bluuebunny/crossref_metadata_2025 huggingface dataset:
What's in the Literature?
Authors: Harati Y
Published: May 2009

I am delighted to be the guest editor for this section of the Journal. Among the many publications related to neuromuscular diseases that appeared in the literature over the past few months, I have selected a few to review. The followings are my personal take of these articles with some added personal opinions on amyotrophic lateral sclerosis (ALS), stiff-person syndrome, complications of needle electromyography (EMG), hereditary neuropathies, and chronic inflammatory (immune-mediated) demyelinating polyneuropathy (CIDP). I hope that the readers of these pages find them interesting.
Necrotizing Enterocolitis: Risk Factor Analysis and Role of Gastric Residuals in Very Low Birth Weight Infants
Authors: Bertino Enrico , Giuliani Francesca , Prandi Giovanna , Coscia Alessandra , Martano Claudio , Fabris Claudio
Published: May 2009

Objective:

Necrotizing enterocolitis (NEC) usually occurs in very low birth weight infants and is the most common gastrointestinal emergency in the neonatal intensive care unit. Inasmuch as NEC mortality and morbidity are extremely high, early diagnosis becomes essential. Increased gastric residuals are used to define NEC stage, but studies on qualitative and quantitative residual features as markers of NEC risk are still lacking. The primary goal of this analysis was evaluation of the role of gastric residuals in early identification of patients at risk for NEC. The secondary goal was investigation of NEC risk factors, besides prematurity and birth weight.

Methods:

In a case‐control study, NEC patients were matched with control infants by gestational age and birth weight. Feeding tolerance was assessed by maximum gastric residual volume, maximum residual as percentage of previous feeding, and residual appearance. Mortality and NEC risk factors were also evaluated.

Results:

In all, 844 very low birth weight infants were admitted to the neonatal intensive care unit during the study period, with an overall mortality before discharge of 14.6%. NEC frequency was 2%. Patent ductus arteriosus was significantly associated with NEC. Mean maximum residual from birth to NEC onset and maximum residual as percentage of the corresponding feed volume were significantly higher in patients than in control infants, as was the percentage of infants with hemorrhagic residuals.

Conclusions:

Gastric residuals are a marker of feeding intolerance, and bloody residuals seem to be the best predictor for NEC. For early detection of very low birth weight infants at risk for NEC, both gastric residual volumes and bloody residuals represent an early relevant marker.
Influence of Esophageal pH Recording on Physical Activity in Children
Authors: Michaud Laurent , Troadec Françoise , Béghin Laurent , Rifai Nahida El , Guimber Dominique , Turck Dominique , Gottrand Frédéric
Published: May 2009

Objectives:

Twenty‐four‐hour pH‐metry represents the gold standard for the diagnosis of gastroesophageal reflux. Ambulatory esophageal pH recording provides a better reflection of occurrences under normal domestic living conditions, but it may influence physical activity. The aim of this study was to assess the influence of ambulatory esophageal pH recording on physical activity in children.

Patients and Methods:

This prospective study included 22 patients (18 boys, 4 girls) 3 to 15 years old (mean age 6.9 ± 2.3 years) who had been referred for ambulatory pH‐metry. The 24‐hour physical activity was measured twice in each child using a triaxial accelerometer 1 week before or after pH‐metry and during pH‐metry. Levels of intensity of physical activity (low: sedentary activities; moderate: walking; high: intense activities such as jumping, running, and sport) were compared by the paired nonparametric Wilcoxon test.

Results:

Physical activity was 53% lower during 24‐hour pH‐metry than when it was not present (P < 0.0005). The duration of low‐level physical activity was longer during pH‐metry (84% vs 73%; P < 0.01). The duration of moderate‐intensity and high‐intensity physical activity was shorter during pH‐metry (16% vs 24% and 0.2% vs 2.2%, respectively; P < 0.005 and P < 0.0001).

Conclusions:

Ambulatory 24‐hour esophageal pH recording substantially decreases physical activity, mainly high‐level physical activity. Whether such changes in activity decrease the sensitivity of pH‐metry and lead to false negative results in some children remains to be assessed.
Exocrine Pancreatic Function Testing in Patients With Cystic Fibrosis and Pancreatic Sufficiency: A Correlation Study
Authors: Weintraub Amir , Blau Hannah , Mussaffi Huda , Picard Elie , Bentur Lea , Kerem Eitan , Stankiewicz Halina , Wilschanski Michael
Published: May 2009

Objectives:

Most patients with cystic fibrosis (CF) have pancreatic insufficiency; however, 15% of the patients are pancreatic sufficient (PS). Several laboratory tests have been developed to distinguish between pancreatic insufficiency and PS. The gold standard to determine pancreatic function apart from direct pancreatic stimulation test is the 72‐hour fecal fat excretion, expressed as coefficient of fat absorption (CFA). The aim was to test the correlation between 2 other tests, fecal elastase‐1 and serum immunoreactive trypsinogen (IRT), as compared with fecal fat excretion.

Patients and Methods:

21 patients with CF‐PS performed the 3 tests of fecal fat excretion, fecal elastase‐1, and IRT. Correlation between the tests was evaluated by the κ statistics test, sensitivity and specificity, and positive and negative predictive values.

Results:

CFA was abnormal in 5 patients, elastase was <200 μg/g in 4 patients, and IRT was <20 ng/mL in 2 patients. The correlation between CFA and IRT was negative (κ = −0.154), and between CFA and fecal elastase‐1 was poor (κ = 0.213). The sensitivity, specificity, and positive and negative predictive values of IRT versus CFA were 0%, 88%, 0%, and 78%, and for fecal elastase‐1 were 40%, 81%, 40%, and 81%, respectively.

Conclusions:

In CF‐PS, poor correlation was found between IRT, fecal elastase‐1, and CFA, therefore neither fecal elastase‐1 in the stool nor IRT in the serum reaches the sensitivity or the specificity of the fecal fat excretion. Thus, fecal fat excretion is required in patients with CF for evaluation of pancreatic function.
Matrix Metalloproteinases in the Urine and Tissue of Patients With Juvenile Polyps: Potential Biomarkers for the Presence of Polyps
Authors: Manfredi Michael A , Fox Victor L , Zurakowski David , Kutok Jeffery L , Glickman Jonathan N , Moses Marsha A
Published: May 2009

Background and Aims:

Juvenile polyps are the most common type of pediatric gastrointestinal polyp and are typically characterized as hamartomatous overgrowths. Juvenile polyps are highly vascularized tissues and display a markedly increased mucosal microcirculation. Matrix metalloproteinases (MMPs) are a family of zinc‐dependent enzymes that play an essential role in the physiological degradation of the extracellular matrix in normal development, tumor invasion, and metastasis, as well as angiogenesis. We hypothesized that the presence of these enzymes in urine may serve as clinical biomarkers of juvenile polyps.

Patients and Methods:

In this preliminary study, we analyzed 32 urine samples collected prospectively from 16 subjects with known or suspected juvenile polyps who presented to the endoscopy unit for colonoscopic evaluation and 16 age‐ and sex‐matched controls. Urinary MMPs were analyzed by zymography and their localized tissue expression was assayed via immunohistochemistry of tissue sections.

Results:

MMPs were detected in the urine of patients with juvenile polyps with significantly higher frequency when compared with urine of control subjects. In addition, immunohistochemistry demonstrated that high levels of MMPs were localized in the epithelium and lamina propria of polyp tissue when compared with colonic tissue collected from healthy control subjects.

Conclusions:

These data are the first to demonstrate that MMPs are present in the urine and tissue of patients with juvenile polyps, and these enzymes have the potential to serve as surrogate markers for the presence of polyps.
Diagnosis Scoring for Clinical Identification of Children With Heterozygous Familial Hypercholesterolemia
Authors: Benlian Pascale , Turquet Anne , Carrat Fabrice , Amsellem Sabine , Sanchez Lydie , Briffaut Dorothée , Girardet Jean Philippe
Published: May 2009

Background:

Familial hypercholesterolemia (FH) is a frequent monogenic condition characterized by progressive atherosclerosis requiring preventive therapy from childhood. In a pediatric setting, heterozygous FH (hFH) in children may not be identified from common forms of hypercholesterolemia (HC).

Objective:

To elaborate a clinical scoring system for the diagnosis of hFH, defined by the presence of a disease‐causing mutation of the gene for the low‐density lipoprotein receptor (LDLR).

Patients and Methods:

A total of 100 unrelated children (6 ± 3 years old, 43 boys, 57 girls) with type IIa HC (LDLC >130 mg/dL) and complete genetic testing (at loci for genes for LDLR, apolipoprotein B, proprotein convertase subtilisin‐like kesin type 9, and apolipoprotein E) were selected for score elaboration. Of 60 criteria from clinical records and family questionnaires, predictors of having hFH were estimated by logistic regression analysis. Scores were validated in 38 other unrelated children with HC.

Results:

Three independent predictors of hFH were identified according to the LDLR genotype (50Mut+/50Mut−): low‐density lipoprotein cholesterol before (262 vs 178 mg/dL, P < 0.001) and after (225 vs 142 mg/dL, P < 0.001) 3 months or more of a lipid‐lowering diet, combined with parental statin usage (odds ratio 6.2; 95% confidence interval 1.4–28.3; P = 0.018). High precision and accuracy of the scoring system (area under the receiver operating characteristic curve = 0.94; 95% confidence interval 0.91–0.98) were translated into 4 probability classes (definite/probable/possible/improbable hFH) with a false‐negative rate of 12%.

Conclusions:

A score distinguishing hFH from common HC provides a simple tool for appropriate clinical decision and care in high‐risk children.
Exclusion of EGFR, HRAS, DSP, JUP, CTNNB1, PLEC1, and EPPK1 as Functional Candidate Genes in 7 Families With Syndromic Diarrhoea
Authors: Fabre Alexandre , Roquelaure Bertrand , Lacoste Caroline , André Nicolas , Sarles Jacques , Breton Anne , Martinez‐Vinson Christine , Cezard Jean‐Pierre , Colomb Virginie , Goulet Olivier , Levy Nicolas , Badens Catherine
Published: May 2009

Syndromic diarrhoea (SD) is a rare disease associating intractable diarrhoea and hair abnormalities. In an attempt to identify the gene causative for SD, we studied several functional candidate genes, based on their implication in overlapping phenotypes in mice (EGFR) or in humans (HRAS, JUP, DSP EPPK1, PLEC1, and CTNNB1) in 8 patients affected by SD. Except for EGFR and HRAS, all selected genes encode for cell adhesion proteins. Using direct sequencing or linkage analysis, we excluded all of the candidate genes as the disease‐causing gene in our group of patients; however, the hypothesis of intercellular junctions defect in SD remains seductive.
Acid Gastroesophageal Reflux in Symptomatic Infants Is Primarily a Function of Classic 2‐phase and pH‐only Acid Reflux Event Types
Authors: Woodley Frederick W , Hayes John , Mousa Hayat
Published: May 2009

Background:

Combined esophageal pH monitoring (EPM) and multichannel intraluminal impedance (MII) reveal 4 unique acid gastroesophageal reflux (AGER) types in infants: classic 2‐phase, single‐phase, pH‐only events (POEs), and re‐reflux episodes. The extent to which different AGER event types contribute to AGER frequency, acid reflux exposure time (ARET), and the number of episodes lasting 5 minutes or longer, has never been reported. In this study, EPM/MII was used to assess AGER in symptomatic infants on the basis of these 4 AGER types.

Materials and Methods:

EPM/MII tracings from 12 symptomatic infants (<12 months old) were examined. Mean frequencies and durations of each AGER type, percentages of total ARET due to each AGER type, and percentages of different AGER types lasting 5 minutes or longer, were measured.

Results:

Of 926 total AGER events, 23.1%, 6.3%, 69.2%, and 1.5% were classic 2‐phase, single‐phase, POEs, and re‐reflux episodes, respectively. In 20.2 hours of combined ARET, 52.3%, 2.3%, 42.4%, and 3.0% occurred during classic 2‐phase, single‐phase, POEs, and re‐reflux episodes, respectively. Classic 2‐phase and POE events were both more frequent than single‐phase (P = 0.002 and P < 0.0001) and re‐reflux (P = 0.002 and P < 0.0001) episodes, respectively. Increasing numbers of AGER episodes were strongly correlated with POEs (P = 0.0001). Of the 35 total AGER episodes that lasted 5 minutes or longer, 94% were classic 2‐phase episodes or POEs (57% and 37%, respectively).

Conclusions:

In symptomatic infants, total AGER episodes, total ARET, and AGER episodes lasting 5 minutes or longer are largely a function of classic 2‐phase and pH‐only AGER types.
Fecal Calprotectin: Cutoff Values for Identifying Intestinal Distress in Preterm Infants
Authors: Campeotto Florence , Baldassarre Mariella , Butel Marie‐José , Viallon Vivian , Nganzali Flore , Soulaines Pascale , Kalach Nicolas , Lapillonne Alexandre , Laforgia Nicola , Moriette Guy , Dupont Christophe , Kapel Nathalie
Published: May 2009

This study aimed to determine cutoff levels for fecal calprotectin as a marker of intestinal distress in preterm neonates. A total of 126 infants born at a median gestational age of 33 weeks (range 25.7–35 weeks) were enrolled. Samples (n = 312) were collected weekly from the end of the first week of life until the end of the first month and if any gastrointestinal event occurred. Receiver operating characteristic curves analysis gave cutoff values of 363 μg/g (sensitivity 0.65, specificity 0.82) and 636 μg/g (sensitivity 0.72, specificity 0.95) for the development of mild or severe enteropathy.
Geographic and Racial Patterns of Anemia Prevalence Among Low‐income Alaskan Children and Pregnant or Postpartum Women Limit Potential Etiologies
Authors: Gessner Bradford D
Published: May 2009

Objectives:

The etiology of the 10‐fold increase in anemia and iron deficiency prevalence among Alaska Native individuals from the culturally traditional southwestern/northern Alaska regions remains unknown. The present study sought to determine anemia prevalence among people enrolled in the Alaska Women, Infant, and Children (WIC) program and reconcile results with etiological hypotheses, particularly nutritional iron deficiency and Helicobacter pylori infection.

Patients and Methods:

An analysis was conducted of 50,964 children 6 to 59 months of age and 30,154 pregnant or postpartum women enrolled in WIC during 1999 to 2006. Based on 3 regional groupings of residence and Alaska Native status, 6 strata were defined.

Results:

Southwestern/northern Alaska Native children—who are known to have high nutritional iron intake based on subsistence diets—had the highest anemia prevalence (35%). However, southwestern/northern residence increased anemia risk similarly for Alaska Native (relative risk 1.6) and non‐Native (relative risk 1.5) children. Anemia prevalence was highest among the youngest children and declined with increasing age at approximately the same rate regardless of race or residence. Alaska Native pregnant or postpartum women from all of the regions had higher anemia prevalences than non‐Native women; southwestern/northern residence conferred additional risk to Alaska Native women.

Conclusions:

A region‐specific environmental factor is supported by the increased risk seen among all of the children residing in the southwestern/northern regions. However, the observed patterns make nutritional iron deficiency or H pylori infection unlikely as the sole or major etiologies of the high anemia prevalences observed in some groups.
Influence of Age and Genetic Risk on Anti‐tissue Transglutaminase IgA Titers
Authors: Vécsei Andreas , Arenz Tina , Heilig Gaby , Arenz Stephan , Bufler Philip , Koletzko Sibylle
Published: May 2009

Objectives:

False‐positive results of anti‐tissue‐transglutaminase (tTG) IgA autoantibodies have been reported in subjects with a genetic risk for celiac disease (CD). The aims of this retrospective study were to assess the prevalence of false‐positive tTG titers in patients at risk of CD compared with symptomatic children and to evaluate the influence of age and indication for testing on tTG titers.

Patients and Methods:

All tTG results measured in our institution during a 33‐month period were evaluated. Patients with known CD were excluded. Indications for testing were either symptoms suggestive of CD (group 1) or history of being at risk for CD (group 2). Duodenal biopsies were recommended if titers were positive (≥10 U/mL) and offered if borderline (≥4 to <10 U/mL).

Results:

The final analysis included 2056 patients, 1707 belonged to group 1, and 349 to group 2. All 65 patients with positive tTG results underwent biopsy (group 1: 57, group 2: 8). Celiac disease was confirmed in 61 subjects (median titer: 107.8 U/mL, range 12.0–1748 mL, NS between group 1 and 2), whereas 4 had normal histology (10.2–25.2 U/mL). Three out of 16 patients with borderline results underwent biopsy and had normal histology. Borderline titers were more common in group 2 patients (2.6% vs 0.4%, P = 0.001). Multiple regression analysis in patients with negative tTG results (n = 1975) revealed that titers were independently related to age (P < 0.05) and indication for testing (P < 0.001).

Conclusions:

The influence of age and genetic predisposition/risk has to be taken into account when interpreting tTG results.
Pharmacological Interventions for Nonalcoholic Fatty Liver Disease in Adults and in Children: A Systematic Review
Authors: Socha Piotr , Horvath Andrea , Vajro Pietro , Dziechciarz Piotr , Dhawan Anil , Szajewska Hania
Published: May 2009

Background:

Uncertainty exists regarding the treatment of patients with nonalcoholic fatty liver disease (NAFLD) who are unable to lose weight and/or change lifestyle. The present study assesses the effectiveness and safety of pharmacological and dietary supplement interventions for NAFLD.

Methods:

MEDLINE, EMBASE, and the Cochrane Library were searched for randomized controlled trials (RCTs) both in adults and in children.

Results:

Fifteen (2 pediatric patients and 13 adults) RCTs met the inclusion criteria. A significant effect on normalization of alanine transaminase was found in patients treated with metformin compared with vitamin E, and in those treated with high‐dose (3 g) carnitine vs diet. In contrast, there was no difference in patients treated with pioglitazone combined with vitamin E versus vitamin E alone, ursodeoxycholic acid (UDCA) combined with vitamin E or alone versus placebo, or UDCA versus combination of vitamin E and vitamin C, and in patients treated with vitamin E, probucol, N‐acetylcysteine, low doses of carnitine, or Yo Jyo Shi Ko compared with placebo. Aspartate aminotransferase normalization was significantly higher in those treated with UDCA combined with vitamin E versus UDCA alone or placebo, and in those treated with metformin. Small number of subjects, high drop‐out rates, and numerous interventions in 1 study limit the value of many studies. Only 7 RCTs analyzed biopsy specimens, but most of them have significant methodological limitations. Pioglitazone had reduced liver necrosis and inflammation in 1 large study.

Conclusions:

Limited data do not allow one to draw firm conclusions on the efficacy of various treatments for NAFLD.
Living‐related Donor Liver Transplantation for Children With Fulminant Hepatic Failure in Israel
Authors: Shouval Dror S , Mor Eytan , Avitzur Yaron , Shamir Raanan , Bar‐Nathan Nathan , Steinberg Ran , Schoenfeld Tommy , Ben‐Ari Ziv , Shapiro Rivka
Published: May 2009

Background:

Liver transplantation is considered the treatment of choice for most children with deteriorating fulminant hepatic failure (FHF). Living‐related donor liver transplantation (LDLT) has been suggested as an alternative to cadaveric liver transplantation to overcome the shortage of organ donors. However, experience with LDLT for children with FHF is limited in the Western world.

Objective:

To present the experience with LDLT for children with FHF in a major referral center in Israel.

Methods:

The files of all children who underwent primary LDLT for FHF were reviewed for demographic, clinical, and laboratory parameters before and after transplantation.

Results:

During 1996 to 2007, 13 children diagnosed with FHF underwent primary LDLT. Median age was 4 years (range 0.75–14 years); the causes of FHF were acute hepatitis A in 4 patients and were unknown in 9 patients. Short‐term complications, documented in 12 children, included mainly hepatic artery thrombosis (n = 5), which warranted retransplantation in 3 cases, and biliary leaks (n = 3). Three patients died within the first month after LDLT of severe intraoperative bleeding (n = 1), severe brain edema (n = 1), and multiorgan failure (n = 1). Long‐term complications were less common and included mainly ascending cholangitis (n = 3). Patient survival rate was 68% at 1 year and 57% at 5 years. None of the donors had long‐term complications.

Conclusions:

Among children with FHF, LDLT can serve as a timely and lifesaving alternative to cadaveric donation, and could reduce the dependence on cadaveric livers in this setting.
Changes in Intestinal Microflora in Obesity: Cause or Consequence?
Authors: Bäckhed Fredrik
Published: May 2009

Obesity and the associated metabolic disorders, such as diabetes and metabolic syndrome, have become major public health issues worldwide. Obesity results from a positive energy balance and is associated with decreased microbial diversity in the human gut with lower levels of Bacteroidetes. However, whether changes in the gut microbiota are a cause or consequence in obesity remains to be definitively proven. Experiments using germ‐free mice have begun to reveal some mechanisms by which the gut microbiota may affect the development of obesity.
Screening and Surveillance Recommendations for Pediatric Gastrointestinal Polyposis Syndromes
Authors: Barnard John
Published: May 2009

Inherited polyposis syndromes are relatively rare disorders in pediatric gastroenterology practice, even in busy academic settings. It is important, however, for pediatric gastroenterologists to be aware of the serious health risks for children and their families affected by these disorders. The diagnosis of a polyp syndrome is often made in the first or second decade of life, long before the risk of gastrointestinal neoplasia. Pediatric gastroenterologists must be prepared then to offer families predictive genetic screening as well as endoscopic surveillance when appropriately indicated. The current overview is designed to provide general guidelines and, whenever possible, evidence‐based recommendations for genetic testing, endoscopic surveillance and other screening approaches for children with inherited gastrointestinal polyposis syndromes. In this presentation, the focus is on screening for neoplastic change and complications in the gastrointestinal tract. It is important to understand that extraintestinal cancers are frequent in some of these disorders and the reader is referred to other authoritative sources (1) for additional information about comprehensive health screening outside the gastrointestinal system.
Colon in Food Allergy
Authors: Troncone Riccardo , Discepolo Valentina
Published: May 2009

The colon is a site of allergic reaction to food proteins. The most common manifestation is allergic proctocolitis. Although frequent in infancy, it may also affect older children. The diagnosis of allergic proctocolitis is mainly based on clinical and histological grounds, but there is a risk of overdiagnosis; challenge is strongly recommended to avoid unnecessary and expensive formula or changes in maternal diet that may discourage continuation of breast‐feeding. The benign clinical course and the spontaneous resolution in most infants suggest the need for further prospective studies to validate markers that allow the identification of those children needing a dietary approach. It remains to be assessed whether lymphoid nodular hyperplasia of the colon is a manifestation of food allergy. Finally, allergic proctitis may present clinically with refractory constipation; the true prevalence of food allergy–related constipation remains to be assessed.
Pharmacotherapy for Functional Gastrointestinal Disorders in Children
Authors: Saps Miguel , Di Lorenzo Carlo
Published: May 2009

Therapy of pediatric functional gastrointestinal disorders is best done within the context of a multidisciplinary biopsychosocial approach. Pharmacotherapy is often sought by patients and families who hope to find a “pill” that will lead to rapid symptom relief. Yet, there is only scant published evidence for the efficacy of a variety of medical interventions in childhood functional abdominal pain and irritable bowel syndrome. This article reviews the pediatric studies that have addressed pharmacotherapy in children with pain predominant functional gastrointestinal disorders.
Novel and Alternative Therapies for Childhood Constipation
Authors: Coccorullo Paola , Quitadamo Paolo , Martinelli Massimo , Staiano Annamaria
Published: May 2009

Constipation is a common and distressing pediatric problem. Even if prevalence of this disorder has increased, treatment of constipation in children is still largely based on clinical experience rather than on evidence‐based studies. The currently recommended treatment includes education, disimpaction, and maintenance therapy, consisting of dietary changes, behavioral modification, and use of laxatives. Among osmotic agents, polyethylene glycol solutions appear to be the first‐line drug to use in pediatrics. Although these measures are effective in the majority of children, a sizable proportion needs long‐term therapy. Chronicity may significantly interfere with the child's emotional growth and development. Advances in the understanding of the gastrointestinal enteric nervous system and epithelial function have led to the development of new classes of drugs. These include substances that bind to serotonin receptors or are chloride channel activators. Further studies are needed to assess the benefits and the risks of these new drugs.
Positive selection inAvrP4avirulence gene homologues across the genusMelampsora
Authors: Van der Merwe Marlien M. , Kinnear Mark W. , Barrett Luke G. , Dodds Peter N. , Ericson Lars , Thrall Peter H. , Burdon Jeremy J.
Published: May 2009

Pathogen genes involved in interactions with their plant hosts are expected to evolve under positive Darwinian selection or balancing selection. In this study a single copy avirulence gene,AvrP4, in the plant pathogenMelampsora lini, was used to investigate the evolution of such a gene across species. Partial translation elongation factor 1-alpha sequences were obtained to establish phylogenetic relationships among theMelampsoraspecies. We amplifiedAvrP4homologues from species pathogenic on hosts from different plant families and orders, across the inferred phylogeny. Translations of theAvrP4sequences revealed a predicted signal peptide and towards the C-terminus of the protein, six identically spaced cysteines were identified in all sequences. Maximum likelihood analysis of synonymous versus non-synonymous substitution rates indicated that positive selection played a role in the evolution of the gene during the diversification of the genus. Fourteen codons under significant positive selection reside in the C-terminal 28 amino acid region, suggesting that this region interacts with host molecules in most sequenced accessions. Selection pressures on the gene may be either due to the pathogenicity or avirulence function of the gene or both.
Triple Loss of Function of Protein Phosphatases Type 2C Leads to Partial Constitutive Response to Endogenous Abscisic Acid
Authors: Rubio Silvia , Rodrigues Americo , Saez Angela , Dizon Marie B. , Galle Alexander , Kim Tae-Houn , Santiago Julia , Flexas Jaume , Schroeder Julian I. , Rodriguez Pedro L.
Published: May 2009

The phytohormone abscisic acid (ABA) is a key regulator of plant growth and development as well as plant responses to situations of decreased water availability. Protein phosphatases type 2C (PP2Cs) from group A, which includes the ABI1/HAB1 and PP2CA branches, are key negative regulators of ABA signaling. Specifically, HAB1, ABI1, ABI2, and PP2CA have been shown to affect both seed and vegetative responses to ABA. To further understand their contribution to ABA signaling and to unravel possible genetic interactions and functional redundancy among them, we have generated different combinations of double and triple mutants impaired in these PP2Cs. Interestingly, hab1-1pp2ca-1 and abi1-2pp2ca-1 double mutants showed reduced water loss and enhanced resistance to drought stress, which further supports the role of PP2CA in vegetative responses to ABA. Two triple hab1-1abi1-2abi2-2 and hab1-1abi1-2pp2ca-1 mutants were generated, which showed an extreme response to exogenous ABA, impaired growth, and partial constitutive response to endogenous ABA. Thus, transcriptomic analysis revealed a partial up-regulation/down-regulation of a subset of ABA-responsive genes in both triple mutants in the absence of exogenous ABA. Comparison of ABA responses in the different pp2c mutants showed that a progressive increase in ABA sensitivity could be obtained through combined inactivation of these PP2Cs. These results indicate that ABA response is finely tuned by the integrated action of these genes, which is required to prevent a constitutive response to endogenous ABA that might have a deleterious effect on growth and development in the absence of environmental stress.
Different Lepidopteran Elicitors Account for Cross-Talk in Herbivory-Induced Phytohormone Signaling
Authors: Diezel Celia , von Dahl Caroline C. , Gaquerel Emmanuel , Baldwin Ian T.
Published: May 2009

Salicylic acid (SA), jasmonic acid (JA), ethylene (ET), and their interactions mediate plant responses to pathogen and herbivore attack. JA-SA and JA-ET cross-signaling are well studied, but little is known about SA-ET cross-signaling in plant-herbivore interactions. When the specialist herbivore tobacco hornworm (Manduca sexta) attacks Nicotiana attenuata, rapid and transient JA and ET bursts are elicited without significantly altering wound-induced SA levels. In contrast, attack from the generalist beet armyworm (Spodoptera exigua) results in comparatively lower JA and ET bursts, but amplified SA bursts. These phytohormone responses are mimicked when the species' larval oral secretions (OSSe and OSMs) are added to puncture wounds. Fatty acid-amino acid conjugates elicit the JA and ET bursts, but not the SA burst. OSSe had enhanced glucose oxidase activity (but not β-glucosidase activity), which was sufficient to elicit the SA burst and attenuate the JA and ET levels. It is known that SA antagonizes JA; glucose oxidase activity and associated hydrogen peroxide also antagonizes the ET burst. We examined the OSMs-elicited SA burst in plants impaired in their ability to elicit JA (antisense [as]-lox3) and ET (inverted repeat [ir]-aco) bursts and perceive ET (35s-etr1b) after fatty acid-amino acid conjugate elicitation, which revealed that both ET and JA bursts antagonize the SA burst. Treating wild-type plants with ethephone and 1-methylcyclopropane confirmed these results and demonstrated the central role of the ET burst in suppressing the OSMs-elicited SA burst. By suppressing the SA burst, the ET burst likely facilitates unfettered JA-mediated defense activation in response to herbivores that otherwise would elicit SA.
Valuing Difference or Securing Compliance? Working to Involve Young People in Community Settings
Authors: Milbourne Linda
Published: May 2009

Recent UK policy changes have generated renewed public and academic interest in the contexts and purposes for work with young people. Emphasis on youth inclusion and participation as components of policy discourse associated with citizenship and community cohesion contrasts with other more regulatory trends in youth policy, while moves towards integrating local services have increased dependence on community providers. The paper draws on empirical study of community organisations working with young people to consider how recent transitions have been reflected in the experiences of community ‘partners’ and activities with young people. Do the greater emphases on community level involvement and young people’s participation mark a shift towards more responsive, better integrated services? Research to date suggests significant gaps between how policy‐makers promote inclusive services and perceptions of delivery at local level. Despite professional initiatives to create new spaces for young people to participate, dominant institutional cultures and contractually led service targets present barriers to involving disengaged young people, undermining alternative models of working. The paper argues the need for a better appreciation of the complexity and challenges of work with young people at community level, together with greater openness to diversity and risk.
Th9 and allergic disease
Authors: Soroosh Pejman , Doherty Taylor A.
Published: May 2009

Helper CD4+ T‐cell subsets have improved our understanding of adaptive immunity in humans and in animal models of disease. These include T helper type 1 (Th1), Th2 and the interleukin‐17 (IL‐17) ‐producing population ‘Th17’. Th2 cells have been described as orchestrating the immune response in allergic disease based on studies with patient samples and animal models. The cytokine IL‐9 has largely been regarded as a Th2 cytokine that makes multifocal contributions to allergic disease. Recent data suggest that under certain conditions relevant to chronic disease (IL‐4 and transforming growth factor‐β), a distinct population of IL‐9‐producing ‘Th9’ helper T cells can exist. The contribution of Th9 cells in allergic disease is currently unknown, and this review will propose a model for how these cells may regulate chronic allergic inflammation.
mTOR: taking cues from the immune microenvironment
Authors: Delgoffe Greg M. , Powell Jonathan D.
Published: May 2009

The ultimate outcome of T cell receptor recognition is determined by the context in which the antigen is encountered. In this fashion both antigen‐presenting cells and T cells must integrate multiple environmental cues in the form of pathogen‐associated molecular patterns, cytokines and accessory molecule signals. The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that plays a central role in integrating environmental signals critical to regulating metabolism and cell survival. In this paper we review the data demonstrating that mTOR integrates signals from the immune microenvironment and therefore facilitates the generation of the adaptive immune response. Specifically, we review the role of mTOR in promoting dendritic cell activation and maturation, in regulating full T cell activation versus anergy, and influencing the induction of regulatory T cells.
Consumers that are not ‘ideal’ or ‘free’ can still approach the ideal free distribution using simple patch‐leaving rules
Authors: Griffen Blaine D.
Published: May 2009

1. The ideal free distribution (IFD) has been widely used to determine whether consumers distribute themselves optimally. However, this theory is based on three assumptions that are clearly violated in many systems. The theory assumes that all individuals know the quality of each available site, are equally free to move between all sites, and have equal competitive abilities.

2. I examine the utility of this theory to predict the distribution of the invasive European green crabCarcinus maenas, a species that likely violates all of these assumptions. I demonstrate three main findings.

3. First, understanding how density‐dependent interference and size alter individual foraging behaviour is important for understanding the density and biomass distribution ofC. maenasin invaded habitats.

4. Second, once behavioural mechanisms of crab foraging are accurately included in the model, the IFD does a good job of predicting the distribution ofC. maenas, even thoughC. maenasviolates the theory’s fundamental assumptions.

5. Third,C. maenas’ distribution can be obtained using simple decision rules and reasonable movement patterns.
The treatment of challenging behaviour in intellectual disabilities: cost‐effectiveness analysis
Authors: Romeo R. , Knapp M. , Tyrer P. , Crawford M. , Oliver‐Africano P.
Published: May 2009

Background  Antipsychotic drugs are used in the routine treatment of adults with intellectual disabilities (ID) and challenging behaviour in the UK despite limited evidence of their effectiveness. There is no evidence on their cost‐effectiveness.

Methods  The relative cost‐effectiveness of risperidone, haloperidol and placebo in treating individuals with an ID and challenging behaviour was compared from a societal perspective in a 26‐week, double‐blind, randomised controlled trial. Outcomes were changes in aggression and quality of life. Costs measured all service impacts and unpaid caregiver inputs.

Results  After 26 weeks, patients randomised to placebo had lower costs compared with those in the risperidone and haloperidol treatment groups. Aggression was highest for patients treated with risperidone and lowest for patients treated with haloperidol; however, quality of life was lowest for patients treated with haloperidol and highest for patients treated with risperidone.

Conclusion  The treatment of challenging behaviour in ID with antipsychotic drugs is not a cost‐effective option.
The nitric oxide synthase inhibitor, Ng‐nitro‐l‐arginine‐methyl‐ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans
Authors: Kuo P. , Gentilcore D. , Nair N. , Stevens J. E. , Wishart J. M. , Lange K. , Gilja O. H. , Hausken T. , Horowitz M. , Jones K. L. , Rayner C. K.
Published: May 2009

Abstract  The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, Ng‐nitro‐l‐arginine‐methyl‐ester (l‐NAME), reverses the effects of acute hyperglycaemia on gastric emptying and antropyloroduodenal (APD) motility. The study had a four‐way randomized crossover (hyperglycaemia vs euglycaemia; l‐NAME vs placebo) design in a clinical laboratory setting. Seven healthy volunteers [four males; age 30.3 ± 3.8 years; body mass index (BMI) 23.6 ± 1.2 kg m−2] were the study subjects. After positioning a transnasal manometry catheter across the pylorus, the blood glucose concentration was maintained at either 15 or 5 mmol L−1 using a glucose/insulin clamp. An intravenous infusion of l‐NAME (180 μg kg−1 h−1) or placebo (0.9% saline) was commenced (T = −30 min) and continued for 150 min. At T = −2 min, subjects ingested a drink containing 50 g of glucose made up to 300 mL with water. Gastric emptying was measured using 3D ultrasound, and APD motility using manometry. Hyperglycaemia slowed gastric emptying (P < 0.05), and this effect was abolished by l‐NAME. l‐NAME had no effect on gastric emptying during euglycaemia. Hyperglycaemia suppressed fasting antral motility [motility index: 3.9 ± 0.8 (hyperglycaemia) vs 6.5 ± 0.6 (euglycaemia); P < 0.01]; l‐NAME suppressed postprandial antral motility [motility index: 3.6 ± 0.2 (l‐NAME) vs 5.1 ± 0.2 (placebo); P < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia (P < 0.001), and lower after administration of l‐NAME (P < 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.
Plasticity and ambiguity of the electrophysiological phenotypes of enteric neurons
Authors: Nurgali K.
Published: May 2009

Abstract  Advances in knowledge of enteric neurons electrophysiological characteristics have led to the realisation that the properties of the neurons are dependent on the state of the intestine, the region, the method of recording and the species. Thus, under different experimental conditions, electrophysiological studies cannot provide a reliable signature that identifies the functional type of neuron. In the normal guinea‐pig small intestine, taken as a model tissue, neurons can be separated into two electrophysiological groups, S and AH neurons. Combined morphological and physiological studies place several classes of motor and interneurons in the S group, and intrinsic primary afferent neurons in the AH group. There is some evidence for subgroups of S neurons, in which electrophysiological differences are correlated with functional subtypes, but these subgroups have been incompletely investigated. Morphologically characterized Dogiel type II (DII) neurons are recognisable in many species, from mouse to human, but their electrophysiological characteristics are only partly conserved across species or cannot be satisfactorily defined due to technical difficulties. There is a strong need for a comprehensive analysis of channels and currents of S/Dogiel type I neuron subtypes, similar to the comprehensive analysis of AH/DII neurons in the guinea‐pig, and similar studies need to be conducted in human and other species. The purpose of this review is to highlight that criteria used for electrophysiological definition of enteric neurons might not be sufficient to distinguish between functional classes of neurons, due to intrinsic properties of neuronal subpopulations, plasticity in pathological conditions and differences in recording techniques.
Populus from high altitude has more efficient protective mechanisms under water stress than from low‐altitude habitats: a study in greenhouse for cuttings
Authors: Yin Chunying , Pang Xueyong , Lei Yanbao
Published: May 2009

Cuttings of Populus przewalskii and P. cathayana, which originated from high and low altitudes in southwest China, were used to examine the effect of water stress on the morphological, physiological and biochemical traits of plants in a greenhouse for one growing season. The dry mass accumulation and allocation, gas exchanges, extent of peroxidation damage, osmotic adjustment and antioxidative defenses, and amounts of pigments were measured to characterize the differences in peroxidation damage and protective mechanisms of two poplar species that contrast in drought tolerance. Under water stress, poplars showed a series of biochemical adjustments and morphological changes as follows: a decrease in leaf relative water content, gas exchanges, plant growth and dry mass accumulation; an increase in relative allocation to roots; an increase in the osmolyte contents (e.g. total amino acids). Additionally, water deficit induced an increase in peroxidation damage [as indicated by an increase in electrolyte leakage, malondialdehyde (MDA), carbonyl (C = O ) and hydrogen peroxide (H2O2) content], enhanced activities or contents of antioxidants (e.g. ascorbate peroxidase, guaiacol peroxidase, glutathione redutase and ascorbic acid) and reduced amounts of leaf pigments (e.g. chlorophyll and carotenoid). Furthermore, there were significant differences in the extent of morphological and biochemical changes between the two poplar species. Compared with P. cathayana, P. przewalskii responded to water stress by allocating relatively more to root dry mass, possessing a higher net photosynthesis rate, and having more efficient protective mechanisms, such as more osmolyte accumulation, stronger antioxidant activities and lower chlorophyll/carotenoid ratio. Thus, P. przewalskii suffered less damage as deduced from lower levels of electrolyte leakage, MDA, C=O and H2O2 content. Therefore, P. przewalskii originating from high altitude could possess more efficient protective mechanisms than P. cathayana, which is from low‐altitude habitats.
Is the maintenance of homeostatic mitochondrial signaling during stress a physiological role for alternative oxidase?
Authors: Vanlerberghe Greg C. , Cvetkovska Marina , Wang Jia
Published: May 2009

All plants maintain a non‐energy‐conserving pathway of mitochondrial electron transport referred to as alternative oxidase (AOX) respiration. Here, we briefly review some of the most prevailing themes for the metabolic and physiological roles of this respiratory pathway. Many of these themes relate to the potential of AOX to provide metabolic homeostasis in response to fluctuating cellular conditions, such as is often seen during stress. We then review reverse genetic experiments that have been used to test these hypotheses. To date, such experiments have been limited to just two dicot species and have only targeted one member (a stress‐induced member) of the AOX multigene family. Nonetheless, the experiments to date strongly reinforce the idea that AOX respiration is of particular importance during abiotic and biotic stress. Finally, we propose that another core role of AOX may be to modulate the strength of a stress‐signaling pathway from the mitochondrion that controls cellular responses to stress. In this way, AOX could be acting to provide a degree of signaling homeostasis from the mitochondrion. This hypothesis may provide explanation for some of the disparate results seen in reverse genetic experiments regarding the impact of AOX on the reactive oxygen network and oxidative damage.
Chilling stress and mitochondrial genome rearrangement in the MSC16 cucumber mutant affect the alternative oxidase and antioxidant defense system to a similar extent
Authors: Szal Bożena , Łukawska Katarzyna , Zdolińska Izabela , Rychter Anna M.
Published: May 2009

The mosaic MSC16 cucumber (Cucumis sativus L.) mutant, which houses a rearranged mitochondrial genome, has altered respiratory chain activity, with a dysfunctional Complex I, increased external NADH dehydrogenases (NDex) activity, and a higher alternative oxidase (AOX) capacity and AOX protein level. In the present study, changes in oxidative defense metabolism resulting from the respiratory chain dysfunction in the MSC16 mutant were compared with those induced by chilling. Chilling increased the enzymatic and non‐enzymatic antioxidant defense systems in the wild‐type (WT) but not in MSC16, which displays elevated antioxidant defenses as a result of the mitochondrial mutation. The high AOX capacity and protein level in MSC16 were unchanged as a result of chilling, whereas chilling increased these parameters in WT leaves. In mitochondria isolated from WT plants, superoxide was produced to a similar extent in the matrix and the intermembrane space, but in MSC16 mitochondria superoxide was produced largely within the intermembrane space. Mitochondria isolated from both genotypes after chilling showed increased superoxide production within the intermembrane space. Cytochemical detection revealed an increased abundance of H2O2 in the mitochondrial membrane in mesophyll cells of MSC16 leaves. The mitochondrial mutation also resulted in changes in the antioxidative defense system, including AOX, which were similar to those observed following chilling. The results presented here support the hypothesis that AOX is an effective marker of the cellular reprogramming resulting from stress. Moreover, we propose a role for reactive oxygen species (ROS) generated within the mitochondria in signal transduction.
Successful salvage therapy with daptomycin after linezolid and vancomycin failure in a liver transplant recipient with methicillin‐resistant Staphylococcus aureus endocarditis
Authors: Vernadakis S. , Saner F.H. , Rath P.‐M. , Kaiser G.M. , Mathe Z. , Treckmann J. , Paul A.
Published: May 2009

Abstract: Infective endocarditis is a rare complication affecting solid organ transplant recipients. Staphylococcus aureus is a common cause of infective endocarditis accounting for about 30% of cases. We present a case of nosocomial methicillin‐resistant S. aureus endocarditis with persistent bacteremia, in a patient following orthotopic liver transplantation. We were unable to eradicate this infection with primary linezolid therapy or with secondary treatment with combined vancomycin and rifampicin, but successfully treated it with daptomycin, in addition to tricuspid and aortic valve replacement.