bluuebunny/crossref_metadata_2025 huggingface dataset:
SNPman: a program for genotype calling using run data from TaqMan allelic discrimination
Authors: Konopac Martin , Dusatkova Petra , Cinek Ondrej
Published: June 2011

Summary: The SNPman program calls the genotypes of single nucleotide polymorphisms (SNP) from TaqMan allelic discrimination assays. It utilizes the fluorescence data collected over the whole PCR run, rather than relying on the end point fluorescence measurements that is the basis of the genotype calling process in most software solutions sold with the real-time instruments. This inspection of run data facilitates genotype calls in difficult sample sets, especially in those containing various concentrations of DNA or inhibitors, as indicated by results of a reanalysis of 3738 genotyping samples. The program works with data from three different widely used PCR instruments.

Availability: The compiled program is available online at http://sourceforge.net/projects/snpman/files/, along with its user documentation and demonstration data files. It is free of charge for non-commercial users.

Contact:  Ondrej.Cinek@Lfmotol.cuni.cz

Supplementary information:  Supplementary data are available at Bioinformatics online.
Sequential Therapy Versus Tailored Triple Therapies for Helicobacter pylori Infection in Children
Authors: Bontems Patrick , Kalach Nicolas , Oderda Giuseppina , Salame Assad , Muyshont Laurence , Miendje D. Yvette , Raymond Josette , Cadranel Samy , Scaillon Michèle
Published: June 2011

Aims:

The aim of the study was to compare sequential versus tailored triple therapy regimens on Helicobacter pylori (H pylori) eradication rates in children and to assess the effect of antimicrobial susceptibility.

Patients and Methods:

Prospective, open‐label, multicenter study. Children received randomly either a 10‐day sequential treatment comprising omeprazole (OME) with amoxicillin for 5 days and OME, clarithromycin (CLA), and metronidazole (MET) for the remaining 5 days, or a 7‐day triple therapy comprising OME with amoxicillin and CLA in cases of a CLA‐susceptible strain or MET in cases of CLA‐resistant strain. H pylori eradication was assessed by 13C‐urea breath test.

Results:

One hundred sixty‐five children, 95 girls and 70 boys, of median age 10.4 years, were included. The intention‐to‐treat (ITT) eradication rate was 76.9% (sequential 68/83 = 81.9%, triple therapy 59/82 = 71.9%, ns), and the per‐protocol (PP) eradication rate was 84.6% (sequential 68/77 = 88.3%, triple therapy 59/73 = 81.8%, ns). Eradication rates tended to be higher using the sequential treatment, but the difference was only statistically significant for ITT analysis in children harboring both CLA‐ and MET‐susceptible strains (87.8% vs 68.5%, odds ratio [OR] 3.3, P = 0.03). Both ITT and PP eradication rates were significantly lower with sequential treatment in CLA‐resistant compared with CLA‐susceptible strains (ITT: 56.2% vs 72.7%, OR 5.5, P = 0.008; PP 64.3% vs 80.0%, OR 7.9, P = 0.009). Both treatments were well tolerated.

Conclusions:

Sequential treatment is greatly effective for eradicating H pylori in children except in CLA‐resistant strains. Sequential treatment can be used as a first‐line therapy, but only in areas with a low CLA resistance rate.
Correlation of Vitamin E, Uric Acid, and Diet Composition With Histologic Features of Pediatric NAFLD
Authors: Vos Miriam B. , Colvin Ryan , Belt Patricia , Molleston Jean P. , Murray Karen F. , Rosenthal Philip , Schwimmer Jeffrey B. , Tonascia James , Unalp Aynur , Lavine Joel E. ,   NASH CRN Research Group
Published: June 2011

Objectives:

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children in the United States. Although changes in diet are often recommended to improve NAFLD, little is known regarding the influence of diet on histologic features of the disease.

Subjects and Methods:

This was a prospective, cross‐sectional registry‐based study. Children (n = 149) enrolled in the multicenter nonalcoholic steatohepatitis (NASH) Clinical Research Network had demographic, anthropometric, clinical, laboratory, and histology data obtained, including the Block Brief Food Questionnaire. Subjects were grouped by presence or absence of steatohepatitis and grades of histologic features according to NASH Clinical Research Network criteria.

Results:

No significant differences were found between children with steatosis compared with steatohepatitis for fraction of energy from fat, carbohydrates, and protein. Sugar‐sweetened beverage consumption was low and did not correlate with histologic features, although uric acid, a surrogate marker for fructose intake, was significantly increased in those with definite NASH (P = 0.008). For all groups, vitamin E consumption was insufficient compared with the recommended daily allowance. Median consumption of vitamin E was lower in children with higher grade of steatosis (8.4 vs 6.1 vs 6.9 for grades I, II, and III, respectively, P = 0.05). Those consuming less vitamin C had increased ballooning degeneration (P = 0.05).

Conclusions:

Children with NAFLD have a diet that is insufficient in vitamin E and this may contribute to the pathophysiology of NAFLD. In children with NAFLD, reported sugar‐sweetened beverage consumption is low; however, uric acid, which may reflect total fructose consumption, was significantly associated with NASH and should be further evaluated.
Celiac Disease in Children With Diarrhea in 4 Cities in China
Authors: Wang Xin‐qiong , Liu Wei , Xu Chun‐di , Mei Hong , Gao Yuan , Peng Han‐ming , Yuan Lan , Xu Jun‐jie
Published: June 2011

Objective:

The aim of the study was to investigate whether celiac disease (CD) could be the cause of chronic diarrhea in Chinese patients.

Patients and Methods:

During the period of January 2005 to December 2008, patients with chronic diarrhea in pediatric hospitals from 4 major cities (Shanghai, Wuhan, Jinan, and Chengdu) in China were included in the study. The clinical history, physical findings, and laboratory data were collected and analyzed.

Results:

Among 199 patients with chronic diarrhea, 118 were enrolled in the study. Fourteen (11.9%) were diagnosed as being affected by CD.

Conclusions:

The 14 patients are the first reported cases of CD in Chinese patients with chronic diarrhea.
Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: development of high levels of viraemia and demonstration of protective immunity
Authors: Omatsu Tsutomu , Moi Meng Ling , Hirayama Takanori , Takasaki Tomohiko , Nakamura Shinichiro , Tajima Shigeru , Ito Mikako , Yoshida Tomoyuki , Saito Akatsuki , Katakai Yuko , Akari Hirofumi , Kurane Ichiro
Published: June 2011

Dengue virus (DENV) causes a wide range of illnesses in humans: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Animal models that constantly develop high levels of viraemia are required for the development of protective and preventive measures. Common marmosets (Callithrix jacchus) demonstrated high levels of viraemia after inoculation with clinical isolates of four serotypes of DENV; in particular, over 106 genome copies ml−1 after inoculation with DENV-2. Non-structural protein 1 and DENV-specific IgM and IgG antibodies were consistently detected. The DENV-2 genome was detected in lymphoid organs including the lymph nodes, spleen and thymus, and also in non-lymphoid organs. DENV antigen was detected by immunohistochemistry in the liver and spleen from inoculated marmosets. Four marmosets were reinoculated with DENV-2 at 33 weeks after primary inoculation with DENV-2. The DENV-2 genome was not detected in any of these marmosets, indicating protection from a secondary infection. The results indicate that common marmosets are highly sensitive to DENV infection, and suggest that marmosets could be a reliable primate model for the evaluation of candidate vaccines.
prM-antibody renders immature West Nile virus infectious in vivo
Authors: Colpitts Tonya M. , Rodenhuis-Zybert Izabela , Moesker Bastiaan , Wang Penghua , Fikrig Erol , Smit Jolanda M.
Published: June 2011

West Nile virus (WNV) is a member of the family Flaviviridae and is a neurotropic pathogen responsible for severe human disease. Flavivirus-infected cells release virus particles that contain variable numbers of precursor membrane (prM) protein molecules at the viral surface. Consequently, antibodies are produced against the prM protein. These antibodies have been shown to activate the infectious potential of fully immature flavivirus particles in vitro. Here, we provide in vivo proof that prM antibodies render immature WNV infectious. Infection with antibody-opsonized immature WNV particles caused disease and death of mice, and infectious WNV was found in the brains and sera.
Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor-2 inhibits type 1 interferon signalling by targeting interferon-stimulated gene factor-3
Authors: Mutocheluh M. , Hindle L. , Aresté C. , Chanas S. A. , Butler L. M. , Lowry K. , Shah K. , Evans D. J. , Blackbourn D. J.
Published: June 2011

Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes four viral interferon regulatory factors (vIRF-1–4). We investigated the mechanism and consequences of vIRF-2-mediated inhibition of interferon-response element signalling following type I interferon (IFN) induction. Western blot and electrophoretic mobility-shift assays identified the interferon-stimulated gene factor-3 (ISGF-3) components STAT1 and IRF-9 as the proximal targets of vIRF-2 activity. The biological significance of vIRF-2 inhibition of ISGF-3 was demonstrated by vIRF-2-mediated rescue of the replication of the IFN-sensitive virus encephalomyocarditis virus. This study provides both a mechanism and evidence for KSHV vIRF-2-mediated suppression of the consequences of type 1 IFN-induced signalling.
Assembly and Sorting of the Tonoplast Potassium Channel AtTPK1 and Its Turnover by Internalization into the Vacuole
Authors: Maîtrejean Marie , Wudick Michael M. , Voelker Camilla , Prinsi Bhakti , Mueller-Roeber Bernd , Czempinski Katrin , Pedrazzini Emanuela , Vitale Alessandro
Published: June 2011

The assembly, sorting signals, and turnover of the tonoplast potassium channel AtTPK1 of Arabidopsis (Arabidopsis thaliana) were studied. We used transgenic Arabidopsis expressing a TPK1-green fluorescent protein (GFP) fusion or protoplasts transiently transformed with chimeric constructs based on domain exchange between TPK1 and TPK4, the only TPK family member not located at the tonoplast. The results show that TPK1-GFP is a dimer and that the newly synthesized polypeptides transiently interact with a thus-far unidentified 20-kD polypeptide. A subset of the TPK1-TPK4 chimeras were unable to assemble correctly and these remained located in the endoplasmic reticulum where they interacted with the binding protein chaperone. Therefore, TPK1 must assemble correctly to pass endoplasmic reticulum quality control. Substitution of the cytosolic C terminus of TPK4 with the corresponding domain of TPK1 was sufficient to allow tonoplast delivery, indicating that this domain contains tonoplast sorting information. Pulse-chase labeling indicated that TPK1-GFP has a half-life of at least 24 h. Turnover of the fusion protein involves internalization into the vacuole where the GFP domain is released. This indicates a possible mechanism for the turnover of tonoplast proteins.
Cell Wall Modifications in Maize Pulvini in Response to Gravitational Stress
Authors: Zhang Qisen , Pettolino Filomena A. , Dhugga Kanwarpal S. , Rafalski J. Antoni , Tingey Scott , Taylor Jillian , Shirley Neil J. , Hayes Kevin , Beatty Mary , Abrams Suzanne R. , Zaharia L. Irina , Burton Rachel A. , Bacic Antony , Fincher Geoffrey B.
Published: June 2011

Changes in cell wall polysaccharides, transcript abundance, metabolite profiles, and hormone concentrations were monitored in the upper and lower regions of maize (Zea mays) pulvini in response to gravistimulation, during which maize plants placed in a horizontal position returned to the vertical orientation. Heteroxylan levels increased in the lower regions of the pulvini, together with lignin, but xyloglucans and heteromannan contents decreased. The degree of substitution of heteroxylan with arabinofuranosyl residues decreased in the lower pulvini, which exhibited increased mechanical strength as the plants returned to the vertical position. Few or no changes in noncellulosic wall polysaccharides could be detected on the upper side of the pulvinus, and crystalline cellulose content remained essentially constant in both the upper and lower pulvinus. Microarray analyses showed that spatial and temporal changes in transcript profiles were consistent with the changes in wall composition that were observed in the lower regions of the pulvinus. In addition, the microarray analyses indicated that metabolic pathways leading to the biosynthesis of phytohormones were differentially activated in the upper and lower regions of the pulvinus in response to gravistimulation. Metabolite profiles and measured hormone concentrations were consistent with the microarray data, insofar as auxin, physiologically active gibberellic acid, and metabolites potentially involved in lignin biosynthesis increased in the elongating cells of the lower pulvinus.
Development and validation of a parenting assessment tool for Chinese parents
Authors: Cheng L. , Dai Y. , Zhu Z. , Xie X. , Chen L.
Published: June 2011

Objective  The objective of this study was to develop a parenting assessment tool (PAT) for parents of children aged 3 to 6 years to assess parenting attitudes and skills within the Chinese socio‐cultural context.

Methods and participants  Focus group discussions were used to gather information for composing the PAT test items. Factor analysis was performed to build and refine the factor structure of PAT. Ten cities included in a larger programme, the Early Childhood Development Promotion Project carried out by the Capital Institute of Pediatrics in China, were chosen as the study area. Six hundred and twelve parents and their single children were chosen from those 10 cities by convenience sampling for the large‐scale investigation of PAT, and the results were used to test and validate the psychometric properties of PAT.

Results  The internal consistency of total PAT scores was 0.87, and those of the eight subscales ranged from 0.53 to 0.79. Test–retest reliability over 2 weeks was also significant for the total scores and all subscales (range: 0.68–0.89). For the factor structure, an eight‐factor solution accounting for 65.54% of the variance was most consistently fit. Concurrent validity was supported by significant positive correlations between total PAT scores and children's language ability, sociability and adaptive ability as assessed by the Developmental Diagnostic Scale of Children Aged 0–6 Years.

Conclusions  The newly devised PAT test is a reliable instrument to assess the parenting skills and attitudes of parents of young children in urban China.
Children's and parents' beliefs regarding the value of walking: rehabilitation implications for children with cerebral palsy
Authors: Gibson B. E. , Teachman G. , Wright V. , Fehlings D. , Young N. L. , McKeever P.
Published: June 2011

Background  Walking for children with cerebral palsy (CP) has physiological and functional benefits, but also holds symbolic significance that largely remains unexplored. The aims of this pilot study were to describe beliefs about the value of walking held by children with CP and their parents, and to examine how these beliefs inform rehabilitation choices and perceptions of ‘success’.

Methods  A critical qualitative design was employed. Six parents and six children with CP (Gross Motor Function Classification System III or IV, aged 9 to 18 years) each participated in a private interview. Analyses examined the relationship between dominant social beliefs regarding walking and participants' accounts.

Results  Parents' accounts revealed that all adopted a stance of doing something/trying anything as part of being a ‘good parent’ and maintaining hope. Tapering of walking interventions contributed to feelings of guilt and doubt. Children primarily viewed walking as exercise rather than functional. Their accounts also demonstrated how they internalized negative attitudes towards disability and judged themselves accordingly.

Conclusions  The results of this pilot study provide provisional evidence regarding how dominant social values regarding walking and disability are taken up by parents and children. They suggest that rehabilitation programmes need to consider how they may unintentionally reinforce potentially harmful choices, and how best to engage families in discussions of their evolving values and treatment priorities. Further research is needed with a larger sample.
The impact of childhood abuse history, domestic violence and mental health symptoms on parenting behaviour among mothers in Japan
Authors: Fujiwara T. , Okuyama M. , Izumi M.
Published: June 2011

Background  To assess the impact of childhood abuse history, domestic violence experiences and mental health symptoms on the parenting behaviour of mothers in Japan who have separated from violent husbands or partners.

Methods  A self‐administered questionnaire survey was conducted on a sample of mothers (n= 304) and their children (n= 498) residing in 83 mother–child homes in Japan. The survey assessed the mothers' childhood abuse history (physical, psychological and sexual abuse and neglect history), domestic violence experiences, current mental health symptoms (dissociative, depressive and traumatic symptoms) and parenting behaviours after moving into the homes to separate from a violent husband or partner.

Results  The mothers' childhood abuse history and experience of domestic violence were not associated with their not playing with their children. In contrast, the mothers' dissociative and depressive symptoms were significantly associated with not playing with their children. Although there was no association between the mothers' total childhood abuse history and not praising their children, their childhood physical abuse history was significantly associated with their not praising their children. The dissociative and depressive symptoms were also associated with no praise. Interestingly, the experience of domestic violence showed an inverse association with no praise.

Conclusions  Mental health symptoms, more specifically dissociative and depressive symptoms, are associated with a decrease in parenting quality. Mothers who were physically abused as children are less likely to praise their own children, independent of maternal mental health symptoms. In contrast, mothers who experienced domestic violence but subsequently separated from their violent husbands or partners are more likely to praise their children. The treatment of mental health symptoms, particularly dissociative and depressive symptoms, therapy for childhood abuse history and separation from violent husbands or partners might be effective ways to enhance the quality of parenting in Japan.
3D post‐stack interval velocity analysis with effective use of datuming
Authors: Reshef Moshe , Lipzer Noam , Dafni Raanan , Landa Evgeny
Published: June 2011

Interval velocity analysis using post‐stack data has always been a desire, mainly for 3D data sets. In this study we present a method that uses the unique characteristics of migrated diffractions to enable interval velocity analysis from three‐dimensional zero‐offset time data. The idea is to perform a standard three‐dimensional prestack depth migration on stack cubes and generate three‐dimensional common image gathers that show great sensitivity to velocity errors. An efficient ‘top‐down’ scheme for updating the velocity is used to build the model. The effectiveness of the method is related to the incorporation of wave equation based post‐stack datuming in the model building process. The proposed method relies on the ability to identify diffractions along redatumed zero‐offset data and to analyse their flatness in the migrated local angle domain. The method can be considered as an additional tool for a complete, prestack depth migration based interval velocity analysis.
Numerical performances of a hybrid local‐time stepping strategy applied to the reverse time migration
Authors: Baldassari Caroline , Barucq Hélène , Calandra Henri , Diaz Julien
Published: June 2011

The numerical simulation of wave propagation in heterogeneous media involves very significant computational costs that can be considerably reduced by using finite elements whose order is adapted to the characteristics of the medium. In this paper, we show that we can further reduce these costs by using a mixed time scheme, combining two discrete formulas and using local time steps. We illustrate the effectiveness of the new scheme considering an application to seismic imaging treated by reverse time migration. We also show that the new scheme greatly reduces the numerical dispersion problems that appear frequently when adapting the orders of approximation in space only.
Elevated CO2 stimulates grassland soil respiration by increasing carbon inputs rather than by enhancing soil moisture
Authors: Carol Adair E. , Reich Peter B. , Trost Jared J. , Hobbie Sarah E.
Published: June 2011

It is not clear whether the consistent positive effect of elevated CO2 on soil respiration (soil carbon flux, SCF) results from increased plant and microbial activity due to (i) greater C availability through CO2‐induced increases in C inputs or (ii) enhanced soil moisture via CO2‐induced declines in stomatal conductance and plant water use. Global changes such as biodiversity loss or nitrogen (N) deposition may also affect these drivers, interacting with CO2 to affect SCF. To determine the effects of these factors on SCF and elucidate the mechanism(s) behind the effect of elevated CO2 on SCF, we measured SCF and soil moisture throughout a growing season in the Biodiversity, CO2, and N (BioCON) experiment. Increasing diversity and N caused small declines in soil moisture. Diversity had inconsistent small effects on SCF through its effects on abiotic conditions, while N had a small positive effect that was unrelated to soil moisture. Elevated CO2 had large consistent effects, increasing soil moisture by 26% and SCF by 45%. However, CO2‐induced changes in soil moisture were weak drivers of SCF: CO2 effects on SCF and soil moisture were uncorrelated, CO2 effect size did not change with soil moisture, within‐day CO2 effects via soil moisture were neutral or weakly negative, and the estimated effect of increased C availability was 14 times larger than that of increased soil moisture. Combined with previous BioCON results indicating elevated CO2 increases C availability to plants and microbes, our results suggest that increased SCF is driven by CO2‐induced increases in substrate availability. Our results provide further support for increased rates of belowground C cycling at elevated CO2 and evidence that, unlike the response of productivity to elevated CO2 in BioCON, the response of SCF is not strongly N limited. Thus, N limited grasslands are unlikely to act as a N sink under elevated CO2.
Temporal trends in N2O flux dynamics in a Danish wetland – effects of plant‐mediated gas transport of N2O and O2 following changes in water level and soil mineral‐N availability
Authors: Jørgensen Christian Juncher , Struwe Sten , Elberling Bo
Published: June 2011

Temporal trends of N2O fluxes across the soil–atmosphere interface were determined using continuous flux chamber measurements over an entire growing season of a subsurface aerating macrophyte (Phalaris arundinacea) in a nonmanaged Danish wetland. Observed N2O fluxes were linked to changes in subsurface N2O and O2 concentrations, water level (WL), light intensity as well as mineral‐N availability. Weekly concentration profiles showed that seasonal variations in N2O concentrations were directly linked to the position of the WL and O2 availability at the capillary fringe above the WL. N2O flux measurements showed surprisingly high temporal variability with marked changes in fluxes and shifts in flux directions from net source to net sink within hours associated with changing light conditions. Systematic diurnal shifts between net N2O emission during day time and deposition during night time were observed when max subsurface N2O concentrations were located below the root zone. Correlation (P < 0.001) between diurnal variations in O2 concentrations and incoming photosynthetically active radiation highlighted the importance of plant‐driven subsoil aeration of the root zone and the associated controls on coupled nitrification/denitrification. Therefore, P. arundinacea played an important role in facilitating N2O transport from the root zone to the atmosphere, and exclusion of the aboveground biomass in flux chamber measurements may lead to significant underestimations on net ecosystem N2O emissions. Complex interactions between seasonal changes in O2 and mineral‐N availability following near‐surface WL fluctuations in combination with plant‐mediated gas transport by P. arundinacea controlled the subsurface N2O concentrations and gas transport mechanisms responsible for N2O fluxes across the soil–atmosphere interface. Results demonstrate the necessity for addressing this high temporal variability and potential plant transport of N2O in future studies of net N2O exchange across the soil–atmosphere interface.
Bone morphogenetic protein signalling activity distinguishes histological subsets of paediatric germ cell tumours
Authors: Fustino N. , Rakheja D. , Ateek C. S. , Neumann J. C. , Amatruda J. F.
Published: June 2011

Germ cell tumours (GCTs) are cancers of the testis, ovary or extragonadal sites that occur in infants, children and adults. Testicular GCT is the most common cancer in young men aged 15–40 years. Abnormalities in developmental signalling pathways such as wnt/β‐catenin, TGF‐β/BMP and Hedgehog have been described in many childhood tumours. To date, however, the status of BMP signalling in GCTs has not been described. Herein, we examine BMP‐SMAD signalling in a set of clinically‐annotated paediatric GCTs. We find that BMP signalling activity is absent in undifferentiated tumours such as seminomas and dysgerminomas, but robustly present in most yolk sac tumours, a differentiated tumour type. Gene expression profiling of TGF‐β/BMP pathway genes in germinomas and yolk sac tumours reveals a set of genes that distinguish the two tumour types. There is significant intertumoural heterogeneity between tumours of the same histological subclass, implying that the BMP pathway can be differentially regulated in individual tumours. Finally, through miRNA expression profiling, we identify differential regulation of a set of miRNAs predicted to target the TGF‐β/BMP pathway at multiple sites. Taken together, these results suggest that the BMP signalling pathway may represent a new therapeutical target for childhood GCTs.
Are Caucasian–European men delaying fatherhood? Results of a 7 year observational study of infertile couples with male factor infertility
Authors: Salonia A. , Matloob R. , Saccà A. , Ferrari M. , Gallina A. , Castiglione F. , Abdollah F. , Raber M. , Brigante C. , Candiani M. , Rigatti P. , Montorsi F.
Published: June 2011

This study was aimed at assessing presence and predictors of a trend towards more advanced paternal age at presentation in a cohort of 1283 Caucasian–European infertile couples with male factor infertility (MFI) over a short time frame. Multivariate linear regression analysis tested the association between predictors [namely, partners’ age, length of infertility at first presentation, patients’ comorbidities as scored with the Charlson Comorbidity Index (CCI) and educational status] and patient’s age at presentation. Using anova, patient’s age at presentation (F ratio: 2.43; p = 0.024) and patients’ educational status (χ2 trend: 142.38; p < 0.001) significantly increased over time. In contrast, length of infertility at first presentation, CCI and partners’ age did not significantly change over time (all p ≥ 0.05). Linear regression analyses showed that CCI, educational status and year of presentation were not correlated with patients’ age at presentation (all p ≥ 0.05), whereas partners’ age (β = 0.170; p < 0.001) and length of infertility (β = 0.123; p = 0.004) were independent predictors of delayed fatherhood. These results showed a significant shift towards advanced paternal age, but a non‐significant increase of maternal age at first presentation among Caucasian–European infertile couples with MFI over a short time frame.
An unblinded randomised controlled trial of preoperative oral supplements in colorectal cancer patients
Authors: Burden S. T. , Hill J. , Shaffer J. L. , Campbell M. , Todd C.
Published: June 2011

Background:  Perioperative oral supplementation has been shown to reduce post‐operative complications. However, the use of preoperative standard oral supplements in a cohort of colorectal cancer patients has not been evaluated. The present study examined whether preoperative supplements are beneficial in this group.

Methods:  In a randomised controlled trial, patients were assigned to receive 400 mL of oral supplement and dietary advice or dietary advice alone. Primary outcome was the number of post‐operative complications. One hundred and twenty‐five patients were recruited (59 randomised to the intervention group and 66 to the control group) and nine were excluded.

Results:  In the intervention group, 24 (44%) patients had a complication compared to 26 (42%) in the control group (P = 0.780). In the intervention and control groups, there were eight (15%) and 16 (25%) surgical site infections, respectively (P = 0.140) and seven (13%) and 11 (17%) chest infections, respectively (P = 0.470). Subgroup analysis for hypothesis generation included 83 (71%) weight‐losing patients, where there was a significant reduction in surgical site infections using the Buzby definition (P = 0.034), although this was not the case for the Centre for Disease Control definition (P = 0.052).

Conclusions:  There was no evidence that preoperative supplements were beneficial in reducing the number of complications, although there may be some benefit for surgical site infections in selected weight‐losing preoperative patients.
Tools for the job: why relying on risk assessment tools is still a risky business
Authors: WEBB L.
Published: June 2011

Accessible summary

This paper examines the use of assessment tools and other decision‐making guidelines in mental health and substance misuse and suggests that clinicians need to understand how the tools were designed in order to judge whether the tool is relevant to the individual client.

It is argued that people with enduring mental health or substance misuse needs present with complex needs which cannot easily be measured by questionnaires or checklists which are often based on simple and straightforward populations of patients.

The importance of this paper is that it highlights the need for clinicians to understand the tools they use rather than rely blindly on the support given to such tools by evidence‐based practice research findings.

This theoretical review paper examines the applicability of assessment tools, guidelines and protocols in mental health and substance use care on the basis of the construction of such tools and their reliance on aggregate and actuarial methodologies. Evidence‐based practice leads clinicians to increasing reliance on tools for assessment of health status, risk and prediction for a range of clinical needs for individual clients. In the longer‐term management of people with enduring and chronic mental health and substance misuse problems, clinicians are often dealing with complex and unstable health needs. The tools available, however, are developed on the basis of majority population evidence and on presumptions of similarity and stability over time. This paper provides explanation of the basis for the development of such tools and argues that clinicians need to be able to evaluate the applicability of tools used for their clients and not just evaluate the internal validity of the tools used to make individual and contextual decisions about individual clients.
Genetic ablation of a Maurer's cleft protein prevents assembly of the Plasmodium falciparum virulence complex
Authors: Dixon Matthew W. A. , Kenny Shannon , McMillan Paul J. , Hanssen Eric , Trenholme Katharine R. , Gardiner Donald L. , Tilley Leann
Published: June 2011

The malaria parasite Plasmodium falciparum assembles knob structures underneath the erythrocyte membrane that help present the major virulence protein, P. falciparum erythrocyte membrane protein‐1 (PfEMP1). Membranous structures called Maurer's clefts are established in the erythrocyte cytoplasm and function as sorting compartments for proteins en route to the RBC membrane, including the knob‐associated histidine‐rich protein (KAHRP), and PfEMP1. We have generated mutants in which the Maurer's cleft protein, the ring exported protein‐1 (REX1) is truncated or deleted. Removal of the C‐terminal domain of REX1 compromises Maurer's cleft architecture and PfEMP1‐mediated cytoadherance but permits some trafficking of PfEMP1 to the erythrocyte surface. Deletion of the coiled‐coil region of REX1 ablates PfEMP1 surface display, trapping PfEMP1 at the Maurer's clefts. Complementation of mutants with REX1 partly restores PfEMP1‐mediated binding to the endothelial cell ligand, CD36. Deletion of the coiled‐coil region or complete deletion of REX1 is tightly associated with the loss of a subtelomeric region of chromosome 2, encoding KAHRP and other proteins. A KAHRP–green fluorescent protein (GFP) fusion expressed in the REX1‐deletion parasites shows defective trafficking. Thus, loss of functional REX1 directly or indirectly ablates the assembly of the P. falciparum virulence complex at the surface of host erythrocytes.
Involvement of protein acetylation in glucose‐induced transcription of a stress‐responsive promoter
Authors: Lima Bruno P. , Antelmann Haike , Gronau Katrin , Chi Bui Khanh , Becher Dörte , Brinsmade Shaun R. , Wolfe Alan J.
Published: June 2011

In eukaryotes, lysine acetylation is a well‐established post‐translational modification that has been implicated in virtually all aspects of eukaryotic physiology. Although homologues of the enzymes that catalyse protein acetylation are widely conserved and distributed among bacterial species, not much is known about the impact of protein acetylation on bacterial physiology. Here, we present evidence that the Gcn5‐like acetyltransferase YfiQ and the sirtuin deacetylase CobB play crucial roles in the transcription regulation of the periplasmic stress‐responsive promoter cpxP when cells of Escherichia coli grow in the presence of glucose, an environment that induces protein acetylation. Under this growth condition, several acetylation sites were detected on three of the RNA polymerase subunits: β, β′ and α. We focused on acetylations of the carboxy‐terminal domain (CTD) of α because of its relative small size and its limited acetylation. We determined that K298 of α is acetylated in a glucose and YfiQ‐dependent manner and that K298 is specifically required for glucose‐induced cpxP transcription. Because the αCTD aids in promoter recognition by RNA polymerase, we propose its acetylation may influence bacterial physiology through effects on gene expression.
ppGpp in Sinorhizobium meliloti: biosynthesis in response to sudden nutritional downshifts and modulation of the transcriptome
Authors: Krol Elizaveta , Becker Anke
Published: June 2011

Sinorhizobium meliloti Rm2011 responds to sudden shifts to nitrogen or carbon starvation conditions by an accumulation of the stringent response alarmone ppGpp and remodelling of the transcriptome. The gene product of relA, RelSm, responsible for synthesis of ppGpp, shows functional similarities to E. coli SpoT. Using promoter–egfp gene fusions, we showed that in Rm2011 relA is expressed at a low rate, as a readthrough from the rpoZ promoter and from its own weak promoter. The low level of relA expression is physiologically relevant, since overexpression of RelSm inhibits ppGpp accumulation. The N‐terminal portion of RelSm is required for ppGpp degradation in nutrient‐sufficient cells and might be involved in regulation of the ppGpp synthase and hydrolase activities of the protein. Expression profiling of S. meliloti subjected to sudden nitrogen or carbon downshifts revealed that repression of ‘house‐keeping’ genes is largely dependent on relA whereas activation of gene targets of the stress sigma factor RpoE2 occurred independently of relA. The regulatory genes nifA, ntrB, aniA and sinR, as well as genes related to modulation of protein biosynthesis and nucleotide catabolism, were induced in a relA‐dependent manner. dksA was required for the majority of the relA‐dependent regulations.
Post‐mortem findings in 10 patients with presumed normal‐pressure hydrocephalus and review of the literature
Authors: Leinonen V. , Koivisto A. M. , Savolainen S. , Rummukainen J. , Sutela A. , Vanninen R. , Jääskeläinen J. E. , Soininen H. , Alafuzoff I.
Published: June 2011

V. Leinonen, A. M. Koivisto, S. Savolainen, J. Rummukainen, A. Sutela, R. Vanninen, J. E. Jääskeläinen, H. Soininen and I. Alafuzoff (2012) Neuropathology and Applied Neurobiology38, 72–86

Post‐mortem findings in 10 patients with presumed normal‐pressure hydrocephalus and review of the literature

Aims: Neuropathological features of idiopathic normal‐pressure hydrocephalus (iNPH) are poorly characterized. Brain biopsy during life may help in the differential diagnosis of dementia, but post‐mortem validation of biopsy findings is scarce. Here we review and report brain biopsy and post‐mortem neuropathological findings in patients with presumed NPH. Methods: We evaluated 10 patients initially investigated by intraventricular pressure monitoring and a frontal cortical biopsy for histological and immunohistochemical assessment as a diagnostic procedure for presumed NPH. Results: Out of the 10 patients, eight were shunted and seven benefited. Until death, six had developed severe and two mild cognitive impairment. One was cognitively unimpaired, and one was mentally retarded. Three subjects displayed amyloid‐β (Aβ) aggregates in their frontal cortical biopsy obtained at the initial procedure. One of these patients developed Alzheimer's disease during a follow‐up time of nearly 10 years. One patient with cognitive impairment and NPH suffered from corticobasal degeneration. In six patients various vascular lesions were seen at the final neuropathological investigation. Five of them were cognitively impaired, and in four vascular lesions were seen sufficient in extent to be considered as causative regarding their symptoms. Conclusions: The frequent finding of vascular pathology in NPH is intriguing, suggesting that vascular alterations might be causative of cognitive impairment in a notable number of patients with NPH and dementia. Brain biopsy can be used to detect Aβ aggregates, but neuropathological characteristics of iNPH as a distinct disease still need to be discovered.
Smith–Lemli–Opitz syndrome among Arabs
Authors: Al‐Owain M , Imtiaz F , Shuaib T , Edrees A , Al‐Amoudi M , Sakati N , Al‐Hassnan Z , Bamashmous H , Rahbeeni Z , Al‐Ameer S , Faqeih E , Meyer B , Al‐Hashem A , Garout W , Al‐Odaib A , Rashed M , Al‐Aama JY
Published: June 2011

Al‐Owain M, Imtiaz F, Shuaib T, Edrees A, Al‐Amoudi M, Sakati N, Al‐Hassnan Z, Bamashmous H, Rahbeeni Z, Al‐Ameer S, Faqeih E, Meyer B, Al‐Hashem A, Garout W, Al‐Odaib A, Rashed M, Al‐Aama JY. Smith–Lemli–Opitz syndrome among Arabs.

Smith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive disorder of variable presentation caused by the deficiency of the 3β‐ hydroxycholesterol Δ7‐ reductase. Over the past 10 years, our biochemical laboratory has screened 191 plasma samples for possible SLOS, measuring the plasma cholesterol and 7‐dehydrocholesterol using gas chromatography–mass spectrometry (GC‐MS). The SLOS was confirmed in only five Arab patients with growth retardation, global developmental delay, dysmorphic features, and 2–3 toe syndactyly, among other findings. All cases represented moderate to severe form of SLOS. One patient had a unique cardiovascular malformation (cor triatriatum with significant obstruction of the right pulmonary veins). Two previously reported N287K (861 C>A) and R352Q (1055 G>A) and a novel R352L (1055 G>T) mutations were identified in the DHCR7 gene in these patients. The paper sheds light on this rare disease among Arabs and reviews all reported SLOS cases in the Arab population.
De novo CDH1 mutation in a family presenting with early‐onset diffuse gastric cancer
Authors: Shah MA , Salo‐Mullen E , Stadler Z , Ruggeri JM , Mirander M , Pristyazhnyuk Y , Zhang L
Published: June 2011

Shah MA, Salo‐Mullen E, Stadler Z, Ruggeri JM, Mirander M, Pristyazhnyuk Y, Zhang L. De novo CDH1 mutation in a family presenting with early‐onset diffuse gastric cancer.

In this report, we describe the first concluded case of a de novo germline mutation in CDH1 in a hereditary diffuse gastric cancer (HDGC) kindred. The incident case was a woman with a personal history of Hodgkin's lymphoma and diffuse gastric cancer, who was then confirmed to have a CDH1 mutation (c.1792 C>T (R598X)). The patient's mother was found to have the same CDH1 germline mutation; however, neither maternal grandparent was found to carry the mutation, thus leading to a conclusion that the proband's mother's mutation is of de novo origin. This case highlights the importance of recognition of the HDGC syndrome and of testing for CDH1 germline mutations in young individuals with diffuse gastric cancer without a family history of the disease.
The use of everolimus in pediatric liver transplant recipients: First experience in a single center
Authors: Nielsen Dirk , Briem‐Richter Andrea , Sornsakrin Marijke , Fischer Lutz , Nashan Bjoern , Ganschow Rainer
Published: June 2011

Nielsen D, Briem‐Richter A, Sornsakrin M, Fischer L, Nashan B, Ganschow R. The use of everolimus in pediatric liver transplant recipients: First experience in a single center.  Pediatr Transplantation 2011: 15: 510–514. © 2011 John Wiley & Sons A/S.

Abstract:  The role of mTOR inhibitors, such as EVL, has not been established for pediatric liver transplant recipients up to now, although data from adult solid organ graft transplantation are very promising. Major complications following pediatric liver transplantation in the long‐term course include chronic graft rejection and CNI‐derived nephrotoxicity. The purpose of our study was to report first results using EVL as a rescue therapy in pediatric liver transplant recipients for the following indications: chronic graft dysfunction n = 12, suspected CNI toxicity n = 3, hepatoblastoma n = 2, and recurrence of primary sclerosing cholangitis post‐Ltx n = 1. Four patients with chronic graft dysfunction developed completely normal liver function tests using EVL, six patients showed partial improvement, and two patients did not respond at all. One patient with CNI‐induced nephropathy showed a slightly improved GFR. Both patients with hepatoblastoma did not develop any metastasis post‐Ltx. First experience with EVL in pediatric liver transplant recipients shows promising results in patients with chronic graft failure when standard immunosuppression has failed. The future role of EVL in immunosuppressive protocols for children post‐Ltx has to be proven by controlled clinical trials.
Adipose‐derived stromal cells cultured in a low‐serum medium, but not bone marrow‐derived stromal cells, impede xenoantibody production
Authors: Saka Yosuke , Furuhashi Kazuhiro , Katsuno Takayuki , Kim Hangsoo , Ozaki Takenori , Iwasaki Kenta , Haneda Masataka , Sato Waichi , Tsuboi Naotake , Ito Yasuhiko , Matsuo Seiichi , Kobayashi Takaaki , Maruyama Shoichi
Published: June 2011

Saka Y, Furuhashi K, Katsuno T, Kim H, Ozaki T, Iwasaki K, Haneda M, Sato W, Tsuboi N, Ito Y, Matsuo S, Kobayashi T, Maruyama S. Adipose‐derived stromal cells cultured in a low‐serum medium, but not bone marrow‐derived stromal cells, impede xenoantibody production. Xenotransplantation 2011; 18: 184–196. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  Although the immunomodulatory effects of mesenchymal stromal cells (MSC) on T cells have been elucidated, little is known about their effects on B cells. Recently, we have established a novel culture method for adipose‐derived MSC (ASC) using low (2%) serum medium containing fibroblast growth factor‐2. We showed that low serum–cultured ASC (LASC) was superior to high (20%) serum–cultured ASC (HASC) when used in regenerative therapy. The aim of this study was to compare the action of LASC, HASC, and bone marrow‐derived MSC (BM‐MSC), on xenoantibody production by B cells.

Methods:  Adipose‐derived mesenchymal stromal cells and BM‐MSC were obtained from humans or F344 rats and expanded in a low‐serum or a high‐serum culture medium. Proliferation of human peripheral mononuclear cells (PBMC) or rat splenocytes was induced by phytohemagglutinin (PHA) or anti‐IgM‐antibody. These cells were then co‐cultured with LASC, HASC, or BM‐MSC, and cell proliferation was studied. Porcine red blood cells (pRBC) were intraperitoneally injected into Lewis rats, and LASC, HASC, or BM‐MSC obtained from F344 rats were injected intravenously or intraperitoneally. The levels of antibodies (IgM and IgG) against pRBC were examined using flow cytometry.

Results:  Human LASC suppressed PBMC proliferation more effectively than human HASC. Human LASC suppressed both T‐cell and B‐cell proliferation when incubated with PHA (a T‐cell stimulus). However, human LASC did not suppress B‐cell proliferation after incubation with anti‐IgM‐antibody (a T‐cell‐independent stimulus). Rat LASC suppressed PHA‐stimulated splenocyte proliferation more effectively than rat HASC or rat BM‐MSC. In vivo studies showed that intravenous injection of rat LASC significantly reduced the levels of IgG antibodies against pRBC, while intravenous administration of the other two types of MSC (rat HASC or rat BM‐MSC) or intraperitoneal administration of rat LASC did not impede IgG production. A significant number of LASC were observed in the spleen when injected intravenously while only a few LASC were observed when given intraperitoneally.

Conclusions:  Administration of LASC effectively impeded xenoantibody production by B cells through the inhibition of T‐cell function, while HASC or BM‐MSC showed less promising effects. These results suggest that intravenous injection of LASC may be useful in attenuating antibody‐mediated rejection.
Clinical pig liver xenotransplantation: how far do we have to go?
Authors: Ekser Burcin , Gridelli Bruno , Veroux Massimiliano , Cooper David K.C.
Published: June 2011

Ekser B, Gridelli B, Veroux M, Cooper DKC. Clinical pig liver xenotransplantation: how far do we have to go? Xenotransplantation 2011; 18: 158–167. © 2011 John Wiley & Sons A/S.

Abstract:  As pigs are currently the preferred species for organ xenotransplantation, initial experience in liver xenotransplantation with wild‐type (WT) pigs, advances in the development of genetically modified pigs, and recent studies using livers from them are reviewed. The xenotransplantation of livers from pigs transgenic for the human complement regulatory protein (CRP) CD55 or from α1,3‐galactosyltransferase gene‐knockout pigs+/− additionally transgenic for the CRP CD46 (GTKO/CD46 pigs) is associated with the survival of approximately 1 week. Satisfactory hepatic function has been documented, lending support to the concept that the pig liver might provide a bridge to allotransplantation. However, although significant features of rejection have not been documented, the development of an immediate thrombocytopenia after graft reperfusion is problematic and leads to spontaneous hemorrhage within the body cavities, native organs, and graft. Current studies are being directed to understand the factors causing the activation, aggregation, or phagocytosis of platelets, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes, and Kupffer cells. If this problem can be resolved, a clinical trial of pig liver xenotransplantation as a bridge to allotransplantation may be both feasible and justified.