bluuebunny/crossref_metadata_2025 huggingface dataset:
Antoine de La Sale's
La Sale
: The Cannonball and the Prince's Head
Authors: Léglu Catherine
Published: March 2011

Antoine de La Sale's didactic treatise
La Sale
(1451), a ‘mirror for princes’ aimed at noble boys, includes an eye-witness account of a dramatic event that occurred in Naples in 1438. This essay examines the ways in which the tale breaks with its frame, a translated and Christianized version of Valerius Maximus's
Facta et dicta memorabilia
, to question subtly the lessons it teaches concerning sacrilege and noble rank. The compilation appears to promote and question the authority and reliability of the tutor. In addition, once it is set against the concluding scene of La Sale's
Jehan de Saintré
(1456), the tale appears to furnish some evidence of the development of the genre of the
nouvelle
from both the narration of recent events, and the genre of the moralizing exemplum.
Assessment of Nutritional Status and Serum Leptin in Children With Inflammatory Bowel Disease
Authors: Aurangzeb Brekhna , Leach Steven T , Lemberg Daniel A , Day Andrew S
Published: March 2011

Objectives:

Children with inflammatory bowel disease (IBD) commonly have altered nutrition and growth. Measurement of serum leptin may enhance other modalities to assess the nutritional state of children with IBD. The aim of the present study was to define the nutritional status of children with newly diagnosed IBD by measuring anthropometry and serum leptin levels.

Patients and Methods:

Twenty‐eight children newly diagnosed with IBD and 56 age‐ and sex‐matched controls were enrolled prospectively. Anthropometry (weight, height, and body mass index [BMI] expressed as z scores) and serum leptin levels were measured.

Results:

The children with IBD had lower mean BMI z scores and weight‐for‐age percentiles than controls (P = 0.05 and P = 0.01, respectively). The mean (standard deviation) serum leptin levels of the children with IBD were 2.4 (±1.9) pg/mL, compared with 5.2 (±4.6) pg/mL for controls (P = 0.01). The BMI percentile correlated positively with leptin levels in both groups. Following adjustment for BMI percentiles, serum leptin levels were lower in children with IBD than in controls (P = 0.02). Leptin levels did not correlate with serum markers of inflammation or disease activity scores.

Conclusions:

Detailed and focused nutritional assessment should be an integral part of the management of all children with IBD. Children at the time of diagnosis of IBD have significant undernutrition and have lower serum leptin levels than controls. The inflammatory state in IBD appears not to alter leptin metabolism. Further study of the effect of leptin in IBD is required.
Temporal Association of Polysomnographic Cardiorespiratory Events With GER Detected by MII‐pH Probe in the Premature Infant at Term
Authors: Nunez Jeanne , Cristofalo Elizabeth , McGinley Brian , Katz Richard , Glen Daniel R , Gauda Estelle
Published: March 2011

Objectives:

The aim of the study was to examine temporal association (TA) between polysomnographic cardiorespiratory (CR) events and gastroesophageal reflux (GER) in premature infants with persistent CR events at >39 weeks postmenstrual age and determine whether the use of multichannel intraluminal impedance (MII)‐pH probe improves sensitivity of the TA compared with pH probe alone.

Patients and Methods:

Seven infants born between 24 and 29 weeks' gestational age with persistent CR events at 39 to 48 weeks' postmenstrual age underwent a polysomnography with MII‐pH probe. Symptom index (SI) and symptom‐associated probability were calculated for diverse types of reflux and CR events. SI and a Fisher exact test with variable association windows were calculated for obstructive apnea (OA). Odds ratios for an OA given a reflux event and for a reflux event given an OA were determined.

Results:

With a Fisher exact test, a subject‐specific association between MII events and OA was found in the 3 patients who required a fundoplication or had the worse clinical GER. Some level of TA was found with SI and symptom‐associated probability in 6 of 7 infants. Association was found for pH >4 and pH ≤4 reflux events. pH‐only events with no change of MII had only a limited role in generating CR events.

Conclusions:

TA between CR events and GER was found in a single‐subject–level analysis in some infants with persistent CR events at term. This TA suggests a causal relation between CR and reflux events that was further strengthened by the clinical outcomes of each infant.
Accuracy in Celiac Disease Diagnostics by Controlling the Small‐bowel Biopsy Process
Authors: Webb Charlotta , Halvarsson Britta , Norström Fredrik , Myléus Anna , Carlsson Annelie , Danielsson Lars , Högberg Lotta , Ivarsson Anneli , Karlsson Eva , Stenhammar Lars , Sandström Olof
Published: March 2011

Objectives:

In a Swedish celiac disease screening study (Exploring the Iceberg of Celiacs in Sweden), we systematically reviewed the clinical diagnostic procedures with the aim to evaluate the diagnostic accuracy and to take advantage of lessons learned for improving diagnostic routines.

Materials and Methods:

A school‐based celiac disease screening study involving 5 Swedish centers, with 10,041 invited 12‐year‐olds with 7567 consenting participation. All 192 children with elevated serological markers were recommended to undergo small‐bowel biopsy, performed and evaluated according to local clinical routines. All of the mucosal specimens were reevaluated by 1 and, when needed, 2 expert pathologists to reach diagnostic consensus.

Results:

Small‐bowel biopsies were performed in 184 children: 130 by endoscopy and 54 by suction capsule. Endoscopic biopsies were inconclusive in 0.6%, compared with 7.4% of biopsies by suction capsule. A patchy enteropathy was found in 9.1%. Reevaluation by the expert pathologist resulted in 6 additional cases with celiac disease and 1 cleared. Sixteen children with normal or inconclusive biopsies, 4 after endoscopy, and 12 after suction capsule were endoscopically rebiopsied, resulting in another 8 cases. The celiac disease prevalence of 30 of 1000 (95% confidence interval 26–34) was not statistically different from that previously reported.

Conclusions:

The present review revealed the importance of controlling each step of the diagnostic procedure. Several cases would have been missed by relying only on local routines. To improve the quality of childhood celiac disease diagnostics, we recommend multiple endoscopic biopsies from both proximal and distal duodenum and standardized evaluation by a pathologist with good knowledge of celiac disease.
Long‐term Follow‐up of Patients After Antegrade Continence Enema Procedure
Authors: Siddiqui Anees A , Fishman Steven J , Bauer Stuart B , Nurko Samuel
Published: March 2011

Background:

Antegrade continence enema (ACE) has become an important therapeutic modality in the treatment of intractable constipation and fecal incontinence. There are little data available on the long‐term performance of the ACE procedure in children.

Methods:

A retrospective review of patients who underwent the ACE procedure was conducted. Irrigation characteristics and complications were noted. Outcome was assessed for individual encounters based on frequency of bowel movements, incontinence, pain, and predictability.

Results:

One hundred seventeen patients underwent an ACE. One hundred five patients had at least 6 months of follow‐up, and were included in the analysis. Diagnoses included myelodysplasia (39%), functional intractable constipation (26%), anorectal malformations (21%), nonrelaxing internal anal sphincter (7%), cerebral palsy (3%), and other diagnoses (4%). The average follow‐up was 68 months (range 7–178 months). At the last follow‐up, 69% of patients had successful bowel management. Of the 31% of patients who did not have successful bowel management, 20% were using the ACE despite suboptimal results, 10% required surgical removal, and 2% were not using the ACE because of behavioral opposition to it. Patients were started on normal saline, but were switched to GoLYTELY (PEG‐3350 and electrolyte solution) if there was an inadequate response (61% at final encounter). Additives were needed in 34% of patients. The average irrigation dose was 23 ± 0.7 mL/kg. The average toilet sitting time was 51.7 ± 3.5 minutes, with infusions running for 12.1 ± 1.2 minutes. Stomal complications occurred in 63% (infection, leakage, and stenosis) of patients, 33% required surgical revision and 6% eventually required diverting ostomies.

Conclusions:

Long‐term use of the ACE gives successful results in 69% of patients, whereas 63% had a stoma‐related complication and 33% required surgical revision of the stoma.
ClpC acts as a negative regulator of competence in Streptococcus thermophilus
Authors: Biørnstad Truls Johan , Håvarstein Leiv Sigve
Published: March 2011

The alternative sigma factor ComX is a key regulator of natural transformation in members of the genus Streptococcus. ComX controls expression of the late competence genes, which are essential for DNA binding, uptake and recombination. In Streptococcus pneumoniae, it has been demonstrated that ComX is degraded by ClpEP at the end of the competence period. In the present study we show that a different Clp protease complex, ClpCP, contributes to ComX degradation in Streptococcus thermophilus. Mutant strains lacking the ClpC chaperone displayed significantly increased transformability compared with the wild-type strain under conditions where ComX was expressed at relatively low levels. At higher expression levels, ClpCP appears to become saturated and unable to prevent the accumulation of ComX. Together, our results suggest that the role of ClpC is to mediate degradation of ComX when the sigma factor is produced in low amounts, i.e. when the environmental stimulus promoting competence development is weak. This would prevent S. thermophilus from developing the competent state at an inappropriate time and/or place.
Impact of infralimbic inputs on intercalated amygdala neurons: A biophysical modeling study
Authors: Li Guoshi , Amano Taiju , Pare Denis , Nair Satish S.
Published: March 2011

Intercalated (ITC) amygdala neurons regulate fear expression by controlling impulse traffic between the input (basolateral amygdala; BLA) and output (central nucleus; Ce) stations of the amygdala for conditioned fear responses. Previously, stimulation of the infralimbic (IL) cortex was found to reduce fear expression and the responsiveness of Ce neurons to BLA inputs. These effects were hypothesized to result from the activation of ITC cells projecting to Ce. However, ITC cells inhibit each other, leading to the question of how IL inputs could overcome the inter-ITC inhibition to regulate the responses of Ce neurons to aversive conditioned stimuli (CSs). To investigate this, we first developed a compartmental model of a single ITC cell that could reproduce their bistable electroresponsive properties, as observed experimentally. Next, we generated an ITC network that implemented the experimentally observed short-term synaptic plasticity of inhibitory inter-ITC connections. Model experiments showed that strongly adaptive CS-related BLA inputs elicited persistent responses in ITC cells despite the presence of inhibitory interconnections. The sustained CS-evoked activity of ITC cells resulted from an unusual slowly deinactivating K+current. Finally, over a wide range of stimulation strengths, brief IL activation caused a marked increase in the firing rate of ITC neurons, leading to a persistent decrease in Ce output, despite inter-ITC inhibition. Simulations revealed that this effect depended on the bistable properties and synaptic heterogeneity of ITC neurons. These results support the notion that IL inputs are in a strategic position to control extinction of conditioned fear via the activation of ITC neurons.
Protein Phosphatase 2A B55 and A Regulatory Subunits Interact with Nitrate Reductase and Are Essential for Nitrate Reductase Activation
Authors: Heidari Behzad , Matre Polina , Nemie-Feyissa Dugassa , Meyer Christian , Rognli Odd Arne , Møller Simon G. , Lillo Cathrine
Published: March 2011

Posttranslational activation of nitrate reductase (NR) in Arabidopsis (Arabidopsis thaliana) and other higher plants is mediated by dephosphorylation at a specific Ser residue in the hinge between the molybdenum cofactor and heme-binding domains. The activation of NR in green leaves takes place after dark/light shifts, and is dependent on photosynthesis. Previous studies using various inhibitors pointed to protein phosphatases sensitive to okadaic acid, including protein phosphatase 2A (PP2A), as candidates for activation of NR. PP2As are heterotrimeric enzymes consisting of a catalytic (C), structural (A), and regulatory (B) subunit. In Arabidopsis there are five, three, and 18 of these subunits, respectively. By using inducible artificial microRNA to simultaneously knock down the three structural subunits we show that PP2A is necessary for NR activation. The structural subunits revealed overlapping functions in the activation process of NR. Bimolecular fluorescence complementation was used to identify PP2A regulatory subunits interacting with NR, and the two B55 subunits were positive. Interactions of NR and B55 were further confirmed by the yeast two-hybrid assay. In Arabidopsis the B55 group consists of the close homologs B55α and B55β. Interestingly, the homozygous double mutant (b55α × b55β) appeared to be lethal, which shows that the B55 group has essential functions that cannot be replaced by other regulatory subunits. Mutants homozygous for mutation in Bβ and heterozygous for mutation in Bα revealed a slower activation rate for NR than wild-type plants, pointing to these subunits as part of a PP2A complex responsible for NR dephosphorylation.
Hydroxycamptothecin‐loaded Fe3O4 nanoparticles induce human lung cancer cell apoptosis through caspase‐8 pathway activation and disrupt tight junctions
Authors: Zhang Gen , Ding Lei , Renegar Randall , Wang Xuemei , Lu Qun , Huo Shouquan , Chen Yan‐Hua
Published: March 2011

10‐Hydroxycamptothecin (HCPT) elicits strong anti‐cancer effects and is less toxic than camptothecin (CPT), making it widely used in recent clinical trials. However, its low solubility limits its application as an effective anti‐cancer therapy. In the present study we investigate the hypothesis that the unique water dispersible oleic acid‐Triton X‐100‐coated Fe3O4 nanoparticles loaded with HCPT disrupt epithelial cell–cell junctions and induce human lung cancer cell apoptosis through the caspase‐8 pathway. We characterized the HCPT‐loaded nanoparticles and determined their effects on lung cancer cell viability and apoptosis by using immunofluorescence light microscopy and SDS‐PAGE/immunoblots. We found that HCPT‐loaded nanoparticles elicited an anti‐proliferative effect in a dose‐dependent manner. HCPT‐loaded nanoparticles reduced the expression of cell–cell junction protein claudins, E‐cadherin and ZO‐1, and transmission electron microcopy demonstrated a disrupted tight junction ultrastructure. Transepithelial electric resistance was also reduced, indicating the reduction of tight junction functions. The HCPT‐loaded nanoparticles increased phosphorylation of p38 and SAPK/JNK while it showed no effects on p42/44 MAP kinase. Compared with void Fe3O4 nanoparticles or HCPT drug alone, HCPT drug‐loaded nanoparticles evoked synergistic effects by increasing cell apoptosis with enhanced activation of the caspase‐8 pathway. Therefore, our current study highlights the potential of HCPT drug‐loaded nanoparticles as a chemotherapeutic agent for increasing anti‐cancer drug efficacy. (Cancer Sci 2011; 102: 1216–1222)
Novel small molecule, XZH‐5, inhibits constitutive and interleukin‐6‐induced STAT3 phosphorylation in human rhabdomyosarcoma cells
Authors: Liu Aiguo , Liu Yan , Xu Zhenghu , Yu Wenying , Wang Hong , Li Chenglong , Lin Jiayuh
Published: March 2011

Signal transducers and activators of transcription 3 (STAT3) signaling is constitutively activated in many types of human cancers and cancer cell lines and represents a promising target for cancer therapy. We previously reported that the STAT3 signaling pathway is constitutively activated in human rhabodomyosarcoma cell lines (RH28, RH30 and RD2). We also demonstrated that inhibition of the STAT3 pathway led to apoptosis in human rhabdomyosarcoma cells. In the present study, we investigated the inhibitory effects of a novel small molecule, XZH‐5, on the STAT3 signaling pathway in human rhabdomyosarcoma cells. XZH‐5 was designed based on STAT3 structure, and our idea was to design peptide mimics to bind to the phosphorylated Tyr705 site and the side pocket. We found that XZH‐5 downregulated STAT3 phosphorylation. The inhibition of STAT3 by XZH‐5 was confirmed by the inhibition of STAT3 DNA binding ability and the downregulation of STAT3 downstream genes, such as Bcl‐2, Bcl‐xL, Cyclin D1 and Survivin; we also demonstrated that blockade of STAT3 phosphorylation in human rhabdomyosarcoma cells with XZH‐5 caused apoptosis and suppressed colony‐forming ability and cell migration. In addition to reducing constitutive STAT3 phosphorylation, XZH‐5 also exhibited the potency to block interleukin‐6 (IL‐6)‐induced STAT3 phosphorylation and nuclear translocation but did not inhibit the stimulation of STAT1 phosphorylation by interferon (IFN)‐γ. Our findings indicate that XZH‐5 has the potential for targeting human rhabdomyosarcoma cells expressing constitutive STAT3. (Cancer Sci 2011; 102: 1381–1387)
Measuring alcohol craving: development of the Alcohol Craving Experience questionnaire
Authors: Statham Dixie J. , Connor Jason P. , Kavanagh David J. , Feeney Gerald F. X. , Young Ross Mc. D. , May Jon , Andrade Jackie
Published: March 2011

Aims  To develop a measure of craving based on the Elaborated Intrusion (EI) theory of desire and to examine the construct, concurrent and discriminant validity of the instrument.

Design  Cross‐sectional.

Setting and participants  Patients from a hospital alcohol and drug out‐patient service (n = 230), participants in a randomized controlled trial (n = 219) and students in a university‐based study of alcohol craving (n = 202) were recruited.

Measurements  The Alcohol Craving Experience questionnaire (ACE) was developed to measure sensory aspects of craving (imagining taste, smell or sensations of drinking and intrusive cognitions associated with craving) when craving was maximal during the previous week (ACE‐S: strength), and to assess frequency of desire‐related thoughts in the past week (ACE‐F: frequency). All participants completed the ACE and the Alcohol Use Disorders Identification Test (AUDIT). The Obsessive Compulsive Drinking Scale (OCDS) and the Depression Anxiety and Stress Scale (DASS) were completed by hospital patients and randomized control trial participants.

Findings  Exploratory factor analysis on the ACE‐S and ACE‐F resulted in a three‐factor structure representing imagery, intensity and intrusion. An attempt to confirm this factor structure required a reduction in items (two from ACE‐S, five from ACE‐F) before a good fit to the three‐factor model was obtained. Concurrent validity with the OCDS, with severity of alcohol dependence and with depression, anxiety and stress, was demonstrated. The ACE discriminated between clinical and non‐clinical populations and between those at higher risk of alcohol dependence and those at lower risk.

Conclusions  A new scale, the Alcohol Craving Experience questionnaire, based on the Elaborated Intrusion theory of desire appears to capture key constructs of the theory and correlate with indices of alcohol dependence.
Mortality among a cohort of drug users after their release from prison: an evaluation of the effectiveness of a harm reduction program in Taiwan
Authors: Huang Yen‐Fang , Kuo Hsu‐Sung , Lew‐Ting Chin‐Yin , Tian Fang , Yang Chin‐Hui , Tsai Tzu‐I. , Gange Stephen J. , Nelson Kenrad E.
Published: March 2011

Aims  To determine the effect of methadone maintenance therapy (MMT) on mortality among injection drug users.

Design  A cohort of prisoners with a history of injecting opiates who were followed after their release from prison in July 2007. Mortality between July 2007 and December 2008 was determined by linking the National Death Registry with the Methadone Maintenance Treatment (MMT) database.

Setting  Taiwan.

Participants  A total of 4357 amnestied prisoners with a history of opiate injection.

Measurements  The total mortality rates (MR) among the cohort were calculated based on their person‐time contribution to methadone attendance and re‐incarceration during follow‐up. We used survival methods with MMT and re‐incarceration as time‐varying covariates adjusted for length of follow‐up in the community.

Results  A total of 142 deaths occurred: 13 in the 1st week after release [MR = 13.7/100 person‐years (pyrs)], which was greater than that in the next 4 weeks [MR = 3.2/100 pyrs, relative rate (RR) = 4.3, P < 0.001]. Overall, 1982 (46%) subjects enrolled in MMT; however, 1282 of them discontinued MMT after enrolling.

Findings  The mortality among those who continued in MMT attendance was lower (MR = 0.24/100 pyrs) than those who never enrolled in MMT (MR = 2.6/100 pyrs) or those who enrolled but dropped out of MMT (MR = 7.0/100 pyrs) after adjusting for age, gender and human immunodeficiency virus status at amnesty (RR = 0.07).

Conclusions  In ex‐prisoners in Taiwan with a history of opiate injecting, enrollment and continued participation in methadone maintenance treatment is associated with substantially lower mortality.
Prospective predictors of quitting behaviours among adult smokers in six cities in China: findings from the International Tobacco Control (ITC) China Survey
Authors: Li Lin , Feng Guoze , Jiang Yuan , Yong Hua‐Hie , Borland Ron , Fong Geoffrey T.
Published: March 2011

Aims  To examine predictors of quitting behaviours among adult smokers in China, in light of existing knowledge from previous research in four western countries and two southeast Asian countries.

Design  Face‐to‐face interviews were carried out with smokers in 2006 using the International Tobacco Control (ITC) China Survey, with follow‐up about 16 months later. A stratified multi‐stage cluster sampling design was employed.

Setting  Beijing and five other cities in China.

Participants  A total of 4732 smokers were first surveyed in 2006. Of these, 3863 were re‐contacted in 2007, with a retention rate of 81.6%.

Measurements  Baseline measures of socio‐demographics, dependence and interest in quitting were used prospectively to predict both making quit attempts and staying quit among those who attempted.

Findings  Overall, 25.3% Chinese smokers reported having made at least one quit attempt between waves 1 and 2; of these, 21.7% were still stopped at wave 2. Independent predictors of making quit attempts included having higher quitting self‐efficacy, previous quit attempts, more immediate intentions to quit, longer time to first cigarette upon waking, negative opinion of smoking and having smoking restrictions at home. Independent predictors of staying quit were being older, having longer previous abstinence from smoking and having more immediate quitting intentions.

Conclusions  Predictors of Chinese smokers' quitting behaviours are somewhat different to those found in previous research from other countries. Nicotine dependence and self‐efficacy seem to be more important for attempts than for staying quit in China, and quitting intentions are related to both attempts and staying quit.
Surveying the range and magnitude of alcohol's harm to others in Australia
Authors: Laslett Anne‐Marie , Room Robin , Ferris Jason , Wilkinson Claire , Livingston Michael , Mugavin Janette
Published: March 2011

Aims  This study aims to document the adverse effects of drinkers in Australia on people other than the drinker.

Design  Cross‐sectional survey.

Setting  In a national survey of Australia, respondents described the harmful effects they experienced from drinkers in their households, family and friendship networks, as well as work‐place and community settings.

Participants  A randomly selected sample of 2649 adult Australians.

Measurements  Problems experienced because of others' drinking were ascertained via computer‐assisted telephone interviews. Respondent and drinker socio‐demographic and drinking pattern data were recorded.

Findings  A total of 70% of respondents were affected by strangers' drinking and experienced nuisance, fear or abuse, and 30% reported that the drinking of someone close to them had negative effects, although only 11% were affected by such a person ‘a lot’. Women were more affected by someone they knew in the household or family, while men were more affected by strangers, friends and co‐workers. Young adults were consistently the most negatively affected across the majority of types of harm.

Conclusions  Substantial proportions of Australians are affected by other people's drinking, including that of their families, friends, co‐workers and strangers. These harms range in magnitude from noise and fear to physical abuse, sexual coercion and social isolation.
Eltrombopag increases plasma rosuvastatin exposure in healthy volunteers
Authors: Allred Alicia J. , Bowen Carolyn J. , Park Jung Wook , Peng Bin , Williams Daphne D. , Wire Mary Beth , Lee Edmund
Published: March 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• OATP1B1 is important for hepatic uptake of rosuvastatin and BCRP is important for rosuvastatin absorption and elimination. Eltrombopag inhibits OATP1B1 and BCRP in vitro at clinically relevant concentrations. Inhibition of these transporters could change cholesterol‐lowering efficacy and increase the risk of exposure‐dependent toxicities. To determine if co‐administration of eltrombopag with rosuvastatin alters plasma rosuvastatin exposure, an open‐label study was conducted in 42 healthy adult subjects.

WHAT THIS STUDY ADDS

• Concomitant administration of eltrombopag with rosuvastatin was associated with increased rosuvastatin exposure via inhibition of drug transporters. The therapeutic index of HMG Co‐A reductase inhibitors may be reduced by the concomitant use of eltrombopag. In subjects taking eltrombopag, a reduced dose of HMG Co‐A reductase inhibitors may be needed.

AIM Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, inhibits the organic anion transporting polypeptide 1B1 (OATP1B1) and breast cancer resistance protein (BCRP) in vitro. OATP1B1 is important for hepatic uptake of rosuvastatin and inhibition of this transporter could reduce cholesterol‐lowering efficacy and increase the risk of exposure‐dependent toxicities. In contrast, BCRP is an efflux transporter and inhibition of this transporter could increase both hepatic and plasma rosuvastatin concentrations, resulting in increased efficacy and toxicity. To determine if co‐administration of eltrombopag with rosuvastatin alters plasma rosuvastatin exposure, an open‐label study was conducted in 42 healthy adult subjects.

METHODS Subjects received rosuvastatin and eltrombopag orally: day 1, rosuvastatin 10 mg single dose; days 6 to 9, eltrombopag 75 mg once daily; day 10, eltrombopag 75 mg once daily and rosuvastatin 10 mg single dose. Adverse event assessments were performed daily and at the follow‐up visit. Plasma samples for pharmacokinetic analysis were collected days 1 to 5 and days 10 to 14.

RESULTS Co‐administration of eltrombopag with rosuvastatin increased geometric mean (90% confidence interval) plasma rosuvastatin AUC(0,∞) by 55% (42%, 69%) and Cmax by 103% (82%, 126%) in the overall study population, with a larger interaction in the non‐Asian compared with Asian subjects.

CONCLUSIONS Concomitant administration of eltrombopag with rosuvastatin was associated with increased rosuvastatin exposure. The therapeutic index of HMG Co‐A reductase inhibitors may be reduced by the concomitant use of eltrombopag. In subjects taking eltrombopag, a reduced dose of HMG Co‐A reductase inhibitors may be needed.
How common are motor problems in children with a developmental disorder: rule or exception?
Authors: Pieters S. , De Block K. , Scheiris J. , Eyssen M. , Desoete A. , Deboutte D. , Van Waelvelde H. , Roeyers H.
Published: March 2011

Background  Few co‐morbidity studies have been conducted since the Leeds Consensus Statement on developmental co‐ordination disorder (DCD) in 2006. In this Statement, international cut‐offs and inclusion criteria were agreed and consequently, the status of DCD changed. Furthermore, most existing co‐morbidity studies are small clinical studies, rather than epidemiological studies, resulting in a broad range of co‐morbidity rates. DCD has a higher incidence for boys in comparison with girls; questions arise if this preponderance remains the same in combination with other developmental disorders. Therefore, in this study we aimed to determine co‐morbidity and gender differences of motor problems in children with a pervasive developmental disorder, a hyperkinetic disorder and/or a speech, language or learning disability.

Methods  Profiles of 3608 children (mean age: 9 years 1 month) referred to rehabilitation centres for behavioural, developmental and sensorineural disorders were studied.

Results  Motor problems were reported in one‐fifth of the total sample. Co‐morbidity of motor problems in specific disorders varied from almost one‐fourth to more than one‐third. The male/female ratio was significantly higher in children with motor problems and two or more other disorders, compared with children with motor problems and less than two other disorders.

Conclusions  This study indicates that co‐morbidity of motor problems with other clinical disorders is not exceptional and developmental deviance is seldom specific to one domain. However, current co‐morbidity studies tend to overestimate the number of children with motor problems. In addition, there may be different patterns of symptoms between the genders. These findings stress the importance of assessing motor skills in children with various developmental disorders.
Expression of CD64 on polymorphonuclear neutrophils in patients with familial Mediterranean fever
Authors: Migita K , Agematsu K , Yamazaki K , Suzuki A , Yazaki M , Jiuchi Y , Miyashita T , Izumi Y , Koga T , Kawakami A , Eguchi K
Published: March 2011

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever and serosal or synovial inflammation. We examined the utility of CD64 (FcγRI) expression in polymorphonuclear neutrophils (PMNs) as clinical and biological parameters in patients with FMF. We studied 12 Japanese FMF patients (mean age; 22·8 ± 15·5 years, male/female: 2/10), along with rheumatoid arthritis patients (RA, n = 38 male/female: 6/32, mean age; 52·2 ± 15·3 years), systemic lupus erythematosus (SLE, n = 15 male/female: 0/15, mean age; 38·5 ± 15·9 years) and 12 healthy subjects (male/female: 3/9, mean age; 37·9 ± 17·2 years). CD64 expression on PMNs was determined using flow cytometry. The quantitative expression of CD64 in patients with FMF (2439·6 ± 2215·8 molecules per PMN) was significantly higher than in healthy subjects (547·8 ± 229·5, P = 0·003) or in patients with RA (606·5 ± 228·2, P < 0·0001) and SLE (681·3 ± 281·1, P = 0·004). The increased CD64 expression on PMNs isolated from untreated FMF patients was down-regulated by colchicine treatment. NACHT-LRR-PYD-containing protein 3 (NLRP3) activation using MurNAc-L-Ala-D-isoGln (MDP) resulted in increased CD64 expression on PMNs from healthy subjects. Our results suggest that quantitative measurement of CD64 expression on PMNs can be a valuable tool to discriminate between FMF and autoimmune diseases.
Mathematical modelling of soybean oil solubility in supercritical carbon dioxide
Authors: Jokić Stela , Svilović Sandra , Zeković Zoran , Vidović Senka
Published: March 2011

The solubility of soybean oil in supercritical carbon dioxide has been determined in the pressure range of 100–300 bar and in the temperature range of 313–323 K. The obtained values (from 0.0005 to 0.02055 g L−1) have been correlated using four different empirical equations proposed correspondingly by Chrastil, del Valle and Aquilera, Adachi and Lu and Sparks et al. Since the Sparks et al. equation provided the lowest average absolute relative deviation (AARD) (10.25%) than other models in the examined experimental range, a modified equation of Sparks et al. model was developed for predicting the solubility of soybean oil in supercritical carbon dioxide as a function of temperature and density. An improved equation showed the lowest deviation (2.15%) between experimental data than the other empirical equations considered in this study. The proposed equation was also applied for correlating the solubility of linoleic acid (AARD was 2.40%).
Effect of different cooking methods on the flavour constituents of mushroom (Agaricus bisporus (Lange) Sing) soup
Authors: Li Qin , Zhang Hai‐Hua , Claver Irakoze Pierre , Zhu Ke‐Xue , Peng Wei , Zhou Hui‐Ming
Published: March 2011

The effect of different cooking methods on the flavour of mushroom soup was assessed. The results indicated that the levels of free amino acids and 5’‐nucleotides in the microwaved mushroom soup were (P < 0.05) higher than those in boiled and autoclaved mushroom soup. The number of volatile compounds identified in the boiled mushroom soup was (P < 0.05) higher than those in autoclaved and microwaved mushroom soup. The main aroma‐active compounds found in mushroom soup were 1‐octen‐3‐one (mushroom‐like), 3‐octen‐2‐one (cooked mushroom‐like), 2,6‐dimethyl pyrazine (roast nut), benzeneacetaldehyde (floral), dihydro‐5‐methyl‐2(3H)‐furanone (sweet) and some unknown compounds with popcorn and sauce flavour. In addition, boiled, autoclaved and microwaved mushroom soup possessed thirteen, ten and nine aroma‐active compounds (with flavour dilution factors > 1), respectively. Thus the flavour of mushroom soup is dependent on the cooking methods as proved by gas chromatography and olfactometry analysis.
Review: exploring the role of mental health nurse‐practitioner in the treatment of early psychosis
Authors: Morse Megan , Procter Nicholas
Published: March 2011

Aims and objectives.  The aim of this paper is to examine high‐level evidence in early intervention in psychosis and scope the potential role of the mental health nurse‐practitioner in the treatment of management of early psychosis.

Background.  Psychosis imposes complex symptoms that impact on the individual and their social network, often resulting in long‐term disability. As specialised early intervention in psychosis is emerging, the nurse‐practitioner role in mental health is also gaining momentum. The background literature highlights several critical synergies between nurse‐practitioners’ scope of practice and needs of patients with early psychosis.

Design.  Literature review.

Method.  Electronic databases including Cochrane Library, CINAHL, Medline, TRIP and EMBASE. Searching was limited to articles published between 1988–2009. Eligible studies were limited to systematic reviews and randomised controlled trials.

Results.  Two systematic reviews and five randomised controlled trials met the inclusion criteria. No studies were located which specifically addressed the nurse‐practitioner role in early psychosis.

Conclusions.  Specific interventions require further research but there is emerging evidence that specialised intervention for people in the early phase of psychotic illness is achievable and possibly essential. It is within the scope of practice of mental health nurse‐practitioners to ensure patient and carer education and support, adherence to medication and other treatments, promotion of social inclusion and social connectedness.

Relevance to clinical practice.  Mental health nurse‐practitioners have the potential to provide specialist support to meet the needs of this complex group. Central to this is an ability to build an evidence‐base around the treatment and management of people with early psychosis and deliver effective education and leadership across clinical, inter‐professional and organisational domains. The paper concludes by positing a set of recommendations for nurse‐practitioners in the field of early psychosis in the Australian mental health setting.
Development of non‐verbal intellectual capacity in school‐age children with cerebral palsy
Authors: Smits D. W. , Ketelaar M. , Gorter J. W. , van Schie P. E. , Becher J. G. , Lindeman E. , Jongmans M. J.
Published: March 2011

Background Children with cerebral palsy (CP) are at greater risk for a limited intellectual development than typically developing children. Little information is available which children with CP are most at risk. This study aimed to describe the development of non‐verbal intellectual capacity of school‐age children with CP and to examine the association between the development of non‐verbal intellectual capacity and the severity of CP.

Methods A longitudinal analysis in a cohort study was performed with a clinic‐based sample of children with CP. Forty‐two children were assessed at 5, 6 and 7 years of age, and 49 children were assessed at 7, 8 and 9 years of age. Non‐verbal intellectual capacity was assessed by Raven's Coloured Progressive Matrices (RCPM). Severity of CP was classified by the Gross Motor Function Classification System, type of motor impairment and limb distribution.manovafor repeated measurements was used to analyse time effects and time × group effects on both RCPM raw scores and RCPM intelligence quotient scores.

Results The development of non‐verbal intellectual capacity was characterised by a statistically significant increase in RCPM raw scores but no significant change in RCPM intelligence quotient scores. The development of RCPM raw scores was significantly associated with the severity of CP. Children with higher levels of gross motor functioning and children with spastic CP showed greater increase in raw scores than children with lower levels of gross motor functioning and children with dyskinetic CP.

Conclusions Children with CP aged between 5 and 9 years show different developmental trajectories for non‐verbal intellectual capacity, which are associated with the severity of CP. The development of non‐verbal intellectual capacity in children with less severe CP seems to resemble that of typically developing children, while children with more severe CP show a limited intellectual development compared to typically developing children.
A phylogeographic, demographic and historical analysis of the short‐tailed pit viper (Gloydius brevicaudus): evidence for early divergence and late expansion during the Pleistocene
Authors: DING LI , GAN XIAO‐NI , HE SHUN‐PING , ZHAO ER‐MI
Published: March 2011

The impact of quaternary glaciation in eastern China on local fanua and flora has been a topic of considerable interest. We used mitochondrial DNA (mtDNA) sequence data and coalescent simulations to test two general biogeographic hypothesis related to the effects of Pleistocene climatic fluctuations for a widespread ophidian species (Gloydius brevicaudus) in eastern China and Korean Peninsula. The phylogenetic analysis revealed three major lineages, the southeast Coastal, Yangtze and North Lineages. The latter two are closely related and jointly form a continental lineage. Divergence dating and coalescent simulations indicate a Late Pliocene to Early Pleistocene divergence between lineages from the southeast coast and continental interior, followed by a mid‐to‐late Pleistocene divergence between lineages from the north and the middle–lower Yangtze Valley across East China, suggesting that all these lineages predated the last glacial maximum. An overlapping range between the two lineages within the continental lineage and a secondary contact associated with ecological transition zones on the margins of the North China Plain were also observed. These results show that vicariance patterns dominated the history of G. brevicaudus. Though the climatic events of the Pleistocene have had a marked effect on the historical distribution and intra‐specific divergence of reptiles in China, coalescent and non‐coalescent demographic analyses indicate that all lineages of G. brevicaudus seem not to have been adversely affected by glacial cycles during the Late Pleistocene, presumably because of an increase in the amount of climatically mild habitat in East Asia due to a decline in elevation and the development of monsoons since the Mid‐End Pleistocene.
The Serratia LuxR family regulator CarR39006 activates transcription independently of cognate quorum sensing signals
Authors: Poulter Simon , Carlton Timothy M. , Spring David R. , Salmond George P.C.
Published: March 2011

In Gram‐negative bacteria, quorum sensing control of gene expression is mediated by transcription factors of the LuxR family, whose DNA‐binding affinity is modulated by diffusible N‐acyl homoserine lactone (AHL) signalling molecules. In Serratia sp. ATCC 39006 and the plant pathogen Erwinia carotovora ssp. carotovora (Ecc), the biosynthesis of the β‐lactam antibiotic 1‐carbapen‐2‐em‐3‐carboxylic acid (Car) is under quorum sensing control. This study has revealed that, uniquely, the LuxR family transcriptional activator CarR39006 from Serratia 39006 has no detectable affinity for cognate AHL molecules. Furthermore, CarR39006 was shown to be naturally competent to bind to its target promoter with high affinity, activate transcription and resist cellular proteolysis, and was unaffected by AHL signals. Experiments with chimeric proteins suggest that the C‐terminal DNA‐binding domain of CarR39006 may be responsible for conferring AHL independence. In contrast, we show that the homologous CarREcc protein binds to its 3O‐C6‐HSL ligand with high affinity, and that the highly conserved Trp‐44 residue is critical for this interaction. Unlike TraR from Agrobacterium tumefaciens, CarREcc is not directly protected from cellular proteolysis by AHL binding, but via AHL‐induced DNA binding. At physiological protein concentrations, AHL binding induces CarREcc to bind to its target promoter with higher affinity and activate transcription.
tmRNA regulates synthesis of the ArfA ribosome rescue factor
Authors: Garza‐Sánchez Fernando , Schaub Ryan E. , Janssen Brian D. , Hayes Christopher S.
Published: March 2011

Translation of mRNA lacking an in‐frame stop codon leads to ribosome arrest at the 3′ end of the transcript. In bacteria, the tmRNA quality control system recycles these stalled ribosomes and tags the incomplete nascent chains for degradation. Although ubiquitous in eubacteria, the ssrA gene encoding tmRNA is not essential for the viability of Escherichia coli and other model bacterial species. ArfA (YhdL) is a mediator of tmRNA‐independent ribosome rescue that is essential for the viability of E. coliΔssrA mutants. Here, we demonstrate that ArfA is synthesized from truncated mRNA and therefore regulated by tmRNA tagging activity. RNase III cleaves a hairpin structure within the arfA‐coding sequence to produce transcripts that lack stop codons. In the absence of tmRNA tagging, truncated ArfA chains are released from the ribosome. The truncated ArfAΔ18 protein (which lacks 18 C‐terminal residues) is functional in ribosome rescue and supports ΔssrA cell viability when expressed from the arfA locus. Other proteobacterial arfA genes also encode hairpins, and transcripts from Dickeya dadantii and Salmonella typhimurium are cleaved by RNase III when expressed in E. coli. Thus, synthesis of ArfA from truncated mRNA appears to be a general mechanism to regulate alternative ribosome rescue activity.
Lipoarabinomannan biosynthesis in Corynebacterineae: the interplay of two α(1→2)‐mannopyranosyltransferases MptC and MptD in mannan branching
Authors: Mishra Arun K. , Krumbach Karin , Rittmann Doris , Appelmelk Ben , Pathak Vibha , Pathak Ashish K. , Nigou Jerome , Geurtsen Jeroen , Eggeling Lothar , Besra Gurdyal S.
Published: March 2011

Lipomannan (LM) and lipoarabinomannan (LAM) are key Corynebacterineae glycoconjugates that are integral components of the mycobacterial cell wall, and are potent immunomodulators during infection. LAM is a complex heteropolysaccharide synthesized by an array of essential glycosyltransferase family C (GT‐C) members, which represent potential drug targets. Herein, we have identified and characterized two open reading frames from Corynebacterium glutamicum that encode for putative GT‐Cs. Deletion of NCgl2100 and NCgl2097 in C. glutamicum demonstrated their role in the biosynthesis of the branching α(1→2)‐Manp residues found in LM and LAM. In addition, utilizing a chemically defined nonasaccharide acceptor, azidoethyl 6‐O‐benzyl‐α‐D‐mannopyranosyl‐(1→6)‐[α‐D‐mannopyranosyl‐(1→6)]7‐D‐mannopyranoside, and the glycosyl donor C50‐polyprenol‐phosphate‐[14C]‐mannose with membranes prepared from different C. glutamicum mutant strains, we have shown that both NCgl2100 and NCgl2097 encode for novel α(1→2)‐mannopyranosyltransferases, which we have termed MptC and MptD respectively. Complementation studies and in vitro assays also identified Rv2181 as a homologue of Cg‐MptC in Mycobacterium tuberculosis. Finally, we investigated the ability of LM and LAM from C. glutamicum, and C. glutamicumΔmptC and C. glutamicumΔmptD mutants, to activate Toll‐like receptor 2. Overall, our study enhances our understanding of complex lipoglycan biosynthesis in Corynebacterineae and sheds further light on the structural and functional relationship of these classes of polysaccharides.
Campylobacter jejuni survival within human epithelial cells is enhanced by the secreted protein CiaI
Authors: Buelow Daelynn R. , Christensen Jeffrey E. , Neal‐McKinney Jason M. , Konkel Michael E.
Published: March 2011

Although it is known that Campylobacter jejuni invade the cells that line the human intestinal tract, the bacterial proteins that enable this pathogen to survive within Campylobacter‐containing vacuoles (CCV) have not been identified. Here, we describe the identification and characterization of a protein that we termed CiaI for Campylobacter invasion antigen involved in intracellular survival. We show that CiaI harbours an amino‐terminal type III secretion sequence and is secreted from C. jejuni through the flagellar type III secretion system. In addition, the ciaI mutant was impaired in intracellular survival when compared with a wild‐type strain, as judged by the gentamicin‐protection assay. Fluorescence microscopy examination of epithelial cells infected with the C. jejuni ciaI mutant revealed that the CCV were more frequently co‐localized with Cathepsin D (a lysosomal marker) than the CCV in cells infected with a C. jejuni wild‐type strain. Ectopic expression of CiaI‐GFP in epithelial cells yielded a punctate phenotype not observed with the other C. jejuni genes, and this phenotype was abolished by mutation of a dileucine motif located in the carboxy‐terminus of the protein. Based on the data, we conclude that CiaI contributes to the ability of C. jejuni to survive within epithelial cells.
Two steps away from novelty – principles of bacterial DNA uptake
Authors: Krüger Nora‐Johanna , Stingl Kerstin
Published: March 2011

Transport of DNA across bacterial membranes during natural transformation is a fascinating and elaborate process. It requires the functional integrity of huge multi‐protein complexes present in the bacterial envelope at distinct loci. After successful mapping of essential gene products involved in natural transformation, current research focuses on the functional interplay of these components in order to understand the mechanisms how DNA enters the bacterium. Here, we discuss the model of a two‐step DNA uptake process in competent Gram‐negative and Gram‐positive bacteria. The first step comprises the transfer of DNA from the bacterial surface to the cytoplasmic membrane. For this purpose, bacteria use a variety of machineries, mostly, but not necessarily, sharing key homologous components. The second step is the translocation of DNA across the cytoplasmic membrane, a tight barrier at which ion gradients are established for energization of the cell. Crossing the latter is mediated by a protein complex harbouring a highly conserved membrane channel. On the basis of current data, at least the first step is uncoupled from the second. This review intends to highlight mechanistic features of both steps of bacterial DNA uptake by the integrative interpretation of genetic, biochemical and biophysical data.