bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing Cannabinoid CB2 Receptor Ligands Using DiscoveRx PathHunter™ β-Arrestin Assay
Authors: Mcguinness Debra , Malikzay Asra , Visconti Richard , Lin Karen , Bayne Marvin , Monsma Frederick , Lunn Charles A.
Published: January 2009

The authors have characterized a set of cannabinoid CB2 receptor ligands, including triaryl bis sulfone inverse agonists, in a cell-based receptor/β-arrestin interaction assay (DiscoveRx PathHunter™). The results were compared with results using a competitive ligand binding assay, and with effects on forskolin-stimulated cAMP levels (PerkinElmer LANCE™). The authors show good correlation between the 3 assay systems tested, with the β-arrestin protein complementation assay exhibiting a more robust signal than the cAMP assay for cannabinoid CB2 agonists. Further assay validation shows that DiscoveRx PathHunter™ HEK293 CB2 β-arrestin assay can be carried out from cryopreserved cell suspensions, eliminating variations caused by the need for multiple cell pools during live cell screening campaigns. These results, and the authors' results evaluating a test set of random library compounds, validate the use of ligand-induced interaction between the human cannabinoid CB2 receptor and β-arrestin as an appropriate and valuable screening platform for compounds specific for the cannabinoid CB2 receptor. ( Journal of Biomolecular Screening 2009:49-58)
Comparison of Variability and Sensitivity between Nuclear Translocation and Luciferase Reporter Gene Assays
Authors: Unterreiner Vincent , Ibig-Rehm Yvonne , Simonen Marjo , Gubler Hanspeter , Gabriel Daniela
Published: January 2009

High-content screening (HCS), a technology based on subcellular imaging by automated microscopy and sophisticated image analysis, has emerged as an important platform in small-molecule screening for early drug discovery. To validate a subcellular imaging assay for primary screening campaigns, an HCS assay was compared with a non—image-based readout in terms of variability and sensitivity. A study was performed monitoring the accumulation of the forkhead transcription factor of the O subfamily (FOXO3a) coupled with green fluorescent protein in the nucleus of human osteosarcoma (U-2 OS) cells. In addition, the transcription of a luciferase gene coupled with a FOXO3a-responsive promoter was monitored. This report demonstrates that both assay formats show good reproducibility in primary and concentration response screening despite differences in statistical assay quality. In primary screening, the correlation of compound activity between the 2 assays was low, in contrast to the good correlation of the IC50values of confirmed compounds. Furthermore, the high-content imaging assay showed a mean shift of 2.63-fold in IC50values compared with the reporter gene assay. No chemical scaffold was specifically found with 1 of the technologies only, however these results validate the HCS technology against established assays for screening of new molecular entities. ( Journal of Biomolecular Screening 2009:59-65)
Optimizing the Expression of Recombinant αβγ GABAAReceptors in HEK293 Cells for High-Throughput Screening
Authors: Gilbert Daniel , Esmaeili Abolghasem , Lynch Joseph W.
Published: January 2009

Despite being important clinical targets, it is not straightforward to reliably express recombinant trimeric αβγ GABA-A receptors (GABAARs) for high-throughput screening. This study therefore sought to devise a simple and reliable means of transiently expressing α1β1γ1 and α1β1γ2 GABAARs in HEK293 cells. Expression efficiencies resulting from 5 different transfection strategies were assessed by flow cytometry and pharmacological analysis using an anion-sensitive yellow fluorescent protein-based assay. PolyFect™ and Effectene™, employed according to the manufacturers' instructions, conferred the strongest and most reliable expression of trimeric αβγ GABAARs. Functional analysis via the yellow fluorescent protein assay revealed dramatic differences in the pharmacological properties of γ1- and γ2-containing receptors, consistent with previous electrophysiological characterizations. The authors conclude that this method of expressing and screening recombinant GABAARs provides an effective means of discovering novel GABAAR modulators for use as therapeutic lead compounds and pharmacological probes. ( Journal of Biomolecular Screening 2009:86-91)
Trichloroisocyanuric Acid (TCCA) as a Mild and Efficient Catalyst for the Synthesis of 2-Arylbenzothiazoles
Authors: Xiao Hui-Long , Chen Jiu-Xi , Liu Miao-Chang , Zhu Dong-Jian , Ding Jin-Chang , Wu Hua-Yue
Published: January 2009

The condensation reaction of 2-aminothiophenol with aldehydes catalyzed by 1 mol % trichloroisocyanuric acid (TCCA) was investigated. As a result, a set of diverse 2-arylbenzothiazoles were obtained in good to excellent yields at room temperature.
Synthesis of 4-Thiopseudoisocytidine and 4-Thiopseudouridine as Components of Triplex-forming Oligonucleotides
Authors: Okamoto Itaru , Cao Shiqi , Tanaka Hiroto , Seio Kohji , Sekine Mitsuo
Published: January 2009

In this paper, we report convenient methods for the synthesis of 4-thiopseudoisocytidine (s4ψiC) and 4-thiopseudouridine (s4Ψ). 1H NMR spectral analysis of these modified nucleosides showed that both s4Ψ and s4ψiC prefer C3′-endo ribose puckering. These conformational properties are favorable for the stabilization of triplex formation.
Pyrolysis of Waste Polypropylene and Characterisation of Tar
Authors: Purevsuren Barnasan , Davaajav Ya , Karaca Fatma , Morgan Trevor J. , George Anthe , Herod Alan A. , Kandiyoti Rafael
Published: January 2009

Waste polypropylene (PP) has been pyrolysed to obtain mainly a liquid tar product of high yield (83.5%) with the balance as gas (15.5%) and a little residue (1.0%). The elemental composition of the PP tar was: C: 87.1%, H: 12.6% and O+others: 0.4% (by difference). The tar samples have been characterised by gas chromatography/mass spectrometry, heated-probe mass spectrometry and laser desorption mass spectrometry (LD-MS), to give molecular mass distributions for comparison with molecular mass ranges indicated by size-exclusion chromatography (SEC). About 50% of the tar was soluble in 1-methyl-2-pyrrolidinone, the solvent used for SEC. It appeared to consist mostly of low molecular mass materials with elution time at 20–27 min. Mass ranges from SEC and LD-MS agreed approximately in showing the upper mass limit of the tar to be about 1200 u, consisting of aromatics, alkenes, dialkenes and only minor quantities of alkanes.
Exploration of Mononucleotides as Fixed Ligands towards Chiral Discrimination of Hexose Monosaccharides by the Kinetic Method
Authors: Kumari Sangeeta , Prabhakar Sripadi , Sivaleela Tallagadda , Lakshmi Vattem Venkata Swarajya , Vairamani Mariappanadar
Published: January 2009

The most recent version of the kinetic method, i.e. fixed ligand method, is applied towards chiral discrimination of three pairs of enantiomeric hexose monosaccharides under mass spectral conditions. Naturally occurring mononucleotides are used as fixed ligands (FL) and the amino acids are selected as the chiral references (ref) to discriminate the analyte (A), the enantiomers of glucose, mannose and galactose. Chiral discrimination is achieved by investigating the collision-induced dissociation spectra of trimeric complex ion, [NiII(FL)(ref)(A)–H]+ generated by electrospraying the solution mixture of d- or l-analyte (A), FL, amino acid (ref) and NiCl2. The relative abundance of product ions resulting from the competitive loss of reference amino acid and analyte are considered for measuring the degree of chiral discrimination by applying the kinetic method. l-Asp, l-Thr, l-Glu, l-Trp and l-Ser are found as suitable reference compounds. Among the tested mononucleotides (5′AMP, 5′GMP, 5′CMP, 5′UMP and 5′TMP), 5′GMP is found to be the best for the studied analytes. Chiral discrimination is found to depend on the nature of the monosaccharide, the functional groups present in the side chain of reference amino acids and the configuration of reference amino acids.
Effect of Potential of Ion Optic System and Gas-Filled Octapole Collision Cell on Mass Discrimination in Lead Isotopic Measurements (206Pb/207Pb, 208Pb/207Pb and 206Pb/208Pb) by Quadrupole-Based Inductively-Coupled Plasma Mass Spectrometry
Authors: Marguí Eva , Hidalgo Manuela , Iglesias Monica
Published: January 2009

The accuracy and precision of lead isotope ratio measurements by quadrupole-based inductively-coupled plasma-mass spectrometry (ICP-MS) can be limited by any of a number of instrumental factors mass bias being one of the most relevant. Mass bias can be defined as the deviation of measured isotope ratios from the “true value” due to the different transmission of ions according to their masses before the final detection. In the present research, a systematic study aimed at obtaining a more profound insight into to what extent the potential of the ion optic system and gas-filled octapole collision cell influence the mass discrimination in lead isotopic measurements (206Pb/207Pb, 208Pb/207Pb and 206Pb/208Pb) using ICP-QMS instrumentation was carried out. From the results obtained, it could be concluded that, in most cases, the effect of ion lens potential variation in mass discrimination is not really significant when working in maximum ion intensity regions. On the other hand, the application of pressurized conditions in the octapole collision/reaction cell using He and H2 as target gases does not lead to an improvement in ion sensitivity but, instead, introduces a significant mass bias effect, particularly when using high He flow rates (6–8 mL min−1). In this latter case, the use of Tl as the internal standard (203Tl/205Tl) proved to be suitable to correct the mass bias drift and the calculated mass discrimination percentage values decreased from 3.61% to 0.33%. The use of the gas-filled octapole collision cell does not lead to an improvement in lead isotope ratio precision compared to vented conditions.
Dipeptidyl peptidase (DP) 6 and DP10: novel brain proteins implicated in human health and disease
Authors: McNicholas Kym , Chen Tong , Abbott Catherine A.
Published: January 2009

Dipeptidyl peptidase (DP) 6 and DP10 are non-enzyme members of the dipeptidyl peptidase IV family, which includes fibroblast activation protein, DP8, and DP9. DP6 and DP10 proteins have been shown to be critical components of voltage-gated potassium (Kv) channels important in determining cellular excitability. The aim of this paper was to review the research to date on DP6 and DP10 structure, expression, and functions. To date, the protein region responsible for modulating Kv4 channels has not been conclusively identified and the significance of the splice variants has not been resolved. Resolution of these issues will improve our overall knowledge of DP6 and DP10 and lead to a better understanding of their role in diseases, such as asthma and Alzheimer's disease.

Clin Chem Lab Med 2009;47:262–7.
Die Vergütung des Sonderinsolvenzverwalters
Authors: Looff Franziska
Published: January 2009

Nach wie vor ist der Sonderinsolvenzverwalter nicht gesetzlich geregelt. Dies bringt Unsicherheiten bei der genauen Definition seiner Rechtsstellung im Verfahren mit sich, die sich jedoch durch konkrete Festlegung des jeweiligen Aufgabengebietes bei der Bestellung kompensieren lässt. Höchst umstritten ist demgegenüber, wie sich die Vergütung des Sonderinsolvenzverwalters bemisst und ob es einer Vergütungsfestsetzung durch das Insolvenzgericht bedarf. In eineraktuellen Entscheidung hatte sich der BGH mit diesen Fragen zu befassen.
Atomic Force Microscopy of Geroler Motor Wear Debris Ferrograms
Authors: Michael Paul , Bergesen Andrew , Blazel Brian , Kimball Aaron , Wanke Thomas S.
Published: January 2009

Hydraulic motors convert the flow produced by a hydraulic pump into rotary motion. These motors are often used to propel skid steers, excavators, loaders, feller bunchers, and other heavy equipment. While hydraulic pumps operate under relatively constant high-speed conditions, motors frequently come to a complete stop and reverse direction, particularly when the payload is engaged. As a result, hydraulic motors operate under boundary lubrication conditions which can promote wear-particle generation. In this study we examined wear particles generated by a geroler-type hydraulic motor under high-load conditions using online particle counters, direct-imaging laser particle analysis, ferrography, and atomic force microscopy (AFM). Relatively high quantities of particles were discharged from the hydraulic motor case drain and return-line during the first 30 min of break-in. After 30 min, the particle count decreased to an ISO 17/15/12 level. At the end of the 6-h break-in process case drain samples were approximately four-times cleaner than return-line samples. Under low-speed and high-speed, high-torque conditions, case drain samples were also very clean. Return-line particle counts were five-times higher at 1 rpm than at 450 rpm. Ferrographic analysis revealed that most of the wear particles were less than 15 μm in longest dimension and therefore may be classified as “normal” wear. AFM imaging of ferrograms was performed in contact and tapping mode using a phosphorus doped silicon probe that had a 10 nm tip radius. The largest particles produced during low-speed, high-torque operation tended to be a few hundred nanometers longer and thicker than those produced under milder break-in conditions. Ferrography proved to be a particularly useful method for preparing wear particles for AFM analysis because the ferrogram substrate is flat in the submicron range.
An Expert System for Estimation of Fatigue Properties from Simple Tensile Data or Hardness
Authors: Lee Kwang-Soo , Song Ji-Ho
Published: January 2009

Fatigue properties such as strain-life (ε-N) curves are usually obtained by performing fatigue tests. However, as fatigue testing requires time and high cost, many methods have been proposed to estimate the strain-life curves from simple tensile data or hardness. Based on results of recent studies, an expert system is developed to estimate with high accuracy fatigue properties (strain-life curves) from simple tensile data or hardness. The expert system is developed by using a commercial expert system shell, Acquire. The expert system consists of two modules, Fatigue Properties Estimation module and Knowledge Base Update module. An important feature of the expert system is to provide results of fatigue properties estimation with information of their anticipated accuracy. The fatigue data used for the performance testing of the expert system are 96 ε-N curves consisting of 663 ε-N data points obtained for 52 materials. The expert system has very good performance for steels, aluminum alloys, and titanium alloys, even when only hardness data are available as well as when simple tensile data are available.
Patent Ductus Arteriosus Therapy: Impact on Neonatal and 18-Month Outcome
Authors: Madan Juliette C. , Kendrick Douglas , Hagadorn James I. , Frantz Ivan D. ,   the National Institute of Child Health and Human Development Neonatal Research Network
Published: January 2009

OBJECTIVE. The purpose of this work was to evaluate therapy for patent ductus arteriosus as a risk factor for death or neurodevelopmental impairment at 18 to 22 months, bronchopulmonary dysplasia, or necrotizing enterocolitis in extremely low birth weight infants.

METHODS. We studied infants in the National Institute of Child Health and Human Development Neonatal Research Network Generic Data Base born between 2000 and 2004 at 23 to 28 weeks' gestation and at <1000-g birth weight with patent ductus arteriosus. Patent ductus arteriosus therapy was evaluated as a risk factor for outcomes in bivariable and multivariable analyses.

RESULTS. Treatment for subjects with patent ductus arteriosus (n = 2838) included 403 receiving supportive treatment only, 1525 treated with indomethacin only, 775 with indomethacin followed by secondary surgical closure, and 135 treated with primary surgery. Patients who received supportive therapy for patent ductus arteriosus did not differ from subjects treated with indomethacin only for any of the outcomes of interest. Compared with indomethacin treatment only, patients undergoing primary or secondary surgery were smaller and more premature. When compared with indomethacin alone, primary surgery was associated with increased adjusted odds for neurodevelopmental impairment and bronchopulmonary dysplasia in multivariable logistic regression. Secondary surgical closure was associated with increased odds for neurodevelopmental impairment and increased adjusted odds for bronchopulmonary dysplasia but decreased adjusted odds for death. Risk of necrotizing enterocolitis did not differ among treatments. Indomethacin prophylaxis did not significantly modify these results.

CONCLUSIONS. Our results suggest that infants treated with primary or secondary surgery for patent ductus arteriosus may be at increased risk for poor short- and long-term outcomes compared with those treated with indomethacin. Prophylaxis with indomethacin in the first 24 hours of life did not modify the subsequent outcomes of patent ductus arteriosus therapy.
Routine Developmental Screening Implemented in Urban Primary Care Settings: More Evidence of Feasibility and Effectiveness
Authors: Schonwald Alison , Huntington Noelle , Chan Eugenia , Risko Wanessa , Bridgemohan Carolyn
Published: January 2009

OBJECTIVES. The purpose of this study was to examine the feasibility and effectiveness of implementation of validated developmental screening by using the Parents' Evaluation of Developmental Status in 2 urban pediatric practices.

DESIGN AND METHODS. We implemented the Parents' Evaluation of Developmental Status at Boston Children's Hospital Primary Care Center and at Joseph Smith Community Health Center as quality improvement initiatives. Each practice offered screening to all of the patients attending well-child care visits between 6 months and 8 years of age. The implementation process was investigated by using preimplementation and postimplementation surveys and a focus group of pediatric primary care providers. To assess outcomes, such as changes in identification rates and referrals for developmental and behavioral concerns, we reviewed medical charts of all of the 2- and 3-year-olds present at Children's Hospital Primary Care Center well-child care visits in the periods before and after screening implementation.

RESULTS. Providers found routine screening easier than expected and feasible to conduct in a busy primary care setting. The practice change resulted in screening of 61.6% of eligible children. Compared with same-aged children before screening, after screening was implemented more behavioral concerns were detected in the 2-year-old group, and more children with developmental concerns were identified in the 3-year-old group. Referral rates for additional evaluation increased only for 3-year-olds, although the types of referrals (ie, audiology and early intervention) were consistent as those found before screening started.

CONCLUSIONS. Implementation of validated screening by using the Parents' Evaluation of Developmental Status was feasible in large, urban settings. Effectiveness was demonstrated via chart review documenting an increased rate of identification of developmental and behavioral concerns. Perceived obstacles, such as the time requirement, should not prevent widespread adoption of screening.
School Recess and Group Classroom Behavior
Authors: Barros Romina M. , Silver Ellen J. , Stein Ruth E. K.
Published: January 2009

OBJECTIVES. This study examines the amount of recess that children 8 to 9 years of age receive in the United States and compares the group classroom behavior of children receiving daily recess with that of children not receiving daily recess.

METHODS. This is a secondary analysis of a public-use data set, the Early Childhood Longitudinal Study, Kindergarten Class of 1998–1999, third-grade data set. Children were categorized into 2 levels of recess exposure, that is, none/minimal break (<1 break of 15 minutes/day) or some recess. Some recess was further categorized into 5 levels on the basis of frequency and duration of recess. Child, parent, school, and classroom characteristics of those with and without recess were compared. The group classroom behavior was assessed by using the teacher's rating of class behavior.

RESULTS. Complete data were available for 10301 to 11624 children 8 to 9 years of age. There were equal numbers of boys and girls (boys: 50.3%). Children exposed to none/minimal break (30%) were much more likely to be black, to be from families with lower incomes and lower levels of education, to live in large cities, to be from the Northeast or South, and to attend public school, compared with those with recess. Teacher's rating of classroom behavior scores were better for children with some recess than for those with none/minimal break. This finding was maintained in multivariate regression analysis. However, among children receiving daily recess, the teacher's rating of class behavior scores did not differ significantly according to the level of exposure.

CONCLUSIONS. These results indicated that, among 8- to 9-year-old children, having ≥1 daily recess period of >15 minutes in length was associated with better teacher's rating of class behavior scores. This study suggests that schoolchildren in this age group should be provided with daily recess.
Brain and Ventricles in Very Low Birth Weight Infants at Term: A Comparison Among Head Circumference, Ultrasound, and Magnetic Resonance Imaging
Authors: Maunu Jonna , Parkkola Riitta , Rikalainen Hellevi , Lehtonen Liisa , Haataja Leena , Lapinleimu Helena ,   and the PIPARI Group
Published: January 2009

OBJECTIVES. The aim of this study was to assess the relationship among the size of the lateral ventricles, head-circumference measure, and brain volumes. In addition, the association between ventricular dilatation and various brain lesions was defined.

PATIENTS AND METHODS. A total of 257 preterm very low birth weight (≤1500 g) infants who met the inclusion criteria were born in Turku University Central Hospital between 2001 and 2006. A total of 209 (84.8%) of 218 survivors participated in the study. The measurements at term included the ventricular brain ratio, the widths of the frontal and occipital horns of the lateral ventricles by ultrasound, total and regional brain volumes by MRI, and head circumference. Brain lesions were defined by ultrasound at 3 to 5, 7 to 10, and 30 days of age monthly until discharge and by MRI and ultrasound at term.

RESULTS. An abnormal ventricular brain ratio (>0.35), an increasing number of dilated ventricular horns, and smaller head circumference were significantly associated with smaller total brain tissue volume. The abnormal ventricular brain ratio and the increasing number of dilated ventricular horns in ultrasound associated with larger ventricular volumes in MRI, and a smaller head circumference was associated significantly with reduced regional brain tissue volumes. Brain lesions were more common in infants with ventriculomegaly.

CONCLUSIONS. The ventricular brain ratio, widths of the lateral ventricular horns, and head circumference are appropriate measures for the estimation of both total and regional brain tissue volumes. Ventriculomegaly is strongly associated with brain lesions.
Effect of Antibiotics for Otitis Media on Mastoiditis in Children: A Retrospective Cohort Study Using the United Kingdom General Practice Research Database
Authors: Thompson Paula Louise , Gilbert Ruth E. , Long Paul F. , Saxena Sonia , Sharland Mike , Wong Ian Chi Kei
Published: January 2009

BACKGROUND. Information is needed on whether mastoiditis has increased in association with the decline in antibiotics prescribed to children by primary care physicians in the United Kingdom.

OBJECTIVE. To determine time trends in mastoiditis incidence, the frequency of antecedent otitis media, and the effect of antibiotics for otitis media on the risk of mastoiditis in children.

PATIENTS AND METHODS. We conducted a retrospective cohort study by using the UK General Practice Research Database. Children aged 3 months to 15 years between 1990 and 2006 were included. Risk of mastoiditis within 3 months after otitis media diagnosis and the protective effect of antibiotics were determined.

RESULTS. There were 2 622 348 children within the General Practice Research Database; 854 had mastoiditis, only one third of whom (35.7%) had antecedent otitis media. Mastoiditis incidence remained stable between 1990 and 2006 (∼1.2 per 10 000 child-years). Risk of mastoiditis, after otitis media, was 1.8 per 10 000 episodes (139 of 792 623) after antibiotics compared with 3.8 per 10 000 (149 of 389 649) without antibiotics, and increased with age. Antibiotics halved the risk of mastoiditis. General practitioners would need to treat 4831 otitis media episodes with antibiotics to prevent 1 child from developing mastoiditis. If antibiotics were no longer prescribed for otitis media, an extra 255 cases of childhood mastoiditis would occur, but there would be 738 775 fewer antibiotic prescriptions per year in the United Kingdom.

CONCLUSIONS. Most children with mastoiditis have not seen their general practitioner for otitis media. Antibiotics halve the risk of mastoiditis, but the high number of episodes needing treatment to prevent 1 case precludes the treatment of otitis media as a strategy for preventing mastoiditis. Although mastoiditis is a serious disease, most children make an uncomplicated recovery after mastoidectomy or intravenous antibiotics. Treating these additional otitis media episodes could pose a larger public health problem in terms of antibiotic resistance.
Noise and Light Exposures for Extremely Low Birth Weight Newborns During Their Stay in the Neonatal Intensive Care Unit
Authors: Lasky Robert E. , Williams Amber L.
Published: January 2009

OBJECTIVES. The objectives of this study were to characterize noise and light levels for extremely low birth weight newborns throughout their stay in the NICU, evaluate factors influencing noise and light levels, and determine whether exposures meet recommendations from the American Academy of Pediatrics.

METHODS. Sound and light were measured inside the beds of extremely low birth weight newborns (n = 22) from birth to discharge. Measurements were recorded for 20 consecutive hours weekly from birth until 36 weeks' postmenstrual age, biweekly until 40 weeks, and every 4 weeks thereafter. Clinical variables including bed type and method of respiratory support were recorded at each session.

RESULTS. Age-related changes in respiratory support and bed type explained the weekly increase of 0.22 dB in sound level and 3.67 lux in light level. Old incubators were the noisiest bed types, and new incubators were the quietest. Light levels were significantly higher in open beds than in incubators. The variations in noise and light levels over time were greatest for open beds. Noise and light levels were much less affected by respiratory support in incubators compared with open beds. A typical extremely low birth weight neonate was exposed to noise levels averaging 56.44 dB(A) and light levels averaging 70.56 lux during their stay from 26 to 42 weeks' postmenstrual age in the NICU. Noise levels were rarely within American Academy of Pediatrics recommendations (5.51% of the time), whereas light levels almost always met recommendations (99.37% of the time).

CONCLUSIONS. Bed type and respiratory support explained differences in noise and light levels that extremely low birth weight newborns experience during their hospital stay. Noise levels exceeded recommendations, although evidence supporting those recommendations is lacking. Well-designed intervention studies are needed to determine the effects of noise reduction on the development of extremely low birth weight newborns.
Does Breastfeeding Protect Against Substantiated Child Abuse and Neglect? A 15-Year Cohort Study
Authors: Strathearn Lane , Mamun Abdullah A. , Najman Jake M. , O'Callaghan Michael J.
Published: January 2009

OBJECTIVES. We explored whether breastfeeding was protective against maternally perpetrated child maltreatment.

METHODS. A total of 7223 Australian mother-infant pairs were monitored prospectively over 15 years. In 6621 (91.7%) cases, the duration of breastfeeding was analyzed with respect to child maltreatment (including neglect, physical abuse, and emotional abuse), on the basis of substantiated child protection agency reports. Multinomial logistic regression was used to compare no maltreatment with nonmaternal and maternally perpetrated maltreatment and to adjust for confounding in 5890 cases with complete data (81.5%). Potential confounders included sociodemographic factors, pregnancy wantedness, substance abuse during pregnancy, postpartum employment, attitudes regarding infant caregiving, and symptoms of anxiety or depression.

RESULTS. Of 512 children with substantiated maltreatment reports, >60% experienced ≥1 episode of maternally perpetrated abuse or neglect (4.3% of the cohort). The odds ratio for maternal maltreatment increased as breastfeeding duration decreased, with the odds of maternal maltreatment for nonbreastfed children being 4.8 times the odds for children breastfed for ≥4 months. After adjustment for confounding, the odds for nonbreastfed infants remained 2.6 times higher, with no association seen between breastfeeding and nonmaternal maltreatment. Maternal neglect was the only maltreatment subtype associated independently with breastfeeding duration.

CONCLUSION. Among other factors, breastfeeding may help to protect against maternally perpetrated child maltreatment, particularly child neglect.
US Infant Mortality Trends Attributable to Accidental Suffocation and Strangulation in Bed From 1984 Through 2004: Are Rates Increasing?
Authors: Shapiro-Mendoza Carrie K. , Kimball Melissa , Tomashek Kay M. , Anderson Robert N. , Blanding Sarah
Published: January 2009

OBJECTIVE. Accidental suffocation and strangulation in bed, a subgroup of sudden, unexpected infant deaths, is a leading mechanism of injury-related infant deaths. We explored trends and characteristics of these potentially preventable deaths.

METHODS. In this descriptive study, we analyzed US infant mortality data from 1984 through 2004. To explore trends in accidental suffocation and strangulation in bed and other sudden, unexpected infant deaths, we calculated cause-specific infant mortality rates and estimated proportionate mortality. Sudden, unexpected infant death was defined as a combination of all deaths attributed to accidental suffocation and strangulation in bed, sudden infant death syndrome, and unknown causes. Finally, we examined factors that were reported as contributing to these accidental suffocation and strangulation in bed deaths.

RESULTS. Between 1984 and 2004, infant mortality rates attributed to accidental suffocation and strangulation in bed increased from 2.8 to 12.5 deaths per 100000 live births. These rates remained relatively stagnant between 1984 and 1992 and increased between 1992 and 2004; the most dramatic increase occurred between 1996 and 2004 (14% average annual increase). In contrast, total sudden, unexpected infant death rates remained stagnant between 1996 and 2004, whereas the proportion of deaths attributed to sudden infant death syndrome declined and to unknown cause increased. Black male infants <4 months of age were disproportionately affected by accidental suffocation and strangulation in bed. Beds, cribs, and couches were reported as places where deaths attributed to accidental suffocation and strangulation in bed occurred.

CONCLUSIONS. Infant mortality rates attributable to accidental suffocation and strangulation in bed have quadrupled since 1984. The reason for this increase is unknown. Prevention efforts should target those at highest risk and focus on helping parents and caregivers provide safer sleep environments.
Longitudinal Brain Volume Changes in Preterm and Term Control Subjects During Late Childhood and Adolescence
Authors: Ment Laura R. , Kesler Shelli , Vohr Betty , Katz Karol H. , Baumgartner Heidi , Schneider Karen C. , Delancy Susan , Silbereis John , Duncan Charles C. , Constable R. Todd , Makuch Robert W. , Reiss Allan L.
Published: January 2009

OBJECTIVE. Although preterm very low birth weight infants have a high prevalence of neuroanatomical abnormalities when evaluated at term-equivalent age, patterns of brain growth in prematurely born infants during school age and adolescence remain largely unknown. Our goal was to test the hypothesis that preterm birth results in long-term dynamic changes in the developing brain.

METHODS. We performed serial volumetric MRI studies at ages 8 and 12 years in 55 preterm infants born weighing 600 to 1250 g and 20 term control children who participated in the follow-up component of a prospective, randomized, placebo-controlled intraventricular hemorrhage prevention study.

RESULTS. Total brain volumes increased 2% to 3% between the ages of 8 and 12 years for both preterm and term children. These changes involved reductions in cerebral gray matter while white matter increased. Between 8 and 12 years of age, preterm subjects experienced a 2% decrease in left cerebral gray matter compared with a 10% reduction in left cerebral gray for term controls. For right cerebral gray matter, preterm children experienced a 3% decrease in volume between years 8 and 12, compared with 9% for term controls (group-by-time). In contrast, preterm subjects had a 10% increase in cerebral white matter volumes bilaterally between ages 8 and 12 years, compared with >26% increases for both hemispheres for term controls. Significant differences in regional volume changes between study groups were found in bilateral temporal gray and in parietal white matter.

CONCLUSIONS. Preterm birth continues to perturb the trajectory of cerebral development during late childhood and early adolescence with preterm children, showing both lower gray matter reduction and less white matter gain over time compared with term control subjects.
Lateral Sinus Thrombosis as a Complication of Otitis Media: 10-Year Experience at the Children's Hospital of Philadelphia
Authors: Bales Christina B. , Sobol Steven , Wetmore Ralph , Elden Lisa M.
Published: January 2009

OBJECTIVES. Lateral sinus thrombosis is a rare intracranial complication of otitis media that is traditionally described in countries with poor access to medical care. Our goal was to describe the clinical presentation, management, and outcome of patients diagnosed with lateral sinus thrombosis in a US tertiary care center and to highlight the clinically relevant differences in presentation between these patients and those described in previous reports.

PATIENTS AND METHODS. The medical charts of 13 patients diagnosed with otogenic lateral sinus thrombosis were reviewed. These patients were identified from a manual search of 156 subjects with International Classification of Diseases, Ninth Revision codes corresponding with a diagnosis of mastoiditis or thromboembolism over a 10-year period (1997–2007) at the Children's Hospital of Philadelphia.

RESULTS. In contrast to previous reports in the literature, the majority of patients in this series exhibited cranial neuropathies and signs of raised intracranial pressure. Nearly all of the patients had a history of acute otitis media treated with antibiotics in the weeks preceding admission. However, many patients denied high fevers or active otomastoid symptoms, which are classically associated with lateral sinus thrombosis. The diagnosis was made in all of the children by using computed tomography and MRI/venography. Treatment strategies included myringotomy tube placement, simple mastoidectomy, intravenous antibiotics, and anticoagulation. Posthospitalization follow-up data revealed no significant long-term complications.

CONCLUSIONS. Despite appropriate antibiotic therapy, lateral sinus thrombosis and other intracranial complications of otitis media are still a threat to children in the modern era. Neurologic, rather than otologic, symptoms may dominate the presentation of otogenic lateral sinus thrombosis. Thus, a high index of suspicion may be critical for ensuring timely diagnosis of this rare condition.
Being Bullied: Associated Factors in Children and Adolescents 8 to 18 Years Old in 11 European Countries
Authors: Analitis Filippos , Velderman Mariska Klein , Ravens-Sieberer Ulrike , Detmar Symone , Erhart Michael , Herdman Mike , Berra Silvina , Alonso Jordi , Rajmil Luis ,   and the European Kidscreen Group
Published: January 2009

OBJECTIVES. To analyze the prevalence of bullying victims among children and adolescents aged 8 to 18 years in 11 European countries and to investigate the associated sociodemographic, physical, and psychosocial factors.

METHODS. Being a bullying victim was measured by using the social acceptance (bullying) scale from the Kidscreen-52, a health-related quality-of-life questionnaire administered to 16 210 children and adolescents aged 8 to 18 and their parents in postal or school-based surveys in 11 European countries. Standardized mean differences (effect size) were computed to measure the percentage of children/adolescents scoring 1 SD below the mean on the Kidscreen bullying scale. Logistic regression models were used to determine which sociodemographic, physical, and psychosocial factors were associated with being bullied.

RESULTS. The percentage of children being bullied was 20.6% for the entire sample, ranging from 10.5% in Hungary to 29.6% in the United Kingdom. In almost all countries the factors most strongly associated with being bullied were younger age, having probable mental health problems, having a low score on the Kidscreen-52 moods and emotions dimensions, and poor social support. Using the grand mean for all countries as the reference category, there was an above-average likelihood of children or adolescents reporting that they had been victims of bullying in 5 countries (Austria, Netherlands, Spain, Switzerland, and the United Kingdom), and a below-average likelihood in 3 countries (France, Greece, Hungary).

CONCLUSIONS. This study indicated considerable variation between countries in the prevalence of those perceiving themselves to be victims of bullying but also revealed a clear profile of those likely to be bullied. The study also suggests that the Kidscreen bullying scale could be useful in identifying potential bullying victims.
Effects of Sleep Deprivation on the Pediatric Electroencephalogram
Authors: DeRoos Steven T. , Chillag Kipp L. , Keeler Martina , Gilbert Donald L.
Published: January 2009

BACKGROUND. The routine electroencephalogram aids in epilepsy syndrome diagnosis. Unfortunately, routine outpatient electroencephalogram results are normal in roughly half of children with epilepsy. To increase the yield, practice guidelines recommend electroencephalograms with sleep and sleep deprivation. The purpose of this study was to rigorously evaluate this recommendation in children.

METHODS. We conducted a randomized, blinded comparison of routine electroencephalograms versus sleep-deprived electroencephalograms in 206 children aged 0 to 18 years. Electroencephalograms were ordered for standard indications after a neurologist's clinical assessment indicated ≥1 seizure (83%) or unclear spell (17%). The primary outcome was the proportion of normal routine electroencephalogram results versus sleep-deprived electroencephalogram results. Logistic regression modeling was used to assess the influence of sleep, as well as other clinical factors.

RESULTS. Although children with sleep-deprived electroencephalograms had less sleep the night before (4.9 vs 7.9 hours) and more sleep during electroencephalograms (73% vs 55%), the increase in electroencephalogram yield was borderline significant (56% normal sleep-deprived electroencephalogram versus 68% normal routine electroencephalogram). Moreover, sleep during the electroencephalogram did not increase its diagnostic yield. Sleep-deprived electroencephalogram yield tended to be higher in children with preelectroencephalogram clinical diagnosis of seizure(s) and at older ages (>3 years).

CONCLUSIONS. Sleep deprivation, but not sleep during the electroencephalogram, modestly increases the yield of the electroencephalogram in children diagnosed with seizures by neurologists. Compared with a routine electroencephalogram, the number needed to test with sleep-deprived electroencephalogram to identify 1 additional child with epileptiform discharges is ∼11.
Spectrum and Management of Hypertriglyceridemia Among Children in Clinical Practice
Authors: Manlhiot Cedric , Larsson Per , Gurofsky Rebecca C. , Smith Ryan W. , Fillingham Catherine , Clarizia Nadia A. , Chahal Nita , Clarke Joseph T. , McCrindle Brian W.
Published: January 2009

OBJECTIVES. The prevalence and identification of hypertriglyceridemia in youths will likely will increase in the future as a consequence of childhood obesity and increased screening for dyslipidemias. We sought to review our clinical experience with hypertriglyceridemia, evaluate factors associated with increased triglyceride levels, and review treatment options to provide guidance for management.

METHODS. Clinical review of data for all patients who had ≥1 elevated triglyceride level (>4 mmol/L [>350 mg/dL]) while being monitored in a specialized lipid disorders clinic was performed.

RESULTS. The study population consisted of 76 patients with 761 clinic visits. Hypertriglyceridemia was secondary to lifestyle factors for 13 patients. The rest had primary hypertriglyceridemia, with 32 patients having familial combined hypertriglyceridemia and hypercholesterolemia (type II), 25 patients having primary hypertriglyceridemia (type IV), 4 patients having familial lipase deficiency (type I), and 2 patients having hyperlipoproteinemia E2/E2 phenotype (type III). Triglyceride levels were highest in type I and III hypertriglyceridemia (>10 mmol/L [>900 mg/dL]), followed by type IV and adiposity-related hypertriglyceridemia (>4 mmol/L [>350 mg/dL]) and finally type II familial combined hypertriglyceridemia and hypercholesterolemia (>2 mmol/L [>180 mg/dL]). A total of 34 patients received 37 trials of drug therapy as part of triglyceride level management (bile acid–binding resins, n = 12; fibrates, n = 19; statins, n = 6). Triglyceride levels were found to decrease over time with the use of fibrates, to increase with the use of bile acid–binding resins, and not to change with the use of statins.

CONCLUSIONS. Lifestyle modifications remain the primary therapeutic avenue for the management of pediatric hypertriglyceridemia. We propose an algorithm for the management of this heterogeneous population to guide clinicians in their treatment decisions.
Performance of a Rapid Antigen-Detection Test and Throat Culture in Community Pediatric Offices: Implications for Management of Pharyngitis
Authors: Tanz Robert R. , Gerber Michael A. , Kabat William , Rippe Jason , Seshadri Roopa , Shulman Stanford T.
Published: January 2009

OBJECTIVES. The goals were to establish performance characteristics of a rapid antigen-detection test and blood agar plate culture performed and interpreted in community pediatric offices and to assess the effect of the pretest likelihood of group A streptococcus pharyngitis on test performance (spectrum bias).

METHODS. Two throat swabs were collected from 1848 children 3 to 18 years of age who were evaluated for acute pharyngitis between November 15, 2004, and May 15, 2005, in 6 community pediatric offices. One swab was used to perform the rapid antigen-detection test and a blood agar plate culture in the office and the other was sent to our laboratory for blood agar plate culture. Clinical findings were used to calculate the McIsaac score for each patient. The sensitivities of the office tests were calculated, with the hospital laboratory culture results as the criterion standard.

RESULTS. Thirty percent of laboratory blood agar plate cultures yielded group A streptococcus (range among sites: 21%–36%). Rapid antigen-detection test sensitivity was 70% (range: 61%–80%). Office culture sensitivity was significantly greater, 81% (range: 71%–91%). Rapid antigen-detection test specificity was 98% (range: 98%–99.5%), and office culture specificity was 97% (range: 94%–99%), a difference that was not statistically significant. The sensitivity of a combined approach using the rapid antigen-detection test and back-up office culture was 85%. Among patients with McIsaac scores of >2, rapid antigen-detection test sensitivity was 78%, office culture sensitivity was 87%, and combined approach sensitivity was 91%. Positive diagnostic test results were significantly associated with McIsaac scores of >2.

CONCLUSIONS. The sensitivity of the office culture was significantly greater than the sensitivity of the rapid antigen-detection test, but neither test was highly sensitive. The sensitivities of each diagnostic modality and the recommended combined approach were best among patients with greater pretest likelihood of group A streptococcus pharyngitis.
Increasing Adherence to Inhaled Steroid Therapy Among Schoolchildren: Randomized, Controlled Trial of School-Based Supervised Asthma Therapy
Authors: Gerald Lynn B. , McClure Leslie A. , Mangan Joan M. , Harrington Kathy F. , Gibson Linda , Erwin Sue , Atchison Jody , Grad Roni
Published: January 2009

OBJECTIVE. We aimed to determine the effectiveness of school-based supervised asthma therapy in improving asthma control. The primary hypothesis was that the supervised-therapy group would have a smaller proportion of children experiencing an episode of poor asthma control each month, compared with those in the usual-care group.

METHODS. Children were eligible if they had physician-diagnosed persistent asthma, the need for daily controller medication, and the ability to use a dry-powder inhaler and a peak flowmeter. The trial used a 2-group, randomized, longitudinal design with a 15-month follow-up period. A total of 290 children from 36 schools were assigned randomly to either school-based, supervised therapy or usual care. Ninety-one percent of the children were black, and 57% were male. The mean age was 11 years (SD: 2.1 years). An episode of poor asthma control was defined as ≥1 of the following each month: (1) an absence from school attributable to respiratory illness/asthma; (2) average use of rescue medication >2 times per week (not including preexercise treatment); or (3) ≥1 red or yellow peak flowmeter reading.

RESULTS. Two hundred forty children completed the study. There were no differences in the likelihood of an episode of poor asthma control between the baseline period and the follow-up period for the usual-care group. For the supervised-therapy group, however, the odds of experiencing an episode of poor asthma control during the baseline period were 1.57 times the odds of experiencing an episode of poor asthma control during the follow-up period. Generalized estimating equation modeling revealed a marginally significant intervention–time period interaction, indicating that children in the supervised-therapy group showed greater improvement in asthma control.

CONCLUSIONS. Supervised asthma therapy improves asthma control. Clinicians who have pediatric patients with asthma with poor outcomes that may be attributable to nonadherence should consider supervised therapy.