bluuebunny/crossref_metadata_2025 huggingface dataset:
Photodynamic Crosslinking of Proteins. III. Kinetics of the FMN‐ and Rose Bengal‐sensitized Photooxidation and Intermolecular Crosslinking of Model Tyrosine‐containing N‐(2‐Hydroxypropyl)methacrylamide Copolymers
Authors: Spikes John D. , Shen Hui‐Rong , Kopečková Pavla , Kopeček Jindřich
Published: January 2008

Abstract.As part of a study on the role of Tyr residues in the photosensitized intermolecular crosslinking of proteins, we have surveyed the kinetics of the rose bengal‐ and flavin mononucleotide (FMN)‐sensitized photooxidation and crosslinking of a water‐soluble N‐(2‐hydroxypro‐pyl)methacrylamide copolymer with attached 6‐carbon side chains terminating in tyrosinamide groups (thus the ‐OH group of the Tyr is free, but both the amino and carboxyl groups are blocked, simulating the situation of a nonterminal Tyr in a protein). The intermolecular photodynamic crosslinking of the Tyr copolymer can result only from the formation of Tyr‐Tyr (dityrosine) bonds, because the copolymer itself is not photooxidizable. Rose bengal, primarily a Type II (singlet oxygen) sensitizer, sensitized the rapid photooxidation of the Tyr residue in the Tyr copolymer only at high pH, where the Tyr phenolic group is ionized; crosslinking did not occur with rose bengal under any of the reaction conditions used. In contrast, FMN, which can sensitize by both Type I (free radical) and Type II processes, sensitized the photooxidation of the Tyr copolymer over the pH range 4–9.5. Also, significant photocrosslinking occurred, but only from pH 4 to 8, with a maximum rate at pH 6. Crosslinking required the presence of oxygen. Studies with inhibitors, D2O as solvent, cataiase and superoxide dismutase indicated that the photooxidation and photocrosslinking of the Tyr copolymer with FMN at pH 6 were not mediated by singlet oxygen, superoxide or hydrogen peroxide. It appears that crosslinking involves the abstraction of an H atom from the Tyr phenolic group to give Tyr and FMN radicals. The Tyr radical in one Tyr copolymer can then react with a Tyr radical in another Tyr copolymer to give an intermolecular dityrosine crosslink.
Oxidation of Guanine in Cellular DNA by Solar UV Radiation: Biological Role†
Authors: Douki Thierry , Perdiz Daniel , Grof Pal , Kuluncsics Zéno , Moustacchi Ethel , Cadet Jean , Sage Evelyne
Published: January 2008

Abstract. The formation of cyclobutane pyrimidine dimers (CPD) and 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodGuo) was investigated in Chinese hamster ovary cells upon exposure to either UVC, UVB, UVA or simulated sunlight (SSL). Two cell lines were used, namely AT3‐2 and UVL9, the latter being deficient in nucleotide excision repair and consequently UV sensitive. For all types of radiation, including UVA, CPD were found to be the predominant lesions quantitatively. At the biologically relevant doses used, UVC, UVB and SSL irradiation yielded 8‐oxodGuo at a rather low level, whereas UVA radiation produced relatively higher amounts. The formation of CPD was 102 and 102 more effective upon UVC than UVB and UVA exposure. These yields of formation followed DNA absorption, even in the UVA range. The calculated relative spectral effectiveness in the production of the two lesions showed that efficient induction of 8‐oxodGuo upon UVA irradiation was shifted toward longer wavelengths, in comparison with those for CPD formation, in agreement with a photosensitization mechanism. In addition, after exposure to SSL, about 19% and 20% of 8‐oxodGuo were produced between 290–320 nm and 320–340 nm, respectively, whereas CPD were essentially (90%) induced in the UVB region. However, the ratio of CPD to 8‐oxodGuo greatly differed from one source of light to the other: it was over 100 for UVB but only a few units for UVA source. The extent of 8‐oxodGuo and CPD was also compared to the lethality for the different types of radiation. The involvement of 8‐oxodGuo in cell killing by solar UV radiation was clearly ruled out. In addition, our previously reported mutation
Sun Exposure at School
Authors: Moise A. F. , Büttner P. G. , Harrison S. L.
Published: January 2008

Abstract. There is strong evidence that sun exposure during childhood and adolescence plays an important role in the etiology of skin cancer, in particular cutaneous melanoma. Between the age of 6 and 18, most children and adolescents will spend around 200 days per year at school and may receive a substantial fraction of their daily total solar ultraviolet radiation (UVR) exposure while at school. This study estimated the average daily erythemally effective dose of 70 grade 8 students from a high school in Townsville during 5 school days in July 1998. Through UV measurements of shade locations at the school and a combination of frequency counts and a questionnaire of grade 8 students, it was possible to determine the fraction of solar UVR reaching under the shade structures during lunch breaks and routine outdoor activities. Also, a routinely operating UV‐Biometer provided the annual variation of the daily dose that was used to calculate exposure levels for the 70 students. Our results suggest that up to 47% of the daily total dose fell within the time periods where students were outdoors during school hours. For students not seeking shade structures during the breaks (which usually was the case when involved in sport activities such as basketball or soccer), the average daily dose could have been as high as 14 SED (standard ery‐themal dose). Using results from the questionnaire of 70 grade 8 students, their average annual dose while at school was 414 SED or 2 SED per schoolday. However, the distribution of average daily erythemal effective dose per grade 8 student over the whole year showed that on 31 % of all school days in 1998, this dose was exceeded. Because most previous attempts to change arguably poor sun‐protective behavior of young Australian children and adolescents at school showed little success, one way of decreasing the amount of harmful UVR reaching unprotected skin is the more careful design of shade structures at schools.
Photodynamic Therapy: Tumor Targeting with Adenoviral Proteins
Authors: Allen Cynthia M. , Sharman Wesley M. , Madeleine Carole La , Weber Joseph M. , Langlois Réjean , Ouellet Réné , van Lier Johan E.
Published: January 2008

A brief summary of the mechanisms involved in photo‐dynamic therapy (PDT) and the role of delivery vehicles for photosensitizer targeting is addressed. Phthalocya‐nines (Pc) have been coupled to adenovirus type 2 capsid proteins including the hexon, the penton base and the fiber to enhance their target selectivity. Adenovirus pen‐ton base proteins contain the arginine‐glycine‐aspartic acid peptidic sequence (RGD) motif known to bind with great affinity and high specificity to integrin receptors, expressed by several types of cancer. Tetrasulfonated aluminum phthalocyanine (AlPcS4) was covalently coupled to the various capsid proteinsviaone or two caproic acid spacer chains (A1or A2) in 7:1 up to 66:1 molar ratios. The capacity of the bioconjugates for singlet oxygen production, as measured by an L‐tryptophan oxidation assay, was strongly reduced, likely reflecting scavenging by the carrier. Cell adsorption andin vitropho‐tocytotoxicity assays were carried out using the A549 and HEp2 human cell lines expressing integrin receptors, and one murine, the EMT‐6 cell line, which lacks receptors for the RGD sequence. The AlPcS4A2‐protein complexes induced greater cytotoxicity as compared to the analogous AlPcS4A1preparations. The penton base‐AIPcS4A2derivative was the more phototoxic for all cell lines tested. Tumor response studies using Balb/c mice with EMT‐6 tumor implants demonstrated that the free AlPcS4A2induced complete tumor regression at a dose of 1 μmol/kg and 400 J/cm2, which is comparable to the activity of the known AlPcS2adJ.A mixture of adenovirus type 2 soluble proteins covalently labeled with AlPcS4A2required 0.5 μmol/kg to induce the same response with the same light dose, suggesting that the high affinity RGD/receptor complex is able to target Pc for PDT.
Radiative Transitions of Singlet Oxygen: New Tools, New Techniques and New Interpretations
Authors: Keszthelyi Tamas , Weldon Dean , Andersen Thomas N. , Poulsen Tina D. , Mikkelsen Kurt V. , Ogilby Peter R.
Published: January 2008

The near‐IR phosphorescence of singlet delta oxygen, O2(a1Δg), has provided a wealth of information since it was first observed in solution‐phase systems. The techniques employed and the quality of the data obtained have unproved significantly over the years that, in turn, presently makes it possible to address a wide variety of problems using both steady‐state and time‐resolved measurements. The development of spectroscopic methods to monitor other transitions in oxygen, specifically those that involve the singlet sigma state, O2(b1σg+), and the incorporation of high‐level computational methods provides access to an even broader range of fundamental issues. The expertise presently available to monitor radiative transitions in oxygen, coupled with the current understanding of the effect of solvent on these transitions as achieved through state‐of‐the‐art theoretical modeling makes it possible to consider the next step forward: the incorporation of spatial resolution and the construction of the singlet oxygen microscope.
Effects of BAPTA‐AM and Forskolin on Apoptosis and Cytochrome c Release in Photosensitized Chinese Hamster V79 Cells
Authors: Inanami O. , Yoshito A. , Takahashi K. , Hiraoka W. , Kuwabara M.
Published: January 2008

The mechanism of caspase‐3‐dependent apoptosis induced by photodynamic therapy (PDT) of cultured Chinese hamster V79 cells with pheophorbide a (PPa) was investigated. The PPa‐PDT induced rapid apoptosis within 30 min after irradiation of cells. This apoptosis was inhibited by the 1O2 quencher N3‐and caspase‐3 inhibitor acetyl‐Asp‐Glu‐Val‐Asp‐aldehyde, suggesting that 1O2 activated caspase‐3 and then caused apoptosis. The intracellular calcium [Ca2+]1 chelator (acetoxymethyl)‐l,2‐bis(o‐aminophenoxy)ethane N,N,N',N,'‐tetraacetic acid (BAPTA‐AM) and the cyclic adenosine monophosphate (cAMP)‐increasing agent forskolin also inhibited not only the PPa‐PDT‐induced activation of caspase‐3 but also apoptosis in V79 cells. Furthermore, PPa‐PDT‐induced cytochrome c release from mitochondria was found to be inhibited by the treatment with BAPTA‐AM but not forskolin. These results indicated that [Ca2+]1 and cAMP independently serve as regulators for PPa‐PDT‐induced apoptosis in the upstream of caspase‐3.
A GENERAL APPROXIMATION ALGORITHM FOR PLANAR MAPS WITH APPLICATIONS
Authors: BOSE PROSENJIT , COLL NARCÍS , HURTADO FERRAN , SELLARÈS J. ANTONI
Published: January 2008

Given an unknown target planar map, we present an algorithm for constructing an approximation of the unknown target based on information gathered from linear probes of the target. Our algorithm is a general purpose reconstruction algorithm that can be applied in many settings. Our algorithm is particularly suited for the setting where computing the intersection of a line with an unknown target is much simpler than computing the unknown target itself. The algorithm maintains a triangulation from which the approximation of the unknown target can be extracted. We evaluate the quality of the approximation with respect to the target both in the topological sense and the metric sense. The correctness of the algorithm and the evaluation of its time complexity are also presented. Finally, we present some experimental results. For example, since generalized Voronoi diagrams are planar maps, our algorithm presents a simpler alternative method for constructing approximations of generalized Voronoi diagrams, which are notoriously difficult to compute.
Identification of penile inputs to the rat gracile nucleus
Authors: Cothron Kyle J. , Massey James M. , Onifer Stephen M. , Hubscher Charles H.
Published: January 2008

Neurons in the medullary reticular formation (MRF) of the rat receive a vast array of urogenital inputs. Using select acute and chronic spinal cord lesions to identify the location of the ascending neural circuitries providing either direct or indirect inputs to MRF from the penis, our previous studies demonstrated that the dorsal columns and dorsal half of the lateral funiculus convey low- and high-threshold inputs, respectively. In the present study, the gracile nucleus was targeted as one of the likely sources of low-threshold information from the penis to MRF. Both electrophysiological recordings and neuroanatomical tracing [injection of cholera toxin B subunit (CTB) into a dorsal nerve of the penis] were used. After discrimination of a single neuron responding to penile stimulation, testing for somatovisceral convergence was done (mechanical stimulation of the distal colon and the skin over the entire hindquarters). In 12 rats, a limited number of neurons (43 in total) responded to penile stimulation. Many of these neurons also responded to scrotal stimulation (53.5%, dorsal and/or ventral scrotum) and/or prepuce stimulation (46.5%). Histological reconstruction of the electrode tracks showed that the majority of neurons responding to penile stimulation were located ventrally within the medial one-third of the gracile nucleus surrounding obex. This location corresponded to sparse innervation by CTB-immunoreactive primary afferent terminals. These results indicate that neurons in the gracile nucleus are likely part of the pathway that provides low-threshold penile inputs to MRF, a region known to play an important role in mating processes.
Fear, the School Organization, and Teacher Evaluation
Authors: Conley Sharon , Glasman Naftaly S.
Published: January 2008

Fear can be conceptualized differently as experienced by those inside and outside the school organization. Internally, participants respond to fear in a politics of maintenance aimed toward protection against anticipated job loss(es). This article examines internal organizational participants' fear, with particular attention to teachers' fear of being evaluated. It is argued that the cellular organization of teaching contributes to fear, as do certain existing conflicts in evaluation. For example, teachers fearing a summative evaluation may be less than forthcoming about their performance shortcomings and/or goals. An analysis of fear in teacher evaluation should take into account (a) teacher controllability of teaching and its evaluation and (b) principals' preference for evaluation rigidity. In environments compromised by fear, for example, administrators might restrict information in teacher evaluation. Reform directions such as union participation and altering the adversarial tone of evaluation may improve evaluation by more fully developing the skills desired in teaching.
Fear and the Preparation of School Leaders
Authors: Young Michelle D. , Brewer Curtis
Published: January 2008

An uncertainty has developed around the “core technology” of preparing educational leaders, making the general public question whether, in particular, university professors know what they are doing. This sense of ambiguity can also be found within the professoriate, where questioning of the knowledge base, standards, pedagogy, and university expectations have become a new norm, promoting reflexivity, uncertainty, and fear. Such uncertainty is neither healthy nor unhealthy in and of itself; the outcome depends in large degree on how it is fostered. In this article, we examine two contemporary reports that critique educational leadership preparation, viewing their critiques and recommendations as exercises of power within the context of late modernity. Using Nyberg's (1981) work on modes of power, Fraser's (1989) work on problem definition and contemporary work on the politics of fear (e.g., Glassner, 1999; Gonzalez & Delgado, 2006), we analyze the content of the reports and their impact.
L1 Interaction with Ankyrin Regulates Mediolateral Topography in the Retinocollicular Projection
Authors: Buhusi Mona , Schlatter Monika C. , Demyanenko Galina P. , Thresher Randy , Maness Patricia F.
Published: January 2008

Dynamic modulation of adhesion provided by anchorage of axonal receptors with the cytoskeleton contributes to attractant or repellent responses that guide axons to topographic targets in the brain. The neural cell adhesion molecule L1 engages the spectrin-actin cytoskeleton through reversible linkage of its cytoplasmic domain to ankyrin. To investigate a role for L1 association with the cytoskeleton in topographic guidance of retinal axons to the superior colliculus, a novel mouse strain was generated by genetic knock-in that expresses an L1 point mutation (Tyr1229His) abolishing ankyrin binding. Axon tracing revealed a striking mistargeting of mutant ganglion cell axons from the ventral retina, which express high levels of ephrinB receptors, to abnormally lateral sites in the contralateral superior colliculus, where they formed multiple ectopic arborizations. These axons were compromised in extending interstitial branches in the medial direction, a normal response to the high medial to low lateral SC gradient of ephrinB1. Furthermore, ventral but not dorsal L1(Y1229H) retinal cells were impaired for ephrinB1-stimulated adhesion through β1 integrins in culture. The retinocollicular phenotype of the L1(Tyr1229His) mutant provides the first evidence that L1 regulates topographic mapping of retinal axons through adhesion mediated by linkage to the actin cytoskeleton and functional interaction with the ephrinB/EphB targeting system.
Mechanisms of Compartmentalized Expression of Mrg Class G-Protein-Coupled Sensory Receptors
Authors: Liu Yang , Yang Fu-Chia , Okuda Tsukasa , Dong Xinzhong , Zylka Mark J. , Chen Chih-Li , Anderson David J. , Kuner Rohini , Ma Qiufu
Published: January 2008

Mrg class G-protein-coupled receptors (GPCRs) are expressed exclusively in sensory neurons in the trigeminal and dorsal root ganglia. Pharmacological activation of Mrg proteins is capable of modulating sensory neuron activities and elicits nociceptive effects. In this study, we illustrate a control mechanism that allows the Runx1 runt domain transcription factor to generate compartmentalized expression of these sensory GPCRs. Expression ofMrgA,MrgB, andMrgCsubclasses is confined to an “A/B/C” neuronal compartment that expresses Runx1 transiently (or does not express Runx1), whereasMrgDexpression is restricted to a “D” compartment with persistent Runx1 expression.Runx1is initially required for the expression of allMrggenes. However, during late development Runx1 becomes a repressor forMrgA/B/Cgenes. As a result,MrgA/B/Cexpression persists only in the Runx1−“A/B/C” compartment. In Δ446mice, in which Runx1 lacks the C-terminal repression domain, expression ofMrgA/B/Cgenes is dramatically expanded into the Runx1+“D” compartment.MrgDexpression, however, is resistant to Runx1-mediated repression in the “D” compartment. Therefore, the creation of Runx1+and Runx1−compartments, in conjunction with different responses ofMrggenes to Runx1-mediated repression, results in the compartmentalized expression ofMrgA/B/CversusMrgDgenes. Within theMrgA/B/Ccompartment,MrgB4-expressing neurons innervate exclusively the hairy skin. Here we found that Smad4, a downstream component of bone morphological protein-mediated signaling, is required selectively for the expression ofMrgB4. Our study suggests a new line of evidence that specification of sensory subtypes is established progressively during perinatal and postnatal development.
A DOUBLE-BLIND RANDOMIZED, CONTROLLED TRIAL OF PROTEIN ENERGY–ENRICHED FORMULA ADMINISTERED TO CRITICALLY ILL INFANTS
Authors: Van Waardenburg Dick , De Betue Carlijn , Joosten Koen
Published: January 2008

INTRODUCTION: Nutritional support is an important aspect of clinical management of critically ill infants, but the nutritional requirements of these infants are not well defined.

OBJECTIVE: Our goal was to compare tolerance, nutritional, and metabolic effects of 2 different infant formulas in critically ill infants in a double-blind, randomized way.

METHODS: Eighteen ventilated infants with respiratory insufficiency caused by respiratory syncytial virus infection were included and received an energy- and protein-enriched (PE) infant formula (Infatrini [Nutricia B. V. Zoetermeer, Zoetermeer, Netherlands]; n = 8) or standard infant formula (Nutrilon 1 [Nutricia B. V. Zoetermeer]; n = 10). Daily intake and tolerance (gastric retention, diarrhea) were recorded. Resting energy expenditure, respiratory quotient, L-amino acid concentrations, and metabolic parameters were measured, and cumulative energy balance, nitrogen balance, and substrate utilization were calculated.

RESULTS: Baseline characteristics were similar in both groups. Both formulas were well tolerated with similar volumes of intake. Results from day 4 are presented in Table 1. Levels of several amino acids (His, Val, Met, Phe, Lys, and ornithine; P < .05) were significantly higher in the infants who received the PE-enriched formula.

CONCLUSIONS: PE-enriched infant formula was well tolerated in critically ill infants and effective in achieving higher nutritional intakes in the first days of admission. PE-enriched formula improved energy balance and plasma amino acid profile, and a trend toward increased nitrogen balance was found.

TABLE 1.Results on Day 4 of AdmissionFormulaProtein Intake, g/kg per dayEnergy Intake, kcal/kg per dayaResting Energy Expenditure, kcal/kg per dayaRespiratory QuotientCumulative Energy Balance, kcal/kg per dayaCumulative Nitrogen Balance, mg/kg per dayPE-enriched (n = 8)2.61 ± 0.24111 ± 1059 ± 50.98 ± 0.02589 ± 115162 ± 32Standard (n = 10)1.46 ± 0.1178 ± 449 ± 40.91 ± 0.01350 ± 5068 ± 16 P <.01<.01.26<.01<.05.08a1 kcal = 4.2 kJ.
LINGUISTIC DEVELOPMENT OF CHILDREN WITH WILLIAMS SYNDROME: A CONTROL STUDY
Authors: Varlokosta Spyridoula , Thomaidis Loretta , Archonti Anastasia , Tsiamaki Dimitra , Fryssira Helen , Joffe Victoria
Published: January 2008

INTRODUCTION: Williams Syndrome (WS; Online Mendelian Inheritance in Man No. 194050) is a rare syndrome that has attracted a great deal of attention because of an uneven neurolinguistic profile characterized by relative strengths in language, facial processing, and social cognition in the context of poorer spatial cognition, planning, and problem solving. WS has also been used as evidence for the existence of dissociations within subsystems of the language module itself. It has been reported that individuals with WS perform better on grammatical versus lexical tasks and on regular versus irregular forms.

OBJECTIVE: This study addressed 2 main questions: (1) Do individuals with WS show differences between language and cognition? (2) Do individuals with WS perform differently across tasks that tap different aspects of language?

METHODS: We investigated nonverbal and verbal abilities of 20 Greek-speaking children with WS (aged 6–18 years with molecular definition of chromosome 7 deletions) and compared their performance to a group of 20 normal children aged 4 to 10 years. The 2 groups were matched on language ability (comprehension and expression) through the Diagnostic Verbal IQ Test. Verbal ability was measured by 3 experimental linguistic measures that assessed comprehension of pronouns and production of verbs and nouns.

RESULTS: Nonverbal IQ was low and ranged from 40 to 68 points. Those in the WS group, as a whole, showed unimpaired performance on pronouns but faced difficulties in using verbs and nouns. Great variation in performance was evident, which highlights the heterogeneity of the group. A subgroup of individuals with WS showed clear dissociations between language and cognition and within language.

CONCLUSIONS: Our results indicate that (1) there is a clear dissociation between language and cognition and (2) children with WS show strengths on some aspects of their linguistic development.
COMPARISON OF INTERNATIONAL OBESITY TASKFORCE CUTOFFS, CENTERS FOR DISEASE CONTROL AND PREVENTION GROWTH CHARTS, AND BODY MASS INDEX Z-SCORE VALUES IN THE PREVALENCE OF CHILDHOOD OBESITY: THE GREEK OBESITY AND LIFESTYLE STUDY
Authors: Mantzouranis Nikolaos , Pilianidis Theofilos , Douda Helen , Tokmakidis Savvas
Published: January 2008

OBJECTIVE: Few epidemiologic studies have compared classification methods of childhood obesity. The aim of the Greek Obesity and Lifestyle Study (GOALS) was to assess the prevalence of childhood obesity by comparing 3 classification methods.

METHODS: The GOALS was conducted on a representative sample of 2056 students (1148 boys and 908 girls), aged to 13 years. Body mass and height were measured, and the BMI (kg/m2) was calculated. The comparisons of obesity prevalence were based on International Obesity Taskforce (IOTF) cutoffs, Centers for Disease Control and Prevention (CDC) growth charts and BMI-for-age z scores (overweight ≥1 SD, obese ≥2 SD).

RESULTS: The higher prevalence of obesity (including overweight) in GOALS was found by using the CDC growth charts (37.6%), whereas the obesity prevalence classified according to the IOTF cutoffs was recorded 1% lower (36.6%). In relation to CDC and IOTF classifications, significant lower prevalence was reported when obesity was estimated as BMI-for-age z scores (15.2%). Adjusted by gender, the Analysis of variance results showed that the obesity prevalence was significantly higher in boys in both CDC and IOTF classifications compared with BMI-for-age z scores.

CONCLUSIONS: The comparison among studies in Greece shows that the prevalence of childhood obesity in GOALS, based on both IOTF and CDC classifications, is the highest ever recorded in Greece and almost similar with the obesity prevalence reported in US teenagers. The lower obesity prevalence recorded in GOALS using the BMI-for-age z scores, compared with IOTF and CDC classifications, did not appropriately specify childhood obesity and cannot be used for public health applications.
A NORMAL LIFE WITH AN UNHEALTHY BODY: SELF-IDENTITY IN ADOLESCENTS GROWING UP WITH CHRONIC ILLNESS
Authors: Van Staa AnneLoes , Jedeloo Susan , Latour Jos , Trappenburg Margo
Published: January 2008

INTRODUCTION: Chronic illness is often described in terms of biographic disruption. However, for those growing up with congenital disorders, an unhealthy body is the norm. An important developmental task in adolescence is the formation of self-identity. How does a chronic disorder influence the development of self-identity in adolescents?

OBJECTIVE: Our aim was to investigate attitudes and preferences of adolescents living with chronic disorders.

METHODS: A qualitative study was conducted by using semistructured interviews that focused on daily life issues. The sample consisted of 31 adolescents (aged 12–19 years) with various chronic disorders who were randomly selected from the patient database of Erasmus Medical Center-Agia Sophia Children's Hospital. Data analysis was performed by using a qualitative analysis computer program (ATLAS.ti, Berlin, Germany).

RESULTS: For most adolescents with chronic disorders, living with illness is “normal.” By comparing themselves with healthy peers, they recurrently stress their own normality. They strongly agreed with the statement, “I am like everyone else, my illness is something extra.” Therefore, disclosure of health problems remains a sensitive issue, and contact with fellow patients is not often sought. Most held optimistic views about their futures, and only a minority told problematic accounts of the acceptance of their dysfunctional bodies.

CONCLUSIONS: Normalization of an unhealthy childhood seems to be an important strategy in identity-forming in adolescents. It may be interpreted as denial, but adolescents consider denial to be “dangerous” and “stupid.” We view normalization as a strategy to accept reality while preventing illness to dominate their life: “I try not to think about it, not because it scares me, but because it's there.”
SHORT-TERM AND LONG-TERM OUTCOME OF 596 INFANTS BORN TO MOTHERS WITH CARDIAC DISEASE
Authors: Kono Yumi , Mishina Jun , Makino Yasuo , Sakuma Izumi , Kusuda Satoshi , Matsuda Yoshio , Nishida Hiroshi , Shinohara Tokuko , Ishii Tetsuko , Nakanishi Toshio
Published: January 2008

INTRODUCTION: The number of pregnancies of women with cardiac disease (CD) has been increasing. Previous studies on outcomes were reported mainly on maternal cardiac outcome.

OBJECTIVE: We focused on the outcome of infants who were born to mothers with CD.

METHODS: Study subjects consisted of 596 singleton live-born infants who were born at Tokyo Women's Medical University Hospital from 1991 to 2005. Women with maternal CD included 295 with congenital heart disease (CHD), 184 with arrhythmias, 84 with acquired valvular disease, 18 with cardiomyopathy, and 16 with miscellaneous CD. Gestational age, birth weight (BW), mortality rate, and complications in the subjects and long-term outcome of the preterm infants (<37 weeks' gestation) were evaluated.

RESULTS: Preterm birth was found in 74 (12.4%) infants, 3 of whom were born at <28 weeks' gestation. Low BW was found in 117 (19.6%) infants, 12 of whom weighed <1500 g. Rates of preterm birth (61%) and low BW (61%) in the infants of mothers with cardiomyopathy were significantly higher than those with other maternal CD. The overall mortality rate was 0.7%; 3 died (1 with Down syndrome with CHD, 1 with neonatal Marfan syndrome, and 1 extremely low BW infant born at 23 weeks' gestation) in the neonatal period, and 1 infant with CHD died at 1 year of age. Seven of the preterm infants (9.5%) had CHD. Other complications included anomalies/chromosomal disorders (5), cerebral palsy (1), mental retardation (2), borderline mentality (1), and hearing impairment (1). The prevalence of major neurologic handicap was 4%.

CONCLUSIONS: The rates of preterm birth and low BW were very high. Adverse outcome of infants born to mothers with CD was related to congenital disorders including CD of offspring and extremely preterm birth.
ANTIBIOTIC SKIN TESTING FOR CHILDREN LABELED WITH TYPE 1 HYPERSENSITIVITY: A USEFUL CLINICAL TOOL
Authors: Kavadas Fotini D. , Seaban Kimberley R. , Nofech-Mozes Yehuda , Husain Maitham , White Elisabeth , Atkinson Adelle R.
Published: January 2008

INTRODUCTION: Children are often unnecessarily labeled as being allergic to antibiotics that may potentially be life saving. Aside from penicillin, good diagnostic testing has not been available in pediatrics to differentiate between type 1 hypersensitivity and other causes of adverse reactions to antibiotics.

OBJECTIVE: We sought to determine the safety of antibiotic skin testing of children and to describe its potential clinical impact.

METHODS: A retrospective chart review was performed of patients between 0 and 18 years of age who were seen in our clinic over a 2-year period with a history of a possible immunoglobulin E–mediated reaction to various antibiotics other than penicillin. We included patients with either extremely limited antibiotic options or complex medical issues that require antibiotics. We did not perform testing if there was a history of a convincing immunoglobulin E–mediated or serum sickness–like reaction. Skin testing was performed by using nonirritating concentrations of the antibiotic in question that have been used in adults. If skin-prick testing results were negative, we performed intradermal testing. A provocative challenge was offered if all skin-testing results were negative.

RESULTS: of 28 visits, 23 met our inclusion criteria; 4 (17%) of 23 could not be skin-tested. Of those who were skin-prick–tested, all 19 (100%) had a negative result, and 17 (89%) of 19 also had a negative intradermal test. Of those 17 (88%), 15 patients agreed to undergo provocative challenge, 14 (93%) of whom were then unlabeled as allergic to the respective antibiotic.

CONCLUSIONS: Skin-prick testing is a novel tool in pediatrics that may have an important clinical impact in the accurate diagnosis of antibiotic allergies by guiding provocative challenges.
INVESTIGATION OF HEARING IMPAIRMENT IN POST–NEONATAL INTENSIVE CARE UNIT INFANTS BY USING AUTOMATED AUDITORY BRAINSTEM RESPONSE
Authors: Mitsiakos George , Giougi Evaggelia , Karagianni Paraskevi , Chatziioannidis Elias , Tsakalidis Christos , Nikolaidis Nikolaos
Published: January 2008

INTRODUCTION: Hearing impairment affects 2% to 4% of NICU graduates and is associated with several risk indicators.

OBJECTIVE: Our goal was to investigate the prevalence of hearing impairment in newborns hospitalized in an NICU and its association with risk indicators.

METHODS: Subjects consisted of 422 post-NICU infants who fulfilled 34 weeks of gestational age and were examined between March 2005 and December 2006. The following parameters were evaluated: perinatal asphyxia, craniofacial deformities, furosemide and aminoglycoside therapy (duration of administration), meningitis, duration of mechanical ventilation, and nursing duration in an incubator. Screening was performed with the last-generation automated auditory brainstem response (AABR) equipment, ALGO 3 (Natus Medical Inc, San Carlos, CA).

RESULTS: Results were considered normal when the newborn showed response to a 35-dBNA signal bilaterally. Newborns with hearing impairment were referred for early intervention. Multivariate analysis with logistic regression was used to identify the independent risk factors for hearing disturbances. The prevalence of AABR impairment was 2.84% (12 of 422 newborns); the impairment was unilateral in 7 of the infants and bilateral in 5 of them. These 12 infants were examined with conventional ABR with the following results: 6 of them showed normal responses, and in the other 6 infants the pathologic result was confirmed. Multivariate analysis revealed a statistically significant association between hearing loss and craniofacial deformities, meningitis, and duration of mechanical ventilation (P < .001, P = .001, and P = .038, respectively).

CONCLUSIONS: Although the study sample was limited, the hearing-loss rate that we found was in accordance with that reported in the literature. The prevalence of hearing impairment found when using AABR is high. The only risk factors directly associated with hearing impairment proved to be craniofacial deformities, meningitis, and duration of mechanical ventilation.
PROBIOTICS REDUCE INCIDENCE AND DURATION OF RESPIRATORY TRACT INFECTION SYMPTOMS IN 3- TO 5-YEAR-OLD CHILDREN
Authors: Ouwehand Arthur , Leyer Greg , Carcano Didier
Published: January 2008

INTRODUCTION: Probiotics are live microorganisms that have a beneficial effect on the host.

OBJECTIVE: Our aim was to investigate whether consumption of probiotics would be able to reduce symptoms of respiratory tract infections during the winter season.

METHODS: Children aged 3 to 5 years were recruited and randomly assigned to 1 of 3 groups to receive placebo (n = 92), Lactobacillus acidophilus NCFM (NCFM) (n = 77), or a combination of L acidophilus NCFM and Bifidobacterium lactis Bi-07 (NCFM+Bi-07) (n = 79). Probiotics were consumed daily at a dose of 1010 colony-forming units for 6 months from November to April. The study was performed in Shanghai, China, and approved by the local authorities.

RESULTS: The incidence of fever was reduced by 63% in the NCFM+Bi-07 group and by 48% in the NCFM group. Cough was reduced by 54% in the NCFM+Bi-07 group and by 42% in the NCFM group. Runny nose was reduced by 44% in the NCFM+Bi-07 group and by 9% in the NCFM group; the latter result was not significant. Antibiotic use was reduced by 80% in the NCFM+Bi-07 group and by 68% in the NCFM group. Children in the placebo group had, on average, 6.5 days with symptoms, those in the NCFM group had 4.5 days with symptoms, and those in the NCFM+Bi-07 group had 3.4 days with symptoms.

CONCLUSIONS: Daily consumption of NCFM and Bi-07 and of NCFM alone significantly reduced the incidence and duration of respiratory tract infection symptoms in children. The combination of the 2 probiotics tended to perform better than the NCFM alone.
SPECTRUM AND MANAGEMENT OF OTITIS MEDIA IN AUSTRALIAN INDIGENOUS AND NON-INDIGENOUS CHILDREN: A NATIONAL STUDY
Authors: Gunasekera Hasantha , Knox Stephanie , Morris Peter , Britt Helena , McIntyre Peter , Craig Jonathan
Published: January 2008

INTRODUCTION: The reported prevalence and severity of otitis media are highest among the world's Indigenous children, but whether their clinical management varies accordingly is unknown.

OBJECTIVE: Our aim was to study the spectrum and management of otitis media in Indigenous and non-Indigenous children in Australia.

METHODS: From a representative Australian cluster survey of consecutive primary health care consultations, we analyzed all consultations with children (aged 0–18 years). We compared the practitioners' investigation, treatment, and referral practices for Indigenous and non-Indigenous children with otitis media after adjusting for clustering.

RESULTS: Over 8 years (1998–2006), 7991 practitioners managed 141 693 problems in 119 503 consultations with children, including 2856 (2.4%) with Indigenous children. Ear problems were the fourth most common problems managed. Otitis media was managed slightly more commonly in Indigenous than non-Indigenous children (9.8% vs 7.3% consultations; P < .05). When otitis media was diagnosed, Indigenous children were significantly more likely to have severe otitis media (chronic and/or suppurative and/or perforation: 7.9% vs 1.7%; P < .001), discharging ears (3.9% vs 0.1%; P < .001), ear swabs (3.9% [95% confidence interval (CI): 1.6–6.2] vs 0.8% [95% CI: 0.6–0.9]), and topical eardrops administered (10.7% [95% CI: 6.8–14.6] vs 4.5% [95% CI: 4.1–5.0]) but not more likely to receive oral antibiotics (71.8% vs 75.9%), have ear syringing (1.1% vs 0.2%), or be referred to an otolaryngologist (6.1% vs 3.4%) or audiologist (1.8% vs 1.1%) (all P > .05).

CONCLUSIONS: In the Australian primary health care setting, Indigenous children are 5 times more likely to be diagnosed with severe otitis media than non-Indigenous children, but reported management is not substantially different, which is inconsistent with established national guidelines. This spectrum-management discordance may contribute to continued worse outcomes for Indigenous children with otitis media.
COMPARISON OF PEDIATRIC LOGISTIC ORGAN DYSFUNCTION (PELOD) SCORE AND PEDIATRIC RISK OF MORTALITY (PRISM) III AS A MORTALITY PREDICTOR IN PATIENTS WITH DENGUE SHOCK SYNDROME
Authors: Iskandar Henny R. , Mulyo Dharma , Agnes Praptiwi , Suryatin Yuliatmoko
Published: January 2008

INTRODUCTION: The mortality rate for dengue shock syndrome (DSS) in the PICU at Children's and Maternity Harapan Kita Hospital is still high (13.2%).

OBJECTIVE: We evaluated performance of the Pediatric Logistic Organ Dysfunction (PELOD) score compared with the Pediatric Risk of Mortality III (PRISM III) for predicting mortality in our PICU.

METHODS: A total of 42 patients (48% boys, 52% girls) admitted to the PICU from January to December 2006 were enrolled onto the study. Diagnosis of DSS was made according to 1997 World Health Organization criteria and confirmed with serologic-positive dengue blot taken on the fifth day of fever (93% secondary infection and 7% primary infection). PELOD and PRISM scores were evaluated on the first day.

RESULTS: From 42 admissions, 1 was excluded for insufficient data. Median age of the children was 7 years. Death occurred in 11.9% of the patients with DSS. Analysis showed that the mean PELOD score was 7.2 (Mann-Whitney U test between survivors and nonsurvivors was significant at P = .001) compared with the PRISM III (mean score was significant also at P = .008). The receiver operating characteristic curves for the PELOD and PRISM III were 0.954 and 0.868, respectively.

CONCLUSIONS: PELOD and PRISM III scores showed a good discrimination for predicting mortality in patients with DSS in our PICU.
CLINICAL STUDIES AND ANALYSIS OF THE RETT SYNDROME GENE (MECP2) IN CHILDREN WITH MENTAL RETARDATION IN THE GREEK POPULATION
Authors: Psoni Stavroula , Traeger-Synodinos Joanne , Sofocleous Christalena , Kitsiou-Tzeli Sophia , Mavrou Ariadni , Kanavakis Emmanuel , Fryssira Helen
Published: January 2008

INTRODUCTION: Mutations in the methyl CpG-binding protein 2 (MECP2) gene are responsible for 70% to 95% of cases of Rett syndrome (RS), an X-linked dominant neurodevelopmental disorder that mostly affects girls. Classical RS is characterized by normal early development followed by psychomotor regression and gradual onset of microcephaly, although variable atypical forms have also been observed. MECP2 has also been implicated in a variety of other mental retardation (MR) phenotypes, including X-linked MR, fragile X syndrome–like and Angelman syndrome (AS)–like phenotypes.

OBJECTIVE: Our goals were to evaluate the incidence and spectrum of MECP2 mutations in children with RS and atypical MR and to correlate the phenotype and genotype.

METHODS: Exons 3 and 4 of the MECP2 gene were analyzed by using denaturing gradient gel electrophoresis, sequencing, and gap polymerase chain reaction for (1) 124 children with FXS-like symptoms (102 boys, 22 girls) and 41 children with AS-like symptoms (14 boys, 27 girls) who tested negative for gene variation at the FXS and AS loci, respectively, (2) 23 girls with classical RS and 25 girls with atypical RS, and (3) 11 boys who were referred with possible RS. Statistical analysis (t and nonparametrical tests) included correlation of RS clinical severity score (Kerr, 2001) with MECP2 mutations and frequency of MECP2 mutations in the various patient categories.

RESULTS: Mutations were detected in 78.3% of classical and 20% of atypical RS cases, respectively. One boy carried the p.R106W mutation, and another boy showed a large rearrangement that required further characterization. Among AS- and FXS-like cases, 7.3% and 2.4% had MECP2 mutations, respectively, including an X-linked MR case.

CONCLUSIONS: MECP2 gene analysis provides an appropriate diagnostic tool for RS and contributes additional information for research into MR.
THE GLOBAL BURDEN OF CHILDHOOD OTITIS MEDIA AND HEARING IMPAIRMENT: A SYSTEMATIC REVIEW
Authors: Gunasekera Hasantha , Haysom Leigh , Morris Peter , Craig Jonathan
Published: January 2008

INTRODUCTION: The World Health Organization resolved that chronic otitis media and resultant hearing impairment are significant global health problems and called for more detailed epidemiological information, particularly the association between prevalence and socioeconomic variables.

OBJECTIVE: We sought to determine the worldwide prevalence of otitis media (OM) and hearing impairment (HI) and their risk factors.

METHODS: We searched Medline, Embase, and Cinahl for population-based studies with incidence or prevalence data on OM and HI (>25 dB) in children (<18 years), without language restrictions. Studies identified through reference lists were also included. We examined the effect of socioeconomic and health variables on OM and HI prevalence.

RESULTS: The search strategy identified 1504 studies with substantial methodologic variation. They included studies (n = 108) that provided a combined sample size of 250 978 children. Acute OM incidence ranged from 0.6 to 1.7 episodes per child per year. The highest OM prevalence rates were in Inuits (81%) and Australian Aborigines (84%). HI prevalence ranged from <1% (Greece) to 23% (Australian Aborigines), and HI was significantly more common in children with OM (odds ratio [OR]: 8.11 [95% confidence interval (CI): 6.91–9.52]). In meta-analysis, increased OM prevalence was associated with not breastfeeding (OR: 1.28 [95% CI: 1.03–1.59]) and parental smoking (OR: 1.73 [95% CI: 1.42–2.10]), but male gender (OR: 1.04 [95% CI: 0.90–1.20]) and urbanization (OR: 0.72 [95% CI: 0.28–1.83]) were not significant. Some studies reported increased OM prevalence with overcrowding, lower maternal education, and poorer household sanitation.

CONCLUSIONS: Indigenous children have the highest prevalence of OM and its complications. OM remains a significant cause of preventable childhood HI, and many of the risk factors are modifiable.
IMPACT OF ZINC SUPPLEMENTATION ON RESPIRATORY AND GASTROINTESTINAL INFECTIONS: A DOUBLE-BLIND, RANDOMIZED TRIAL AMONG URBAN IRANIAN SCHOOLCHILDREN
Authors: Masoodpoor Nahid , Darakhshan Shokoofeh , Darakhshan Darakhshan , Tabatabaei Seyed Taghi , Mosavat Seyed Abualghasem
Published: January 2008

INTRODUCTION: In addition to inhibiting growth, mild zinc deficiency is probably associated with reduced resistance to infection in children, but it has been difficult to establish this link; however, children with severe zinc deficiency have been found to be at increased risk for diarrhea and respiratory diseases.

OBJECTIVE: The aim of this study was to evaluate the roles of zinc supplementation in the episodes of respiratory and gastrointestinal infections in children.

METHODS: This study was a randomized, double-blind, placebo-controlled trial of 90 children (50 boys and 40 girls aged 7–12 years) who were underweight or had stunted growth. They were supplemented with 10 mg of zinc or placebo on school days for 6 months. Episodes of respiratory and gastrointestinal infections were recorded monthly.

RESULTS: At the end of this study, significant effects of zinc supplementation on the decreased number of episodes of respiratory and gastrointestinal infections were seen during the full 6 months.

CONCLUSIONS: On the basis of this study, zinc supplementation decreased the number of episodes of respiratory and gastrointestinal infections in schoolchildren who were underweight or had stunted growth.
USING Q-METHODOLOGY TO EXPLORE PREFERENCES FOR CARE OF ADOLESCENTS WITH CHRONIC DISORDERS: 4 PROFILES
Authors: Van Staa AnneLoes , Jedeloo Susan , Latour Jos , van Exel Job
Published: January 2008

INTRODUCTION: Adolescents with chronic disorders are seldom asked to give opinions about their preferences for care, even though they are frequent health care users and soon need to take over the responsibility of managing their own care.

OBJECTIVE: The aim of the study was to investigate care-related preferences of adolescents with chronic disorders.

METHODS: A Q-methodologic study was conducted in a random sample of 31 adolescents with various congenital and acquired disorders from the total population of Erasmus Medical Center-Agia Sophia Children's Hospital (12–19 years). Adolescents rank-ordered 37 statements about preferences for care and self-care using a quasi-normal distribution. Factor analysis was applied to identify clusters in the Q-sorts, groups of adolescents with common preferences.

RESULTS: Four profiles were distinguished: concerned and compliant, backseat patient, opinionated and careless, and worried and insecure. Differences between profiles are related to independence competencies, level of involvement in management of the illness, adherence to therapeutic regimens, and appreciation of their parents' role. All adolescents want to have an important say in treatment-related decisions. Although adolescents are used to being accompanied by their parents in the consultation room, they sometimes prefer to be on their own.

CONCLUSIONS: Four different preference profiles were uncovered. Caregivers recognize these profiles in daily practice. Because the goal of Q-methodology is to establish different patterns but not their prevalence, the distribution of profiles will be explored in a large follow-up survey. Additional use of these profiles in daily practice will be also explored, because rank-ordering the statements stimulated adolescents to talk about care issues.