF) (p = 0.001) than those who did not. The incidence of IH at 6 weeks of life was 2.6%.
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Forehead pressure necrosis in neonates following continuous positive airway pressure.
Pediatr Dermatol
PUBLISHED: 10-13-2011
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After treatment with continuous positive airway pressure (CPAP) via nasal masks and a face mask, three neonates developed pressure necrosis involving their central forehead and left eyebrow. The pressure necrosis resulted in permanent scarring in all three infants. We describe a case series of a new cutaneous iatrogenic complication of CPAP.
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Copper is toxic to PrP-ablated mice and exacerbates disease in a mouse model of E200K genetic prion disease.
Neurobiol. Dis.
PUBLISHED: 09-30-2011
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The pathogenesis of the diverse forms of prion disease was attributed solely to the accumulation of the misfolded PrP forms, and not to the potential loss of normal PrP(C) function during disease propagation. In this respect, it was also not established whether mutant PrPs linked to genetic prion diseases, as is the case for E200K PrP, preserve the function of PrP(C). We now show that fibroblasts generated from both PrP-ablated mice and TgMHu2ME199K, a transgenic mouse line mimicking E200KCJD, were significantly more sensitive to copper toxicity than wt fibroblasts. Long-term administration of copper significantly accelerated the onset and progression of spontaneous prion disease in TgMHu2ME199K mice and caused marked irritability and cerebellar associated tip-toe walking in PrP(0/0) mice, while wt mice were not affected. Our results are consistent with the hypothesis that a functional PrP(C) is required to protect cells from high levels of copper, and that its substitution for a nonfunctional mutant PrP may accelerate the onset of genetic prion disease during oxidative insults.
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The anti-inflammatory drug carprofen improves long-term outcome and induces gliogenesis after traumatic brain injury.
J. Neurotrauma
PUBLISHED: 08-29-2011
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Traumatic brain injury (TBI) initiates acute and chronic inflammatory processes involving cyclooxygenase-2 (COX-2), which may have detrimental effects on outcome and especially on brain regeneration. Therefore we aimed to study whether carprofen, a COX-2 inhibitor, would improve outcome and increase neurogenesis after TBI. TBI was induced in Sabra mice that were then treated with vehicle or carprofen for 7 days. Functional outcome was evaluated with the Neurological Severity Score (NSS).Cytokine levels were assessed 4?h post-TBI and water content was measured 24?h post TBI. Mice were given BrdU to label newborn cells for 10 days. The animals were killed 90 days post-TBI and the lesion size as well as newborn cell fate were assessed. Carprofen significantly reduced lesion size (p=0.002), decreased water content in the lesioned cortex (p=0.03), reduced the number of microglia in the lesioned cortex (p<0.0001), and lowered the levels of proinflammatory cytokines (IL-1?, p=0.03; IL-6, p=0.02). Carprofen led to significantly larger improvements in functional outcome (p?0.008) which were durable over 90 days. Carprofen also induced a threefold increase in the proliferation of new cells in the peri-lesion area (p?0.002), but newborn cells differentiated mainly into glia in both groups. Carprofen is neuroprotective and induces cell proliferation and gliogenesis after TBI. Treatment with carprofen is consistently associated with better functional outcome. Our results imply that anti-inflammatory drugs may represent novel therapeutic options for TBI.
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Childhood wheeze while taking propranolol for treatment of infantile hemangiomas.
Pediatr. Pulmonol.
PUBLISHED: 08-23-2011
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While it is recognized that beta-blockers can exacerbate asthma symptoms in older children and adults, there are few descriptions of a similar effect in infants. We describe three infants who developed wheeze during treatment with a beta-blocker for infantile hemangiomas and conclude that physicians should inquire about respiratory symptoms in this group of children.
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Juvenile xanthogranuloma: challenges in complicated cases.
Australas. J. Dermatol.
PUBLISHED: 07-28-2011
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Juvenile xanthogranuloma (JXG) is one of the most common forms of non-Langerhans cell histiocytosis in children. Although it usually presents as a self-limited skin lesion with typical histopathology, JXG can be challenging to diagnose due to an atypical initial presentation with corresponding variable histopathology for different stages of development. We present challenging cases of JXG from Sydney Childrens Hospital, collected over 10 years - two with multisystem involvement and concomitant urticaria, one associated with neurofibromatosis, and one case of giant JXG with an initial histopathological challenge. Although JXG has been reported with urticaria pigmentosa, in two of our cases persistent urticaria, in association with JXG is discussed.
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A randomized controlled trial of propranolol for infantile hemangiomas.
Pediatrics
PUBLISHED: 07-25-2011
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Propranolol hydrochloride is a safe and effective medication for treating infantile hemangiomas (IHs), with decreases in IH volume, color, and elevation.
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Priming of spatial distance enhances childrens creative performance.
J Exp Child Psychol
PUBLISHED: 07-03-2011
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According to construal level theory, psychological distance promotes more abstract thought. Theories of creativity, in turn, suggest that abstract thought promotes creativity. Based on these lines of theorizing, we predicted that spatial distancing would enhance creative performance in elementary school children. To test this prediction, we primed spatial distance by presenting 6- to 9-year-olds with pictures of increasingly distal objects (from their own desk to the galaxy) or increasingly proximal objects (from the galaxy to their own desk) and then assessed the fluency and originality of their ideas in a creativity test. We found, consistent with the hypothesis, that after priming of spatial distance, compared with priming of spatial proximity, children were more creative, as reflected in higher scores of both fluency and originality. This result was not qualified by childrens age or gender.
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Pay-for-performance incentives for preventive care: views of family physicians before and after participation in a reminder and recall project (P-PROMPT).
Can Fam Physician
PUBLISHED: 06-16-2011
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The Provider and Patient Reminders in Ontario: Multi-Strategy Prevention Tools (P-PROMPT) project was designed to increase the rates of delivery of 4 targeted preventive care services to eligible patients in primary care network and family health network practices eligible for pay-for-performance incentives.
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Lymphatic malformations: clinical course and management in 64 cases.
Australas. J. Dermatol.
PUBLISHED: 06-09-2011
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Lymphatic malformations (LM) are rare vascular malformations.
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Delayed motor skill acquisition in kindergarten children with language impairment.
Res Dev Disabil
PUBLISHED: 04-12-2011
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The acquisition and consolidation of a new grapho-motor symbol into long-term memory was studied in 5-year-old children with language impairment (LI) and peers matched for age and visual-motor integration skills. The children practiced the production of a new symbol and were tested 24h and two weeks post-practice day. Differences in performance speed emerged between the groups: children with LI showed a later onset of rapid learning in the practice phase, and only the comparison group exhibited delayed, consolidation, gains 24h post-training. At two weeks post-training, children with LI improved, closing the gap in performance speed. Speed-accuracy trade-off was characteristic of speed improvements in LI. These results indicate atypical and delayed acquisition in children with LI, and support the view that deficient skill acquisition in LI goes beyond the language system.
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An Australian tuberous sclerosis cohort: are surveillance guidelines being met?
J Paediatr Child Health
PUBLISHED: 03-30-2011
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This study aims to describe the phenotypic and genotypic characteristics of 45 Australian patients with tuberous sclerosis complex (TSC), to assess risk factors for intellectual disability, to compare patients with TSC1 and TSC2 mutations and to assess adherence to surveillance recommendations.
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Sex specific response of cultured human bone cells to ER? and ER? specific agonists by modulation of cell proliferation and creatine kinase specific activity.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 03-02-2011
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We have previously reported that human cultured bone cells (hObs) respond to estradiol-17? (E2) by stimulating DNA synthesis, creatine kinase BB specific activity (CK) and other parameters sex-specifically. We now investigate the sex specificity of the response of these hObs to estrogen receptor (ER) ? and ER? specific agonists. Real time PCR revealed that all cells express mRNA for both ERs. ER? mRNA but not ER? mRNA was stimulated by all estrogenic compounds in both pre- and post-menopausal hObs with no effect in male hObs. Cells treated with E2, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; ER? specific agonist) and 4,4,4?-[4-propyl-(1H)-pyrazol-1,3,5-triyl] tris-phenol (PPT; ER? specific agonist) showed increased DNA synthesis and CK in all female but not male hObs. Raloxifene (Ral), a specific ER? antagonist, inhibited the stimulation of DNA synthesis and CK by E2 or PPT, but not by DPN. DPN and PPT like E2 modulated the expression of both 12 and 15 lipooxygenase (LO) mRNA in both female but not male hObs. 12 and 15 HETE production was modulated only by DPN and PPT in these cells. The LO inhibitor baicaleine inhibited only E2 and PPT but not DPN effects in both female hObs. In conclusion, we provide herein evidence for the separation of age- and sex-dependent mediation via both ER? and ER? pathways in the effects of estrogens on hObs, with a yet unknown mechanism.
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Observed maternal responses to adolescent behaviour predict the onset of major depression.
Behav Res Ther
PUBLISHED: 02-22-2011
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Two mechanisms have been proposed regarding relations between parental responses to adolescent affective behaviours and the development of depression: the elicitation of parental negativity and the suppression of parental aggression. This study aimed to investigate the boundary conditions under which these two mechanisms operate in relation to the prospective prediction of Major Depressive Disorder (MDD) onset in adolescence. A community sample of 159 adolescents (aged 11-13 years) with no history of MDD completed a family interaction assessment with their mothers, and were followed-up with a diagnostic interview 2-3 years later. Results showed that onset of MDD was prospectively predicted by the elicitation of maternal aggression in response to adolescent aggression (in girls only) and maternal dysphoria in response to adolescent aggression, as well as the suppression of maternal aggression and dysphoria in response to adolescent dysphoria. Thus, support was obtained for both the elicitation of negativity mechanism in relation to maternal responses to adolescents aggressive behaviours, and the suppression of aggression mechanisms in relation to maternal responses to adolescents dysphoric behaviours. Mothers responses to adolescents aggressive and dysphoric behaviours may differentially influence the risk of MDD onset for adolescents over time.
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BK-virus-associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 02-18-2011
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BK-virus-induced hemorrhagic cystitis (BK-HC) is a serious complication in children undergoing hematopoietic stem cell transplantation (HSCT). Data of BK-HC in children undergoing HSCT are still limited.
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Putative cholinergic interneurons in the ventral and dorsal regions of the striatum have distinct roles in a two choice alternative association task.
Front Syst Neurosci
PUBLISHED: 01-31-2011
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The striatum consists of GABAergic projection neurons and various types of interneurons. Despite their relative scarcity, these interneurons play a key role in information processing in the striatum. One such class of interneurons is the cholinergic tonically active neurons (TANs). In the dorsal striatum, TANs are traditionally considered to be responsive to events of motivational significance. However, in recent years, studies have suggested that TANs are not exclusively related to reward and reward-predicting stimuli, but may contribute to other processes, including responses to aversive stimuli, detecting the spatial location of stimuli and generating movement. Currently there is little data concerning TAN activity in the ventral striatum (VS) of behaving animals. Here, we simultaneously recorded neurons in the ventral and the dorsolateral (DLS) regions of the striatum while animals performed a two choice alternative association task. Our data show that a large percentage of the putative TANs in both regions responded around movement initiation and execution. The majority of these neurons exhibited directional selectivity which was stronger in DLS relative to VS. In addition, the preferred directions in VS were mostly contralateral to the recording site whereas the observed preferred directions in DLS were equally distributed contralaterally and ipsilaterally to the recording site. The most interesting difference between DLS and VS was that DLS TANs maintained activity alterations throughout the movement whereas TANs in VS exhibited short-lasting phasic activity alterations that were maintained throughout the movement by different neurons. Our findings suggest that coding of movement by TANs in both regions overlaps to some degree, yet the differences in response patterns support the notion that the TANs in DLS participate in the motor loop whereas TANs in VS convey event-related information such as movement initiation, movement direction, and end of movement.
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Three cases of osteoma cutis occurring in infancy. A brief overview of osteoma cutis and its association with pseudo-pseudohypoparathyroidism.
Australas. J. Dermatol.
PUBLISHED: 01-12-2011
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We report three cases of primary osteoma cutis in children, two of whom (siblings) were associated with Albrights hereditary osteodystrophy (AHO), manifesting as short stature with autosomal dominant inheritance from the father, but no dysmorphic features and no parathyroid hormone (PTH) resistance. Osteoma cutis can manifest as an isolated skin disease, a secondary condition to other skin diseases (such as acne), or in association with several syndromes, including AHO, which in turn may be associated with PTH resistance. The management and prognosis of patients diagnosed with osteoma cutis is determined by whether the skin manifestation has occurred in isolation, in association with a syndrome, or as a secondary skin disease. These three paediatric cases highlight the importance of understanding the aetiology and associations of osteoma cutis in order to appropriately investigate and manage patients who present with this rare skin disease.
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A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS). II. Studies in mice and ferrets and mechanism of adjuvanticity.
Vaccine
PUBLISHED: 01-09-2011
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We recently showed that lipid assemblies comprised of a novel polycationic sphingolipid (ceramide carbamoyl-spermine, CCS) are an effective adjuvant/carrier when complexed with cholesterol (CCS/C) for influenza and other vaccines administered parenterally and intranasally (i.n.) in mice. Here we expand these studies to ferrets, an established model of influenza infection. We also address the question of why the CCS/C-based liposomal vaccine (also known as VaxiSome™) in mice is superior to vaccines based on liposomes of other lipid compositions (neutral, anionic or cationic). Ferrets immunized i.n. with CCS/C-influenza vaccine produced significantly higher hemagglutination inhibition (HI) antibody titers compared to ferrets immunized intramuscularly with the unadjuvanted influenza vaccine, indicating that the CCS/C-based vaccine is very immunogenic. Furthermore, the i.n. adjuvanted vaccine was shown to significantly reduce the severity of influenza virus infection in ferrets following homologous viral challenge as determined by weight loss, temperature rise and viral titer. No adverse reactions were observed. Pharmacokinetic and biodistribution studies following i.n. administration in mice of CCS/C-based vaccine showed that both the lipids and antigens are retained in the nose and lung for at least 24h, and it appears that this retention correlates with the superior immunogenicity elicited by the adjuvanted vaccine formulation. The CCS lipid also increases production of cytokines (mainly IFN gamma, IL-2 and IL-12) and co-stimulatory molecules expression, which might further explain the robust adjuvantation of this liposome-based vaccine.
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Propranolol: useful therapeutic agent for the treatment of ulcerated infantile hemangiomas.
J. Pediatr. Surg.
PUBLISHED: 01-07-2011
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Infantile hemangioma (IH) is the most common vascular tumor in early childhood. Ulceration is the most frequent complication, and its management can be challenging. We present 6 cases of ulcerated IH at a single pediatric center, which responded to oral propranolol within 2 to 6 weeks. We recommend that oral propranolol therapy be considered for the management of ulcerated IH as first-line treatment.
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Hospitalization of children with influenza A(H1N1) virus in Israel during the 2009 outbreak in Israel: a multicenter survey.
Arch Pediatr Adolesc Med
PUBLISHED: 11-03-2010
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To describe the clinical characteristics of children hospitalized with 2009 influenza A(H1N1) infection in Israel and the risk factors associated with this infection.
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Aging and sexuality: how much do gynecologists know and care?
J Women Aging
PUBLISHED: 10-23-2010
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Enhanced knowledge and healthy attitudes toward aging sexuality can help promote the perception that full sexual expression is part of the entire extent of adulthood. We sought to determine gynecologists knowledge and attitude regarding sexuality in older women. A total of 141 gynecologists in five hospitals responded to the survey: Aging Sexual Attitude and Knowledge Scale (ASKAS). No correlation was found between respondents knowledge and attitude (r = .06, p = .54); no correlation found between respondents age and knowledge (r = .20, p = .02), but 20% of the variance in attitude could be explained by age (beta 0.20, p = .02). Neither gender, ethnicity, level of training, nor hospital location demonstrated a significant correlation to either knowledge or attitude scores.
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Short communication: Transmitted drug resistance and molecular epidemiology in antiretroviral naive HIV type 1-infected patients in Rhode Island.
AIDS Res. Hum. Retroviruses
PUBLISHED: 10-18-2010
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Transmission of HIV-1 drug resistance has important clinical and epidemiological consequences including earlier treatment failure and forward transmission of resistance strains in high-risk groups. To evaluate the prevalence and molecular epidemiology of transmitted drug resistance in Rhode Island, we collected genotypic, demographic, clinical, and laboratory data from treatment-naive individuals presenting to the largest outpatient HIV clinic in the state from January 2007 to November 2007. Sequences from 35 treatment-naive individuals were available, 83% of whom were men who had sex with men (MSM). All sequences were HIV-1 subtype B. Drug resistance mutations were identified in 7/35 [20%; 95% confidence interval (CI), 0.08-0.37] patients, six of whom had K103N. Two phylogenetic transmission clusters were found, involving 17% (6/35) of individuals, three in each cluster. We did not find an association between belonging to a cluster and age, gender, AIDS-defining illness, CD4 cell count, or viral load. Drug resistance mutations were more commonly observed in transmission clusters (p?=?0.08). Individuals in one cluster all had K103N and were MSM who had attended local bathhouses. Individuals forming clusters were significantly more likely to have visited a bathhouse compared to nonclusters (p?=?0.02). The prevalence of transmitted drug resistance in Rhode Island is high, further justifying genotypic testing on presentation to care and prior to treatment initiation. Molecular epidemiological analysis and association of resistance with phylogenetic networks using data obtained for clinical purposes may serve as useful tools for the prevention of drug resistance transmission and for contact tracing.
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How calmodulin binding transcription activators (CAMTAs) mediate auxin responses.
Plant Signal Behav
PUBLISHED: 10-01-2010
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Phenotypic plasticity is an adaptive feature of all organisms, which, in land plants, entails changes in orientation of growth (tropism), patterns of development, organ architecture, timing of developmental processes, and resource allocation. However, little is known about the molecular components that integrate exogenous environmental cues with internal hormonal signaling pathways. This addendum describes a role for calcium-regulated calmodulin-binding transcription 1 (CAMTA1) in auxin signaling and stress responses. We discuss possible mechanisms that may underlie this role of CAMTA1, and speculate on the more general roles of CAMTAs in auxin responses and phenotypic plasticity.
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Metalloprotease type III effectors that specifically cleave JNK and NF-?B.
EMBO J.
PUBLISHED: 06-29-2010
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Two major arms of the inflammatory response are the NF-?B and c-Jun N-terminal kinase (JNK) pathways. Here, we show that enteropathogenic Escherichia coli (EPEC) employs the type III secretion system to target these two signalling arms by injecting host cells with two effector proteins, NleC and NleD. We provide evidence that NleC and NleD are Zn-dependent endopeptidases that specifically clip and inactivate RelA (p65) and JNK, respectively, thus blocking NF-?B and AP-1 activation. We show that NleC and NleD co-operate and complement other EPEC effectors in accomplishing maximal inhibition of IL-8 secretion. This is a remarkable example of a pathogen using multiple effectors to manipulate systematically the host inflammatory response signalling network.
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The EPPIC follow-up study of first-episode psychosis: longer-term clinical and functional outcome 7 years after index admission.
J Clin Psychiatry
PUBLISHED: 06-25-2010
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To describe the longer-term clinical and functional outcome of a large, epidemiologic representative cohort of individuals experiencing a first episode of psychosis.
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Jun proteins inhibit autophagy and induce cell death.
Autophagy
PUBLISHED: 05-16-2010
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Starvation induces a vigorous autophagic response to enhance cellular survival, whereas nutrient and serum supplementation inhibit autophagy and induce an intensive transcriptional burst that enables cellular proliferation. We recently found that some of the genes induced by serum and growth factors--the immediate early proteins JunB and c-Jun--inhibit autophagy. Deregulation of JunB expression when autophagy is specifically required, tilts the fate of starved cells to apoptosis.
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Immunogenicity, protective efficacy and mechanism of novel CCS adjuvanted influenza vaccine.
Vaccine
PUBLISHED: 03-27-2010
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We optimized the immunogenicity of adjuvanted seasonal influenza vaccine based on commercial split influenza virus as an antigen (hemagglutinin = HA) and on a novel polycationic liposome as a potent adjuvant and efficient antigen carrier (CCS/C-HA vaccine). The vaccine was characterized physicochemically, and the mechanism of action of CCS/C as antigen carrier and adjuvant was studied. The optimized CCS/C-HA split virus vaccine, when administered intramuscularly (i.m.), is significantly more immunogenic in mice, rats and ferrets than split virus HA vaccine alone, and it provides for protective immunity in ferrets and mice against live virus challenge that exceeds the degree of efficacy of the split virus vaccine. Similar adjuvant effects of optimized CCS/C are also observed in mice for H1N1 swine influenza antigen. The CCS/C-HA vaccine enhances immune responses via the Th1 and Th2 pathways, and it increases both the humoral responses and the production of IL-2 and IFN-? but not of the pro-inflammatory factor TNF?. In mice, levels of CD4(+) and CD8(+) T-cells and of MHC II and CD40 co-stimulatory molecules are also elevated. Structure-function relationship studies of the CCS molecule as an adjuvant/carrier show that replacing the saturated palmitoyl acyl chain with the mono-unsaturated oleoyl (C18:1) chain affects neither size distribution and zeta potential nor immune responses in mice. However, replacing the polyalkylamine head group spermine (having two secondary amines) with spermidine (having only one secondary amine) reduces the enhancement of the immune response by ? 50%, while polyalkylamines by themselves are ineffective in improving the immunogenicity over the commercial HA vaccine. This highlights the importance of the particulate nature of the carrier and the polyalkylamine secondary amines in the enhancement of the immune responses against seasonal influenza. Altogether, our results suggest that the CCS/C polycationic liposomes combine the activities of a potent adjuvant and efficient carrier of seasonal and swine flu vaccines and support further development of the CCS/C-HA vaccine.
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Down syndrome and respiratory syncytial virus infection.
Pediatr. Infect. Dis. J.
PUBLISHED: 03-16-2010
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We reviewed the medical records of all children with Down syndrome (DS), hospitalized in our medical center due to infection with respiratory syncytial virus. During the 9-year study period, there were 41 hospitalizations of 39 children with DS. Mean age was 1.3 years; mean duration of hospitalization was 10.9 days. Patients with DS were older than healthy controls with respiratory syncytial virus infection and needed longer hospitalization.
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Calmodulin-binding transcription activator 1 mediates auxin signaling and responds to stresses in Arabidopsis.
Planta
PUBLISHED: 03-15-2010
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Auxin is a key plant hormone that regulates various aspects of plant development. However, the mechanisms integrating auxin growth effects with stress responses are not fully understood. In this study, we investigated the possible role of calmodulin-binding transcription activator 1 (CAMTA1), an Arabidopsis thaliana calcium/calmodulin-binding transcription activator, in auxin signaling and its responses to different stresses. Plants harboring the AtCAMTA1 promoter fused to the GUS reporter gene revealed cell-specific expression patterns reminiscent of auxin responses. The responsiveness of CAMTA1 to auxin was further assessed by chemical disturbances in polar auxin transport, and by RT-PCR analysis of gene expression of dissected leaf sections from plants exposed to the auxin transport inhibitor NPA. Furthermore, the intensity and cell-specific expression patterns of CAMTA1 changed significantly and differentially on exposure to increasing salt concentrations and heat. Transcriptome analysis of a camta1 T-DNA insertion mutant revealed 63 up-regulated genes, of which 17 are associated with auxin signaling. Finally, analysis of hypocotyl elongation in the presence and absence of auxin revealed that camta1 T-DNA insertion mutants and CAMTA1-repressor lines are hyper-responsive to auxin compared to wild-type seedlings. Thus, CAMTA1 participates in auxin signaling and responds to abiotic stresses.
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Jun proteins are starvation-regulated inhibitors of autophagy.
Cancer Res.
PUBLISHED: 03-02-2010
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The growing number of biological functions affected by autophagy ascribes a special significance to identification of factors regulating it. The activator protein-1 (AP-1) transcription factors are involved in most aspects of cellular proliferation, death, or survival, yet no information regarding their involvement in autophagy is available. Here, we show that the AP-1 proteins JunB and c-Jun, but not JunD, c-Fos, or Fra-1, inhibit autophagy. JunB inhibits autophagy induced by starvation, overexpression of a short form of ARF (smARF), a potent inducer of autophagy, or even after rapamycin treatment. In agreement, acute repression of JunB expression, by JunB knockdown, potently induces autophagy. As expected from autophagy-inhibiting proteins, Jun B and c-Jun expression is reduced by starvation. Decrease in JunB mRNA expression and posttranscriptional events downregulate JunB protein expression after starvation. The inhibition of autophagy by JunB is not mediated by mammalian target of rapamycin (mTOR) regulation, as it occurs also in the absence of mTOR activity, and autophagy induced by JunB knockdown is not correlated with changes in mTOR activity. Nevertheless, the transcriptional activities of c-Jun and JunB are required for autophagy inhibition, and JunB incapable of heterodimerizing is a less effective inhibitor of autophagy. Most importantly, inhibition of autophagy in starved HeLa cells by JunB enhances apoptotic cell death. We suggest that JunB and c-Jun are regulators of autophagy whose expression responds to autophagy-inducing signals.
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Mycosis fungoides in the pediatric population: report from an international Childhood Registry of Cutaneous Lymphoma.
J Cutan Med Surg
PUBLISHED: 02-05-2010
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There are limited data on the clinical presentation and progression of pediatric cutaneous lymphoma. This study focuses on the clinical characteristics of pediatric patients with mycosis fungoides (MF).
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Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response.
PLoS Biol.
PUBLISHED: 02-03-2010
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In eukaryotes, fumarase (FH in human) is a well-known tricarboxylic-acid-cycle enzyme in the mitochondrial matrix. However, conserved from yeast to humans is a cytosolic isoenzyme of fumarase whose function in this compartment remains obscure. A few years ago, FH was surprisingly shown to underlie a tumor susceptibility syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). A biallelic inactivation of FH has been detected in almost all HLRCC tumors, and therefore FH was suggested to function as a tumor suppressor. Recently it was suggested that FH inhibition leads to elevated intracellular fumarate, which in turn acts as a competitive inhibitor of HPH (HIF prolyl hydroxylase), thereby causing stabilization of HIF (Hypoxia-inducible factor) by preventing proteasomal degradation. The transcription factor HIF increases the expression of angiogenesis regulated genes, such as VEGF, which can lead to high microvessel density and tumorigenesis. Yet this mechanism does not fully explain the large cytosolic population of fumarase molecules. We constructed a yeast strain in which fumarase is localized exclusively to mitochondria. This led to the discovery that the yeast cytosolic fumarase plays a key role in the protection of cells from DNA damage, particularly from DNA double-strand breaks. We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. This function of fumarase depends on its enzymatic activity, and its absence in cells can be complemented by high concentrations of fumaric acid. Our findings suggest that fumarase and fumaric acid are critical elements of the DNA damage response, which underlies the tumor suppressor role of fumarase in human cells and which is most probably HIF independent. This study shows an exciting crosstalk between primary metabolism and the DNA damage response, thereby providing a scenario for metabolic control of tumor propagation.
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Vascular endothelial growth factor increases neurogenesis after traumatic brain injury.
J. Cereb. Blood Flow Metab.
PUBLISHED: 01-13-2010
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Activation of endogenous stem cells has been proposed as a novel form of therapy in a variety of neurologic disorders including traumatic brain injury (TBI). Vascular endothelial growth factor (VEGF) is expressed in the brain after TBI and serves as a potent activator of angiogenesis and neurogenesis. In this study, we infused exogenous VEGF into the lateral ventricles of mice for 7 days after TBI using mini-osmotic pumps to evaluate the effects on recovery and functional outcome. The results of our study show that VEGF significantly increases the number of proliferating cells in the subventricular zone and in the perilesion cortex. Fate analysis showed that most newborn cells differentiated into astrocytes and oligodendroglia and only a few cells differentiated into neurons. Functional outcome was significantly better in mice treated with VEGF compared with vehicle-treated animals after TBI. Injury size was significantly smaller at 90 days after TBI in VEGF-treated animals, suggesting additional neuroprotective effects of VEGF. In conclusion, VEGF significantly augments neurogenesis and angiogenesis and reduces lesion volumes after TBI. These changes are associated with significant improvement in recovery rates and functional outcome.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.