bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards better management of Australia's shark fishery: genetic analyses reveal unexpected ratios of cryptic blacktip species Carcharhinus tilstoni and C. limbatus
Authors: Ovenden J. R. , Morgan J. A. T. , Kashiwagi T. , Broderick D. , Salini J.
Published: February 2010

The common blacktip shark (Carcharhinus limbatus) and the Australian blacktip shark (C. tilstoni) are morphologically similar species that co-occur in subtropical and tropical Australia. In striking contrast to what has been previously reported, we demonstrate that the common blacktip shark is not rare in northern Australia but occurs in approximately equal frequencies with the Australian blacktip shark. Management of shark resources in northern Australia needs to take account of this new information. Species identification was performed using nucleotide sequences of the control, NADH dehydrogenase subunit 4 (ND4) and cytochrome oxidase I (COI) regions in the mitochondrial genome. The proportion of overall genetic variation (FST) between the two species was small (0.042, P < 0.01) based on allele frequencies at five microsatellite loci. We confirm that a third blacktip species (C. amblyrhynchoides, graceful shark) is closely related to C. tilstoni and C. limbatus and can be distinguished from them on the basis of mtDNA sequences from two gene regions. The Australian blacktip shark (C. tilstoni) was not encountered among 20 samples from central Indonesia that were later confirmed to be common blacktip and graceful sharks. Fisheries regulators urgently need new information on life history, population structure and morphological characters for species identification of blacktip shark species in Australia.
Surface charge characteristics and sorption properties of bauxite-processing residue sand
Authors: Phillips I. R. , Chen C.
Published: February 2010

Bauxite-processing residue sand (BRS) is the primary growth medium used to rehabilitate Alcoa’s residue storage areas (RSAs) in south-west Western Australia. This material is typically coarse-textured, highly saline, highly alkaline, extremely sodic, and deficient in plant nutrients. To develop appropriate fertiliser strategies for optimising rehabilitation performance, a fundamental understanding of the surface charge and nutrient retention properties of BRS is essential. The contribution of permanent (σp) and variable (σv) charge to the overall magnitude and sign of the surface charge, and ammonium (NH4) and phosphorus (P) sorption, as a function of pH were studied. Samples of BRS were obtained from Alcoa’s Kwinana (KW), Pinjarra (PJ), and Wagerup (WG) Refineries. Each sample exhibited predominantly variable charge (σv ≈ 8–12 cmol/kg at pH 12), and negligible permanent negative charge (σp ≈ 0.2 cmol/kg). The point of zero net charge (PZNC) was observed at pH 6.96, 6.89, and 5.98 for the KW, PJ, and WG samples, respectively. These values are consistent with those reported for soils dominated by Fe and Al oxides and hydroxides but containing negligible organic matter. Solution and adsorbed NH4 decreased with increasing pH (pH 7–11) for BRS. It was suggested that ammonia volatilisation was a major loss pathway for NH4 applied to BRS. Phosphorus sorption decreased with increasing pH for each BRS. It was suggested that the presence of competing anions (i.e. carbonate) and increasing negative surface charge density were the major causes for this behaviour. The results from this study have major implications for the selection of suitable types of fertilisers (particularly nitrogen) for rehabilitating alkaline BRS.
Fear selectively modulates visual mental imagery and visual perception
Authors: Borst Grégoire , Kosslyn Stephen M.
Published: February 2010

Emotions have been shown to modulate low-level visual processing of simple stimuli. In this study, we investigate whether emotions only modulate processing of visual representations created from direct visual inputs or whether they also modulate representations that underlie visual mental images. Our results demonstrate that when participants visualize or look at the global shape of written words ( low-spatial-frequency visual information), the prior brief presentation of fearful faces enhances processing, whereas when participants visualize or look at details of written words ( high-spatial-frequency visual information), the prior brief presentation of fearful faces impairs processing. This study demonstrates that emotions have similar effects on low-level processing of visual percepts and of internal representations created on the basis of information stored in long-term memory.
Risk Factors for Healthcare-Associated, Laboratory-Confirmed Influenza in Hospitalized Pediatric Patients: A Case-Control Study
Authors: Leckerman Kateri H. , Sherman Eileen , Knorr Jillian , Zaoutis Theoklis E. , Coffin Susan E.
Published: February 2010

We conducted a case-control study of 46 hospitalized pediatric patients with healthcare-associated laboratory-confirmed influenza (HA-LCI). We sought to determine the characteristics and outcomes of children with HA-LGI and to identify risk factors for HA-LCI. Although we failed to identify any differences in clinical exposures during the 3 days prior to onset of HA-LCI, multivariate analysis showed that asthma was an independent risk factor for HA-LCI (odds ratio, 3.49 [95% confidence interval, 1.25–9.75]).
h3/Acidic Calponin: An Actin-binding Protein That Controls Extracellular Signal-regulated Kinase 1/2 Activity in Nonmuscle Cells
Authors: Appel Sarah , Allen Philip G. , Vetterkind Susanne , Jin Jian-Ping , Morgan Kathleen G.
Published: February 2010

Migration of fibroblasts is important in wound healing. Here, we demonstrate a role and a mechanism for h3/acidic calponin (aCaP, CNN3) in REF52.2 cell motility, a fibroblast line rich in actin filaments. We show that the actin-binding protein h3/acidic calponin associates with stress fibers in the absence of stimulation but is targeted to the cell cortex and podosome-like structures after stimulation with a phorbol ester, phorbol-12,13-dibutyrate (PDBu). By coimmunoprecipitation and colocalization, we show that extracellular signal-regulated kinase (ERK)1/2 and protein kinase C (PKC)α constitutively associate with h3/acidic calponin and are cotargeted with h3/acidic calponin in the presence of PDBu. This targeting can be blocked by a PKC inhibitor but does not require phosphorylation of h3/acidic calponin at the PKC sites S175 or T184. Knockdown of h3/acidic calponin results in a loss of PDBu-mediated ERK1/2 targeting, whereas PKCα targeting is unaffected. Caldesmon is an actin-binding protein that regulates actomyosin interactions and is a known substrate of ERK1/2. Both ERK1/2 activity and nonmuscle l-caldesmon phosphorylation are blocked by h3/acidic calponin knockdown. Furthermore, h3/acidic calponin knockdown inhibits REF52.2 migration in an in vitro wound healing assay. Our findings are consistent with a model whereby h3/acidic calponin controls fibroblast migration by regulation of ERK1/2-mediated l-caldesmon phosphorylation.
Mso1p Regulates Membrane Fusion through Interactions with the Putative N-Peptide–binding Area in Sec1p Domain 1
Authors: Weber Marion , Chernov Konstantin , Turakainen Hilkka , Wohlfahrt Gerd , Pajunen Maria , Savilahti Harri , Jäntti Jussi
Published: February 2010

Sec1p/Munc18 (SM) family proteins regulate SNARE complex function in membrane fusion through their interactions with syntaxins. In addition to syntaxins, only a few SM protein interacting proteins are known and typically, their binding modes with SM proteins are poorly characterized. We previously identified Mso1p as a Sec1p-binding protein and showed that it is involved in membrane fusion regulation. Here we demonstrate that Mso1p and Sec1p interact at sites of exocytosis and that the Mso1p–Sec1p interaction site depends on a functional Rab GTPase Sec4p and its GEF Sec2p. Random and targeted mutagenesis of Sec1p, followed by analysis of protein interactions, indicates that Mso1p interacts with Sec1p domain 1 and that this interaction is important for membrane fusion. In many SM family proteins, domain 1 binds to a N-terminal peptide of a syntaxin family protein. The Sec1p-interacting syntaxins Sso1p and Sso2p lack the N-terminal peptide. We show that the putative N-peptide binding area in Sec1p domain 1 is important for Mso1p binding, and that Mso1p can interact with Sso1p and Sso2p. Our results suggest that Mso1p mimics N-peptide binding to facilitate membrane fusion.
GLUT4 Is Sorted to Vesicles Whose Accumulation Beneath and Insertion into the Plasma Membrane Are Differentially Regulated by Insulin and Selectively Affected by Insulin Resistance
Authors: Xiong Wenyong , Jordens Ingrid , Gonzalez Eva , McGraw Timothy E.
Published: February 2010

Insulin stimulates glucose transport by recruiting the GLUT4 glucose transporter to the plasma membrane. Here we use total internal reflection fluorescence microscopy to show that two trafficking motifs of GLUT4, a FQQI motif and a TELE-based motif, target GLUT4 to specialized vesicles that accumulate adjacent to the plasma membrane of unstimulated adipocytes. Mutations of these motifs redistributed GLUT4 to transferrin-containing recycling vesicles adjacent to the plasma membrane, and the degree of redistribution correlated with the increases of the GLUT4 mutants in the plasma membrane of basal adipocytes. These results establish that GLUT4 defaults to recycling endosomes when trafficking to specialized vesicles is disrupted, supporting the hypothesis that the specialized vesicles are derived from an endosomal compartment. Insulin stimulates both the accumulation of GLUT4 in the evanescent field and the fraction of this GLUT4 that is inserted into the plasma membrane. Unexpectedly, these two steps are differentially affected by the development of insulin resistance. We ascribe this selective insulin resistance to inherent differences in the sensitivities of GLUT4 vesicle accumulation and insertion into the plasma membrane to insulin. Differences in insulin sensitivities of various processes may be a general mechanism for the development of the physiologically important phenomenon of selective insulin resistance.
Septin 14 Is Involved in Cortical Neuronal Migration via Interaction with Septin 4
Authors: Shinoda Tomoyasu , Ito Hidenori , Sudo Kaori , Iwamoto Ikuko , Morishita Rika , Nagata Koh-ichi
Published: February 2010

Septins are a family of conserved guanosine triphosphate/guanosine diphosphate-binding proteins implicated in a variety of cellular functions such as cell cycle control and cytokinesis. Although several members of septin family, including Septin 14 (Sept14), are abundantly expressed in nervous tissues, little is known about their physiological functions, especially in neuronal development. Here, we report that Sept14 is strongly expressed in the cortical plate of developing cerebral cortex. Knockdown experiments by using the method of in utero electroporation showed that reduction of Sept14 caused inhibition of cortical neuronal migration. Whereas cDNA encoding RNA interference-resistant Sept14 rescued the migration defect, the C-terminal deletion mutant of Sept14 did not. Biochemical analyses revealed that C-terminal coiled-coil region of Sept14 interacts with Septin 4 (Sept4). Knockdown experiments showed that Sept4 is also involved in cortical neuronal migration in vivo. In addition, knockdown of Sept14 or Sept4 inhibited leading process formation in migrating cortical neurons. These results suggest that Sept14 is involved in neuronal migration in cerebral cortex via interaction with Sept4.
Attention in the Brain and Early Infancy
Authors: Richards John E.
Published: February 2010

This chapter reviews the hypothesis that changes in brain areas controlling attention strongly influence the development of attention in infant participants. It examines the methodological advances in imaging showing what is inside the infant's head and how to measure brain activity in infant participants. It focuses on work using cortical source analysis of event related potentials (ERP) in the spatial cueing procedure as an example of how this might be done. The goal of research in this area is to link measures of infant brain development and measures of attention development.
All Together Now: Learning through Multiple Sources
Authors: Kirkham Natasha
Published: February 2010

This chapter describes a theory of multiple cue integration, supporting the acquisition of complex knowledge. The “great blooming, buzzing confusion” of the perceptual world actually holds a wealth of information for an infant in the form of statistical structure and cross-modal regularities. It also contains many distractions, in terms of noise and extraneous information. When learning about the world, how do infants pay attention to the right set of multiple cues at the right time? This theory posits a developmental trajectory out of this problem: At early ages, infants rely on multiple, cross-modal cues in learning about sequences and locations; later on, they are better able to ignore unhelpful information and learn from a narrower set of cues.
Perceptual Completion in Infancy
Authors: Johnson Scott P.
Published: February 2010

This chapter describes a set of object perception skills that develop early in infancy, focusing on three ways in which observers fill in the gaps in perception imposed by occlusion: spatial completion, spatiotemporal completion, and 3D object completion. It describes experiments designed to examine developmental mechanisms of perceptual completion in infants. The best evidence to date suggests that newborn infants do not fill in the gaps in perception, and therefore do not perceive objects as do adults. Instead, the visual world of neonates seems to consist solely of surface fragments that have no substance, volume, or continuity. Infants initially appear to process complex stimuli as simple isolated units, and subsequently integrate them into higher-order patterns.
Numerical Identity and the Development of Object Permanence
Authors: Moore M. Keith , Meltzoff Andrew N.
Published: February 2010

This chapter proposes an identity development (ID) account of object permanence that locates the origins and development of permanence in infants' notions of how to determine and trace numerical identity. The arguments and evidence generated from this approach suggest a number of conclusions: (a) object permanence understanding is not an all-or-none attainment; (b) permanence is understood for some disappearance transforms but not others; (c) the development of infants' spatiotemporal criteria for numerical identity provide the form and ordering of the disappearance transforms over which they understand permanence; (d) apparent violations of permanence can cause negative emotion; and (e) taking seriously the conceptual distinctions between representation, identity, and permanence offers considerable theoretical power. The chapter presents a mechanism of change to account for the transition from having no concept of permanence to having permanence.
Connectionist Explorations of Multiple-Cue Integration in Syntax Acquisition
Authors: Christiansen Morten H. , Dale Rick , Reali Florencia
Published: February 2010

This chapter hypothesizes that integrating multiple probabilistic cues (phonological, prosodic, and distributional) by perceptually attuned general-purpose learning mechanisms, may hold promise for explaining how children solve the bootstrapping problem. Multiple cues can provide reliable evidence about linguistic structure that is unavailable from any single source of information. The chapter first reviews empirical evidence suggesting that infants may use a combination of phonological, prosodic, and distributional cues to bootstrap into syntax. It then reports a series of simulations demonstrating the computational efficacy of multiple-cue integration within a connectionist framework.
Musical Enculturation: How Young Listeners Construct Musical Knowledge through Perceptual Experience
Authors: Hannon Erin E.
Published: February 2010

This chapter explores the question of how infants and children build musical representations, with particular focus on perception, and knowledge of temporal structure in music, such as rhythm and meter. It reviews published and new evidence that infants can perceive rhythm and meter by attending to the same statistical properties that underlie adults' perception, that representations of rhythm and meter undergo reorganization as a result of culture-specific perceptual experience, and that infants and adults share some basic temporal processing constraints despite infants' initial flexibility. In addition to examining development of music-specific knowledge, a parallel goal is to understand the emergence of domain-specific representations in auditory cognition. If we assume that early representations of music are primarily domain-general and become culture-specific through perceptual experience, then a question of great interest is whether overlapping structures are present and detected in the musical and linguistic input available to infants and children. The chapter briefly reviews some new evidence suggesting that this is may be the case.
Integrating Top-down and Bottom-up Approaches to Children’s Causal Inference
Authors: Sobel David M.
Published: February 2010

This chapter suggests a description of causal inference based on Bayesian inference, which illustrates how children engage in causal learning. This description is meant at the computational level of analysis, which means that an obvious limitation of this approach is that it should not be taken for the actual algorithm by which children learn causal knowledge, nor should it be considered how the brain instantiates such inference. However, describing the way in which children learn causal knowledge provides insight into these questions.
The Acquisition of Expertise as a Model for the Growth of Cognitive Structure
Authors: Quinn Paul C.
Published: February 2010

This chapter begins by asking whether infants can form category representations for nonhuman animals, via what stimulus attributes such representations might be formed, and whether infants are forming these category representations on the basis of stimulus images presented in the laboratory. It then discusses whether infants categorize humans, and whether the category structure that infants use to represent humans differs from the structure they use to represent nonhuman animals. Also considered will be the stimulus information infants use to represent humans, as well as whether infants respond to human images presented in the laboratory based on knowledge about humans acquired prior to arrival at the laboratory. The chapter concludes with the thesis that what infants know about nonhuman animals can be likened to what novices know about generic object categories, whereas what infants know about humans can be likened to what experts know about their domain of expertise.
Building Intentional Action Knowledge with One’s Hands
Authors: Gerson Sarah , Woodward Amanda
Published: February 2010

This chapter considers the potential origins of the ability to discern others' intentions in acting. It focuses on a category of experience that has long been hypothesized to contribute to intentional understanding: namely, first-person agentive experience. Theoretically, it seems reasonable that one's own experience as an agent could provide useful information for understanding other agents. A true test of this general hypothesis requires (1) measuring infants' analysis of observed action structure and (2) relating this measure to variations in infants' own actions. The chapter turns first to recent studies that have done just this, and in so doing provided initial evidence that this general proposal is on the right track. It then turns to the much harder question of why self-produced experience might have an effect on the development of action understanding. This question will leads to the consideration of recent work on mirror systems, the limits of mirror systems, and the role of analogy in conceptual development.
A Neoconstructivistic Approach to the Emergence of a Face Processing System
Authors: Simion Francesca , Leo Irene
Published: February 2010

This chapter examines (1) whether some constraints or prewired attentional biases are present at birth; (2) if these constraints are general or specific; and (3) how they contribute to guide and shape cognitive activity. In order to address these issues, a peculiar class of visual stimuli, namely faces, will be taken into consideration, because faces form a special class of visual objects elaborated in adults by a specific face system. The first part of the chapter focuses on the mechanisms underlying infants' visual preference for faces, and on the visuoperceptual constraints that induce newborns to prefer faces. The second part of the chapter reviews the studies on the nature of the information newborns actually process and encode when they look at faces as compared to nonface stimuli; more specifically, whether the recognition of faces at birth requires the same nonspecific generalized perceptual abilities that are involved in processing all types of visual stimuli.
Immunomodulatory Polysaccharide from Chlorophytum borivilianum Roots
Authors: Thakur Mayank , Connellan Paul , Deseo Myrna A. , Morris Carol , Dixit Vinod K.
Published: February 2010

Chlorophytum borivilianum Santapau & Fernandes (Liliaceae) is an ayurvedic Rasayana herb with immunostimulating properties. The polysaccharide fraction (CBP) derived from hot water extraction of C. borivilianum (CB), comprising of ~31% inulin‐type fructans and ~25% acetylated mannans (of hot water‐soluble extract), was evaluated for its effect on natural killer (NK) cell activity (in vitro). Human peripheral blood mononuclear cells (PBMCs), isolated from whole blood on a Ficoll‐Hypaque density gradient, were tested in the presence or absence of varying concentrations of each C. borivilianum fraction for modulation of NK cell cytotoxic activity toward K562 cells. Preliminary cytotoxicity evaluation against P388 cells was performed to establish non‐cytotoxic concentrations of the different fractions. Testing showed the observed significant stimulation of NK cell activity to be due to the CBP of C. borivilianum. Furthermore, in vivo evaluation carried out on Wistar strain albino rats for humoral response to sheep red blood cells (SRBCs) and immunoglobulin‐level determination using enzyme‐linked immunosorbent assay (ELISA), exhibited an effectiveness of C. borivilianum aqueous extract in improving immune function. Present results provide useful information for understanding the role of CBP in modulating immune function.
Influence of Oreocnide integrifolia (Gaud.) Miq on IRS‐1, Akt and Glut‐4 in Fat‐Fed C57BL/6J Type 2 Diabetes Mouse Model
Authors: Ansarullah  , Jayaraman Selvaraj , Hardikar Anandwardhan A. , Ramachandran A. V.
Published: February 2010

Oreocnide integrifolia (OI) leaves are used as folklore medicine by the people of northeast India to alleviate diabetic symptoms. Preliminary studies revealed hypoglycemic and hypolipidemic potentials of the aqueous leaf extract. The present study was carried out to evaluate whether the OI extract induces insulin secretion in vivo and in vitro and also whether it is mediated through the insulin‐signaling pathway. The experimental set‐up consisted of three groups of C57BL/6J mice strain: (i) control animals fed with standard laboratory diet, (ii) diabetic animals fed with a high‐fat diet for 24 weeks and (iii) extract‐supplemented animals fed with 3% OI extract along with high‐fat diet for 24 weeks. OI‐extract supplementation lowered adiposity and plasma glucose and insulin levels. Immunoblot analysis of IRS‐1, Akt and Glut‐4 protein expressions in muscles of extract‐supplemented animals revealed that glucoregulation was mediated through the insulin‐signaling pathway. Moreover, immunostaining of pancreas revealed increased insulin immunopositive cells in OI‐extract‐treated animals. In addition, the insulin secretogogue ability of the OI extract was demonstrated when challenged with high glucose concentration using isolated pancreatic islets in vitro. Overall, the present study demonstrates the possible mechanism of glucoregulation of OI extract suggestive of its therapeutic potential for the management of diabetes mellitus.
Early Onset of Ulcerative Colitis: Long‐term Follow‐up With Special Reference to Colorectal Cancer and Primary Sclerosing Cholangitis
Authors: Lindberg Jan , Stenling Roger , Palmqvist Richard , Rutegård Jörgen
Published: February 2010

Objectives:

Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC) and primary sclerosing cholangitis (PSC). The onset of UC at a young age has been considered a specific risk factor for CRC. This study reports the outcome with respect to DNA aneuploidy, dysplasia, CRC, and PSC in a cohort of patients with early‐onset UC from a defined catchment area who were followed up for 45 years.

Patients and Methods:

The study period was from 1961 through 2005. In all, 46 children and adolescents, ages 18 or younger from our catchment area, were affected with UC during this time. Data were collected from our colonoscopic surveillance program and other medical records in the same hospital.

Results:

The incidence rate of UC was 1.6 children or adolescents per 100,000 inhabitants per year. The onset of disease was at age 14 years (mean and median), and the observed duration of disease was 0 to 44 years. Five patients died, 3 of them of intercurrent disease. CRC developed in 1 patient, and no death caused by this disease was observed. PSC was diagnosed in 4 patients, in all of whom the onset of UC occurred before age 15.

Conclusions:

The earlier reports of increased risk of CRC in patients with early‐onset UC was not seen in this study. This could be due to a high frequency of surgery together with a well‐functioning surveillance program with excellent compliance. The recommendation of surgery in cases of high‐grade dysplasia or repeated findings of low‐grade dysplasia seems to be effective in the attempt to minimize the risk for CRC. We observed a rather high incidence of PSC, which may indicate that more attention should be paid to a search for this diagnosis in patients with early‐onset UC.
Endoscopic Ultrasonography in Pediatric Patients With Gastrointestinal Disorders
Authors: Cohen Shlomi , Kalinin Michael , Yaron Ayala , Givony Shlomo , Reif Shimon , Santo Erwin
Published: February 2010

Background:

Endoscopic ultrasound is a diagnostic tool for evaluation of gastrointestinal diseases in adults, but in children the use of endoscopic ultrasound is limited. This study retrospectively evaluates endoscopic ultrasound indications in, safety in, and impact on children.

Patients and Methods:

We reviewed the data of all of the pediatric patients (<18 years old) that underwent endoscopic ultrasound in our institution. The main goal was to evaluate the impact of endoscopic ultrasound in this patient population. Significant impact was defined as a new diagnosis or treatment attributed to the endoscopic ultrasound examination.

Results:

Thirty‐two children (21 boys, 11 girls) at mean age 12 ± 5 years; (range = 1.5–18 years) underwent endoscopic ultrasound during a period of 6 years. The pancreas and biliary tract were examined in 19 children, esophagus in 8, and the stomach and rectum in 2 children each. Only 1 child had endoscopic ultrasound for duodenal indication. The indications in the pancreas and biliary tract group were recurrent pancreatitis in 9 children, cyst or mass in 6 children, and obstructive jaundice in 4 children. Indications in the esophagus group were stenosis in 4 children, and suspected duplication and esophageal mass in 2 children each. We used conscious sedation in 18 children and unconscious sedation in 12. Two children underwent endoscopic ultrasound with no anesthesia at all. In 7 cases, endoscopic ultrasound–guided fine‐needle aspiration was performed. The procedure was successful in all of the patients with no complications. Endoscopic ultrasound changed the diagnosis or therapy in 14 cases.

Conclusions:

Endoscopic ultrasound is an effective tool in the evaluation of pediatric gastrointestinal patients, mostly with pancreatobiliary or esophageal disorders. Endoscopic ultrasound is a safe procedure with a significant impact in almost half of the children examined.
Prevalence of Celiac Disease in Children With Type 1 Diabetes Mellitus Increased in the Mid‐1990s: An 18‐year Longitudinal Study Based on Anti‐endomysial Antibodies
Authors: Salardi Silvana , Volta Umberto , Zucchini Stefano , Fiorini Erica , Maltoni Giulio , Vaira Bernardino , Cicognani Alessandro
Published: February 2010

Between 1987 and 2004, 331 consecutive children, all newly diagnosed with type 1 diabetes mellitus in our pediatric clinic, underwent repeated serological screening for celiac disease (CD) by means of anti‐endomysial antibodies, measured prospectively between 1994 and 2004, and retrospectively, using frozen banked serum, between 1987 and 1993. There were 22 cases (6.6%) of biopsy‐proven CD among the 331 diabetic children. The prevalence of CD was significantly (P = 0.015) higher after 1994 (10.6%) than before 1994 (3.3%). The rapid change in the risk of CD among Italian diabetic children that occurred in the mid‐1990s could be related to changes in environmental factors, namely, eating habits and viral infections.
Impact of Neonatal Protein Metabolism and Nutrition on Screening for Phenylketonuria
Authors: Ponzone Alberto , Spada Marco , Roasio Luca , Porta Francesco , Mussa Alessandro , Ferraris Silvio
Published: February 2010

Objectives:

Early blood phenylalanine (Phe) elevation after birth enables screening for and anticipation of the diagnosis of phenylketonuria. The differential impact of factors involved in this phenomenon, however, has not been elucidated. To solve this question, phenotype, genotype, dietary Phe intake, timing of blood collection, and Phe metabolism were retrospectively analyzed in 21 phenylketonuria newborns and prospectively in 1.

Patients and Methods:

Patients were assigned to 1 of 4 classes of phenylalanine hydroxylase (PAH) deficiency (severe, moderate, mild, and benign) on the basis of their Phe tolerance. Phe ingested, tolerated, and released from endogenous catabolism was assessed.

Results:

From birth to screening test, the amount of Phe tolerated ranged from 704 to 1620 mg, according to the class of PAH deficiency. The amount of Phe ingested ranged only from 204 to 405 mg, whereas the endogenous Phe breakdown ranged from 812 to 1534 mg, resulting in a rate of Phe catabolism ranging from 262 to 341 mg/day, regardless of the class of PAH deficiency.

Conclusions:

The high rate of protein catabolism is the main determinant of neonatal hyperphenylalaninemia. It is sufficient to turn to positive the screening test in severe and moderate PAH deficiency. In mild and benign PAH deficiency, the outcome of screening procedures can be substantially altered by the concurrence of genetic and peristatic factors. These results imply that the value of blood Phe at the screening test is not fully predictive of the phenylketonuria phenotype, and strengthen concerns regarding the reliability of early screening procedures.
Effect of Lactulose on Bacterial Translocation and Intestinal Adaptation in a Rat Model of Short Bowel Syndrome
Authors: Sukhotnik Igor , Srugo Isaac , Mogilner Jorge G , Lurie Michael , Coran Arnold G , Shaoul Ron
Published: February 2010

Background:

It is frequently assumed that dietary nondigestible carbohydrates improve host resistance to intestinal infections by stimulating proliferation of the protective gut microflora. Therefore, the aim of this study was to define the effect of lactulose, a nondigestible carbohydrate, on bacterial translocation and intestinal adaptation in a rat model of short bowel syndrome (SBS).

Materials and Methods:

Male Sprague‐Dawley rats were divided into 3 experimental groups. Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS‐LAC rats underwent bowel resection and were treated with oral lactulose given in drinking water at a dose of 1.5 g · kg−1 · day−1 from the 3rd to the 15th postoperative day. Bacterial translocation (to mesenteric lymph nodes, liver, and portal and peripheral blood) and parameters of intestinal adaptation were determined on day 15.

Results:

Treatment with lactulose did not change bacterial translocation, but decreased ileal mucosal weight (20%; P < 0.05), ileal mucosal DNA (2‐fold decrease; P < 0.05) and protein (26%; P < 0.05), villus height in jejunum (21%; P < 0.05) and crypt depth in ileum (17%; P < 0.05), proliferation rates in jejunum (18%; P < 0.05) and ileum (15%; P < 0.05), and apoptotic index in jejunum (40%; P < 0.05) and ileum (36%; P < 0.05) compared with SBS animals. Bax expression was upregulated in SBS rats compared with control animals, but decreased following treatment with lactulose.

Conclusions:

In a rat model of SBS, oral lactulose does not improve bacterial translocation from the intestine, but inhibits intestinal adaptation.
What Is the Role of the Metabolic Activity of the Gut Microbiota in Inflammatory Bowel Disease? Probing for Answers With Stable Isotopes
Authors: Barclay Andrew R , Morrison Douglas J , Weaver Lawrence T
Published: February 2010

The pathogenesis of inflammatory bowel disease remains obscure. However, there has been increasing interest in the role of the gut microbiota, focusing in particular on the “unculturable majority” of luminal and mucosal bacteria, which until recently have been difficult to study owing to the technical challenges of identification and elucidating function. Bacterial components and metabolites have been implicated in signalling to host immune systems and regulating inflammatory responses. Although the rapid expansion in techniques of molecular microbiology has increased our understanding of bacterial diversity, the tools to assess bacterial metabolic activity, and to link the 2, lag behind. Stable isotope probing is a powerful technique to link the metabolic activity and diversity of “unculturable” bacteria through isotopic labelling of biomarkers such as DNA and RNA. Progression of current stable isotope probing methodology with high‐resolution oligonucleotide 16s rRNA probe technology and high precision liquid chromatographic isotope ratio mass spectrometry may facilitate application in human microbial ecology. Progress towards stable isotope probing use in vivo, in concert with other advances in bacterial metabolome analysis, will lead to the development of a dynamic picture of the metabolic activity and diversity of intestinal bacteria in inflammatory bowel disease. Such insights will, over time, lead to fuller understanding of inflammatory bowel disease pathogenesis and the development of targeted therapies to reverse the “dysbiosis” that precedes disease relapse.
Altered Bile Acid Metabolism in Childhood Functional Constipation: Inactivation of Secretory Bile Acids by Sulfation in a Subset of Patients
Authors: Hofmann Alan F , Loening‐Baucke Vera , Lavine Joel E , Hagey Lee R , Steinbach Joseph H , Packard Christine A , Griffin Terrance L , Chatfield Dale A
Published: February 2010

Objective:

An elevated concentration in the colon of the primary bile acid chenodeoxycholic acid (CDCA) or the secondary bile acid deoxycholic acid (DCA) is known to induce water secretion, causing diarrhea. We hypothesized that of the many fecal bile acids, only CDCA and DCA function as endogenous laxatives; therefore, a decrease in their proportion may be a cause of childhood functional constipation. To test this possibility, fecal bile acid composition was determined in children with functional constipation and in nonconstipated control children.

Patients and Methods:

Fecal samples were obtained from 207 children, 103 with functional constipation and 104 with normal bowel habits. Bile acid classes were determined by use of electrospray ionization—single ion monitoring—mass spectrometry (ESI‐SIM‐MS), and individual bile acids were measured by gas chromatography (GC)‐MS (GC‐MS). The structure of individual sulfated bile acids was obtained by use of liquid chromatography (LC)‐MS (LC‐MS).

Results:

By ESI‐SIM‐MS, the proportions of DCA did not differ in constipated children (n = 73) from that in control children (n = 92), but monosulfated dihydroxy bile acids were greater (P < 0.05). The difference was attributable to 6 patients in the constipated group whose major fecal bile acid by LC‐MS was the 3‐sulfate of CDCA. Sulfation of CDCA is known to abolish its secretory activity. By GC‐MS, the bile acid profile was identical in the 2 groups.

Conclusions:

In most children with functional constipation, the fecal bile acid profile seems to be normal. There is a small subset of children, however, whose dominant fecal bile acid is the 3‐sulfate of CDCA, indicating a novel disturbance in bile acid metabolism. Such sulfation abolishes the secretory activity of CDCA and may contribute to constipation.
Long‐chain Polyunsaturated Fat Supplementation in Children With Low Docosahexaenoic Acid Intakes Alters Immune Phenotypes Compared With Placebo
Authors: Mazurak VC , Lien V , Field CJ , Goruk SD , Pramuk K , Clandinin MT
Published: February 2010

Objectives:

The objectives of this study were to assess the effects of long‐term supplementation with arachidonic acid (AA; 20:4n‐6) and docosahexaenoic acid (DHA; 22:6n‐3) on cell phenotypes and cytokine production in children.

Patients and Methods:

This randomized, double‐blind, placebo‐controlled trial provided children, (ages 5–7 years; n = 37) who had low intakes of DHA, with a dietary supplement containing AA (20–30 mg daily) and DHA (14–21 mg daily) or a placebo supplement for 7 months. After the supplementation period, a series of stimulants (pokeweed mitogen, phytohemagluttinin, lipopolysaccharide, β‐lactoglobulin, and ibuprofen) was used to stimulate peripheral blood mononuclear cells ex vivo. Antigen expression on T cells (CD25 and CD80), B cells, and macrophages (CD54), as well as cytokine production (interleukin [IL]‐4, IL‐10, tumor necrosis factor, IL‐2, IL‐6, and interferon‐γ), were measured using flow cytometry, monoclonal antibodies, and cytometric bead array, respectively.

Results:

Mononuclear cells from children provided long‐chain polyunsaturated fatty acids (LCPUFAs) had fewer CD8+ cells expressing CD25 and CD80 compared with placebo after exposure to each mitogen. The LCPUFA group also exhibited lower proportions of CD14+ cells after stimulation with β‐lactoglobulin and ibuprofen. The proportion of CD54+ cells was 2‐fold higher for the LCPUFA group compared with placebo after exposure to ibuprofen and β‐lactoglobulin (P < 0.05). Each of these immune effects related to the amount of AA and/or DHA in the plasma and erythrocyte phospholipids.

Conclusions:

Alterations in cell phenotypes were evident when children were supplemented with AA and DHA. The results of this study have important implications for immune development and sensitivity to antigens in children.
Carotenoids, Retinol, and Intestinal Barrier Function in Children From Northeastern Brazil
Authors: Vieira Milena M , Paik Jisun , Blaner William S , Soares Alberto M , Mota Rosa MS , Guerrant Richard L , Lima Aldo AM
Published: February 2010

Objectives:

To investigate the association of carotenoids and retinol (vitamin A) with intestinal barrier function in children in an urban community in Fortaleza, northeastern Brazil.

Methods:

Descriptive analysis of serum carotenoids and retinol concentrations with intestinal barrier function in 102 children from an urban community, July 2000 to August 2001.

Results:

The weight for height z score (wasting) showed that 19.6% (20/102) had mild malnutrition (−1 to −2 z score). All of the children's serum retinol concentrations were determined and none were severely deficient (≤0.35 μmol/L), 2.9% (3/102) were moderately (0.36–0.70 μmol/L) deficient, 20.6% (21/102) were mildly (0.71–1.05 μmol/L) deficient; 76.5% (78/102) were vitamin A sufficient (>1.05 μmol/L). The lactulose:mannitol (L/M) ratio was elevated (≥0.0864) in 49% (47/97) of children when compared with healthy children with normal L/M ratio (<0.0864) in the same geographic area. Serum carotenoids, lutein, β‐cryptoxanthin and β‐carotene showed significant inverse correlations with the L/M ratio, but not lutein after adjusting for age. Acute phase proteins (C‐reactive protein and α‐acid glycoprotein) were significantly inversely correlated with retinol but not with carotenoids. Retinol and retinol‐binding protein were not significantly associated with L/M ratio.

Conclusions:

These data suggest a disruption of intestinal barrier function in the paracellular pathway with low serum concentrations of carotenoids. Carotenoids may provide a better marker for disrupted intestinal barrier function than retinol‐binding protein or retinol.
Germline APC Mutations Are Not Commonly Seen in Children With Sporadic Hepatoblastoma
Authors: Harvey JJ , Clark SK , Hyer W , Hadzic N , Tomlinson IPM , Hinds R
Published: February 2010

Hepatoblastoma is the most common primary liver tumor in childhood and occurs more commonly in families with familial adenomatous polyposis. Germline mutations of the gene responsible for familial adenomatous polyposis—adenomatous polyposis coli (APC)—are described in patients with hepatoblastoma even without a family history. We investigated children presenting with apparently sporadic hepatoblastoma between 1991 and 2004. Blood samples were available from 29 children (18 boys) whose conditions were diagnosed at a median age of 22 months (range 6–119 months). No germline APC mutations were found, which does not support the need for routine screening in sporadic hepatoblastoma in the absence of a suggestive family history of colorectal cancer or suspicion of familial adenomatous polyposis.
Aetiology and Management of Extrahepatic Portal Vein Obstruction in Children: King's College Hospital Experience
Authors: Abd El‐hamid Nehal , Taylor Rachel M , Marinello Daniela , Mufti GJ , Patel Raj , Mieli‐Vergani Giorgina , Davenport Mark , Dhawan Anil
Published: February 2010

Objective:

To study a single‐centre experience of the management of extrahepatic portal vein obstruction (EHPVO) in children during the last 3 decades.

Materials and Methods:

The medical records of 108 children (67 male, median age 4.75 years, range = 1 day–16.3 years) presenting with EHPVO between 1979 and 2005 were reviewed retrospectively.

Results:

Extended prothrombotic screening performed in 30 patients revealed low protein C activity (6 patients), low free protein S (2), and a positive lupus anticoagulant (1); factor V Leiden mutations and the JAK2V617F mutation were not identified. Associated congenital anomalies were found in 26 of the 108 children (24%). Clinical presentation included splenomegaly in 98 (91%) and ascites in 3 (3%). Elevation of liver enzymes and prolonged international normalized ratio were seen in 13 (12%) and 14 (13%) children, respectively. Haematological parameters of hypersplenism were present in 13 (12%). Bleeding occurred in 83 (77%) patients with a median age of 4.58 (0.02–16.37) years. On first endoscopy, oesophageal varices were present in 92 patients; of those subjects, 70 (76%) received sclerotherapy, 5 (5%) had band ligation, and 16 (17%) received both. Complications of endoscopy occurred in 34 (37%) patients: oesophageal ulcers in 16, oesophageal stricture in 10, both in 7, and erosive gastritis in 1. Seventeen (16%) children underwent shunt surgery for uncontrolled bleeding at a median age of 9.7 (5.2–23.7) years.

Conclusions:

The aetiology of EHPVO in the majority of patients remains unknown. Sclerotherapy and banding are effective treatments for bleeding varices with good long‐term outcome. Procoagulant state is an infrequent cause of EHPVO in children.
Quality of Life in Adolescents With Treated Coeliac Disease: Influence of Compliance and Age at Diagnosis
Authors: Wagner Gudrun , Berger Gabriele , Sinnreich Ursula , Grylli Vasileia , Schober Edith , Huber Wolf‐Dietrich , Karwautz Andreas
Published: February 2010

Objective:

To assess the influence of gluten‐free diet (GFD) compliance on the quality of life (QOL) of adolescents with coeliac disease (CD), and the impact of patient's age at time of diagnosis.

Study design:

Participants included 365 subjects: 283 adolescents (10–20 years old) with biopsy‐proven CD and 82 adolescents without a chronic condition matched for age, sex, education, and social status. Their subjective QOL—comprising physical, mental, and social dimensions as defined by the World Health Organization—was measured and has been analyzed according to compliance status and age at CD diagnosis.

Results:

Adolescents noncompliant with GFD reported a lower general QOL, more physical problems, a higher burden of illness, more family problems, and more problems in leisure time than adolescents who are compliant with GFD. More frequent GFD transgressions were associated with poorer QOL. Higher problem anticipation and higher feelings of “ill‐being” were found in the noncompliant group. No differences between compliant patients with CD and adolescents without any chronic condition were found in all QOL aspects. Adolescents with a late CD diagnosis showed more problems at school and in social contact with peers, as well as worse physical health and higher CD‐associated burden.

Conclusions:

Compliance with GFD is an essential factor to obtain optimal QOL. Psychosocial and educational support should be provided for patients having difficulties strictly adhering to GFD. Early CD onset and diagnosis is associated with better physical health, lower CD‐associated burden and fewer social problems, indicating the importance of the earliest CD diagnosis possible.
Expression of Intestinal and Lung Alkaline Sphingomyelinase and Neutral Ceramidase in Cystic Fibrosis F508del Transgenic Mice
Authors: Ohlsson Lena , Hjelte Lena , Hühn Michael , Scholte Bob J , Wilke Martina , Flodström‐Tullberg Malin , Nilsson Åke
Published: February 2010

Objectives:

The intestinal brush border enzymes alkaline sphingomyelinase (alk‐SMase) and neutral ceramidase (CDase) digest milk sphingomyelin in suckling neonates. In addition, alk‐SMase, CDase, and acid sphingomyelinase (acid‐SMase) have been implicated in sphingolipid signaling, which exhibits abnormalities in cystic fibrosis (CF). In this study, we tested the hypothesis that the expression of these enzymes is different in CF.

Materials and Methods:

We used mice with F508del (Cftrtm1Eur) mutation, a CF mouse model with well‐characterized intestinal pathology. Enzyme activities were measured using radiolabeled sphingolipid substrates incubated with tissue homogenates from different organs and intestinal contents of wild‐type mice, homozygous, and heterozygous F508del mice.

Results:

No difference was found in levels of CDase and alk‐SMase in the small intestinal mucosa or in their longitudinal distribution. Acid‐SMase activity was significantly lower in the mucosa of the distal half of the small intestine of F508del compared with wild‐type mice. Despite a lower body weight of F508del mice, length and weight of the small intestine and weight per centimeter of colon were larger than in wild‐type. Neutral CDase and alk‐SMase activities in lungs were lower than in the gut, whereas acid‐SMase activity was comparable in both organs. CDase activity in the spleen was significantly higher in F508del than in wild‐type mice.

Conclusions:

Alk‐SMase and neutral CDase are normally expressed in F508del CF mice, whereas activity of acid‐SMase in the distal small intestine is decreased. We found no differences in activity of these enzymes in lungs in this mouse model.