bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza virus infection induces cellular Ebp1 gene expression
Authors: Ejima Miho , Kadoi Koji , Honda Ayae
Published: July 2011

Influenza virus RNA‐dependent RNA polymerase is composed of three viral proteins, PB1, PB2, and PA. The host protein Ebp1 (ErbB3‐binding protein1) interacts with PB1, and inhibits both in vitro RNA synthesis and virus replication. On Western blotting, the induction of Ebp1 was observed after influenza virus infection. To understand the induction of Ebp1 by influenza virus infection, we introduced a series of deletions within the 981‐nucleotide long sequence located upstream of the Ebp1 gene (−664 to +317 nt from the transcription initiation site) and ligated them to the GFP gene. GFP expression assays indicated that the 981‐nt upstream region was required for expression of GFP in not all cells but some cells. Microscopic analysis of the transformants showed that GFP expression was up‐regulated by the influenza virus infection. Furthermore, quantitative real‐time PCR indicated that influenza virus infection induced Ebp1 mRNA expression. Our data showed that (i) the newly synthesized vRNP of influenza virus induces Ebp1 expression; (ii) the Ebp1 promoter localizes between −664 nt and the initiation site of the Ebp1 gene, +317‐nt long sequence in the noncoding region is required for regulation of Ebp1 gene expression; and (iii) Ebp1 expression level is correlated with virus protein expression level.
Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1
Authors: Koebis Michinori , Ohsawa Natsumi , Kino Yoshihiro , Sasagawa Noboru , Nishino Ichizo , Ishiura Shoichi
Published: July 2011

Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by a CTG repeat expansion in the 3′‐UTR of dystrophia myotonica‐protein kinase. Aberrant regulation of alternative splicing is a characteristic feature of DM. Dozens of genes have been found to be abnormally spliced; however, few reported splicing abnormalities explain the phenotypes of DM1 patients. Thus, we hypothesized that other, unknown abnormal splicing events exist. Here, by using exon array, we identified aberrant inclusion of myomesin 1 (MYOM1) exon 17a as a novel splicing abnormality in DM1 muscle. A cellular splicing assay with a MYOM1 minigene revealed that not only MBNL1‐3 but also CELF1 and 2 decreased the inclusion of MYOM1 exon 17a in HEK293T cells. Expression of expanded CUG repeat impeded MBNL1 activity but did not affect CELF1 activity on the splicing of MYOM1 minigene. Our results suggest that the downregulation of MBNL proteins should lead to the abnormal splicing of MYOM1 exon 17a in DM1 muscle.
Rates and timing of nitrogen fertilizer application on yield, nutritive value and nutrient‐use efficiency of early‐ and late‐sown forage maize
Authors: Islam M. R. , Garcia S. C.
Published: July 2011

The outcomes of previous studies have resulted in differing recommendations on the rate and timing of fertilizer N applications for forage maize. In order to gain an improved understanding of the role of N fertilizer, a field experiment was carried out to investigate the effects of time and rate of N application on total and plant‐fraction yield, nutritive value and efficiency of nutrient utilization in early‐ and late‐sown forage maize. Treatments included two sowing dates (early, late), two rates of N (0, 135 kg ha−1) applied pre‐sowing (N1) and three rates of N (0, 79, 158 kg ha−1) applied post‐sowing (N2) at the six‐leaf stage (V6). Application of N at N1 (N0 vs. N135) increased dry‐matter (DM) stover yield by 11% and total yield by 7%. Application of fertilizer N at N2 (N0 vs. N158) increased grain yield by 44% and total yield by 34%. Application of N2 also increased irrigation and total water‐use efficiency (WUE) from 30 to 40 and 46 to 61 kg DM ml−1 water respectively. Late sowing increased DM yield by 6%, but decreased WUE compared with early sowing. The results indicate that application of N at both N1 and N2 is essential to maximize total DM yield from forage maize, but application at V6 is recommended when N input is reduced.
Exploring internet needs and use among adolescents with haemophilia: a website development project
Authors: STERLING L. , NYHOF‐YOUNG J. , BLANCHETTE V. S. , BREAKEY V. R.
Published: July 2011

Summary.  Youth frequently access health information online, yet little is known about internet use among adolescents with haemophilia (AWH). A youth‐centred, age‐appropriate online programme is being developed to address the heightened educational needs of AWH as they transit from paediatric to adult care. To describe internet needs and use among AWH treated at the Hospital for Sick Children and determine the features that would make the website useable and desirable for this population. Semi‐structured interviews addressed participants’ internet use and thoughts about a website for AWH. The interviews were audio‐recorded and transcribed verbatim. Three independent reviewers coded the data to determine descriptive categories and grouped them into themes. Eleven of 12 subjects approached consented to interviews. Data saturation was achieved. Most participants had used the internet to find haemophilia information, although none could recall specific websites they had visited for information. Some felt more comfortable using the internet than asking health care providers. Others liked the 24/7 availability of the internet if questions arose. Overall, they felt a website for AWH would help them to learn about haemophilia and explain it to others. Online social networking with an older peer mentor with haemophilia, as well as with others of their age was cited as a potentially valuable source of support. AWH are interested in a haemophilia website and have identified a variety of features which they believe may help to support them during transition to adult care and beyond. Website development is ongoing.
Characterisation of zein–oleic acid films and applications in fruit coating
Authors: Scramin Juliana A. , de Britto Douglas , Forato Lucimara A. , Bernardes‐Filho Rubens , Colnago Luiz A. , Assis Odilio B. G.
Published: July 2011

Pure zein films are known to be very hydrophobic, but are inappropriate for edible coating applications because of their brittle nature. In an attempt to improve the flexibility of these coatings, the influence of low concentrations of oleic acid (OA) as a plasticiser on mechanical, topographical and wetting properties of zein thin films was evaluated. Films were first obtained by casting from aqueous ethanol solutions with 4.0% in mass of zein and additions of 0%; 0.25%; 0.50%; and 1.0% (w/w) of OA. The results indicate an improvement in mechanical properties with increasing plasticiser leading to a reduction in the elastic modulus. An increase in the elongation at break has been observed, but with minor influence on tensile strength. All plasticised zein films have similar initial contact angle (approximately 69°) with a time‐dependent receding drop behaviour. An increase in plasticiser concentration increases film’s affinity towards water. As measured by atomic force microscopy, a consistent linear relation (R2 = 0.991) was estimated between film composition and surface adhesion and consequently on the hydrophilicity. Surface topography also varied with plasticiser addition, becoming smoother as the OA concentration increases. When tested as an edible coating on pears (Pyrus communis L.), a formulation with 0.25% wt of plasticiser achieved the best results in preserving the pear mass as measured during the evaluated storage time (12 days) at room temperature. A 0.5% concentration of plasticiser had no influence and higher amounts resulted in a reduction in fruit protection.
In discourse: Bourdieu’s theory of practice and habitus in the context of a communication‐oriented nursing interaction model
Authors: Sieger Margot , Fritz Elfriede , Them Christa
Published: July 2011

sieger m., fritz e. & them c. (2012) In discourse: Bourdieu’s theory of practice and habitus in the context of a communication‐oriented nursing interaction model. Journal of Advanced Nursing 68(2), 480–489.

Aims.  This paper presents a discussion on the potential of the theories of practice and habitus as espoused by the sociologist Bourdieu.

Background.  The interaction between nurses and patients is a constitutive element in the nursing process and a central aspect in the theories developed by Paterson and Zderad, and Orlando. Bourdieu′s theory of habitus and practices assists in understanding and explaining differentiated results concerning nurse–patient interaction.

Data sources.  In a study on interactions with paraplegic patients, distinguished levels of interactions, which show considerable diversity among one another, could be identified. The data were collected over a period of 20 months in 2004–2006. The results present the central topics of interaction and show that understanding‐oriented interaction is rare.

Discussion.  Communicative acting in nursing always takes place in a social context. In the interaction with patients, nurses assign a higher distinctive value to the standardized concepts of care facilities than to the actually perceived need of care. An understanding‐oriented interaction assumes that the nurses with their own contributions, themes and authorities, prove themselves in the eyes of the patient. It is expected from nurses that they habitualize their own concepts so that they can be represented in a convincing manner.

Conclusion.  If an understanding‐oriented interaction is to extend into the practice of nursing, it is of crucial importance that both interaction partners assure each other how and with what capital their interaction is to be realized. Nurses need professional habitus to become agents in the social field of health.
Multimodal dynamic response of the Buchnera aphidicola pLeu plasmid to variations in leucine demand of its host, the pea aphid Acyrthosiphon pisum
Authors: Viñuelas José , Febvay Gérard , Duport Gabrielle , Colella Stefano , Fayard Jean‐Michel , Charles Hubert , Rahbé Yvan , Calevro Federica
Published: July 2011

Aphids, important agricultural pests, can grow and reproduce thanks to their intimate symbiosis with the γ‐proteobacterium Buchnera aphidicola that furnishes them with essential amino acids lacking in their phloem sap diet. To study how B. aphidicola, with its reduced genome containing very few transcriptional regulators, responds to variations in the metabolic requirements of its host, we concentrated on the leucine metabolic pathway. We show that leucine is a limiting factor for aphid growth and it displays a stimulatory feeding effect. Our metabolic analyses demonstrate that symbiotic aphids are able to respond to leucine starvation or excess by modulating the neosynthesis of this amino acid. At a molecular level, this response involves an early important transcriptional regulation (after 12 h of treatment) followed by a moderate change in the pLeu plasmid copy number. Both responses are no longer apparent after 7 days of treatment. These experimental data are discussed in the light of a re‐annotation of the pLeu plasmid regulatory elements. Taken together, our data show that the response of B. aphidicola to the leucine demand of its host is multimodal and dynamically regulated, providing new insights concerning the genetic regulation capabilities of this bacterium in relation to its symbiotic functions.
The GABRIEL Advanced Surveys: study design, participation and evaluation of bias
Authors: Genuneit Jon , Büchele Gisela , Waser Marco , Kovacs Katalin , Debinska Anna , Boznanski Andrzej , Strunz‐Lehner Christine , Horak Elisabeth , Cullinan Paul , Heederik Dick , Braun‐Fahrländer Charlotte , von Mutius Erika ,   the GABRIELA Study Group
Published: July 2011

Genuneit J, Büchele G, Waser M, Kovacs K, Debinska A, Boznanski A, Strunz‐Lehner C, Horak E, Cullinan P, Heederik D, Braun‐Fahrländer C, von Mutius E, the GABRIELA Study Group. The GABRIEL Advanced Surveys: study design, participation and evaluation of bias. Paediatric and Perinatal Epidemiology 2011; 25: 436–447.

Exposure to farming environments has been shown to protect substantially against asthma and atopic disease across Europe and in other parts of the world. The GABRIEL Advanced Surveys (GABRIELA) were conducted to determine factors in farming environments which are fundamental to protecting against asthma and atopic disease.

The GABRIEL Advanced Surveys have a multi‐phase stratified design. In a first‐screening phase, a comprehensive population‐based survey was conducted to assess the prevalence of exposure to farming environments and of asthma and atopic diseases (n = 103 219). The second phase was designed to ascertain detailed exposure to farming environments and to collect biomaterial and environmental samples in a stratified random sample of phase 1 participants (n = 15 255). A third phase was carried out in a further stratified sample only in Bavaria, southern Germany, aiming at in‐depth respiratory disease and exposure assessment including extensive environmental sampling (n = 895).

Participation rates in phase 1 were around 60% but only about half of the participating study population consented to further study modules in phase 2. We found that consenting behaviour was related to familial allergies, high parental education, wheeze, doctor diagnosed asthma and rhinoconjunctivitis, and to a lesser extent to exposure to farming environments. The association of exposure to farm environments with asthma or rhinoconjunctivitis was not biased by participation or consenting behaviour.

The GABRIEL Advanced Surveys are one of the largest studies to shed light on the protective ‘farm effect’ on asthma and atopic disease. Bias with regard to the main study question was able to be ruled out by representativeness and high participation rates in phases 2 and 3. The GABRIEL Advanced Surveys have created extensive collections of questionnaire data, biomaterial and environmental samples promising new insights into this area of research.
Fusarium oxysporum Fo47 confers protection to pepper plants against Verticillium dahliae and Phytophthora capsici, and induces the expression of defence genes
Authors: Veloso J. , Díaz J.
Published: July 2011

The application of the nonpathogenic isolate Fusarium oxysporum 47 (Fo47) reduced the symptoms of verticillium wilt, phytophthora root rot and phytophthora blight in pepper plants. Botrytis cinerea was also tested on the leaves of plants treated with Fo47, but no protection was observed. Verticillium dahliae colonies cultured in the presence of Fo47 grew slower than control cultures, but Phytophthora capsici growth was unaffected by Fo47. At least part of the protection effect observed against V. dahliae could therefore be due to antagonism or competition. In order to search for induced resistance mechanisms, three defence genes previously related to pepper resistance were monitored over time. These genes encode a basic PR‐1 protein (CABPR1), a class II chitinase (CACHI2) and a sesquiterpene cyclase (CASC1) involved in the synthesis of capsidiol, a phytoalexin. These three genes were transiently up‐regulated in the roots by Fo47 in the absence of inoculation with the pathogen, but in the stem only CABPR1 was up‐regulated. In plants that were inoculated with V. dahliae after the Fo47 treatment, the three genes had a higher relative expression level than the control in both the roots and the stem.
Incidence and risk factors for infections after liver transplant: single‐center experience at the University Hospital Fundación Santa Fe de Bogotá, Colombia
Authors: Vera A. , Contreras F. , Guevara F.
Published: July 2011

A. Vera, F. Contreras, F. Guevara. Incidence and risk factors for infections after liver transplant: single‐center experience at the University Hospital Fundación Santa Fe de Bogotá, Colombia. Transpl Infect Dis 2011: 13: 608–615. All rights reserved

Abstract: The incidence of infections in liver transplant patients is higher compared with recipients of other organs, and infections are one of the major complications after transplantation. The aim of our study was to evaluate the incidence, presentation and risk factors of infections in liver transplant recipients in a Latin‐American population, and to compare the results with data worldwide. We performed a retrospective analysis of 94 consecutive patients undergoing liver transplantation between 2004 and 2008 at the University Hospital Fundación Santa Fe de Bogotá, Colombia. The patients contributed a total of 64.4 person years (PY). Fifty‐two patients (55.3%) developed one or more infections, in total 83 events (128.9 infections/100 PY). Bacterial infections represented the most frequent event (71.1%), followed by viral (19.3%) and fungal infections (8.4%). In 1%, no causative organism was identified. More than one‐third of infections (37%) occurred during the first 30 days, whereas 83% of all events were seen during the first 6 months. The most common site of pathogen localization was the bloodstream (25.3%), followed by the urinary tract (15.7%), liver with bile tract (14.5%), abdomen (10.8%), surgical site (7.2%), and lungs (9.6%). The overall mortality after 1 year was 14.9%, and 57.1% of the deaths were attributed to infections. We found that risk factors significantly associated with increased incidence rate ratio for infection were prolonged stay at the intensive care unit, the need for parenteral nutrition, and blood transfusion requirement. Our data provide additional information about etiology and epidemiology of infections after liver transplantation.
Tobramycin pharmacokinetics in patients with cystic fibrosis before and after bilateral lung transplantation
Authors: Walsh K.A. , Davis G.A. , Hayes D. Jr , Kuhn R.J. , Weant K.A. , Flynn J.D.
Published: July 2011

K.A. Walsh, G.A. Davis, D. Jr Hayes, R.J. Kuhn, K.A. Weant, J.D. Flynn. Tobramycin pharmacokinetics in patients with cystic fibrosis before and after bilateral lung transplantation. Transpl Infect Dis 2011: 13: 616–621. All rights reserved

Study objectives. To compare the pharmacokinetics (PK) of tobramycin in patients with cystic fibrosis (CF) before and after bilateral lung transplantation, in order to evaluate optimal dosing practices post transplant.

Design. Retrospective, single‐center, chart review study, in which tobramycin concentrations from CF patients were used to calculate PK parameters, including elimination rate constant, half‐life, volume of distribution (Vd), area under the curve (AUC), and clearance before and after lung transplantation.

Setting. Medical school‐affiliated teaching hospital.

Patients. Eight patients with CF, who received a bilateral lung transplant from January 1, 2005 through August 1, 2009 (4 males, 4 females; mean age 26.3 years).

Interventions. None.

Main results. Sixty‐nine sets of pre‐ (n=52) and post transplant (n=17) tobramycin concentrations were available. PK parameters were significantly altered post transplant. Elimination rate constant decreased 38% from 0.26±0.1 to 0.16±0.1 h‐1 (P<0.001), with a related increase of 200% in half‐life from 2.8±0.8 to 8.4±8.7 h (P<0.001). Clearance decreased 25% post transplant from 67.3±32.3 to 50.2±15.9 mL/min (P=0.04). No statistically significant change occurred in AUC or Vd after transplant, although a trend was seen toward increased Vd. Dosage requirements after transplantation were significantly lower, 10.7±2.5 and 7.6±1.6 mg/kg/day, pre and post transplant, respectively (P<0.001). Concentrations were also evaluated in 2 time periods: 0–3 weeks and ≥6 weeks post transplant, based on available data. Clearance and Vd ≥6 weeks post transplant did not significantly differ from pre‐transplant values (P=0.28 and 0.54, respectively), suggesting that these changes may be temporary.

Conclusions. The results suggest that tobramycin PK are altered in patients with CF after bilateral lung transplantation, although no clear trend was seen owing to inter‐patient variability. We propose that PK parameters should be reassessed during each treatment course post transplant.
Safety evaluation of self‐expanding metallic biliary stents eluting gemcitabine in a porcine model
Authors: Chung Moon Jae , Kim Hyunki , Kim Kyung Sik , Park Sangsoo , Chung Jae Bock , Park Seung Woo
Published: July 2011

Background and Aim:  Palliative biliary decompression by metal stent is the treatment of choice for unresectable malignant biliary obstruction; however, conventional stents provide only mechanical palliation and exert no anti‐tumor effects. Gemcitabine (GEM) has been reported to be more effective in unresectable pancreatic cancer and biliary cancer compared with other chemotherapeutic drugs. We evaluated the safety of a GEM‐eluting stent by analyzing histologic responses of the porcine bile duct.

Methods:  Stents containing GEM (0%, 10%, 15%, and 20% [w/v]) were surgically inserted into bile ducts of pigs (each group, n = 2). The animals were euthanized after 4 weeks, and the stented bile duct segment underwent gross and microscopic examination. Laboratory assay was performed for aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, and gamma‐glutamyl transferase (γ‐GTP).

Results:  Moderate to severe inflammation was observed in the bile ducts in contact with stents containing 15 and 20% GEM, compared with no inflammation with 0% GEM and mild inflammation with 10% GEM. Fibrous reactions observed in the submucosal layer did not differ among groups. Transmural necrosis and perforations were not observed in any animal. No abnormal laboratory test findings were directly caused by GEM.

Conclusion:  Our newly developed GEM eluting stents can be used safely in normal bile ducts. Our results indicated that 10% GEM produced mild histologic changes in the stented segment and adjacent tissue; this concentration may be appropriate for clinical application.
Colorectal cancer screening practise is influenced by ethnicity of medical practitioner and patient
Authors: Koo Jenn Hian , You Matthew Yibin , Liu Ken , Athureliya Maneesha D , Tang Catherine W Y , Redmond Diane M , Connor Susan J , Leong Rupert W L
Published: July 2011

Background and Aim:  Colorectal cancer (CRC) screening improves survival and requires appropriate recommendation by general practitioners (GPs). Screening practises may be influenced by barriers related to ethnicity and training.

Methods:  A mail survey assessed GPs' practises and the barriers towards CRC screening. The association of screening practises and demography, including GP ethnicity, medical training and practise characteristics, were evaluated.

Results:  Of 212 GPs (median age 54 years, 73% men, 27% Caucasian, 38% foreign graduates), 87% agreed that fecal occult blood test (FOBT) screening improved survival in the average‐risk patient. Considerable variations existed in the starting age (40–49 years: 31%; 50 years: 65%) and frequency (1–2 years: 77%; 3–5 years: 22%) of screening. FOBT was used for indications other than screening: anemia (59%), altered bowel habits (54%), abdominal pain (24%), and rectal bleeding (23%), and these were significantly more frequent in Asian GPs independent of medical training. GPs were less likely to recommend screening to immigrants, and most reported that immigrants were less likely to participate. More Asian and Middle Eastern GPs reported a major barrier with FOBT inaccuracy compared with Caucasian GPs (22% vs 9%, P = 0.03; and 27% vs 9%, P = 0.03, respectively).

Conclusions:  Considerable differences existed in GPs' CRC screening practises. Indications for use of FOBT and the subsequent investigation of a positive FOBT also varied according to GPs' ethnicity, independent of medical training. Patient's ethnicity and associated language and cultural barriers may affect screening uptake, which may negatively affect the health of immigrants. Resources and culture‐specific interventions are recommended to improve overall screening participation.
Effect of melatonin and misoprostol on bacterial translocation in portal hypertensive rats
Authors: Topuz Ömer , İlhan Yavuz Selim , Doğru Osman , Aygen Erhan , Sözen Selim
Published: July 2011

Background and Aim:  Portal hypertension is the main complication of cirrhosis and it is responsible for its most common complications. Bacterial translocation increases the morbidity and mortality rates in patients with portal hypertension. We aimed to investigate the effects of melatonin and misoprostol on bacterial translocation induced by portal hypertension.

Methods:  We established four groups, each containing eight rats. Except for the control and sham groups, the animals in the other groups (treatment groups) received misoprostol or melatonin for 3 days after the first operation. In the sham group, a laparotomy was carried out and only the portal vein was dissected. Calibrated portal vein ligation was carried out in the other groups. All animals were given 1010Escherichia coli by orogastric intubation 12 h before sampling. Seventy‐two hours after the first operation, mesenteric lymph node and blood samples were obtained and cultured. Two cc blood samples were obtained for a polymerase chain reaction study. A piece of terminal ileum was also sampled for histopathologic examination.

Results:  Mesenteric lymph node and blood cultures of all control animals were positive for microbiological growth, and polymerase chain reaction results were positive in seven of the eight rats. Histopathologically, edema, vasodilatation and inflammatory cell infiltration were found to be less in the other groups in comparison to the control group. The incidence of bacterial translocation was decreased in all treatment groups as compared to the control group.

Conclusions:  In this study, bacterial translocation occurred in portal hypertension. Melatonin and misoprostol reduced the incidence of bacterial translocation in portal hypertensive rats.
Immediate re‐transplantation following early kidney transplant thrombosis
Authors: PHELAN PAUL J , MAGEE COLM , O'KELLY PATRICK , J O'BRIEN FRANK , LITTLE DILLY , CONLON PETER J
Published: July 2011

Allograft thrombosis is a devastating early complication of renal transplantation that ultimately leads to allograft loss. We report here on our experience of nine cases of immediate re‐transplantation following early kidney transplant thrombosis at a single centre between January 1990 and June 2009. The mean age was 42.9 years at time of transplant. For seven patients, the allograft thrombosis was their first kidney transplant and seven of the nine cases had a deceased donor transplant. The initial transplants functioned for a mean of 1.67 days and the patients received a second allograft at a mean of 3.1 days after graft failure. All of the re‐transplants worked immediately. Four allografts failed after a mean of 52.5 months (2–155 months). Two of these died with a functioning allograft, one failed owing to chronic allograft nephropathy and one owing to persistent acute cellular rejection. The remaining five patients still have a functioning allograft after a mean of 101.8 months (7–187 months). One year allograft and patient survival after re‐transplantation were 87.5% and 100% respectively (after 5 years, both were 57%). Immediate re‐transplantation following early kidney transplant thrombosis can be a success. It may be considered in selected cases after allograft thrombosis.
Pre‐vaccination epidemiology of human papillomavirus infections in Japanese women with abnormal cytology
Authors: Yamasaki Kentaro , Miura Kiyonori , Shimada Takako , Ikemoto Rie , Miura Shoko , Murakami Makoto , Sameshima Tetsuro , Fujishita Akira , Kotera Kouhei , Kinoshita Akira , Yoshiura Koh‐ichiro , Masuzaki Hideaki
Published: July 2011

Aim:  To investigate the pre‐vaccination epidemiology of genital human papillomavirus (HPV) infections and genotypes in women with abnormal cytology in Nagasaki, Japan.

Material and Methods:  We performed Pap smear tests, biopsies and HPV genotype testing in Nagasaki Prefecture from August 2007 through November 2009.

Results:  During the study period, serial samples of uterine cervical specimens were obtained from 539 subjects with abnormal cytology and/or squamous intraepithelial lesions (SIL) confirmed previously, or with clinically suspected invasive cervical cancer. In 119 HPV‐positive subjects with low‐grade SIL, the three most prevalent high‐risk HPV genotypes were HPV52 (21.8%; 26/119), HPV16 (20.2%; 24/119) and HPV56 (17.6%; 21/119). In 199 women, 127 HPV‐positive subjects with high‐grade SIL and 67 HPV‐positive subjects with squamous cell carcinoma (SCC), the three most prevalent high‐risk HPV genotypes were HPV16 (44.3%; 86/194), HPV52 (20.6%; 40/194) and HPV58 (16.0%; 31/194).

Conclusion:  Compared with the distribution of high‐risk HPV genotypes in other countries, HPV52 was a more common genotype in Nagasaki. With disease progression to SCC, the distribution of high‐risk HPV56 belonging to the A6 HPV family decreased, while HPV16 and HPV52 belonging to the A9 HPV family persisted. Our data provide an important resource to address the case for vaccination against HPV genotypes other than HPV16 and HPV18 in Japan.
Relationships between fetal growth and maternal body mass indices, plasma glucose level, and plasma insulin level in Japanese women with mildly impaired glucose tolerance
Authors: Morikawa Mamoru , Cho Kazutoshi , Yamada Takashi , Yamada Takahiro , Shono Rina , Koyama Takahiro , Takeda Masamitsu , Nishida Ryutaro , Minakami Hisanori
Published: July 2011

Aim:  To identify variables which are strongly associated with fetal growth.

Material and Methods:  The study subjects were 203 Japanese women who had a plasma glucose level ≥140 mg/dL (7.8 mmol/L) on a 50‐g glucose challenge test but were normoglycemic when challenged with a 75‐g oral glucose tolerance test (GTT) according to the criteria previously used in Japan. All the subjects subsequently gave birth to singleton infants. The correlations between the standard deviation for birthweight (birthweight SD) and 15 other variables, including the maternal body mass index (BMI), plasma levels of glucose and insulin on the GTT, and various indices calculated using data from the GTT, were then examined. Univariate and multivariate regression analyses were performed.

Results:  Univariate analyses revealed significant correlations between the birthweight SD and the fasting plasma glucose level (P = 0.0063), the pre‐pregnancy BMI (P = 0.0001), and the BMI at delivery (P < 0.0001). Only the BMI at delivery remained as a significant factor that was independently correlated with the birthweight SD after a multivariate regression analysis.

Conclusion:  The suppression of maternal weight gain, rather than the suppression of the plasma glucose level, may be effective for avoiding infants with overgrowth among Japanese women with mildly impaired glucose tolerance.
Evaluation of visual inspection with acetic acid as a feasible screening test for cervical neoplasia
Authors: Hasanzadeh Malihe , Esmaeili Habibollah , Tabaee Samane , Samadi Fariba
Published: July 2011

Aim:  Alternative methods for cervical cancer screening have been sought. One method, direct visualization with acetic acid (VIA), has proven itself in many clinical trials as an adequate alternative to Pap‐smears in developing countries. This study was designed to assess if visual inspection with acetic acid (VIA test) could be an appropriate alternative method for cervical cancer screening. Therefore, we compared VIA, as a stand‐alone test, with the gold standard test (colposcopy) in detecting significant cervical pathology in our setting.

Materials and Methods:  The study population consisted of the women who attended the Gynecological Clinic in Ghaem Hospital from April 2008 to April 2009. All of them were tested with VIA. Then, 100 test‐positive women and 100 test‐negative women were randomly selected and underwent cytology and colposcopy. Cervical biopsies were conducted for the women with abnormal colposcopic findings. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for each test and then were compared.

Results:  Sixty‐nine women in the VIA‐positive group and 61 women in the VIA‐negative group had abnormal cytology. After studying the biopsies, 58 women with positive VIA, and two women with negative VIA had a final diagnosis of dysplasia. Positive predictive value for VIA and cytology were 58% and 33%, respectively.

Conclusion:  The results of this study indicate that VIA may be a useful and feasible alternative screening test for cervical precancerous and cancerous lesions.
Prognostic implications of lymph node involvement in bladder cancer: are we understaging using current methods?
Authors: Watts Kara L. , Ristau Benjamin T. , Yamase Harold T. , Taylor III John A.
Published: July 2011

To review the current and newer, alternative methods for evaluating lymph nodes for tumor involvement in bladder cancer as relapse rates for organ‐confined disease remain high despite improvements in surgical technique, suggesting the possibility of understaging. To propose a research agenda based on these findings. A PubMed literature search was performed to identify studies examining the prognostic implications of and outcomes associated with lymph node involvement in bladder cancer as well as those that utilized newer methodologies to identify the possibility for metastatic disease. Lymph node involvement remains one of the strongest predictors of clinical outcome in bladder cancer. Histologic and molecular techniques for identification of lymph node metastasis provide a sensitivity and specificity equal to if not higher than standard pathologic evaluation. Further research into this field would help to elucidate the potential utility of these techniques with regard to proper staging and potential relevance to clinical outcomes.
SOFT BUDGET CONSTRAINT RECONSIDERED
Authors: Vahabi Mehrdad
Published: July 2011

This paper demonstrates that Kornai's original concept of the soft budget constraint (SBC) as a theoretical innovation in micro‐theory disguises income redistributions that are essentially macroeconomic relationships. The SBC also postulates a competitive market economy as the benchmark of hard budget constraint (HBC) and efficiency. A recent formal theory explains the SBC as a component of profit‐maximizing strategic behaviour. From this perspective, the SBC can be integrated into the new microeconomics, but it loses its specific institutional connotation and its macroeconomic dimension. The SBC is thus included in ubiquitous market‐type relationships, particularly complete (optimal) contractual arrangements.
Chemotherapy and targeted agents for colorectal cancer in a real‐life setting anticipate guidelines: the COLCHIC cohort study
Authors: Smith Denis , Terrebonne Eric , Rouyer Magali , Blanc Jean‐Frédéric , Breilh Dominique , Pedeboscq Stéphane , Le Monies Alise , Lecomte Coralie , Lassalle Régis , Moore Nicholas , Fourrier‐Réglat Annie
Published: July 2011

Introduction of new agents for the treatment for colorectal cancer (CRC) has been accompanied by the publication of guidelines. The COLCHIC cohort was set up to evaluate CRC treatment practices and the use of these innovative and expensive agents. Patients initiating CRC treatment at the Bordeaux teaching hospital between 1 March 2005 and 1 March 2006 were identified, and treatment courses from 1 March 2005 to 31 December 2006 were studied; 192 patients were included, 188 with analysable data: 43 patients initiated 51 courses for non‐metastatic cancer, 153 initiated 366 courses for metastatic cancer, eight patients initiated courses for both non‐metastatic and metastatic cancer. Most treatments were used for indications found in guidelines published during the study (83.9%). Of the others, nearly half were approved in guidelines published subsequently. In this teaching hospital, prescribing practice was generally in line with recommendations, with an anticipation of future guidelines. This mostly concerned monoclonal antibodies, which were new at the time of the study.
DISTINGUISHING AMBER AND COPAL CLASSES BY PROTON MAGNETIC RESONANCE SPECTROSCOPY
Authors: LAMBERT J. B. , TSAI C. Y.‐H. , SHAH M. C. , HURTLEY A. E. , SANTIAGO‐BLAY J. A.
Published: July 2011

Fossilized resin, or amber, has been examined from 120 worldwide sources by 1D and 2D proton magnetic resonance spectroscopy in solution. These spectra fall into five categories, corresponding to the classes already established by mass spectrometry and carbon‐13 magnetic resonance spectroscopy. The wide availability of this technique provides a straightforward method to classify amber rapidly and inexpensively.
Stress‐induced anhedonia is associated with an increase in Alzheimer's disease‐related markers
Authors: Briones A , Gagno S , Martisova E , Dobarro M , Aisa B , Solas M , Tordera R , Ramírez MJ
Published: July 2011

BACKGROUND AND PURPOSE Stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD‐related markers.

EXPERIMENTAL APPROACH Anhedonia induced by a chronic mild stress (CMS) procedure, applied for 6 weeks, was used to select rats vulnerable or resistant to stress. Sucrose intake, the Porsolt forced swimming test and cognitive deficits in the novel object recognition test (NORT) were used to characterize vulnerable and resilient rats. The antidepressant venlafaxine (20 mg·kg−1 p.o.) or saline was administered daily during the last 2 weeks of CMS. Biochemical markers affected by stress, PKB, ERK and synaptophysin, and those associated with AD, amyloid β‐protein (Aβ), β‐secretase (BACE1) and τ phosphorylation, were measured in the hippocampus.

KEY RESULTS After CMS, 40% of rats were resistant to the development of anhedonia (CMS‐resistant to stress), whereas the remaining were responsive [CMS‐anhedonic (CMSA)]. Only CMSA rats displayed significant increases in immobility time in the forced swimming test and cognitive deficits in the NORT, and significant decreases in synaptophysin, phosphorylated PKB and phosphorylated ERK1/2 expression in the hippocampus. Increased levels of Aβ40, BACE1 and τ phosphorylation were also found only in CMSA rats. All these effects in CMSA rats were reverted by treatment with venlafaxine.

CONCLUSIONS AND IMPLICATIONS Vulnerability to stress might constitute a risk factor for the development of AD, and pharmacological treatment with venlafaxine may represent a therapeutic strategy for the treatment of stress‐related disorders, including AD.
Cardamonin sensitizes tumour cells to TRAIL through ROS‐ and CHOP‐mediated up‐regulation of death receptors and down‐regulation of survival proteins
Authors: Yadav Vivek R , Prasad Sahdeo , Aggarwal Bharat B
Published: July 2011

BACKGROUND AND PURPOSE TNF‐related apoptosis‐inducing ligand (TRAIL) is currently in clinical trials as a treatment for cancer, but development of resistance is a major drawback. Thus agents that can overcome resistance to TRAIL are urgently needed. Cardamonin (2′,4′‐dihydroxy‐6′‐methoxychalcone) has been shown to affect cell growth by modulating various cell signalling pathways. Hence, we investigated the effect of cardamonin on the actions of TRAIL.

EXPERIMENTAL APPROACH The effect of cardamonin on TRAIL was measured by plasma membrane integrity, phosphatidylserine exposure, mitochondrial activity, and activation of caspase‐8, caspase‐9, and caspase‐3 in human colon cancer cells.

KEY RESULTS Cardamonin potentiated TRAIL‐induced apoptosis and this correlated with up‐regulation of both the TRAIL death receptor (DR) 4, 5 at mRNA and protein levels. TRAIL‐decoy receptor DcR1 was down‐regulated by cardamonin. Induction of DRs by cardamonin occurred in a variety of cell types. Gene silencing of the DRs by small interfering RNA (siRNA) abolished the effect of cardamonin on TRAIL‐induced apoptosis, suggesting that sensitization was mediated through the DR. Induction of the DR by cardamonin was p53‐independent but required CCAAT/enhancer binding protein homologous protein (CHOP); cardamonin induced CHOP, and its silencing by siRNA eliminated the induction of DR5. Cardamonin increased the production of reactive oxygen species (ROS) and quenching ROS abolished its induction of receptors and enhancement of TRAIL‐induced apoptosis. Cardamonin also decreased the expression of various cell survival proteins.

CONCLUSIONS AND IMPLICATIONS Cardamonin potentiates TRAIL‐induced apoptosis through ROS‐CHOP‐mediated up‐regulation of DRs, decreased expression of decoy receptor and cell survival proteins. Thus, cardamonin has the potential to make TRAIL more effective as an anticancer therapy.
Trypanosoma cruzi invades host cells through the activation of endothelin and bradykinin receptors: a converging pathway leading to chagasic vasculopathy
Authors: Andrade Daniele , Serra Rafaela , Svensjö Erik , Lima Ana Paula C , Ramos Junior Erivan S , Fortes Fabio S , Morandini Ana Carolina F , Morandi Verônica , Soeiro Maria de N , Tanowitz Herbert B , Scharfstein Julio
Published: July 2011

BACKGROUND AND PURPOSE Independent studies in experimental models of Trypanosoma cruzi appointed different roles for endothelin‐1 (ET‐1) and bradykinin (BK) in the immunopathogenesis of Chagas disease. Here, we addressed the hypothesis that pathogenic outcome is influenced by functional interplay between endothelin receptors (ETAR and ETBR) and bradykinin B2 receptors (B2R).

EXPERIMENTAL APPROACH Intravital microscopy was used to determine whether ETR/B2R drives the accumulation of rhodamine‐labelled leucocytes in the hamster cheek pouch (HCP). Inflammatory oedema was measured in the infected BALB/c paw of mice. Parasite invasion was assessed in CHO over‐expressing ETRs, mouse cardiomyocytes, endothelium (human umbilical vein endothelial cells) or smooth muscle cells (HSMCs), in the presence/absence of antagonists of B2R (HOE‐140), ETAR (BQ‐123) and ETBR (BQ‐788), specific IgG antibodies to each GPCRs; cholesterol or calcium‐depleting drugs. RNA interference (ETAR or ETBR genes) in parasite infectivity was investigated in HSMCs.

KEY RESULTS BQ‐123, BQ‐788 and HOE‐140 reduced leucocyte accumulation in HCP topically exposed to trypomastigotes and blocked inflammatory oedema in infected mice. Acting synergistically, ETAR and ETBR antagonists reduced parasite invasion of HSMCs to the same extent as HOE‐140. Exogenous ET‐1 potentiated T. cruzi uptake by HSMCs via ETRs/B2R, whereas RNA interference of ETAR and ETBR genes conversely reduced parasite internalization. ETRs/B2R‐driven infection in HSMCs was reduced in HSMC pretreated with methyl‐β‐cyclodextrin, a cholesterol‐depleting drug, or in thapsigargin‐ or verapamil‐treated target cells.

CONCLUSIONS AND IMPLICATIONS Our findings suggest that plasma leakage, a neutrophil‐driven inflammatory response evoked by trypomastigotes via the kinin/endothelin pathways, may offer a window of opportunity for enhanced parasite invasion of cardiovascular cells.

LINKED ARTICLE This paper is commented on by D'Orléans‐Juste et al., pp. 1330–1332 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01636.x
A Role for Dynamin in Triggering Ethanol Tolerance
Authors: Krishnan Harish R. , Al‐Hasan Yazan M. , Pohl Jascha B. , Ghezzi Alfredo , Atkinson Nigel S.
Published: July 2011

Background:  A prevailing hypothesis is that the set of genes that underlie the endophenotypes of alcoholism overlap with those responsible for the addicted state. Functional ethanol tolerance, an endophenotype of alcoholism, is defined as a reduced response to ethanol caused by prior ethanol exposure. The neuronal origins of functional rapid tolerance are thought to be a homeostatic response of the nervous system that counters the effects of the drug. Synaptic proteins that regulate neuronal activity are an important evolutionarily conserved target of ethanol.

Methods:  We used mutant analysis in Drosophila to identify synaptic proteins that are important for the acquisition of rapid tolerance to sedation with ethanol. Tolerance was assayed by sedating flies with ethanol vapor and comparing the recovery time of flies after their first sedation and their second sedation. Temperature‐sensitive paralytic mutants that alter key facets of synaptic neurotransmission, such as the propagation of action potentials, synaptic vesicle fusion, exocytosis, and endocytosis, were tested for the ability to acquire functional tolerance at both the permissive and restrictive temperatures.

Results:  The shibire gene encodes Drosophila Dynamin. We tested 2 temperature‐sensitive alleles of the gene. The shits1 allele blocked tolerance at both the permissive and restrictive temperatures, while shits2 blocked only at the restrictive temperature. Using the temperature‐sensitive property of shits2, we showed that Dynamin function is required concomitant with exposure to ethanol. A temperature‐sensitive allele of the Syntaxin 1A gene, Syx1A3–69, also blocked the acquisition of ethanol tolerance.

Conclusions:  We have shown that shibire and Syntaxin 1A are required for the acquisition of rapid functional tolerance to ethanol. Furthermore, the shibire gene product, Dynamin, appears to be required for an immediate early response to ethanol that triggers a cellular response leading to rapid functional tolerance.
Mood and Implicit Alcohol Expectancy Processes: Predicting Alcohol Consumption in the Laboratory
Authors: Wardell Jeffrey D. , Read Jennifer P. , Curtin John J. , Merrill Jennifer E.
Published: July 2011

Background:  Implicit positive alcohol expectancy (PAE) processes are thought to respond phasically to external and internal stimuli—including mood states—and so they may exert powerful proximal influences over drinking behavior. Although social learning theory contends that mood states activate mood‐congruent implicit PAEs, which in turn lead to alcohol use, there is a dearth of experimental research examining this mediation model relative to observable drinking. Moreover, an expectancy theory perspective might suggest that, rather than influencing PAEs directly, mood may moderate the association between PAEs and drinking. To test these models, this study examined the role of mood in the association between implicitly measured PAE processes (i.e., latency to endorse PAEs) and immediate alcohol consumption in the laboratory. Gender differences in these processes also were examined.

Method:  College students (N = 146) were exposed to either a positive, negative, or neutral mood induction procedure, completed a computerized PAE reaction time (RT) task, and subsequently consumed alcohol ad libitum.

Results:  The mood manipulation had no direct effects on drinking in the laboratory, making the mediation hypothesis irrelevant. Instead, gender and mood condition moderated the association between RT to endorse PAEs and drinking in the laboratory. For males, RT to tension reduction PAEs was a stronger predictor of volume of beer consumed and peak blood alcohol concentration in the context of general arousal (i.e., positive and negative mood) relative to neutral mood. RT to PAEs did not predict drinking in the laboratory for females.

Conclusions:  The results show that PAE processes are important determinants of immediate drinking behavior in men, suggesting that biased attention to mood‐relevant PAEs—as indicated by longer RTs—predicts greater alcohol consumption in the appropriate mood context. The findings also highlight the need to consider gender differences in PAE processes. This study underscores the need for interventions that target automatic cognitive processes related to alcohol use.