bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived Shape Similarity among Unfamiliar Objects and the Organization of the Human Object Vision Pathway
Authors: Op de Beeck Hans P. , Torfs Katrien , Wagemans Johan
Published: October 2008

Humans rely heavily on shape similarity among objects for object categorization and identification. Studies using functional magnetic resonance imaging (fMRI) have shown that a large region in human occipitotemporal cortex processes the shape of meaningful as well as unfamiliar objects. Here, we investigate whether the functional organization of this region as measured with fMRI is related to perceived shape similarity. We found that unfamiliar object classes that are rated as having a similar shape were associated with a very similar response pattern distributed across object-selective cortex, whereas object classes that were rated as being very different in shape were associated with a more different response pattern. Human observers, as well as object-selective cortex, were very sensitive to differences in shape features of the objects such as straight versus curved versus “spiky” edges, more so than to differences in overall shape envelope. Response patterns in retinotopic areas V1, V2, and V4 were not found to be related to perceived shape. The functional organization in area V3 was partially related to perceived shape but without a stronger sensitivity for shape features relative to overall shape envelope. Thus, for unfamiliar objects, the organization of human object-selective cortex is strongly related to perceived shape, and this shape-based organization emerges gradually throughout the object vision pathway.
Perceptual Systems Controlling Speech Production
Authors: Dhanjal Novraj S. , Handunnetthi Lahiru , Patel Maneesh C. , Wise Richard J. S.
Published: October 2008

It is proposed that the acquisition and maintenance of fluent speech depend on the rapid temporal integration of motor feedforward and polysensory (auditory and somatosensory) feedback signals. In a functional magnetic resonance imaging study on 21 healthy right-handed, English-speaking volunteers, we investigated activity within these motor and sensory pathways and their integration during speech. Four motor conditions were studied: two speech conditions (propositional and nonpropositional speech) and two silent conditions requiring repetitive movement of the principal articulators (jaw and tongue movements). The scanning technique was adapted to minimize artifact associated with overt speech production. Our result indicates that this multimodal convergence occurs within the left and right supratemporal planes (STPs), with peaks of activity at their posteromedial extents, in regions classically considered as unimodal auditory association cortex. This cortical specialization contrasted sharply with the response of somatosensory association cortex (SII), in which activity was suppressed during speech but not during the silent repetitive movement of the principal articulators. It was also clearly distinct from the response of lateral auditory association cortex, which responded to auditory feedback alone, and from that within a left lateralized ventrolateral temporal and inferior frontal system, which served lexical- and sentence-level language retrieval. This response of cortical regions related to speech production is not predicted by the classical model of hierarchical cortical processing, providing new insights into the role of the STP in polysensory integration and into the modulation of activity in SII during normal speech production. These findings have novel implications for the acquisition and maintenance of fluent speech.
Zebrafish TRPA1 Channels Are Required for Chemosensation But Not for Thermosensation or Mechanosensory Hair Cell Function
Authors: Prober David A. , Zimmerman Steven , Myers Benjamin R. , McDermott Brian M. , Kim Seok-Hyung , Caron Sophie , Rihel Jason , Solnica-Krezel Lilianna , Julius David , Hudspeth A. J. , Schier Alexander F.
Published: October 2008

Transient receptor potential (TRP) ion channels have been implicated in detecting chemical, thermal, and mechanical stimuli in organisms ranging from mammals toCaenorhabditis elegans. It is well established that TRPA1 detects and mediates behavioral responses to chemical irritants. However, the role of TRPA1 in detecting thermal and mechanical stimuli is controversial. To further clarify the functions of TRPA1 channels in vertebrates, we analyzed their roles in zebrafish. The two zebrafish TRPA1 paralogs are expressed in sensory neurons and are activated by several chemical irritantsin vitro. High-throughput behavioral analyses oftrpa1aandtrpa1bmutant larvae indicate that TRPA1b is necessary for behavioral responses to these chemical irritants. However, TRPA1 paralogs are not required for behavioral responses to temperature changes or for mechanosensory hair cell function in the inner ear or lateral line. These results support a role for zebrafish TRPA1 in chemical but not thermal or mechanical sensing, and establish a high-throughput system to identify genes and small molecules that modulate chemosensation, thermosensation, and mechanosensation.
DrosophilaPainless Is a Ca2+-Requiring Channel Activated by Noxious Heat
Authors: Sokabe Takaaki , Tsujiuchi Seiya , Kadowaki Tatsuhiko , Tominaga Makoto
Published: October 2008

Thermal changes activate some members of the transient receptor potential (TRP) ion channel super family. They are primary sensors for detecting environmental temperatures. TheDrosophilaTRP channel Painless is believed responsible for avoidance of noxious heat becausepainlessmutant flies display defects in heat sensing. However, no studies have proven its heat responsiveness. We show that Painless expressed in human embryonic kidney-derived 293 (HEK293) cells is a noxious heat-activated, Ca2+-permeable channel, and the function is mostly dependent on Ca2+. In Ca2+-imaging, Painless mediated a robust intracellular Ca2+(Ca2+i) increase during heating, and it showed heat-evoked inward currents in whole-cell patch-clamp mode. Ca2+permeability was much higher than that of other cations. Heat-evoked currents were negligible in the absence of extracellular Ca2+(Ca2+o) and Ca2+i, whereas 200 nmCa2+ienabled heat activation of Painless. Activation kinetics were significantly accelerated in the presence of Ca2+i. The temperature threshold for Painless activation was 42.6°C in the presence of Ca2+i, whereas the threshold was significantly increased to 44.1°C when only Ca2+owas present. Temperature thresholds were further reduced after repetitive heating in a Ca2+-dependent manner. Ca2+-dependent heat activation of Painless was observed at the single-channel level in excised membranes. We found that a Ca2+-regulatory site is located in the N-terminal region of Painless. Painless-expressing HEK293 cells were insensitive to various thermosensitive TRP channel activators including allyl isothiocyanate, whereas mammalian TRPA1 inhibitors, ruthenium red, and camphor, reversibly blocked heat activation of Painless. Our results demonstrate that Painless is a direct sensor for noxious heat inDrosophila.
HIV-1 Clade-Specific Differences in the Induction of Neuropathogenesis
Authors: Rao Vasudev R. , Sas Andrew R. , Eugenin Eliseo A. , Siddappa Nagadenahalli B. , Bimonte-Nelson Heather , Berman Joan W. , Ranga Udaykumar , Tyor William R. , Prasad Vinayaka R.
Published: October 2008

Human immunodeficiency virus (HIV)-associated dementia (HAD) is common among clade B HIV-infected individuals, but less common and less severe among individuals infected with clade C HIV-1, suggesting clade-specific differences in neuropathogenicity. Although differences in neuropathogenicity have been investigatedin vitrousing viral proteins responsible for HAD, to date there are no virological studies using animal models to address this issue. Therefore, we investigated neuropathogenesis induced by HIV-1 clades using the severe combined immune deficiency (SCID) mouse HIV encephalitis model, which involves intracranial injection of macrophages infected with representative clade B (HIV-1ADA) or clade C (HIV-1Indie-C1) HIV-1 isolates into SCID mice. In cognitive tests, mice exposed to similar inputs of HIV-1 clade C made fewer memory errors than those exposed to HIV-1 clade B. Histopathological analysis of mice exposed to clade B exhibited greater astrogliosis and increased loss of neuronal network integrity.In vitroexperiments revealed differences in a key characteristic of HIV-1 that influences HAD, increased monocyte infiltration. HIV-1Indie-C1-infected macrophages recruited monocytes poorlyin vitrocompared with HIV-1ADA-infected macrophages. Monocyte recruitment was HIV-1 Tat and CCL2 dependent. This is the first demonstration, ever since HIV neuropathogenesis was first recognized, that viral genetic differences between clades can affect disease severity and that such studies help identify key players in neuropathogenesis by HIV-1.
Intrabulbar Projecting External Tufted Cells Mediate a Timing-Based Mechanism That Dynamically Gates Olfactory Bulb Output
Authors: Zhou Zhishang , Belluscio Leonardo
Published: October 2008

In the mammalian olfactory system, intrabulbar projections (IBPs) mediated by a class of external tufted cells (ET cells) specifically link isofunctional odor columns within the same olfactory bulb. To study the function of these ET cells within the glomerular network, we developed a “hemibulb” preparation that maintains IBPs intact enabling the select activation of ET cells associated with specific glomeruli. Using P2-GFP mice, a line in which the P2 glomeruli are labeled with green fluorescent protein, we recorded from P2 mitral cells (MT cells) while selectively stimulating P2 ET cells. Here, we show that ET-cell activity evokes a slow modulatory (SM) potential within MT cells, which is mediated by the glomerular network and consists of both excitatory and inhibitory components. Interestingly, the timing of the SM potential with respect to olfactory nerve (ON) stimulation can produce converse effects on MT-cell output. When ET-cell activity precedes ON stimulation, the MT-cell response is potentiated; however, when ET-cell activity follows ON stimulation, the MT-cell response is inhibited. Thus, intrabulbar projecting ET cells can shape olfactory bulb output through intraglomerular modulation of MT cells.
Dopaminergic and Glutamatergic Signaling Crosstalk in Huntington's Disease Neurodegeneration: The Role of p25/Cyclin-Dependent Kinase 5
Authors: Paoletti Paola , Vila Ingrid , Rifé Maria , Lizcano José Miguel , Alberch Jordi , Ginés Silvia
Published: October 2008

Altered glutamatergic and dopaminergic signaling has been proposed as contributing to the specific striatal cell death observed in Huntington's disease (HD). However, the precise mechanisms by which mutant huntingtin sensitize striatal cells to dopamine and glutamate inputs remain unclear. Here, we demonstrate in knock-in HD striatal cells that mutant huntingtin enhances dopamine-mediated striatal cell death via dopamine D1receptors. Moreover, we show that NMDA receptors specifically potentiate the vulnerability of mutant huntingtin striatal cells to dopamine toxicity as pretreatment with NMDA increased D1R-induced cell death in mutant but not wild-type cells. As potential underlying mechanism of increased striatal vulnerability, we identified aberrant cyclin-dependent kinase 5 (Cdk5) activation. We demonstrate that enhanced Cdk5 phosphorylation and increased calpain-mediated conversion of the Cdk5 activator p35 into p25 may account for the deregulation of Cdk5 associated to dopamine and glutamate receptor activation in knock-in HD striatal cells. Moreover, supporting a detrimental role of Cdk5 in striatal cell death, neuronal loss can be widely prevented by roscovitine, a potent Cdk5 inhibitor. Significantly, reduced Cdk5 expression together with enhanced Cdk5 phosphorylation and p25 accumulation also occurs in the striatum of mutantHdhQ111mice and HD human brain suggesting the relevance of deregulated Cdk5 pathway in HD pathology. These findings provide new insights into the molecular mechanisms underlying the selective vulnerability of striatal cells in HD and identify p25/Cdk5 as an important mediator of dopamine and glutamate neurotoxicity associated to HD.
The Posterior Parietal Cortex Encodes in Parallel Both Goals for Double-Reach Sequences
Authors: Baldauf Daniel , Cui He , Andersen Richard A.
Published: October 2008

The parietal reach region (PRR) is known to be involved in the preparation of visually guided arm movements to single targets. We explored whether PRR encodes only the target of the next movement or, alternatively, also a subsequent goal in a double-reach sequence. Two monkeys were trained to memorize the locations of two peripheral cues and to prepare for a memory-guided delayed double-reach sequence. On a GO-signal they had to reach in a predefined order to both remembered target locations without breaking eye fixation. The movement goals were arranged such that either the first or the second target was inside the response field of an isolated neuron. We analyzed the neural activity of single cells in PRR during the late memory period between cue offset and the GO-signal. During this memory period, most PRR cells encoded the first as well as the second goal of the planned reaching sequence. The results indicate that the posterior parietal cortex is involved in the spatial planning of more complex action patterns and represents immediate and subsequent movement goals.
Control of Precerebellar Neuron Development byOlig3bHLH Transcription Factor
Authors: Liu Zijing , Li Hong , Hu Xuemei , Yu Ling , Liu Hongbin , Han Ruifa , Colella Rita , Mower George D. , Chen Yiping , Qiu Mengsheng
Published: October 2008

The rhombic lip (RL) is the neuroepithelium immediately adjacent to the roof plate of the fourth ventricle, and it gives rise to various brainstem and cerebellar cell types. Our study shows that the bHLH (basic helix-loop-helix) transcription factorOlig3is expressed in the progenitors of RL, and ablation ofOlig3significantly affects the development of RL. InOlig3−/− caudal RL, the expression level ofMath1in the dorsal interneuron 1 (dI1) domain is reduced, and the formation of four mossy-fiber nuclei is compromised; dI2–dI3 neurons are misspecified to dI4 interneurons, and the climbing-fiber neurons (inferior olive nucleus) are completely lost. In addition, the formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is also dependent onOlig3. Therefore,Olig3plays an important role in the fate specification and differentiation of caudal RL-derived neurons.
Ein objektorientierter Ansatz zur Modellierung des menschlichen Herz-Kreislauf-Systems An Object-Oriented Approach to Modelling the Human Cardiovascular System
Authors: Brunberg Anja , Autschbach Rüdiger , Abel Dirk
Published: October 2008

Zur Analyse körpereigener Regelungen, zur Synthese von Unterstützungsgeräten für gestörte physiologische Regelkreise und zur Ableitung von Maßnahmen zur Therapie wird ein objektorientiertes Modell in Form einer an den Organen orientierten, offen erweiterbaren Bibliothek entwickelt. Die Einsatzmöglichkeiten der Modelle reichen von Forschung und Entwicklung bis hin zur Ausbildung.
Multi-modales Biofeedback System zur Vorbeugung von Stürzen Multi-modal Biofeedback System for the Prevention of Falls
Authors: Burger Jürgen , Meyes Simon , Tschanz Roger , Davis Justin R. , Carpenter Mark G. , Debrunner Daniel , Allum John H. J.
Published: October 2008

Das Biofeedback des Körperschwankens stellt eine Möglichkeit dar, Patienten mit statischen und dynamischen Gleichgewichtsproblemen alternative Sinnesreize zur Erlangung eines stabilen Gleichgewichts zur Verfügung zu stellen, was zu einer Verbesserung ihrer Lebensqualität führt. Das Biofeedback-System erzeugt mittels am Kopf befestigter Signalwandler auditive, vibro-taktile und vibro-vestibuläre Sinneseindrücke. Die Ergebnisse sowohl an jungen als auch an älteren Probanden ergaben, dass mit Hilfe des Biofeedbacks eine bemerkenswerte 40–60%ige Reduktion des Körperschwankens erzielt werden konnte.
Iterativ Lernende Regelung einer Gang-Neuroprothese Iterative Learning Control of a Gait Neuroprosthesis
Authors: Nahrstaedt Holger , Schauer Thomas , Hesse Stefan , Raisch Jörg
Published: October 2008

Dieser Beitrag beschreibt den Entwurf einer linearen Iterativ Lernenden Regelung (ILR) im Zeitbereich für die automatische Anpassung einer Neuroprothese bei Schlaganfallpatienten. Eine unzureichende Fußhebung in der Schwungphase des Ganges soll durch die gezielte Stimulation des Fußhebers kompensiert werden. Für die Erfassung des Gelenkwinkels wird ein neuartiges Messverfahren verwendet, bei welchem durch Bewegung hervorgerufene Bio-Impedanz-Änderungen im Bein registriert werden. Für die Regelung ist ferner eine Gangphasenerkennung mittels Drucksensoren unter der Fußsohle notwendig, um die Stimulation exakt mit der Schwungphase zu synchronisieren. Ein erster Test des Regelungskonzepts und des neuen Ansatzes zur Winkelmessung wurde an einem gesunden Probanden durchgeführt.
Strukturanalyse von Betonpfählen durch eingebettete faseroptische Sensoren Analysis of Concrete Foundation Piles Using Structure-Integrated Fibre-Optic Sensors
Authors: Schallert Matthias , Hofmann Detlef , Habel Wolfgang R.
Published: October 2008

Zur Gründung von Bauwerken auf weichen, gering tragfähigen Böden werden unter anderem Betonpfähle, einzeln oder in Pfahlgruppen, eingesetzt. Deren Bewertung bzgl. Tragverhalten bzw. Integrität ist bei bestimmten Baugrundverhältnissen und Pfahlgeometrien schwierig. Hierfür werden statische und dynamische Pfahlprüfungen durchgeführt. Aus Messwerten vom Pfahlkopf bzw. vom oberen Pfahlbereich werden üblicherweise die notwendigen Aussagen abgeleitet. Eine genauere Bewertung ist möglich, wenn präzise Messwerte über die gesamte Pfahllänge vorliegen. Deshalb wurden hochauflösende betoneinbettbare Messwertaufnehmer auf Basis von Faser-Fabry-Perot-Sensoren entwickelt, die in Modell- und in realen Rammpfählen getestet wurden. Der Beitrag beschreibt den Sensor, die Installation und exemplarisch einige Testergebnisse zur Erfassung der Wellenausbreitung im Modellpfahl. Feldtests wurden zurzeit der Erstellung des Manuskripts erfolgreich begonnen.
Messtechnische Charakterisierung elektrostatischer Entladungen Metrological Characterization of Electrostatic Discharges
Authors: Langer Tim , Beyer Michael , von Pidoll Ulrich
Published: October 2008

Die Einflüsse von Ladungspolarität und Luftfeuchte auf zwei Verfahren zum Messen von Impulsladungen werden untersucht. Des Weiteren wird ein Modell entwickelt für die Messunsicherheitsbestimmung nach dem “Guide to the Expression of Uncertainty in Measurement” im Zusammenhang mit den Untersuchungen der Polaritäts- und Luftfeuchteabhängigkeit der beiden Messverfahren.
The appearance of the adrenal glands on computed tomography in multiple endocrine neoplasia type 1
Authors: Whitley S A , Moyes V J , Park K M , Brooke A M , Grossman A B , Chew S L , Rockall A G , Monson J P , Reznek R H
Published: October 2008

Aims

To review the morphology of the adrenal glands in multiple endocrine neoplasia type 1 (MEN1) on computed tomography (CT) to compare the results with established normal values for adrenal size and nodularity and to correlate adrenal size with serum cortisol secretory dynamics.

Materials and methods

Two observers independently reviewed the adrenal CT in 28 patients with MEN1, measuring the maximum width of the body of the gland and the medial and lateral limbs. Incidence and location of nodules >5 mm within the gland were recorded. Following exclusion of known cases of Cushing's syndrome, adrenal gland size was compared with previously documented normative data. Adrenal gland size was compared between patients with normal and abnormal cortisol dynamics.

Results

Comparison of mean adrenal size in MEN1 patients with normative data showed that the adrenal limbs were significantly larger in MEN1 than normal (P<0.0001 in all four limbs). Adrenal body was also significantly larger (P<0.05). Nodules were demonstrated in 17 (60%) of patients (versus 0.4–2% in the normal population). No statistically significant correlation was demonstrated between adrenal limb hyperplasia and abnormal cortisol dynamics.

Conclusions

In patients with MEN1, adrenal limb hyperplasia and adrenal nodules are significantly more common than in the normal population, a phenomenon not previously documented in a quantitative manner. There was no significant correlation between adrenal limb hyperplasia and abnormal cortisol dynamics.
Cytogenetic damage in preimplantation mouse embryos generated after paternal and parental γ-irradiation and the influence of vitamin C
Authors: Mozdarani Hossein , Nazari Elmina
Published: October 2008

Cytogenetic damage expressed as micronuclei (MN) in 4–8-cell embryos generated after irradiation of male or male and female mice in the absence and presence of vitamin C was investigated. Male NMRI mice were whole body exposed to 4 Gy γ-rays and mated with non-irradiated superovulated female mice in 6 successive weeks after irradiation in a weekly interval. In experiments involving irradiation of both male and female mice, irradiated male mice for 6 weeks post irradiation were mated with female mice irradiated after induction of superovulation. Effect of 100 mg/kg vitamin C (ascorbic acid) on the frequency of MN was also studied. Pregnant animals were euthanized and embryos flushed from the oviducts and fixed on slides. The rate of MN observed in embryos generated from irradiated male compared with control group dramatically increased (P<0.01). Frequency of MN in this group decreased dramatically after vitamin C treatment (P<0.01). Frequency of MN in embryos generated by mating both male and female irradiated mice was higher than that observed for those embryos generated by irradiated male mice alone. However, a considerable modifying effect of vitamin C was observed for this group too (P<0.05). Results indicate that irradiation of gonads during spermatogenesis and preovulatory stage oocytes may lead to unstable chromosomal aberrations and probably stable chromosomal abnormalities affecting pairing and disjunction of chromosomes in successive preimplantation embryos expressed as MN. The way vitamin C reduces clastogenic effects of radiation on germ cells leading to reduced frequency of MN in pre-embryos might be due to its antioxidation and radical scavenging properties.
Awakening the oocyte: controlling primordial follicle development
Authors: McLaughlin Eileen A , McIver Skye C
Published: October 2008

Oocytes are sequestered in primordial follicles before birth and remain quiescent in the ovary, often for decades, until recruited into the growing pool throughout the reproductive years. Therefore, activation of follicle growth is a major biological checkpoint that controls female reproductive potential. However, we are only just beginning to elucidate the cellular mechanisms required for either maintenance of the quiescent primordial follicle pool or initiation of follicle growth. Understanding the intracellular signalling systems that control oocyte maintenance and activation has significant implications for improving female reproductive productivity and longevity in mammals, and has application in domestic animal husbandry, feral animal population control and infertility in women.
Inflammation and Lung Disease in the Neonatal Period
Authors: Yoder Bradley A. , Albertine Kurt H.
Published: October 2008

A variety of insults can contribute to lung inflammation in the neonatal period. Many of these insults exert their effects through activation or suppression of critical transcription factor pathways. The effect of these pathways on gene transcription/protein translation has a direct impact on lung development, labor induction and the intra-amniotic milieu, and postnatal lung inflammation.
Inherited Surfactant Disorders
Authors: Gower W. Adam , Wert Susan E. , Nogee Lawrence M.
Published: October 2008

Inherited disorders of surfactant metabolism are rare causes of respiratory disease in newborns but are associated with significant morbidity and mortality. This review outlines the molecular basis and pathophysiology of the three currently identified single-gene disorders of surfactant metabolism as well as the clinical presentations and evaluation of potentially affected infants. Implications for the understanding of normal surfactant metabolism and the potential roles of surfactant dysfunction mutations in more common neonatal disorders, such as respiratory distress syndrome, also are discussed.
Lung Transplantation for Inherited Disorders of Surfactant Metabolism
Authors: Faro Albert , Hamvas Aaron
Published: October 2008

Inherited disorders of surfactant metabolism are rare diseases that provide unique opportunities for understanding the mechanisms of surfactant function and metabolism. Presenting both as acute respiratory dysfunction in the neonatal period with a predictably lethal outcome as well as chronic respiratory insufficiency of variable onset and unpredictable natural histories, these disorders present unique challenges for clinicians and families because the treatment options are limited to lung transplantation and compassionate care. We briefly review the known inherited surfactant disorders, the challenges associated with offering lung transplantation for these disorders, and the outcomes.
Parents With Doubts About Vaccines: Which Vaccines and Reasons Why
Authors: Gust Deborah A. , Darling Natalie , Kennedy Allison , Schwartz Ben
Published: October 2008

OBJECTIVES. The goals were (1) to obtain national estimates of the proportions of parents with indicators of vaccine doubt, (2) to identify factors associated with those parents, compared with parents reporting no vaccine doubt indicators, (3) to identify the specific vaccines that prompted doubt and the reasons why, and (4) to describe the main reasons parents changed their minds about delaying or refusing a vaccine for their child.

METHODS. Data were from the National Immunization Survey (2003–2004). Groups included parents who ever got a vaccination for their child although they were not sure it was the best thing to do (“unsure”), delayed a vaccination for their child (“delayed”), or decided not to have their child get a vaccination (“refused”).

RESULTS. A total of 3924 interviews were completed. Response rates were 57.9% in 2003 and 65.0% in 2004. Twenty-eight percent of parents responded yes to ever experiencing ≥1 of the outcome measures listed above. In separate analyses for each outcome measure, vaccine safety concern was a predictor for unsure, refused, and delayed parents. The largest proportions of unsure and refused parents chose varicella vaccine as the vaccine prompting their concern, whereas delayed parents most often reported “not a specific vaccine” as the vaccine prompting their concern. Most parents who delayed vaccines for their child did so for reasons related to their child's illness, unlike the unsure and refused parents. The largest proportion of parents who changed their minds about delaying or not getting a vaccination for their child listed “information or assurances from health care provider” as the main reason.

CONCLUSIONS. Parents who exhibit doubts about immunizations are not all the same. This research suggests encouraging children's health care providers to solicit questions about vaccines, to establish a trusting relationship, and to provide appropriate educational materials to parents.
Distinct Hemodynamic Patterns of Septic Shock at Presentation to Pediatric Intensive Care
Authors: Brierley Joe , Peters Mark J.
Published: October 2008

OBJECTIVE. Early aggressive resuscitation is accepted best practice for severe pediatric sepsis. Targeting of therapy to individual hemodynamic patterns is recommended, but assessment of patterns is difficult early in the disease process. New technologies enabling earlier hemodynamic assessment in shock may inform choices for vasoactive drugs in fluid-resistant cases.

METHODS. This was a prospective observational study of 30 children with suspected fluid-resistant septic shock (minimum: 40 mL/kg) admitted to the PICU of a tertiary care children's hospital between July 2004 and July 2005. Children were classified according to admission diagnosis (community-acquired sepsis or central venous catheter-associated infection) and assessed within 4 hours after the onset of shock with a noninvasive cardiac output device. Cardiac index and systemic vascular resistance index were measured for all patients. Central venous oxygen saturation was measured for patients with accessible central venous lines at the time of hemodynamic measurements (typically at the superior vena cava-right atrium junction).

RESULTS. Fluid-resistant septic shock secondary to central venous catheter-associated infection was typically “warm shock” (15 of 16 patients; 94%), with high cardiac index and low systemic vascular resistance index. In contrast, this pattern was rarely seen in community-acquired sepsis (2 of 14 patients; 14%), where a normal or low cardiac index was predominant.

CONCLUSIONS. The hemodynamic patterns of fluid-resistant septic shock by the time children present to the PICU are distinct, depending on cause, with little overlap. If these findings can be reproduced, then targeting the choice of first-line vasoactive infusions in fluid-resistant shock (vasopressors for central venous catheter-associated infections and inotropes for community-acquired sepsis) should be considered.
Management of Atopic Dermatitis in the Pediatric Population
Authors: Krakowski Andrew C. , Eichenfield Lawrence F. , Dohil Magdalene A.
Published: October 2008

Atopic dermatitis, one of the most common skin disorders in young children, has a prevalence of 10% to 20% in the first decade of life. It is a chronic illness that requires a multifaceted treatment strategy in the setting of limited therapeutic options. Balancing safety concerns with efficacious treatment is of particular importance in the pediatric population. Parents of patients with atopic dermatitis turn to their primary caregivers for guidance regarding this physically demanding and psychologically stressful condition. In addition to serving as a review of atopic dermatitis, this article delves into the state-of-the-art therapeutic options and includes a detailed review of the differences between topical corticosteroids and topical calcineurin inhibitors. We also discuss new treatment strategies that are being used by atopic dermatitis specialists, such as comprehensive “education-as-intervention” models, wet wraps, bleach baths, and systemic immunomodulatory therapies.
Growth Patterns and Obesity Development in Overweight or Normal-Weight 13-Year-Old Adolescents: The STRIP Study
Authors: Lagström Hanna , Hakanen Maarit , Niinikoski Harri , Viikari Jorma , Rönnemaa Tapani , Saarinen Maiju , Pahkala Katja , Simell Olli
Published: October 2008

OBJECTIVE. Our goal was to study childhood growth patterns and development of overweight in children who were overweight or normal weight at 13 years of age.

PARTICIPANTS AND METHODS. This study is part of a prospective atherosclerosis-prevention trial Special Turku Coronary Risk Factor Intervention Project for Children). At 7 months of age, 1062 children were randomly assigned to an intervention group (n = 540) receiving biannual fat-oriented dietary counseling or to a control group (n = 522). Height and weight of the children and their parents were monitored annually. Our study group comprised those children who participated in the 13-year study visit (n = 541). At 13 years of age, the child was classified as overweight (n = 84) if his or her BMI exceeded the international age- and gender-specific overweight criteria.

RESULTS. In overweight girls, the annual weight gain increased from 2.8 kg during the third and fourth year of life to 7.5 kg during the 12th year of life, whereas the annual weight gain of the girls who were normal weight ranged from 2.1 to 4.8 kg during the same period. The annual weight gain was similar of overweight boys and in their normal-weight peers until the age of 5 years, but after that it increased from 3.5 to 7.9 kg in overweight and from 2.6 to 5.5 kg in normal-weight boys. The BMI of the girls and boys who were overweight at the age of 13 exceeded the international cutoff point for overweight from the age of 5 and 8 years onward, respectively. The mean BMIs of the mothers and fathers of the overweight children were higher than those of the parents of the normal-weight children. The STRIP intervention had no effect on the examined growth parameters or on parental BMI.

CONCLUSIONS. The children who were overweight at 13 years of age gained more weight than their normal-weight peers by the age of 2 or 3 years onward. The girls became overweight by the age of 5 years, whereas the boys only after 8 years of age. Parental BMI and steep weight gain in early childhood indicate markedly increased risk for becoming overweight.
Sodium Bicarbonate: Basically Useless Therapy
Authors: Aschner Judy L. , Poland Ronald L.
Published: October 2008

Common clinical practices often are unsupported by experimental evidence. One example is the administration of sodium bicarbonate to neonates. Despite a long history of widespread use, objective evidence that administration of sodium bicarbonate improves outcomes for patients in cardiopulmonary arrest or with metabolic acidosis is lacking. Indeed, there is evidence that this therapy is detrimental. This review examines the history of sodium bicarbonate use in neonatology and the evidence that refutes the clinical practice of administering sodium bicarbonate during cardiopulmonary resuscitation or to treat metabolic acidosis in the NICU.
Skin Conductance Versus the Modified COMFORT Sedation Score as a Measure of Discomfort in Artificially Ventilated Children
Authors: Gjerstad Ann Christin , Wagner Kari , Henrichsen Thore , Storm Hanne
Published: October 2008

OBJECTIVE. We wanted to use skin conductance as a measure of increased stress in artificially ventilated children. The aim was to examine how changes in skin conductance, arterial blood pressure, and heart rate are associated with changes in the modified COMFORT sedation score during suction from the trachea. Nociceptive stimulation induces an outgoing sympathetic nervous burst to the skin and the palmar and plantar sweat glands are filled, which creates a skin conductance fluctuation.

METHODS. Twenty children who were 1 day to 11 years of age were studied. All patients were artificially ventilated and circulatory stable. The data were obtained before, during, and 10 minutes after endotracheal suction. The number of skin conductance fluctuations, the amplitude of skin conductance fluctuations, the mean skin conductance level, arterial blood pressure, heart rate, and the modified COMFORT sedation score were recorded and tested from before to during and from during to after suction in the trachea.

RESULTS. The number of skin conductance fluctuations, mean skin conductance level, arterial blood pressure, and the modified COMFORT sedation score increased during suction in the trachea, in contrast to heart rate and amplitude of skin conductance fluctuations. The number of skin conductance fluctuations from before to during and from during to after endotracheal suctioning correlated with changes in the modified COMFORT sedation score. This was in contrast to the other variables that did not.

CONCLUSIONS. The number of skin conductance fluctuations during endotracheal suctioning showed better correlation with the increase in the modified COMFORT sedation score than heart rate and arterial blood pressure. Thus, the number of skin conductance fluctuations seems to be an objective supplement to the modified COMFORT sedation score for monitoring increased stress in artificially ventilated and circulatory stable children.
Modifiable Risk Factors for Suboptimal Control and Controller Medication Underuse Among Children With Asthma
Authors: Smith Lauren A. , Bokhour Barbara , Hohman Katherine H. , Miroshnik Irina , Kleinman Kenneth P. , Cohn Ellen , Cortés Dharma E. , Galbraith Alison , Rand Cynthia , Lieu Tracy A.
Published: October 2008

OBJECTIVES. Our aims were (1) to describe rates of suboptimal control and controller medication underuse in a diverse population of children with asthma and (2) to identify potentially modifiable parental behaviors and beliefs associated with these outcomes.

METHODS. We conducted telephone interviews with parents of 2- to 12-year-old children with persistent asthma, in a Medicaid plan and a large provider group. Suboptimal control was defined as ≥4 symptom days, ≥1 symptom night, or ≥4 albuterol use days in the previous 2 weeks. Controller medication underuse was defined as suboptimal control and parent report of <6 days/week of inhaled steroid use. Multivariate analyses identified factors that were independently associated with suboptimal control and controller medication underuse.

RESULTS. Of the 754 study children, 280 (37%) had suboptimal asthma control; this problem was more common in Hispanic children (51%) than in black (37%) or white (32%) children. Controller medication underuse was present for 133 children (48% of those with suboptimal asthma control and 18% overall). Controller medication underuse was more common among Hispanic (44%) and black (34%) children than white (22%) children. In multivariate analyses, suboptimal control was associated with potentially modifiable factors including low parental expectations for symptom control and high levels of worry about competing household priorities. Controller medication underuse was associated with potentially modifiable factors including parental estimation of asthma control that was discordant with national guidelines and no set time to administer asthma medications.

CONCLUSIONS. Deficiencies in asthma control and controller medication use are associated with potentially modifiable parental beliefs, which seem to mediate racial/ethnic and socioeconomic disparities in suboptimal control and controller medication underuse.
Preventing Unintentional Scald Burns: Moving Beyond Tap Water
Authors: Lowell Gina , Quinlan Kyran , Gottlieb Lawrence J.
Published: October 2008

OBJECTIVE. The goal was to examine in detail the mechanisms of significant scald burns among children <5 years of age, to discover insights into prevention.

METHODS. Medical records for children <5 years of age who were admitted with scald burns between January 1, 2002, and December 31, 2004, were identified through the University of Chicago Burn Center database. Demographic data and details of the circumstances and mechanisms of injury were extracted from the medical records.

RESULTS. Of 640 admissions to the University of Chicago Burn Center during the 3-year study period, 140 (22%) involved children <5 years of age with scald burns. Of the 137 available charts reviewed, 118 involved unintentional injuries. Of those unintentional injuries, 14 were tap water scalds and 104 were non–tap water scalds. Of the non–tap water scalds, 94 scalds (90.4%) were related to hot cooking or drinking liquids. Two unexpected patterns of injury were discovered. Nine children (8.7%) between the ages of 18 months and 4 years were scalded after opening a microwave oven and removing the hot substance themselves. Seventeen children (16.3%) were scalded while an older child, 7 to 14 years of age, was cooking or carrying the scalding substance or supervising the younger child.

CONCLUSIONS. Current prevention strategies and messages do not adequately address the most common mechanisms of scald injury requiring hospitalization. Easy access to a microwave oven poses a significant scald risk to children as young as 18 months of age, who can open the door and remove the hot contents. An engineering fix for microwave ovens could help protect young children from this mechanism of scalding. Involvement of older children in a subset of scald injuries is a new finding that may have prevention implications.
Oral Probiotics Prevent Necrotizing Enterocolitis in Very Low Birth Weight Preterm Infants: A Multicenter, Randomized, Controlled Trial
Authors: Lin Hung-Chih , Hsu Chyong-Hsin , Chen Hsiu-Lin , Chung Mei-Yung , Hsu Jen-Fu , Lien Rey-in , Tsao Lon-Yen , Chen Chao-Huei , Su Bai-Horng
Published: October 2008

OBJECTIVE. The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants.

METHODS. A prospective, blinded, randomized, multicenter controlled trial was conducted at 7 NICUs in Taiwan, to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants (birth weight: <1500 g). Very low birth weight infants who survived to start enteral feeding were eligible and were assigned randomly to 2 groups after parental informed consent was obtained. Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus, added to breast milk or mixed feeding (breast milk and formula), twice daily for 6 weeks. Infants in the control group were fed with breast milk or mixed feeding. The clinicians caring for the infants were blinded to the group assignment. The primary outcome measurement was death or necrotizing enterocolitis (Bell's stage ≥2).

RESULTS. Four hundred thirty-four infants were enrolled, 217 in the study group and 217 in the control group. The incidence of death or necrotizing enterocolitis (stage ≥2) was significantly lower in the study group (4 of 217 infants vs 20 of 217 infants). The incidence of necrotizing enterocolitis (stage ≥2) was lower in the study group, compared with the control group (4 of 217 infants vs 14 of 217 infants). No adverse effect, such as sepsis, flatulence, or diarrhea, was noted.

CONCLUSION. Probiotics, in the form of Bifidobacterium and Lactobacillus, fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis.
Prophylactic Phenobarbital Administration After Resolution of Neonatal Seizures: Survey of Current Practice
Authors: Guillet Ronnie , Kwon Jennifer M.
Published: October 2008

OBJECTIVE. Child neurologists and neonatologists often discharge newborn infants with phenobarbital treatment for weeks to months despite the absence of continuing seizure activity. We conducted a national survey to determine the degree of variation in this practice.

METHODS. Surveys were sent to a randomly generated list of board-certified child neurologists (N = 609) and neonatologists (N = 579). The survey consisted of 3 parts, that is, questions related to overall attitudes and practices, specific patient scenarios, and respondent demographic characteristics. Responses were tabulated and analyzed for all respondents combined and for child neurologists and neonatologists separately. Variation in practices between respondents and the consistency between the respondents' stated use of phenobarbital in practice and their answers to various clinical scenarios were evaluated.

RESULTS. Responses were received from 118 child neurologists (20.7%) and 125 neonatologists (23.1%). There was wide variation in practices, with little difference in the response frequencies between child neurologists and neonatologists. Physicians were more likely to respond yes to continuation of phenobarbital treatment in a given clinical situation than would be predicted on the basis of their answers regarding overall frequency of use.

CONCLUSIONS. Since the survey of practices 15 years ago, child neurologists and neonatologists are reporting less frequent and shorter phenobarbital treatment after resolution of neonatal seizures, although there remains considerable variation in practices. Moreover, what physicians report as their practice in general is inconsistent with how they respond to specific clinical cases of neonatal seizures.
Procalcitonin in Young Febrile Infants for the Detection of Serious Bacterial Infections
Authors: Maniaci Vincenzo , Dauber Andrew , Weiss Scott , Nylen Eric , Becker Kenneth L. , Bachur Richard
Published: October 2008

OBJECTIVES. The objectives of the study were (1) to study the test performance of procalcitonin for identifying serious bacterial infections in febrile infants ≤90 days of age without an identifiable bacterial source and (2) to determine an optimal cutoff value to identify infants at low risk for serious bacterial infections.

METHODS. A prospective observational study was performed with febrile infants ≤90 days of age presenting to an urban, pediatric, emergency department. Serum procalcitonin levels were measured by using an automated high-sensitivity assay. An optimal procalcitonin cutoff value was selected to maximize sensitivity and negative predictive value for the detection of serious bacterial infections. Infants were classified as having definite, possible, or no serious bacterial infections.

RESULTS. A total of 234 infants (median age: 51 days) were studied. Thirty infants (12.8%) had definite serious bacterial infections (bacteremia: n = 4; bacteremia with urinary tract infections: n = 2; urinary tract infections: n = 24), and 12 infants (5.1%) had possible serious bacterial infections (pneumonia: n = 5; urinary tract infections: n = 7). Mean procalcitonin levels for definite serious bacterial infections (2.21 ± 3.9 ng/mL) and definite plus possible serious bacterial infections (2.48 ± 4.6 ng/mL) were significantly higher than that for no serious bacterial infection (0.38 ± 1.0 ng/mL). The area under the receiver operating characteristic curve was 0.82 for definite serious bacterial infections and 0.76 for definite and possible serious bacterial infections. For identifying definite and possible serious bacterial infections, a cutoff value of 0.12 ng/mL had sensitivity of 95.2%, specificity of 25.5%, negative predictive value of 96.1%, and negative likelihood ratio of 0.19; all cases of bacteremia were identified accurately with this cutoff value.

CONCLUSIONS. Procalcitonin has favorable test characteristics for detecting serious bacterial infections in young febrile infants. Procalcitonin measurements performed especially well in detecting the most serious occult infections.
Systematic Review of Digital Imaging Screening Strategies for Retinopathy of Prematurity
Authors: Kemper Alex R. , Wallace David K. , Quinn Graham E.
Published: October 2008

BACKGROUND. Retinal imaging with remote interpretation could decrease the number of diagnostic eye examinations that premature infants need for the detection of retinopathy of prematurity and thus decrease the time demand on the relatively small pool of ophthalmologists who perform retinopathy of prematurity examinations.

OBJECTIVE. Our goal was to review systematically the evidence regarding the reliability, validity, safety, costs, and benefits of retinal imaging to screen infants who are at risk for retinopathy of prematurity.

METHODS. We searched Medline, the Cochrane library, CINAHL, and the bibliographies of all relevant articles. All English-language studies regardless of design with primary data about our study questions were included. We excluded (1) studies that only included subjects with retinopathy of prematurity, (2) hypothetical models other than cost-effectiveness studies, and (3) validity studies without sufficient data to determine prevalence, sensitivity, and specificity or that only evaluated subjects for 1 component of retinopathy of prematurity (eg, plus disease only).

RESULTS. Studies of only 1 retinal imaging device (RetCam [Clarity Medical Systems, Inc, Pleasanton, CA]) met the inclusion criteria. There was a wide range in reported sensitivity, but specificity was high. There were several important limitations noted, including the eye as the unit of analysis instead of the individual or variations in the criteria for determining a true-positive or true-negative screening result. The risk of retinal hemorrhage resulting from imaging is low, and systemic effects (eg, bradycardia, hypertension, decreased oxygen saturation) are mild. No generalizable cost-effectiveness data were found.

CONCLUSIONS. The evidence base is not sufficient to recommend that retinal imaging be routinely adopted by NICUs to identify infants who have serious retinopathy of prematurity.