bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel FK506-Like Binding Protein Interacts with the Glucocorticoid Receptor and Regulates Steroid Receptor Signaling
Authors: McKeen Hayley D. , McAlpine Kerry , Valentine Andrea , Quinn Derek J. , McClelland Keeva , Byrne Christopher , O'Rourke Martin , Young Sheila , Scott Christopher J. , McCarthy Helen O. , Hirst David G. , Robson Tracy
Published: August 2008

FKBP-like (FKBPL) protein is a novel immunophilin-like protein that plays a role in the cellular stress response. Its three tetratricopeptide repeat motifs are homologous to the heat shock protein 90 interaction sites of other immunophilins that have roles in steroid hormone receptor signaling. In this study, using biomolecular complementation and coimmunoprecipitation techniques, we show that FKBPL also colocalizes and interacts with the components of the heat shock protein 90-glucocorticoid receptor (GR) complex and demonstrate that the PPIase domain of FKBPL is important for the interaction between this complex and the dynein motor protein, dynamitin. Treatment of DU145 cells with the GR ligand, dexamethasone, induced a rapid and coordinated translocation of both GR and FKBPL to the nucleus; this response was perturbed when FKBPL was knocked down with a targeted small interfering RNA. Furthermore, overexpression of FKBPL increased GR protein levels and transactivation of a luciferase reporter gene in response to dexamethasone in DU145 cells. However, these responses were cell line dependent. In summary, these data suggest that FKBPL can be classed as a new member of the FKBP protein family with a role in steroid receptor complexes and signaling.
Up-Regulation of 3′5′-Cyclic Guanosine Monophosphate-Specific Phosphodiesterase in the Porcine Cumulus-Oocyte Complex Affects Steroidogenesis during in Vitro Maturation
Authors: Sasseville Maxime , Côté Nancy , Gagnon Marie-Claude , Richard François J.
Published: August 2008

The 3′5′-cyclic GMP (cGMP) pathway is known to influence ovarian functions, including steroidogenesis, ovulation, and granulosa cell proliferation. We show here that cGMP-phosphodiesterase (PDE) activity increased in a gonadotropin-dependent manner more than 3-fold in the cumulus-oocyte complex (COC) after 24 h in vitro maturation (IVM) and up to 5-fold after 48 h. Further characterization of this increase demonstrated that the activity was located primarily in cumulus cells, and was sensitive to sildenafil and zaprinast, two inhibitors specific to both type 5 and 6 PDEs. RT-PCR experiments showed that the mRNAs for cGMP-degrading PDEs 5A and 6C are present in the COC before and after 30 h IVM. Western blotting confirmed the presence of PDE 5A in the COC. Western blotting of PDE 6C revealed a significant up-regulation in the COC during IVM. Isolation and analysis of detergent-resistant membranes suggested that PDE 6C protein, along with half of the total sildenafil-sensitive cGMP-degradation activity, is associated with detergent-resistant membrane in the COC after 30 h IVM. Treatment of porcine COC with sildenafil during IVM caused a significant decrease in gonadotropin-stimulated progesterone secretion. Together, these results constitute the first report exploring the contribution of cGMP-PDE activity in mammalian COC, supporting a functional clustering of the enzyme, and providing the first evidence of its role in steroidogenesis.
Selective Inactivation of Socs3 in SF1 Neurons Improves Glucose Homeostasis without Affecting Body Weight
Authors: Zhang Ren , Dhillon Harveen , Yin Huali , Yoshimura Akihiko , Lowell Bradford B. , Maratos-Flier Eleftheria , Flier Jeffrey S.
Published: August 2008

Suppressor of cytokine signaling 3 (Socs3) has been identified as a mediator of central leptin resistance, but the identity of specific neurons in which Socs3 acts to suppress leptin signaling remains elusive. The ventromedial hypothalamus (VMH) was recently shown to be an important site for leptin action because deleting leptin receptor within VMH neurons causes obesity. To examine the role of VMH Socs3 in leptin resistance and energy homeostasis, we generated mice lacking Socs3 specifically in neurons positive for steroidogenic factor 1 (SF1), which is expressed abundantly in the VMH. These mice had increased phosphorylation of signal transducer and activator of transcription-3 in VMH neurons, suggesting improved leptin signaling, and consistently, food intake and weight-reducing effects of exogenous leptin were enhanced. Furthermore, on either chow or high-fat diets, these mice had reduced food intake. Unexpectedly, energy expenditure was reduced as well. Mice lacking Socs3 in SF1 neurons, despite no change in body weight, had improved glucose homeostasis and were partially protected from hyperglycemia and hyperinsulinemia induced by high-fat diets. These results suggest that Socs3 in SF1 neurons negatively regulates leptin signaling and plays important roles in mediating leptin sensitivity, glucose homeostasis, and energy expenditure.
A Mass Spectrometric Approach for the Study of the Metabolism of Clomiphene, Tamoxifen and Toremifene by Liquid Chromatography Time-of-Flight Spectroscopy
Authors: Mazzarino Monica , Fiacco Ilaria , de la Torre Xavier , Botrè Francesco
Published: August 2008

In this paper, we discuss the capabilities of liquid chromatography coupled to mass spectrometry with a time-of-flight system with accurate mass measurement for the detection and characterisation of drug metabolites in biological samples for anti-doping purpose. Urinary excretion samples of three selective oestrogen receptor modulators (SERMs) with a common triphenylethylene structure: clomiphene, toremifene and tamoxifen, obtained after oral administration of a single dose of each drug, were analysed using a time-offlight system, after automatic tuning and calibration of the equipment, in positive full scan mode using an electrospray ionisation source. Following this approach we detected most of all significant metabolites reported by others and postulated new metabolites, especially for toremifene, have been characterised: N-demethyl-3-hydroxy-4-methoxy-toremifene and 3-hydroxy-4-methoxy-toremifene; in addtion to this, in the urinary excretion samples of toremifene some metabolites, without the characteristic chlorine isotope pattern, discarded in previous studies, that are also metabolites of tamoxifen, were identified. The lack of certified reference materials does not allow an accurate determination of the limit of detection (LODs) of all metabolites; however, an estimation taking into account the response factor of similar compounds allows to estimate that all metabolites are clearly detectable in a range of concentration comprised between 10 ng mL−1 and 30 ng mL−1.
Screening of In Vitro Synthesised Metabolites of 4,9,11-Trien-3-One Steroids by Liquid Chromatography-Mass Spectrometry
Authors: Kuuranne Tiia , Pystynen Kati-Henna , Thevis Mario , Leinonen Antti , Schänzer Wilhelm , Kostiainen Risto
Published: August 2008

The aim of the work was to develop a flexible in vitro synthesis procedure, which can be applied in order to study and predict the metabolic patterns of new derivatives of anabolic androgenic steroids (AAS) with respect to most prominent target compounds for doping control purposes. Microsomal and S9 fraction of human liver preparations were used as a source of metabolising enzymes and the co-substrates of the synthesis mixture were selected to favour phase-I metabolic reactions and glucuronidation as phase-II conjugation reactions. Model compounds within the study were 4,9,11-trien-3-one steroids, structural derivatives of gestrinone and trenbolone, which both are included in the list of prohibited compounds in sports by the World Anti-Doping Agency (WADA). The correlation between in vitro metabolism of human microsomes and in vivo excretion studies in human was compared with gestrinone and subsequently, the applicability of the in vitro model for prediction of AAS metabolic pathways for new doping agents was evaluated. All the AAS examined within this study were successfully metabolised using the developed in vitro model, hydroxylation, reduction and glucuronide-conjugation being the most prominent reaction pathways. Hydroxylated and glucuronide-conjugated metabolites of in vivo experiment with gestrinone were the same metabolites formed in the enzyme-driven process, thus showing good in vitro-in vivo correlation. Liquid chromatographic-mass spectrometric and tandem mass spectrometric methods were developed, relying on the positive polarity of electrospray ionisation, which also allowed the direct detection of intact glucuronide-conjugated AAS metabolites. Due to charge delo-calisation and high proton affinity, the developed method was proven effective in the analysis of AAS metabolites bearing extensive conjugated double bond systems in their structures.
Determination of Selected Stimulants in Urine for Sports Drug Analysis by Solid Phase Extraction via Cation Exchange and Means of Liquid Chromatography-Tandem Mass Spectrometry
Authors: Thomas Andreas , Sigmund Gerd , Guddat Sven , Schänzer Wilhelm , Thevis Mario
Published: August 2008

Stimulatory substances applied during competition possess a reasonable potential as performance enhancing agents and their misuse in elite sport has been frequently reported during the last few decades. An analytical method for the qualitative determination of selected stimulants containing a primary or secondary amine moiety in human urine for doping control purposes was developed. A rapid and highly specific procedure based on a sample preparation using weak cation exchange solid phase extraction (SPE-XCW) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a C6-Phenyl analytical column allowed the unambiguous identification of the target analytes down to low ng mL−1 concentration levels. Validation provided recovery rates of better than 75%, precisions of less than 20% and a linear approximation in the required working range (10–750 ng mL−1) were obtained for 19 different target compounds. This method provides a rugged and highly specific alternative to the established method utilising gas or liquid chromatography after liquid–liquid extraction.
Estimating the Influence of Fairness on Bargaining Behavior
Authors: De Bruyn Arnaud , Bolton Gary E.
Published: August 2008

The strength of bargainers' preferences for fair settlements has important implications for predicting negotiation outcomes and guiding bargaining strategy. Existing literature reports a few calibration exercises for social utility models, but the predictive accuracy of these models for out-of-sample forecasting remains unknown. Therefore, we investigate whether fairness considerations are stable enough across bargaining situations to be quantified and used to forecast bargaining behavior accurately. We develop a model that embeds a preference for fair treatment in a quantal response framework to account for noise and experience. In addition, we estimate preference for fairness (willingness to pay) using the simplest, one-round version of sequential bargaining games and then employ it to perform out-of-sample forecasts of multiple-round games of various lengths, discount factors, pie sizes, and levels of bargainer experience. Except in circumstances in which the bargaining pie is very small, the fitted model has significant and substantial out-of-sample explanatory power. The stability we find implies that the model and techniques might ultimately be extended to estimates of the influence of fairness on field negotiations, as well as across subpopulations.
Snapback Primer Genotyping with Saturating DNA Dye and Melting Analysis
Authors: Zhou Luming , Errigo Roscoe J , Lu Hongzhe , Poritz Mark A , Seipp Michael T , Wittwer Carl T
Published: August 2008

Background: DNA hairpins have been used in molecular analysis of PCR products as self-probing amplicons. Either physical separation or fluorescent oligonucleotides with covalent modifications were previously necessary.

Methods: We performed asymmetric PCR for 40–45 cycles in the presence of the saturating DNA dye, LCGreen Plus, with 1 primer including a 5′ tail complementary to its extension product, but without any special covalent modifications. Samples were amplified either on a carousel LightCycler for speed or on a 96/384 block cycler for throughput. In addition to full-length amplicon duplexes, single-stranded hairpins were formed by the primer tail “snapping back” and hybridizing to its extension product. High-resolution melting was performed on a HR-1 (for capillaries) or a LightScanner (for plates).

Results: PCR products amplified with a snapback primer showed both hairpin melting at lower temperature and full-length amplicon melting at higher temperature. The hairpin melting temperature was linearly related to the stem length (6–28 bp) and inversely related to the log of the loop size (17–135 bases). We easily genotyped heterozygous and homozygous variants within the stem, and 100 blinded clinical samples previously typed for F5 1691G>A (Leiden) were completely concordant by snapback genotyping. We distinguished 7 genotypes in 2 regions of CFTR exon 10 with symmetric PCR using 2 snapback primers followed by product dilution to favor intramolecular hybridization.

Conclusions: Snapback primer genotyping with saturating dyes provides the specificity of a probe with only 2 primers that are free of special covalent labels in a closed-tube system.
Educational Perspectives
Authors: Izatt Susan
Published: August 2008

The ability to communicate effectively with families in the neonatal intensive care unit (NICU) is an essential skill for clinicians. Parental satisfaction and trust depend on the perception of open communication that reflects compassion, honesty, and caring. Families struggling with difficult situations in the NICU derive great benefit from discussions in which information is provided clearly and with empathy. Strategies for delivering bad news have been developed within the medical community and can be adapted for difficult discussions in the NICU. Such strategies can be integrated within an interactive curriculum that emphasizes simulation and role play to promote competency in communication skills.
Influence of Having Breakfast on Cognitive Performance and Mood in 13- to 20-Year-Old High School Students: Results of a Crossover Trial
Authors: Widenhorn-Müller Katharina , Hille Katrin , Klenk Jochen , Weiland Ulrike
Published: August 2008

OBJECTIVE. The goal was to determine whether breakfast had effects on the cognitive performance and mood of high school students.

METHODS. A crossover trial was performed in boarding schools, involving 104 students between 13 and 20 years of age. The participants were randomly assigned to 2 equal-size groups on the morning of the first testing day. One half of the total sample received a standardized breakfast, whereas the other half received no breakfast. Seven days later, the treatment order was reversed. Measurements of cognitive function included standardized tests of attention and concentration, as well as tests of verbal and spatial memory. In addition, mood was rated with a self-administered questionnaire covering the dimensions of positive and negative affect, information uptake, arousal, and alertness. Statistical analysis consisted of repeated-measures analysis of variance.

RESULTS. Breakfast had no effect on sustained attention among high school students. Visuospatial memory was improved in male students. Self-reported alertness improved significantly in the entire study population. Male students reported feeling more positive after consuming breakfast, compared with the fasting condition.

CONCLUSIONS. This crossover trial demonstrated positive short-term effects of breakfast on cognitive functioning and self-reported alertness in high school students.
Exposure of US Adolescents to Extremely Violent Movies
Authors: Worth Keilah A. , Gibson Chambers Jennifer , Nassau Daniel H. , Rakhra Balvinder K. , Sargent James D.
Published: August 2008

OBJECTIVE. Despite concerns about exposure to violent media, there are few data on youth exposure to violent movies. In this study we examined such exposure among young US adolescents.

METHODS. We used a random-digit-dial survey of 6522 US adolescents aged 10 to 14 years fielded in 2003. Using previously validated methods, we determined the percentage and number of US adolescents who had seen each of 534 recently released movies. We report results for the 40 that were rated R for violence by the Motion Picture Association of America, UK 18 by the British Board of Film Classification and coded for extreme violence by trained content coders.

RESULTS. The 40 violent movies were seen by a median of 12.5% of an estimated 22 million US adolescents aged 10 to 14 years. The most popular violent movie, Scary Movie, was seen by >10 million (48.1%) children, 1 million of whom were 10 years of age. Watching extremely violent movies was associated with being male, older, nonwhite, having less-educated parents, and doing poorly in school. Black male adolescents were at particularly high risk for seeing these movies; for example Blade, Training Day, and Scary Movie were seen, respectively, by 37.4%, 27.3%, and 48.1% of the sample overall versus 82.0%, 81.0%, and 80.8% of black male adolescents. Violent movie exposure was also associated with measures of media parenting, with high-exposure adolescents being significantly more likely to have a television in their bedroom and to report that their parents allowed them to watch R-rated movies.

CONCLUSIONS. This study documents widespread exposure of young US adolescents to movies with extreme graphic violence from movies rated R for violence and raises important questions about the effectiveness of the current movie-rating system.
Placental Growth Factor and Vascular Endothelial Growth Factor Receptor-2 in Human Lung Development
Authors: Janér Joakim , Andersson Sture , Haglund Caj , Karikoski Riitta , Lassus Patrik
Published: August 2008

OBJECTIVE. We examined the pulmonary expression of 2 proangiogenic factors, namely, placental growth factor and vascular endothelial growth factor receptor-2, during lung development and acute and chronic lung injury in newborn infants.

METHODS. Six groups were included in an immunohistochemical study of placental growth factor and vascular endothelial growth factor receptor-2, that is, 9 fetuses, 4 preterm and 8 term infants without lung injury who died soon after birth, 5 preterm infants with respiratory distress syndrome of <2 days and 7 with respiratory distress syndrome of >10 days, and 6 with bronchopulmonary dysplasia. Placental growth factor concentrations in tracheal aspirate fluid were measured in 70 samples from 20 preterm infants during the first postnatal week.

RESULTS. In immunohistochemical analyses, placental growth factor staining was seen in bronchial epithelium and macrophages in all groups. Distal airway epithelium positivity was observed mostly in fetuses and in preterm infants who died soon after birth. Vascular endothelial growth factor receptor-2 staining was seen in vascular endothelium in all groups and also in lymphatic endothelium in fetuses. Vascular endothelial growth factor receptor-2 staining in arterial endothelium was associated with higher and staining in venous endothelium with lower gestational age. In capillaries, less vascular endothelial growth factor receptor-2 staining was seen in bronchopulmonary dysplasia. The mean placental growth factor protein concentration in tracheal aspirate fluid during the first postnatal week was 0.64 ± 0.42 pg/mL per IgA-secretory component unit. Concentrations during the first postnatal week were stable. Lower placental growth factor concentrations correlated with chorioamnionitis and lactosyl ceramide positivity.

CONCLUSIONS. The vascular endothelial growth factor receptor-2 staining pattern seems to reflect ongoing differentiation and activity of different endothelia. Lower vascular endothelial growth factor receptor-2 expression in capillary endothelium in bronchopulmonary dysplasia might be a reflection of the dysregulation of vascular development that is characteristic of bronchopulmonary dysplasia.
Pediatric Residents’ Use of Jargon During Counseling About Newborn Genetic Screening Results
Authors: Farrell Michael , Deuster Lindsay , Donovan Jodi , Christopher Stephanie
Published: August 2008

OBJECTIVE. The goal was to investigate pediatric residents’ usage of jargon during discussions about positive newborn screening test results.

METHODS. An explicit-criteria abstraction procedure was used to identify jargon usage and explanations in transcripts of encounters between residents and standardized parents of a fictitious infant found to carry cystic fibrosis or sickle cell hemoglobinopathy. Residents were recruited from a series of educational workshops on how to inform parents about positive newborn screening test results. The time lag from jargon words to explanations was measured by using “statements,” each of which contained 1 subject and 1 predicate.

RESULTS. Duplicate abstraction revealed reliability κ of 0.92. The average number of unique jargon words per transcript was 20; the total jargon count was 72.3 words. There was an average of 7.5 jargon explanations per transcript, but the explained/total jargon ratio was only 0.17. When jargon was explained, the average time lag from the first usage to the explanation was 8.2 statements.

CONCLUSION. The large number of jargon words and the small number of explanations suggest that physicians’ counseling about newborn screening may be too complex for some parents.
Effects of the Accreditation Council for Graduate Medical Education Duty Hour Limits on Sleep, Work Hours, and Safety
Authors: Landrigan Christopher P. , Fahrenkopf Amy M. , Lewin Daniel , Sharek Paul J. , Barger Laura K. , Eisner Melanie , Edwards Sarah , Chiang Vincent W. , Wiedermann Bernhard L. , Sectish Theodore C.
Published: August 2008

OBJECTIVE. To mitigate the risks of fatigue-related medical errors, the Accreditation Council for Graduate Medical Education introduced work hour limits for resident physicians in 2003. Our goal was to determine whether work hours, sleep, and safety changed after implementation of the Accreditation Council for Graduate Medical Education standards.

METHODS. We conducted a prospective cohort study in which residents from 3 large pediatric training programs provided daily reports of work hours and sleep. In addition, they completed reports of near-miss and actual motor vehicle crashes, occupational exposures, self-reported medical errors, and ratings of educational experience. They were screened for depression and burnout. Concurrently, at 2 of the centers, data on medication errors were collected prospectively by using an established active surveillance method.

RESULTS. A total of 220 residents provided 6007 daily reports of their work hours and sleep, and 16 158 medication orders were reviewed. Although scheduling changes were made in each program to accommodate the standards, 24- to 30-hour shifts remained common, and the frequency of residents’ call remained largely unchanged. There was no change in residents’ measured total work hours or sleep hours. There was no change in the overall rate of medication errors, and there was a borderline increase in the rate of resident physician ordering errors, from 1.06 to 1.38 errors per 100 patient-days. Rates of motor vehicle crashes, occupational exposures, depression, and self-reported medical errors and overall ratings of work and educational experiences did not change. The mean length of extended-duration (on-call) shifts decreased 2.7% to 28.5 hours, and rates of resident burnout decreased significantly (from 75.4% to 57.0%).

CONCLUSIONS. Total hours of work and sleep did not change after implementation of the duty hour standards. Although fewer residents were burned out, rates of medication errors, resident depression, and resident injuries and educational ratings did not improve.
Supplemental Oxygen Compromises the Use of Pulse Oximetry for Detection of Apnea and Hypoventilation During Sedation in Simulated Pediatric Patients
Authors: Keidan Ilan , Gravenstein Dietrich , Berkenstadt Haim , Ziv Amitai , Shavit Itay , Sidi Avner
Published: August 2008

OBJECTIVE. The goal was to assess the time to recognition of apnea in a simulated pediatric sedation scenario, with and without supplemental oxygen.

METHODS. A pediatric human patient simulator mannequin was used to simulate apnea in a 6-year-old patient who received sedation for resetting of a fractured leg. Thirty pediatricians participating in a credentialing course for sedation were randomly assigned to 2 groups. Those in group 1 (N = 15) used supplemental oxygen, and those in group 2 (N = 15) did not use supplemental oxygen. A third group (N = 10), consisting of anesthesiology residents (postgraduate years 2 and 3 equivalent), performed the scenario with oxygen supplementation, to ensure validity and reliability of the simulation. The time interval from simulated apnea to bag-mask ventilation was recorded. Oxygen saturation and Paco2 values were recorded. All recorded variables and measurements were compared between the groups.

RESULTS. The time interval for bag-mask ventilation to occur in group 1 (oxygen supplementation) was significantly longer than that in group 2 (without oxygen supplementation) (173 ± 130 and 83 ± 42 seconds, respectively). The time interval for bag-mask ventilation to occur was shorter in group 3 (anesthesiology residents) (24 ± 6 seconds). Paco2 reached a higher level in group 1 (75 ± 26 mmHg), compared with groups 2 and 3 (48 ± 10 and 42 ± 3 mmHg, respectively). There was no significant difference between the groups in oxygen saturation values at the time of clinical detection of apnea (93 ± 5%, 88 ± 5%, and 94 ± 7%, respectively).

CONCLUSIONS. Hypoventilation and apnea are detected more quickly when patients undergoing sedation breathe only air. Supplemental oxygen not only does not prevent oxygen desaturation but also delays the recognition of apnea.
Growth Characteristics of Infantile Hemangiomas: Implications for Management
Authors: Chang Linda C. , Haggstrom Anita N. , Drolet Beth A. , Baselga Eulalia , Chamlin Sarah L. , Garzon Maria C. , Horii Kimberly A. , Lucky Anne W. , Mancini Anthony J. , Metry Denise W. , Nopper Amy J. , Frieden Ilona J. ,   for the Hemangioma Investigator Group
Published: August 2008

OBJECTIVES. Infantile hemangiomas often are inapparent at birth and have a period of rapid growth during early infancy followed by gradual involution. More precise information on growth could help predict short-term outcomes and make decisions about when referral or intervention, if needed, should be initiated. The objective of this study was to describe growth characteristics of infantile hemangioma and compare growth with infantile hemangioma referral patterns.

METHODS. A prospective cohort study involving 7 tertiary care pediatric dermatology practices was conducted. Growth data were available for a subset of 526 infantile hemangiomas in 433 patients from a cohort study of 1096 children. Inclusion criteria were age younger than 18 months at time of enrollment and presence of at least 1 infantile hemangioma. Growth stage and rate were compared with clinical characteristics and timing of referrals.

RESULTS. Eighty percent of hemangioma size was reached during the early proliferative stage at a mean age of 3 months. Differences in growth between hemangioma subtypes included that deep hemangiomas tend to grow later and longer than superficial hemangiomas and that segmental hemangiomas tended to exhibit more continued growth after 3 months of age. The mean age of first visit was 5 months. Factors that predicted need for follow-up included ongoing proliferation, larger size, deep component, and segmental and indeterminate morphologic subtypes.

CONCLUSIONS. Most infantile hemangioma growth occurs before 5 months, yet 5 months was also the mean age at first visit to a specialist. Recognition of growth characteristics and factors that predict the need for follow-up could help aid in clinical decision-making. The first few weeks to months of life are a critical time in hemangioma growth. Infants with hemangiomas need close observation during this period, and those who need specialty care should be referred and seen as early as possible within this critical growth period.
Blood Pressure Variability and Classification of Prehypertension and Hypertension in Adolescence
Authors: Falkner Bonita , Gidding Samuel S. , Portman Ronald , Rosner Bernard
Published: August 2008

OBJECTIVE. There is little information in pediatrics on the persistence of the prehypertension and hypertension classifications or on the progression of prehypertension to hypertension. This study aimed to examine those issues.

METHODS. An analysis of data from the National Childhood Blood Pressure database was conducted to examine the longitudinal blood pressure outcomes for adolescents classified after a single measurement of blood pressure. Adolescent subjects (N = 8535) for whom serial single blood pressure measurements were obtained at intervals of 2 years were identified. Subjects were stratified according to blood pressure status at the initial measurement, as having normotension, prehypertension, or hypertension.

RESULTS. Among subjects designated as having prehypertension (n = 1470), 14% of boys and 12% of girls had hypertension 2 years later. Among subjects designated as having hypertension, 31% of boys and 26% of girls continued to exhibit hypertension, and 47% of boys and 26% of girls had blood pressure values in the prehypertensive range. Regression models showed no significant effect of race on blood pressure changes but significant effects of initial BMI and changes in BMI.

CONCLUSIONS. These data indicated that the rate of progression of prehypertension to hypertension was ∼7% per year. Prehypertension can be predictive of future hypertension and may benefit from preventive interventions, especially lifestyle changes.
A Video Game Improves Behavioral Outcomes in Adolescents and Young Adults With Cancer: A Randomized Trial
Authors: Kato Pamela M. , Cole Steve W. , Bradlyn Andrew S. , Pollock Brad H.
Published: August 2008

OBJECTIVE. Suboptimal adherence to self-administered medications is a common problem. The purpose of this study was to determine the effectiveness of a video-game intervention for improving adherence and other behavioral outcomes for adolescents and young adults with malignancies including acute leukemia, lymphoma, and soft-tissue sarcoma.

METHODS. A randomized trial with baseline and 1- and 3-month assessments was conducted from 2004 to 2005 at 34 medical centers in the United States, Canada, and Australia. A total of 375 male and female patients who were 13 to 29 years old, had an initial or relapse diagnosis of a malignancy, and currently undergoing treatment and expected to continue treatment for at least 4 months from baseline assessment were randomly assigned to the intervention or control group. The intervention was a video game that addressed issues of cancer treatment and care for teenagers and young adults. Outcome measures included adherence, self-efficacy, knowledge, control, stress, and quality of life. For patients who were prescribed prophylactic antibiotics, adherence to trimethoprim-sulfamethoxazole was tracked by electronic pill-monitoring devices (n = 200). Adherence to 6-mercaptopurine was assessed through serum metabolite assays (n = 54).

RESULTS. Adherence to trimethoprim-sulfamethoxazole and 6-mercaptopurine was greater in the intervention group. Self-efficacy and knowledge also increased in the intervention group compared with the control group. The intervention did not affect self-report measures of adherence, stress, control, or quality of life.

CONCLUSIONS. The video-game intervention significantly improved treatment adherence and indicators of cancer-related self-efficacy and knowledge in adolescents and young adults who were undergoing cancer therapy. The findings support current efforts to develop effective video-game interventions for education and training in health care.
A Critique of Criteria for Evaluating Vaccines for Inclusion in Mandatory School Immunization Programs
Authors: Opel Douglas J. , Diekema Douglas S. , Marcuse Edgar K.
Published: August 2008

Several new vaccines for children and young adults have been introduced recently and now appear on the Advisory Committee on Immunization Practices’ recommended childhood and adolescent immunization schedule (meningococcal, rotavirus, human papillomavirus). As new vaccines are introduced, states face complex decisions regarding which vaccines to fund and which vaccines to require for school or child care entry. This complexity is evidenced by the current debate surrounding the human papillomavirus vaccine. We present a critique to the approach and criteria for evaluating vaccines for inclusion in mandatory school immunization programs that have been adopted by the Washington State Board of Health by illustrating how these criteria might be applied to the human papillomavirus vaccine. We conclude that these 9 criteria can help ensure a deliberate and informed approach to important public policy decisions, but we argue that several clarifications of the review process are needed along with the addition of a 10th criterion that ensures that a new vaccine mandate relates in some manner to increasing safety in the school environment.
Reduced Exercise Capacity in Children Born Very Preterm
Authors: Smith Lucia Jane , van Asperen Peter Paul , McKay Karen Olwyn , Selvadurai Hiran , Fitzgerald Dominic Adam
Published: August 2008

OBJECTIVE. In the past 20 years, there has been an increase in survivors of very preterm birth, but little is known regarding their long-term respiratory and fitness outcomes. We aimed to assess the 10-year lung function and fitness outcomes for children who were born weighing <1000 g and before 32 weeks' gestation in 1992–1994.

METHODS. A cross-sectional study was conducted of 126 children (mean age: 10 years) who were born at a mean gestation of 27 weeks and 34 term-born control subjects. Extensive lung function (spirometry, lung volumes, and gas exchange) and fitness (6-minute walk and 20-m shuttle run tests) assessments were conducted at a single visit according to previously validated techniques.

RESULTS. The preterm group had significantly lower values for all measured spirometric parameters compared with the control group. In contrast to airflow, the preterm group had significantly higher percentage predicted values in all standard lung-volume parameters and transfer factor than the control group. The exercise capacity of the preterm group was approximately half that of the control group. There was no significant difference in the distance walked in the 6-minute walk test.

CONCLUSIONS. In the largest cohort of school-aged children (born very preterm in the 1990s) to undergo extensive lung function and fitness assessments, we demonstrated significant impairment in exercise capacity despite evidence of only mild small-airway obstruction and gas trapping. Additional studies are required to evaluate the cause of this exercise limitation and whether it can be improved with a training program.
Unexpected Infant Deaths Associated With Use of Cough and Cold Medications
Authors: Rimsza Mary E. , Newberry Susan
Published: August 2008

OBJECTIVE. The objective of this study was to determine whether caregivers had given infants who died unexpectedly over-the-counter cough and cold medications before the infant deaths to identify sociodemographic risk factors for their use.

METHODS. The Arizona Child Fatality Review Program reviews the circumstances surrounding every child death that occurs in the state each year. By statute, the multidisciplinary review teams have access to all medical charts, autopsy reports, law enforcement reports, and other records for their review and use these data to determine the cause of death and its preventability. The data on all infants who died unexpectedly in 2006 and had an autopsy and postmortem toxicologic studies were reviewed for this analysis.

RESULTS. Ten unexpected infant deaths that were associated with cold-medication use were identified. The infants ranged in age from 17 days to 10 months. Postmortem toxicology testing found evidence of recent administration of pseudoephedrine, antihistamine, dextromethorphan, and/or other cold-medication ingredients in these infants. The families who used these medications were poor and publicly insured, and 50% of them had limited English proficiency. Only 4 of these infants had received medical care for their current illness before their death. The over-the-counter cough and cold medication had been prescribed by a clinician for only 1 of these infants.

CONCLUSIONS. Review of these infants' deaths raises concern about the role of the over-the-counter cough and cold medications in these deaths. These findings support the recommendation that such medications not be given to infants. In addition, these findings suggest that warnings on these medications “to consult a clinician” before use are not being followed by parents. Educational campaigns to decrease the use of over-the-counter cough and cold medications in infants need to be increased.
Diving-Related Injuries in Children <20 Years Old Treated in Emergency Departments in the United States: 1990–2006
Authors: Day Coral , Stolz Uwe , Mehan Tracy J. , Smith Gary A. , McKenzie Lara B.
Published: August 2008

OBJECTIVE. The purpose of this work was to comprehensively examine diving-related injuries in the United States among children and adolescents <20 years of age.

METHODS. We conducted a retrospective analysis of diving-related injury data from the National Electronic Injury Surveillance System, including patients aged <20 years old who were seen in an emergency department for a diving-related injury from 1990 through 2006.

RESULTS. An estimated 111341 patients aged ≤19 years were treated in emergency departments for diving-related injuries over the 17-year period of the study. The average annual injury rate was 8.4 injuries per 100000 US residents <20 years old. Patients aged 10 to 14 years composed the largest group (36.3%) of injured divers. Injuries to the head and/or neck (38.2%) and face (21.7%) were the most common, with the most frequent diagnoses being lacerations (33.9%) and soft tissue injuries (24.3%). Collision with a diving board and/or platform was the leading cause of injuries (43.9%). Children <10 years old had increased odds of sustaining a laceration, children <5 years old had increased odds of injury to the face, and 10- to 19-year-olds had increased odds of sustaining a fracture or an injury to the extremities. The odds of injury caused by contact with the diving board dramatically increased if the child was performing a flip and/or handstand or a backward dive.

CONCLUSIONS. To our knowledge, this is the first study to examine recreational and competitive diving-related injuries among children and adolescents using a nationally representative sample. These results can help inform pediatricians, parents, coaches, and trainers regarding injuries seen during recreational and competitive diving and can help guide future prevention efforts.
Pediatric Injuries From Needles Discarded in the Community: Epidemiology and Risk of Seroconversion
Authors: Papenburg Jesse , Blais Denis , Moore Dorothy , Al-Hosni Mohammed , Laferrière Céline , Tapiero Bruce , Quach Caroline
Published: August 2008

OBJECTIVES. Although anxiety exists concerning the perceived risk of transmission of bloodborne viruses after community-acquired needlestick injuries, seroconversion seems to be rare. The objectives of this study were to describe the epidemiology of pediatric community-acquired needlestick injuries and to estimate the risk of seroconversion for HIV, hepatitis B virus, and hepatitis C virus in these events.

METHODS. The study population included all of the children presenting with community-acquired needlestick injuries to the Montreal Children's Hospital between 1988 and 2006 and to Hôpital Sainte-Justine between 1995 and 2006. Data were collected prospectively at Hôpital Sainte-Justine from 2001 to 2006. All of the other data were reviewed retrospectively by using a standardized case report form.

RESULTS. A total of 274 patients were identified over a period of 19 years. Mean age was 7.9 ± 3.4 years. A total of 176 (64.2%) were boys. Most injuries occurred in streets (29.2%) or parks (24.1%), and 64.6% of children purposely picked up the needle. Only 36 patients (13.1%) noted blood on the device. Among the 230 patients not known to be immune for hepatitis B virus, 189 (82.2%) received hepatitis B immunoglobulin, and 213 (92.6%) received hepatitis B virus vaccine. Prophylactic antiretroviral therapy was offered beginning in 1997. Of the 210 patients who presented thereafter, 82 (39.0%) received chemoprophylaxis, of whom 69 (84.1%) completed a 4-week course of therapy. The use of a protease inhibitor was not associated with a significantly higher risk of adverse effects or early discontinuation of therapy. At 6 months, 189 were tested for HIV, 167 for hepatitis B virus, and 159 for hepatitis C virus. There were no seroconversions.

CONCLUSIONS. We observed no seroconversions in 274 pediatric community-acquired needlestick injuries, thereby confirming that the risk of transmission of bloodborne viruses in these events is very low.
Clinical Effort Against Secondhand Smoke Exposure: Development of Framework and Intervention
Authors: Winickoff Jonathan P. , Park Elyse R. , Hipple Bethany J. , Berkowitz Anna , Vieira Cecilia , Friebely Joan , Healey Erica A. , Rigotti Nancy A.
Published: August 2008

OBJECTIVE. The purpose of this work was to describe a novel process and present results of formative research to develop a pediatric office intervention that uses available systems of care for addressing parental smoking.

METHODS. The scientific development of the intervention occurred in 3 stages. In stage 1, we designed an office system for parental tobacco control in the pediatric outpatient setting on the basis of complementary conceptual frameworks of preventive services delivery, conceptualized for the child health care setting through a process of key interviews with leaders in the field of implementing practice change; existing Public Health Service guidelines that had been shown effective in adult practices; and adaptation of an evidence-based adult office system for tobacco control. This was an iterative process that yielded a theoretically framed intervention prototype. In stage 2, we performed focus-group testing in pediatric practices with pediatricians, nurses, clinical assistants, and key office staff. Using qualitative methods, we adapted the intervention prototype on the basis of this feedback to include 5 key implementation steps for the child health care setting. In stage 3, we presented the intervention to breakout groups at 2 national meetings of pediatric practitioners for additional refinements.

RESULTS. The main result was a theoretically grounded intervention that was responsive to the barriers and suggestions raised in the focus groups and at the national meetings. The Clinical Effort Against Secondhand Smoke Exposure intervention was designed to be flexible and adaptable to the particular practices' staffing, resources, and physical configuration. Practice staff can choose materials relevant to their own particular systems of care (www.ceasetobacco.org).

CONCLUSIONS. Conceptually grounded and focus-group–tested strategies for parental tobacco control are now available for implementation in the pediatric outpatient setting. The tobacco-control intervention-development process might have particular relevance for other chronic pediatric conditions that have a strong evidence base and have available treatments or resources that are underused.
Maternal Phenylketonuria
Authors:   Committee on Genetics
Published: August 2008

Elevated maternal phenylalanine concentrations during pregnancy are teratogenic and may result in growth retardation, microcephaly, significant developmental delays, and birth defects in the offspring of women with poorly controlled phenylketonuria during pregnancy. Women of childbearing age with all forms of phenylketonuria, including mild variants such as mild hyperphenylalaninemia, should receive counseling concerning their risks for adverse fetal effects, optimally before conceiving. The best outcomes occur when strict control of maternal phenylalanine concentration is achieved before conception and continued throughout pregnancy. Included are brief descriptions of novel treatments for phenylketonuria.
The attendance of the second screening period (2004–2005) of the Hungarian organized breast cancer screening program
Authors: Boncz Imre , Sebestyén Andor , Döbrőssy Lajos , Péntek Zoltán , Kovács Attila , Budai András , Kövi Rita , Ember István
Published: August 2008

Célkitűzés:
Az országos kiterjedésű, szervezett emlőszűrési program 2002 januárjában indult el Magyarországon a 45–65 év közötti nők számára 2 éves szűrési intervallummal. A dolgozat célja a szervezett emlőszűrési program részvételi mutatóinak meghatározása, beleértve a szűrési és diagnosztikus célú képalkotó emlőfelvételek gyakoriságának elemzését.
Adatok és módszerek:
Az elemzésben szereplő adatok az Országos Egészségbiztosítási Pénztár finanszírozási adatbázisából származnak, és a 2000–2005 közötti 6 évet ölelik fel. A 45–65 éves nők körében meghatározták azok arányát, akik a szervezett szűrést megelőző két évben (2000–2001), illetve a program első két ciklusában (2002–2003, 2004–2005) akár szűrési, akár diagnosztikai célú képalkotó emlővizsgálaton vettek részt.
Eredmények:
A szűrési célú képalkotó emlőfelvételen részt vettek aránya (átszűrtség) a 2000–2001-es 7,4%-ról a 2002–2003-as, illetve 2004–2005-ös szervezett emlőszűrési ciklusban 34,0, illetve 29,5%-ra emelkedett. A diagnosztikus célú képalkotó emlőfelvételen részt vettek aránya (átvizsgáltság) pedig ugyanezen időszakokban 19,8%-ról 22,1 (2002–2003), illetve 23,2%-ra (2004–2005) emelkedett. Az országos lefedettség (átszűrtség + átvizsgáltság) ennek megfelelően a szervezett szűrés hatására 26,2%-ról (2000–2001) 53,5%-ra (2002–2003), illetve 50,8%-ra (2004–2005) nőtt a vizsgált kétéves ciklusban a 45–65 év közötti nők esetében.
Következtetés:
A magyar emlőszűrési program kezdeti részvételi arányai 2004–2005-ben kissé csökkentek; az emlőrák miatti halálozás érdemi csökkentéséhez ennek emelése szükséges.
Annealing effects on the elastic modulus of tungsten oxide nanowires
Authors: Zhu Yanwu , Zhang Yousheng , Cheong Fook-Chiong , Sow Chorng-Haur , Lim Chwee-Teck
Published: August 2008

Three-point bend test coupled with transmission electron microscopy (TEM) analysis was carried out on individual tungsten oxide nanowires (NWs) before and after annealing. Three-point bend test monitors the change in the Young’s modulus of the NW after annealing, while TEM provides nanostructural detail changes on the same NW. In this way, insight into the correlation between the mechanical properties of a NW and its nanostructure details can be obtained. Annealing increased the diameter of the NWs by forming a uniform amorphous/polycrystalline outer coating. The coating results in a decrease in Young’s moduli for thicker NWs. On the other hand, annealing led to increased Young’s moduli of thinner NWs, which is attributed to the improved crystallinity in these NWs after annealing. This study points to a more refined strategy for more in-depth understanding of the relationship between the nanostructures and elastic mechanical properties of NWs.