bluuebunny/crossref_metadata_2025 huggingface dataset:
Excess Costs and Utilization Associated with Methicillin Resistance for Patients with Staphylococcus aureus Infection
Authors: Filice Gregory A. , Nyman John A. , Lexau Catherine , Lees Christine H. , Bockstedt Lindsay A. , Como-Sabetti Kathryn , Lesher Lindsey J. , Lynfield Ruth
Published: February 2010

Objective.

To determine differences in healthcare costs between cases of methicillin-susceptible Staphylococcus aureus (MSSA) infection and methicillin-resistant S. aureus (MRSA) infection in adults.

Design.

Retrospective study of all cases of S. aureus infection.

Setting.

Department of Veterans Affairs hospital and associated clinics.

Patients.

There were 390 patients with MSSA infections and 335 patients with MRSA infections.

Methods.

We used medical records, accounting systems, and interviews to identify services rendered and costs for Minneapolis Veterans Affairs Medical Center patients with S. aureus infection with onset during the period from January 1, 2004, through June 30, 2006. We used regression analysis to adjust for patient characteristics.

Results.

Median 6-month unadjusted costs for patients infected with MRSA were $34,657, compared with $15,923 for patients infected with MSSA. Patients with MRSA infection had more comorbidities than patients with MSSA infection (mean Charlson index 4.3 vs 3.2; P < .001). For patients with Charlson indices of 3 or less, mean adjusted 6-month costs derived from multivariate analysis were $51,252 (95% CI, $46,041–$56,464) for MRSA infection and $30,158 (95% CI, $27,092–$33,225) for MSSA infection. For patients with Charlson indices of 4 or more, mean adjusted costs were $84,436 (95% CI, $79,843–$89,029) for MRSA infection and $59,245 (95% CI, $56,016–$62,473) for MSSA infection. Patients with MRSA infection were also more likely to die than were patients with MSSA infection (23.6% vs 11.5%; P < .001). MRSA infection was more likely to involve the lungs, bloodstream, and urinary tract, while MSSA infection was more likely to involve bones or joints; eyes, ears, nose, or throat; surgical sites; and skin or soft tissue (P < .001).

Conclusions.

Resistance to methicillin in S. aureus was independently associated with increased costs. Effective antimicrobial stewardship and infection prevention programs are needed to prevent these costly infections.
Hand Hygiene Noncompliance and the Cost of Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Infection
Authors: Cummings Keith L. , Anderson Deverick J. , Kaye Keith S.
Published: February 2010

Background.

Hand hygiene noncompliance is a major cause of nosocomial infection. Nosocomial infection cost data exist, but the effect of hand hygiene noncompliance is unknown.

Objective.

To estimate methicillin-resistant Staphylococcus aureus (MRSA)-related cost of an incident of hand hygiene noncompliance by a healthcare worker during patient care.

Design.

Two models were created to simulate sequential patient contacts by a hand hygiene-noncompliant healthcare worker. Model 1 involved encounters with patients of unknown MRSA status. Model 2 involved an encounter with an MRSA-colonized patient followed by an encounter with a patient of unknown MRSA status. The probability of new MRSA infection for the second patient was calculated using published data. A simulation of 1 million noncompliant events was performed. Total costs of resulting infections were aggregated and amortized over all events.

Setting.

Duke University Medical Center, a 750-bed tertiary medical center in Durham, North Carolina.

Results.

Model 1 was associated with 42 MRSA infections (infection rate, 0.0042%). Mean infection cost was $47,092 (95% confidence interval [CI], $26,040–$68,146); mean cost per noncompliant event was $1.98 (95% CI, $0.91–$3.04). Model 2 was associated with 980 MRSA infections (0.098%). Mean infection cost was $53,598 (95% CI, $50,098–$57,097); mean cost per noncompliant event was $52.53 (95% CI, $47.73–$57.32). A 200-bed hospital incurs $1,779,283 in annual MRSA infection-related expenses attributable to hand hygiene noncompliance. A 1.0% increase in hand hygiene compliance resulted in annual savings of $39,650 to a 200-bed hospital.

Conclusions.

Hand hygiene noncompliance is associated with significant attributable hospital costs. Minimal improvements in compliance lead to substantial savings.
A 5-Year Epidemiological Study of Nosocomial Bloodstream Infections in a Neurosurgery Department
Authors: Tsitsopoulos Parmenion P. , Iosifidis Elias , Antachopoulos Charalampos , Tsivitanidou Maria , Anagnostopoulos Ioannis , Roilides Emmanuel , Tsitsopoulos Philippos D.
Published: February 2010

The characteristics of nosocomial bloodstream infections (BSIs) in a neurosurgical department were studied over a 5-year period. The rate of nosocomial BSI was 3.0%. Gram-negative bacteria were the most commonly isolated pathogens (65.9% of isolates). For all the pathogens isolated, the rate of resistance to commonly used antimicrobial agents was high. Of the 101 patients with nosocomial BSI, 50 (49.5%) died during their stay at the Department of Neurosurgery. At the same time, overall mortality rate among neurosurgical inpatients without nosocomial BSI was 5.4% (ie, 175 of 3,216 patients died).
Arginylation Regulates Intracellular Actin Polymer Level by Modulating Actin Properties and Binding of Capping and Severing Proteins
Authors: Saha Sougata , Mundia Maureen M. , Zhang Fangliang , Demers Ryan W. , Korobova Farida , Svitkina Tatyana , Perieteanu Alex A. , Dawson John F. , Kashina Anna
Published: February 2010

Actin arginylation regulates lamella formation in motile fibroblasts, but the underlying molecular mechanisms are unknown. To understand how arginylation affects the actin cytoskeleton, we investigated the biochemical properties and the structural organization of actin filaments in wild-type and arginyltransferase (Ate1) knockout cells. We found that Ate1 knockout results in a dramatic reduction of the actin polymer levels in vivo accompanied by a corresponding increase in the monomer level. Purified nonarginylated actin has altered polymerization properties, and actin filaments from Ate1 knockout cells show altered interactions with several associated proteins. Ate1 knockout cells have severe impairment of cytoskeletal organization throughout the cell. Thus, arginylation regulates the ability of actin to form filaments in the whole cell rather than preventing the collapse of preformed actin networks at the cell leading edge as proposed in our previous model. This regulation is achieved through interconnected mechanisms that involve actin polymerization per se and through binding of actin-associated proteins.
The Protein Tyrosine Phosphatase PTP1B Is Required for Efficient Delivery of N-Cadherin to the Cell Surface
Authors: Hernández Mariana V. , Wehrendt Diana P. , Arregui Carlos O.
Published: February 2010

PTP1B bound to mature N-cadherin promotes the association of β-catenin into the complex, the stable expression of the complex at cell surface, and cadherin-mediated adhesion. Here we show that PTP1B is also required for N-cadherin precursor trafficking through early stages of the secretory pathway. This function does not require association of PTP1B with the precursor. In PTP1B null cells, the N-cadherin precursor showed higher sensitivity to endoglycosidase H than in cells reconstituted with the wild-type enzyme. It also showed slower kinetics of ER-to-Golgi translocation and processing. Trafficking of the viral stomatitis vesicular glycoprotein, VSV-G, however, revealed no differences between PTP1B null and reconstituted cells. N-cadherin precursor complexes contained similar levels of α- and β-catenin regardless of PTP1B expression. In contrast, the associated p120 catenin (p120) was significantly reduced in absence of PTP1B expression. An N-cadherin precursor construct defective in p120 binding, and expressed in PTP1B reconstituted cells, showed higher sensitivity to endoglycosidase H and slower kinetics of processing than the wild-type precursor. Our results suggest that PTP1B promotes the association of p120 to the N-cadherin precursor, facilitating the trafficking of the complex from the ER to the Golgi complex.
Introduction
Authors: Richards John E.
Published: February 2010

This introductory chapter begins with a brief background of the term neoconstructivism, which was generated by combining neo, taken from the Greek neos, meaning “new,” and constructivism, taken from (among other sources) the pioneering theorist and researcher Jean Piaget. It then discusses the origins of this book, the idea of which was motivated in part by research on cognitive development.
Shape, Action, Symbolic Play, and Words: Overlapping Loops of Cause and Consequence in Developmental Process
Authors: Smith Linda B. , Pereira Alfredo F.
Published: February 2010

Human beings are remarkably inventive, possessing the ability to solve problems and to create novel things. This chapter focuses on an early form of inventiveness that has long intrigued developmentalists—what is sometimes called symbolic play, but more narrowly, is also known as “object substitution in play.” The specific phenomenon consists of young children using some object, not for what it is, but as a “stand in” for something else in play—a banana as a phone, a box as a doll bed, a shoe as a toy car. The chapter considers how and why these object substitutions may be linked to language.
What Is Statistical Learning, and What Statistical Learning Is Not
Authors: Saffran Jenny R.
Published: February 2010

This chapter discusses statistical learning and its role in language acquisition. It focuses on three issues that are implicit in this characterization of statistical learning: the nature of the computations, the complexity of the learning problem, and the role of artificial languages.
Processing Constraints on Learning
Authors: Gómez Rebecca
Published: February 2010

This chapter discusses three types of processing constraints on learning. The first type arises from the learning process itself. The other two constraints arise from two naturally occurring memory processes: consolidation and reconsolidation. With respect to learning constraints, the chapter discusses research suggesting that learning is a dynamically guided process, arising in the interaction of internal and external pressures, and one that is fairly robust with respect to noisy input. With respect to memory processes instrumental in learning, it describes findings that demonstrate a type of memory consolidation occurring with sleep; one that results in generalization to novel cases. Another set of findings demonstrates how the process of memory reconsolidation enables memory change. Both memory processes are important for understanding how children sustain sensitivity to prior knowledge while incorporating new information.
Development of Inductive Inference in Infancy
Authors: Rakison David H. , Cicchino Jessica B.
Published: February 2010

This chapter challenges the predominant “top-down” view of early inductive inference. According to this view, induction and categorization by infants as young as 9 to 11 months of age is based on abstract knowledge about the properties of things that is acquired through specialized mechanisms, modules, or innate principles. This perspective is contested both on theoretical and empirical grounds. First, it is proposed that infants' concepts for objects and entities are generated via general rather than specific mechanisms. As a corollary of this view, it is argued that early knowledge about the properties of things in the world involves associative links between specific surface features and those properties, and that such representations are not in place until the middle or end of the second year of life. Second, it is argued that care must be taken in interpreting infants' behavior within the inductive generalization procedure. In particular, (1) infants' behavior in the task is not always driven by knowledge acquired prior to arriving at the laboratory; and (2) the basis for induction for any property must be studied before conclusions can be drawn about the nature and content of infants' concepts. In support of these views, data is provided from inductive generalization studies with 14- to 26-month-olds, which show that infants are influenced by the model exemplar used by the experimenter, and that perceptual features—such as legs and wheels— act as the basis for early induction for motion properties.
Similarity, Induction, Naming, and Categorization: A Bottom-up Approach
Authors: Sloutsky Vladimir M.
Published: February 2010

This chapter considers two broad theoretical approaches to cognitive development. One approach advocates the importance of a priori constraints in cognitive development (i.e. the top-down approach). The other approach argues that people have powerful learning mechanisms enabling them to extract regularities from the input (i.e. the bottom-up approach). It then reviews a recently proposed bottom-up model of inductive generalization and several phenomena predicted by the model; some of these phenomena present challenges to the top-down approach. It focuses on the role of label and appearance information in induction and presents evidence that labels affect induction by contributing to the overall similarity of compared items. The chapter also considers a mechanism that may underlie the effects of labels on generalization. It suggests that labels (and other sounds) contribute to similarity by overshadowing (or attenuating processing of) corresponding visual input, and presents supporting evidence from studies with infants and young children. Finally, the chapter discusses how effects of words may change in the course of development as a function of increasing familiarity of human speech.
Role of Acid and Nonacid Reflux in Children With Eosinophilic Esophagitis Compared With Patients With Gastroesophageal Reflux and Control Patients
Authors: Rosen Rachel , Furuta Glenn , Fritz Julia , Donovan Kate , Nurko Samuel
Published: February 2010

Objectives:

Because of the relationship between food and eosinophilic diseases, we hypothesize that patients with eosinophilic esophagitis (EE) may be repeatedly exposed to nonacid ingested foodstuffs compared with patients without EE. Because inflammation is found throughout the esophagus in patients with EE, we further hypothesize that there would be more full‐column reflux in EE patients compared with patients with gastroesophageal reflux disease (GERD) and control patients.

Materials and Methods:

We retrospectively reviewed pH‐multichannel intraluminal impedance tracings of EE patients who were age‐matched with control and GERD patients and compared the reflux profiles among the 3 groups.

Results:

There were no significant differences between the mean numbers of nonacid reflux events in EE patients (4.7 ± 3.3) compared with GERD (7.5 ± 5.3) or control patients (6.8 ± 4.6) (P = 0.36). There were significantly more acid reflux events in patients with GERD (47.4 ± 17.1) compared with patients with EE (24.9 ± 20.0) and control patients (28.4 ± 16.5) (P = 0.02). Patients with EE did not have a higher percentage of full‐column reflux (31.9 ± 20.9) compared with control patients (24.4 ± 19.8) or patients with GERD (30.5 ± 14.9) (P = 0.64).

Conclusions:

Neither full‐column reflux nor nonacid reflux is a significant contributor to the pathogenesis of EE.
Natural History of Paediatric Inflammatory Bowel Diseases Over a 5‐Year Follow‐up: A Retrospective Review of Data From the Register of Paediatric Inflammatory Bowel Diseases
Authors: Newby Elizabeth A , Croft Nick M , Green Michael , Hassan Kamal , Heuschkel Robert B , Jenkins Huw , Casson David H
Published: February 2010

Objectives:

The natural history of paediatric inflammatory bowel diseases (IBDs) is poorly understood. We aim to describe the disease course in this cohort and generate prognostic information for patients and clinicians.

Materials and Methods:

Patient records from 6 tertiary paediatric gastroenterology centres were reviewed to generate data concerning original diagnosis, change in diagnosis, family history, surgical interventions, growth, and presence of extragastrointestinal manifestations.

Results:

Data were collected on 116 children with Crohn disease (CD), 74 with ulcerative colitis (UC), and 20 with indeterminate colitis (IC), followed for a mean period of 3.42, 3.3, and 2.9 years from date of diagnosis, respectively.

A male predominance is demonstrated in CD. Revision of diagnosis in patients with IC is mainly to UC, with most children receiving a definitive diagnosis within 2 years of initial presentation. Of the children with UC, 17.6% underwent 1 or more major operations with a median time to surgery of 1.92 years. Of children with CD, 11.6% underwent 1 or more major intraabdominal procedures with a median time to surgery of 1.83 years. We recorded a positive family history in 2.7%, 8.2%, and 10% of cases for CD, UC, and IC, respectively. For both boys and girls with CD, but only for boys with UC, height standard deviation score became more negative over time.

Conclusions:

This retrospective study quantifies certain distinctions between IBDs diagnosed in paediatric and adult populations. We document a trend toward male predominance in children with CD. We also note impaired linear growth in children with CD, whereas it appears maintained in girls with UC. We also have recorded a low incidence of IBDs in the families of this cohort and suggest that environmental influences may be of greater importance. We document that major intraabdominal surgery may be required in about 15% of patients with either UC or CD within 2 years of diagnosis, and that the majority of those diagnosed initially with IC will be reclassified as either UC or CD within 2 years.
Molecular Studies of Fecal Anaerobic Commensal Bacteria in Acute Diarrhea in Children
Authors: Balamurugan Ramadass , Janardhan Harish P , George Sarah , Raghava M Venkata , Muliyil Jayaprakash , Ramakrishna Balakrishnan S
Published: February 2010

Background and Objective:

The commensal bacterial flora of the colon may undergo changes during diarrhea, owing to colonization of the intestine by pathogens and to rapid intestinal transit. This study used molecular methods to determine changes in the composition of selected commensal anaerobic bacteria during and after acute diarrhea in children.

Materials and Methods:

Fecal samples were obtained from 46 children with acute diarrhea in a rural community during an episode of acute diarrhea, immediately after recovery from diarrhea, and 3 months after recovery. DNA was extracted and quantitative polymerase chain reaction using SYBR green and genus‐ and species‐specific primers targeting 16S rDNA were undertaken to quantitate the following groups of bacteria: Bifidobacterium spp., Bifidobacterium longum group, Bacteroides‐Prevotella group, Bacteroides fragilis, Lactobacillus acidophilus group, Faecalibacterium prauznitzii, and Eubacterium rectale, relative to amplification of universal bacterial domain 16S rDNA.

Results:

Bacteria belonging to the Bacteroides‐Prevotella‐Porphyromonas group, E rectale, L acidophilus, and F prauznitzii groups were low during acute diarrhea compared with their levels after recovery from diarrhea. The pattern was similar in rotavirus diarrhea and nonrotavirus diarrhea. Administration of amylase‐resistant maize starch as adjuvant therapy was associated with lower levels of F prauznitzii at the time of recovery but did not lead to other changes in the floral pattern.

Conclusions:

Specific classes of fecal bacteria are lower during episodes of acute diarrhea in children than during periods of normal gastrointestinal health, suggesting specific alterations in the flora during diarrhea.
Autophagy: Healthy Eating and Self‐digestion for Gastroenterologists
Authors: Hussey Séamus , Terebiznik Mauricio R , Jones Nicola L
Published: February 2010

Autophagy is an evolutionary conserved mechanism in eukaryotic cells that is known to process redundant or defective cellular proteins and organelles. The recent renewal of interest in autophagy research has led to a significant expansion in our understanding of the importance of autophagy in cellular health and disease. This invited review summarizes key elements of autophagy research, emphasizes those of particular interest to gastroenterologists, and offers insights into present and future research directions.
Rapid Determination of the Bacterial Composition of Commercial Probiotic Products by Terminal Restriction Fragment Length Polymorphism Analysis
Authors: Marcobal Angela , Underwood Mark A , Mills David A
Published: February 2010

Label claims on probiotic products often do not represent the true constituents. With the increased use of probiotics in clinical studies, it is necessary to know the true composition of probiotic products to better interpret study outcomes. We used terminal restriction fragment length polymorphism analysis to rapidly determine the overall bacterial composition of 14 commercial probiotic products and validated the results with species‐specific polymerase chain reaction. The results show that many probiotic products contain unadvertised additional lactobacilli and bifidobacteria, whereas others are missing species listed on the product label. In summary, terminal restriction fragment length polymorphism is a rapid method for profiling the microbial contents of probiotic products used in clinical studies.
Lack of Diagnostic Utility of Specific Immunoglobulin M in Helicobacter pylori Infection in Children
Authors: Serrano Carolina A , González Carmen G , Rollan Antonio R , Duarte Ignacio , Torres Javiera , Peña Alfredo J , Harris Paul R
Published: February 2010

Background:

Helicobacter pylori infection results in a systemic immune response characterized by the initial rise of immunoglobulin (Ig) M followed by the elevation of IgG‐ and IgA‐specific antibody levels in serum. Age and regional considerations may modify the accuracy of serological tests.

Objectives:

To determine the accuracy of specific IgG, IgA, and IgM in H pylori infection determination in different age groups.

Patients and Methods:

We enrolled 179 patients referred for endoscopy. Patients were considered infected if they had positive histological or urease test results for H pylori. Titers of IgG, IgA, and IgM were determined in serum by enzyme‐linked immunosorbent assay. Through receiver operator characteristic curves, cutoff, sensitivity, and specificity values were obtained. Agreement and correlation between immunoglobulin titers and inflammation markers were explored.

Results:

Infection with H pylori was present in 58% of adults, 62% of adolescents, and 25% of children. Sensitivity and specificity were higher in children younger than 12 years old for IgG and IgA. All diagnostic performance values were lower for IgM. Agreement measures were approximately 0.5 in adults and reached values of approximately 0.7 for adolescents and children. IgM had negative agreement with other methods. There was a correlation between inflammation markers, H pylori load, and immunoglobulin titers for IgG and IgA. These associations decreased with age and were not observed for IgM.

Conclusions:

IgG and IgA serological tests reached high performance values, particularly in children younger than 12 years old, indicating that they are reasonable screening methods once cutoff values are adjusted to local population and age. IgM does not present an additional contribution.
Sterol Profiling in Red Blood Cell Membranes and Plasma of Newborns Receiving Total Parenteral Nutrition
Authors: Pianese P , Salvia G , Campanozzi A , D'Apolito O , Russo A Dello , Pettoello‐Mantovani M , Corso G
Published: February 2010

Background and Objectives:

Total parenteral nutrition (TPN) is a lifesaving therapy in children with intestinal failure, frequently complicated by liver dysfunction. Plant sterols (phytosterols) of lipid emulsions have been supposed to contribute to cholestasis in TPN‐treated children. The present study aimed to evaluate the plasma and red blood cell membrane (RBCM) phytosterol levels in newborns after a short period of TPN.

Patients and Methods:

Phytosterols, cholesterol, and other sterol levels were quantified by gas chromatography‐mass spectrometry in 15 healthy control infants, 22 patients after TPN, and 11 patients before TPN. Sterols of lipid emulsions were quantified.

Results:

Plasma and RBCM phytosterol levels were, respectively, on average 56 μmol/L and 83 μmol/g per protein in patients after TPN, 13 μmol/L and 15 μmol/g per protein in patients before TPN, and 9 μmol/L and 13 μmoL/g per protein in control infants (P < 0.05 for differences). The days of TPN and the total amount of infused lipids correlated significantly with RBCM phytosterol (P < 0.05); correlations for plasma were positive but not significant. No correlation was observed with plasma bilirubin, γ‐glutamyltransferase, or alanine transaminase.

Conclusions:

Plasma and RBCM phytosterols increase significantly in newborns after a short period of TPN. Higher phytosterol levels were observed in some patients that could have been due to their individual variability in phytosterol metabolism and/or clearance. A greater accumulation of phytosterols in membranes may induce TPN‐related cholestasis.
Treatment Regimen Adherence in Pediatric Gastroenterology
Authors: Hommel Kevin A , Mackner Laura M , Denson Lee A , Crandall Wallace V
Published: February 2010

Objective:

To review and critically evaluate the extant research pertaining to adherence in pediatric gastroenterological diseases, particularly inflammatory bowel disease and celiac disease, and to provide recommendations for future research development.

Materials and Methods:

A literature search with no date restriction was conducted using PubMed and PsychInfo electronic databases and bibliographies of relevant articles.

Results:

Adherence rates in inflammatory bowel disease and celiac disease range considerably from 16% to 62% and 5% to 70%, respectively, across treatments and assessment method; nonadherence frequency was generally not reported. Measures used to assess adherence included self‐report, interview, diet record, and bioassay methods, and each measure demonstrated strengths and limitations. Limited evidence suggests that adherence in both disease populations is related to patient and family behavioral factors and that nonadherence is related to poor disease outcome. Treatment outcome research for nonadherence is scant in the current literature.

Conclusions:

Future research should focus on refining assessment method, examining adherence and concomitant behavioral factors longitudinally, testing theoretical models of adherence, and developing efficacious treatments for nonadherence.
Desquamative Enteropathy and Pyloric Atresia Without Skin Disease Caused by a Novel Intracellular β4 Integrin Mutation
Authors: Salvestrini Camilla , McGrath John A , Ozoemena Linda , Husain Khaled , Buhamrah Eman , Sabery Nasim , Leichtner Alan , Rufo Paul A , Perez‐Atayde Antonio , Orteu Cate H , Torrente Franco , Heuschkel Robert B , Thomson Michael A , Murch Simon H
Published: February 2010

Background:

Mutations in α6 or β4 integrins (ITGA6, ITGB4) are known to cause junctional epidermolysis bullosa with pyloric atresia (JEB‐PA), often lethal in infancy through skin desquamation. There is 1 report of pyloric atresia associated with a desquamatory enteropathy but without skin disease, of unknown molecular basis.

Patients and Methods:

We report 2 Kuwaiti siblings with pyloric atresia and life‐threatening intestinal desquamation without significant skin abnormality. The older sibling died of intractable diarrhoea, and the younger sibling suffered episodes of massive protein‐losing enteropathy, triggered by viral infections, in addition to obstructive uropathy. Mutation analysis was performed for ITGA6 and ITGB4 and expression of ITGA6 and ITGB4 protein was examined in skin and intestinal biopsies. Her serum also was incubated with normal intestine.

Results:

We identified a novel mutation in ITGB4, with homozygous deletion of a single residue (isoleucine 1314) within the intracellular plectin‐binding domain. Expression of ITGA6 and ITGB4 within skin, duodenal, and colonic epithelium was normal or minimally reduced, in contrast to previous reports. Biopsies taken during relapse showed accumulation of immunoglobulin G and C1q within intestinal basement membrane, whereas immunoglobulin G from her serum bound to basement membrane of normal small intestine. Immunomodulatory therapy induced significant improvement following relapses.

Conclusions:

ITGB4 mutation may induce a desquamative enteropathy in infancy without significant skin disease. A history of pyloric atresia is important in infants with severe chronic diarrhoeal disease and should prompt investigation for JEB‐PA associated mutations. Acquired immune responses may exacerbate primary genetic disorders of epithelial adhesion and immunomodulatory therapy may be beneficial.
Liver Disease Associated with ZZ α1‐Antitrypsin Deficiency and Ursodeoxycholic Acid Therapy in Children
Authors: Lykavieris Panayotis , Ducot Béatrice , Lachaux Alain , Dabadie Alain , Broué Pierre , Sarles Jacques , Bernard Olivier , Jacquemin Emmanuel
Published: February 2010

Objectives:

To investigate the effect of ursodeoxycholic acid (UDCA) in children with liver disease associated with ZZ α1‐antitrypsin (AAT) deficiency.

Patients and Methods:

A total of 42 affected children received UDCA (30 mg · kg−1 · day−1) and underwent clinical and biochemical follow‐up at least yearly.

Results:

In group 1, 22 children whose mean initial γ‐glutamyl‐transpeptidase (GGT) was 7.4 × N normalized serum liver test results after a mean treatment of 2.6 years. In 16 of these children, UDCA was discontinued. Relapse was observed in 11 children, and liver test results returned to normal after UDCA resumption. In the other 5 children, liver test results remained normal during a mean period of 2.5 years. In group 2, 11 children (mean initial GGT 12.8 × N) had improved liver test results after a mean treatment of 2.3 years. In group 3, 9 children (mean initial GGT 33.8 × N) had no liver test result improvement and evolution toward cirrhosis, requiring liver transplantation in 7. Most of the children in group 1 had normal results of clinical examination after UDCA treatment, versus none in group 3 (P ≤ 0.00001). Initial GGT (P ≤ 0.002) and total bilirubin (P ≤ 0.05) levels were significantly lower in group 1 than in group 3. Combined initial values of GGT ≤5.5 × N and total bilirubin ≤66 μmol/L were associated with normalization of liver test results in 90% of children.

Conclusions:

UDCA may significantly improve clinical status and liver test results in some children with liver disease associated with ZZ AAT deficiency. No beneficial effect of UDCA was shown in children with the most severe liver involvement. Initial levels of GGT and total bilirubin may be of prognostic value for therapy effectiveness.
Serum Linoleic Acid Status as a Clinical Indicator of Essential Fatty Acid Status in Children With Cystic Fibrosis
Authors: Maqbool Asim , Schall Joan I , Garcia‐Espana J Felipe , Zemel Babette S , Strandvik Birgitta , Stallings Virginia A
Published: February 2010

Background:

Children with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at increased risk for essential fatty acid (EFA) deficiency.

Objectives:

To investigate serum markers of EFA status in children with CF and PI and their association with growth, body composition, and lung function.

Patients and Methods:

Serum phospholipid fatty acid, growth, and forced expiratory volume at 1 second (FEV1, percentage predicted) status were assessed at baseline and 12 months in 77 children with CF and PI, 7 to 10 years old. Longitudinal mixed‐effects models were used to compare associations of the triene:tetraene ratio (ratio of eicosatrienoic acid to arachidonic acid) and serum linoleic acid (as a molar percentage of total serum phospholipid fatty acids, or mol%) with the clinical outcomes. Controls for serum fatty acid were 23 healthy white age‐ and sex‐matched children.

Results:

Children with CF and PI had higher median triene:tetraene ratio and lower linoleic acid than healthy controls. Depending on the triene:tetraene ratio cutoff point used (0.04 or 0.02), either 17% or 52% of the children with CF had EFA deficiency, respectively. Only linoleic acid was significantly and positively associated with z scores for weight, height, body mass index, upper arm muscle area, and FEV1 at baseline. Children with linoleic acid at 21 mol% or higher had significantly better growth and pulmonary status than those with lower concentrations.

Conclusions:

Serum phospholipid linoleic acid at 21 mol% or higher was associated with better growth, body composition, and FEV1. No clinical outcome associations were found with the triene:tetraene ratio. These findings suggest that linoleic acid concentration was a more clinically relevant biomarker of EFA status than the triene:tetraene ratio in children with CF and PI. Further research is warranted to validate this specific percentage of linoleic acid cutoff point as a new recommendation for clinical use.
Detection of Polyethylene Glycol–based Laxatives in Stool
Authors: Sadilek Martin , Feldman Kenneth , Murray Karen F , Young Melissa , Mazor Suzan
Published: February 2010

The ability to test stool for laxatives is an important part of patient care in some clinical circumstances. Some patients take or are given laxatives surreptitiously. Additionally, failure to take prescribed laxatives may result in treatment failure in children with constipation or encopresis. Although laboratory methods have been available to identify many laxatives in the stool, tests are not available for detecting polyethylene glycol (PEG)–based laxatives. PEG‐based laxatives are frequently used in the treatment of children with constipation. We developed a mass spectrometry (MS)–based analysis for detecting PEG in stool and verified the technique in an adult volunteer. We then piloted the assay on stools from children taking PEG for constipation versus children with diarrhea who were not taking PEG. Eleven subjects with diarrhea and 8 receiving PEG were enrolled. Nine of the children with diarrhea and 7 receiving PEG were evaluated by MS. All 3 subjects with PEG who had a stool osmolal gap determined had elevated gaps. Stools of all 7 subjects with PEG were positive for PEG by MS, whereas none of the 9 subjects with diarrhea had stool positive for PEG. This new MS methodology to test stool for PEG is described. It is likely to prove useful in the documentation of surreptitious PEG administration and in evaluation of PEG treatment failure.
Effects of Timing, Sex, and Age on Site‐specific Gastrointestinal Permeability Testing in Children and Adults
Authors: McOmber Mark E , Ou Ching‐Nan , Shulman Robert J
Published: February 2010

Objectives:

Measurement of gastrointestinal (GI) permeability is commonly used in research and often used clinically. Despite its utility, little is known about sugar excretion timeframes or the potential effects of age and sex on GI permeability testing. We seek to determine the timeframes of sugar excretion and the potential effects of age and sex on urinary recovery of the sugars.

Subjects and Methods:

Healthy adults (n = 17) and children (n = 15) fasted 4 hours after the evening meal and then ingested a solution of sucrose, lactulose, mannitol, and sucralose. Urine was collected at 30, 60, and 90 minutes after ingestion and then each time the subjects voided during the next 24 hours. Each urine void was collected separately.

Results:

Median age for the adults was 47.5 years (range 21–57 years) and for children 10 years (range 5–17 years). There were no differences between children and adults in mean percent dose of sugar recovered. The time of peak urinary recovery of the sugars was generally similar between children and adults. Sucrose urinary recovery declined with age (P = 0.008; r2 = 0.19) unrelated to sex. Lactulose and sucralose urinary recovery declined with age in females (P = 0.05, r2 = 0.24 and P = 0.011, r2 = 0.41; respectively) but not in males.

Conclusions:

Overall, sugar urinary recovery is comparable in children and adults. Specific sugar urinary recovery may change as a function of age and/or sex. These results need to be taken into account when planning and interpreting gastrointestinal permeability studies.
Functional Constipation in Children: A Systematic Review on Prognosis and Predictive Factors
Authors: Pijpers MAM , Bongers MEJ , Benninga MA , Berger MY
Published: February 2010

Background and Aim:

Knowledge regarding prognosis and factors influencing the clinical course of functional constipation in children is important to enable general practitioners and paediatricians to give accurate patient information, to compare treatment strategies, and identify children with high risk for unfavourable outcome. The objective of the study was to investigate and summarize the quantity and quality of evidence on prognosis of childhood constipation with and without treatment and its predictive factors.

Methods:

An extensive literature search in MEDLINE and Embase was performed to identify prospective follow‐up studies evaluating the prognosis or prognostic determinants of functional constipation. Methodological quality was assessed using a standardised list. Results on prognosis of constipation were statistically pooled, and the influence of prognostic factors was summarised in a best evidence synthesis.

Results:

The search strategy resulted in a total of 2882 abstracts. Only 14 publications met our inclusion criteria, of which 21% scored high methodological quality. Included studies showed large heterogeneity in study populations and outcome measures. Without regard to these differences, 49.3% ± 11.8% of all of the children followed for 6 to 12 months were found to recover and taken off laxatives. The percentage of children who were free from complaints, regardless of laxative use, after 6 to 12 months was 60.6% ± 19.2%. There is substantial evidence that defecation frequency and a positive family history are not associated with recovery from constipation.

Conclusions:

The few studies published on prognosis of childhood functional constipation and predictive factors showed large heterogeneity and poor methodological quality. Overall, 60.6% of children are found to be free from symptoms after 6 to 12 months. Recovery rate showed no relation with defecation frequency or positive family history. Based on the present literature, we are unable to identify a group of children with high risk for poor prognosis.
Association of the CLCA1 p.S357N Variant With Meconium Ileus in European Patients With Cystic Fibrosis
Authors: van der Doef HPJ , Slieker MG , Staab D , Alizadeh BZ , Seia M , Colombo C , van der Ent CK , Nickel R , Witt H , Houwen RHJ
Published: February 2010

In Cftr−/− mice that mostly die because of intestinal obstruction, intestinal expression of Clca3 is decreased, whereas upregulation of Clca3 results in amelioration of intestinal disease. The aim of the study was to investigate whether the p.S357N variant in CLCA1, the human orthologue of Clca3, acts as a modifier gene in a cohort of 682 European patients with cystic fibrosis (CF)–99 patients with meconium ileus. The 357SS genotype was significantly overrepresented in both patients with meconium ileus and also with a severe CFTR genotype (P = 0.009) and in p.F508del homozygotes (P = 0.002). This suggests that CLCA1 has similar important functions in CF‐related intestinal obstruction in humans as in Cftr−/− mice.
Risk Factors, Complications, and Outcomes of Gallstones in Children: A Single‐center Review
Authors: Bogue Conor O , Murphy Amanda J , Gerstle J Ted , Moineddin Rahim , Daneman Alan
Published: February 2010

Background and Objective:

The increasing use of sonography has resulted in an increase in the proportion of children with gallstones who are asymptomatic at the time of diagnosis. In adults, the literature supports expectant management of clinically silent gallstones. The evidence for this management approach in children is limited to a number of small series. Our objective was to review the risk factors, complications, and outcomes of gallstones at our institution, particularly in those patients who are asymptomatic at the time of initial diagnosis.

Materials and Methods:

We reviewed 382 cases of gallstones in children. These patients were diagnosed with sonography. Data on age at diagnosis, presentation, sonographic findings, risk factors, complications, surgery, and follow‐up were collected. A χ2 test was used to compare the complication rates between symptomatic and asymptomatic groups. Descriptive statistics were used to analyze the sample.

Results:

At diagnosis, 50.5% of children were asymptomatic; these patients were diagnosed at a mean age of 8.23 years. Compared with symptomatic patients, they were less likely to have a hemolytic anemia but more likely to have other risk factors, including cardiac surgery, leukemia and lymphoma, short bowel syndrome, or exposure to total parenteral nutrition or cephalosporins. These patients had a lower rate of complications than the symptomatic patients (4.6% vs 28.2% of symptomatic, P < 0.0001) and only 3.1% developed symptoms that necessitated surgery (vs 59.0% of symptomatic). Of the 58 (15.1%) diagnosed in infancy, 47 (81.0%) were asymptomatic. The infant group also had low rates of complications (8.6%) and cholecystectomy (1.7%). In cases with sonographic follow‐up, resolution of gallstones was demonstrated in 16.5% of asymptomatic patients and in 34.1% of infants.

Conclusions:

The data suggest that clinically silent gallstones in children and infants are associated with low rates of complications and can be managed conservatively, unless complications occur. Patients with sickle cell disease, spherocytosis, and elliptocytosis had high complication rates and required surgery more often.
Antennal regulation of migratory flight in the neotropical mothUrania fulgens
Authors: Sane Sanjay P. , Srygley Robert B. , Dudley Robert
Published: February 2010

Migrating insects use their sensory systems to acquire local and global cues about their surroundings. Previous research on tethered insects suggests that, in addition to vision and cephalic bristles, insects use antennal mechanosensory feedback to maintain their airspeeds. Owing to the large displacements of migratory insects and difficulties inherent in tracking single individuals, the roles of these sensory inputs have never been tested in freely migrating insects. We tracked individual uraniid moths (Urania fulgens) as they migrated diurnally over the Panama Canal, and measured airspeeds and orientation for individuals with either intact or amputated flagella. Consistent with prior observations that antennal input is necessary for flight control, 59 per cent of the experimental moths could not fly after flagella amputation. The remaining fraction (41%) was flight-capable and maintained its prior airspeeds despite severe reduction in antennal input. Thus, maintenance of airspeeds may not involve antennal input alone, and is probably mediated by other modalities. Moths with amputated flagella could not recover their proper migratory orientations, suggesting that antennal integrity is necessary for long-distance navigation.
Experimental evidence that sentinel behaviour is affected by risk
Authors: Ridley A. R. , Raihani N. J. , Bell M. B. V.
Published: February 2010

Sentinels are a conspicuous feature of some cooperative societies and are often assumed to provide benefits in terms of increased predator detection. Similar to other cooperative behaviours, variation in investment in sentinel behaviour should reflect variation in the benefits of such behaviour. However, evidence for this is inconclusive: to date experiments have manipulated the cost of sentinel behaviour, and considerations of changes in the benefits of sentinel activity on investment patterns are lacking. Here, we experimentally manipulated the benefits of sentinel behaviour in the cooperatively breeding pied babbler (
Turdoides bicolor
) to assess whether this had any impact on sentinel activity. We simulated the presence of an unseen predator using playbacks of heterospecific alarm calls, and the presence of an actual predator using a model snake. In both cases, the increase in perceived predation risk caused an increase in sentinel activity, demonstrating that investment in sentinel activity increases when the benefits are greater.
The blood parasiteHaemoproteusreduces survival in a wild bird: a medication experiment
Authors: Puente Josué Martínez-de la , Merino Santiago , Tomás Gustavo , Moreno Juan , Morales Judith , Lobato Elisa , García-Fraile Sonia , Belda Eduardo Jorge
Published: February 2010

While avian chronic haemoparasite infections induce reproductive costs, infection has not previously been shown to affect survival. Here, we experimentally reduced, through medication, the intensity of infection byHaemoproteusparasites in wild-breeding female blue titsCyanistes caeruleus. However, this treatment did not reduce the intensity of infection in males or the intensity of infection byLeucocytozoon. Medicated females, but not males, showed increased local survival until the next breeding season compared with control birds. To our knowledge, this is the first empirical evidence showing long-term direct survival costs of chronicHaemoproteusinfections in wild birds.
Protective immunity induced by a LLO‐deficient Listeria monocytogenes
Authors: Yin Yuelan , Zhang Chenju , Dong Hui , Niu Zhongwei , Pan Zhiming , Huang Jinlin , Jiao Xinan
Published: February 2010

Listeria monocytogenes is a food‐borne pathogen able to cause serious disease in human and animals. Listeriolysin O (LLO), a major virulence factor secreted by this bacterium, is a vacuole‐specific lysin that facilitates bacterial entrance into the host cytosol. Thus, LLO plays a key role in the translocation and intracellular spread of L. monocytogenes. To study the effect of LLO on virulence and immunopotency, a LLO‐deficient L. monocytogenes mutant was constructed using a shuttle vector followed by homologous recombination. The mutant strain had lost hemolytic activity, which resulted in an extremely reduced virulence, 5 logs lower than that of the parent strain, yzuLM4, in BALB/c mice. The number of bacteria detected in the spleens and livers of mice infected with the mutant was greatly reduced, and the bacteria were rapidly eliminated by the host. Kinetics studies in this murine model of infection showed that the invasion ability of the mutant strain was much lower than that of the parent strain. Moreover, immunization with the mutant strain conferred protective immunity against listerial infection. In particular, stimulation with Ag85B240‐259, strong specific Th1 type cellular immunity was elicited by vaccination C57BL/6 mice with hly deficient strain delivering Mycobacterium tuberculosis fusion antigen Ag85B‐ESAT‐6 via intravenous inoculation. These results clearly show that highly attenuated LLO‐deficient L. monocytogenes is an attractive vaccine carrier for delivering heterologous antigens.