bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the performance of direct fluorescent antibody staining, a point-of-care rapid antigen test and virus isolation with that of RT-PCR for the detection of novel 2009 influenza A (H1N1) virus in respiratory specimens
Authors: Ganzenmueller Tina , Kluba Jeanette , Hilfrich Birgit , Puppe Wolfram , Verhagen Willem , Heim Albert , Schulz Thomas , Henke-Gendo Cornelia
Published: March 2010

Although infections with the novel pandemic 2009 influenza A (H1N1) virus (A/H1N1/2009) appeared to be relatively mild during the first summer of circulation (‘off season’), there has been significant morbidity and hospitalization and several fatal cases. Thus, rapid detection of A/H1N1/2009 is crucial for efficient treatment and infection control measures. In contrast to seasonal influenza, where point-of-care (POC) rapid antigen tests and direct fluorescent antibody (DFA) staining ensure rapid detection, diagnosis of A/H1N1/2009 has so far been based on RT-PCR. This study retrospectively compared the performance of the Quidel QuickVue POC test, DFA staining and virus isolation with that of RT-PCR for A/H1N1/2009 detection in 526 respiratory specimens collected during the first wave of the outbreak from May to September 2009. A/H1N1/2009 was detected in 9.1 % (48/526) of samples. One hundred and thirty-seven of the A/H1N1/2009 PCR-negative samples were additionally tested using a RealAccurate Respiratory RT-PCR panel, revealing other respiratory viruses (mainly entero/rhino- and adenoviruses) in 42.3 % (58/137). All methods analysed detected A/H1N1/2009 with excellent specificity but different sensitivities (POC test: 18.2 %; DFA staining: 38.7 %; virus isolation: 45.7 %). Therefore, the POC test was not suitable for diagnosis, detecting A/H1N1/2009 only if present in high concentrations (corresponding medianCtvalue=19.0; range=16.5–21.4). DFA staining was also able to detect A/H1N1/2009 in specimens with a lower virus concentration (medianCtvalue=24.0; range=16.5–29.8). Virus isolation, which was positive after a median time of 7.5 days, was too time-consuming. In summary, DFA staining is superior to POC testing and may be appropriate for patients expected to have a rather high level of virus replication. Nevertheless, in DFA-negative specimens, A/H1N1/2009 should be excluded by RT-PCR.
Probing the Reproducibility of Leaf Growth and Molecular Phenotypes: A Comparison of Three Arabidopsis Accessions Cultivated in Ten Laboratories
Authors: Massonnet Catherine , Vile Denis , Fabre Juliette , Hannah Matthew A. , Caldana Camila , Lisec Jan , Beemster Gerrit T.S. , Meyer Rhonda C. , Messerli Gaëlle , Gronlund Jesper T. , Perkovic Josip , Wigmore Emma , May Sean , Bevan Michael W. , Meyer Christian , Rubio-Díaz Silvia , Weigel Detlef , Micol José Luis , Buchanan-Wollaston Vicky , Fiorani Fabio , Walsh Sean , Rinn Bernd , Gruissem Wilhelm , Hilson Pierre , Hennig Lars , Willmitzer Lothar , Granier Christine
Published: March 2010

A major goal of the life sciences is to understand how molecular processes control phenotypes. Because understanding biological systems relies on the work of multiple laboratories, biologists implicitly assume that organisms with the same genotype will display similar phenotypes when grown in comparable conditions. We investigated to what extent this holds true for leaf growth variables and metabolite and transcriptome profiles of three Arabidopsis (Arabidopsis thaliana) genotypes grown in 10 laboratories using a standardized and detailed protocol. A core group of four laboratories generated similar leaf growth phenotypes, demonstrating that standardization is possible. But some laboratories presented significant differences in some leaf growth variables, sometimes changing the genotype ranking. Metabolite profiles derived from the same leaf displayed a strong genotype × environment (laboratory) component. Genotypes could be separated on the basis of their metabolic signature, but only when the analysis was limited to samples derived from one laboratory. Transcriptome data revealed considerable plant-to-plant variation, but the standardization ensured that interlaboratory variation was not considerably larger than intralaboratory variation. The different impacts of the standardization on phenotypes and molecular profiles could result from differences of temporal scale between processes involved at these organizational levels. Our findings underscore the challenge of describing, monitoring, and precisely controlling environmental conditions but also demonstrate that dedicated efforts can result in reproducible data across multiple laboratories. Finally, our comparative analysis revealed that small variations in growing conditions (light quality principally) and handling of plants can account for significant differences in phenotypes and molecular profiles obtained in independent laboratories.
Concerted Modification of Flowering Time and Inflorescence Architecture by Ectopic Expression of TFL1-Like Genes in Maize
Authors: Danilevskaya Olga N. , Meng Xin , Ananiev Evgueni V.
Published: March 2010

TERMINAL FLOWER1 (TFL1)-like genes are highly conserved in plants and are thought to function in the maintenance of meristem indeterminacy. Recently, we described six maize (Zea mays) TFL1-related genes, named ZEA CENTRORADIALIS1 (ZCN1) to ZCN6. To gain insight into their functions, we generated transgenic maize plants overexpressing their respective cDNAs driven by a constitutive promoter. Overall, ectopic expression of the maize TFL1-like genes produced similar phenotypes, including delayed flowering and altered inflorescence architecture. We observed an apparent relationship between the magnitude of the transgenic phenotypes and the degree of homology between the ZCN proteins. ZCN2, -4, and -5 form a monophylogenetic clade, and their overexpression produced the strongest phenotypes. Along with very late flowering, these transgenic plants produced a “bushy” tassel with increased lateral branching and spikelet density compared with nontransgenic siblings. On the other hand, ZCN1, -3, and -6 produced milder effects. Among them, ZCN1 showed moderate effects on flowering time and tassel morphology, whereas ZCN3 and ZCN6 did not change flowering time but still showed effects on tassel morphology. In situ hybridizations of tissue from nontransgenic plants revealed that the expression of all ZCN genes was associated with vascular bundles, but each gene had a specific spatial and temporal pattern. Expression of four ZCN genes localized to the protoxylem, whereas ZCN5 was expressed in the protophloem. Collectively, our findings suggest that ectopic expression of the TFL1-like genes in maize modifies flowering time and inflorescence architecture through maintenance of the indeterminacy of the vegetative and inflorescence meristems.
Diffraction gratings as small-angle X-ray scattering calibration standards
Authors: Nygård K. , Bunk O. , Perret E. , David C. , van der Veen J. F.
Published: March 2010

It is shown that diffraction gratings can be used as accurate momentum-transfer calibration standards in small-angle X-ray scattering experiments. For demonstration purposes, a silicon diffraction grating with a period of 400 nm is used. The data exhibit 50 diffraction peaks evenly distributed in the momentum-transfer rangeq= 0.0–0.8 nm−1, a regime that is not accessible using the traditional silver behenate standard.
Clinicopathological significance of nuclear factor‐kappa B, HIF‐1 alpha, and vascular endothelial growth factor expression in stage III colorectal cancer
Authors: Kwon Hyuk‐Chan , Kim Sung Hyun , Oh Sung Yong , Lee Suee , Kwon Kyung A , Lee Jong Hoon , Choi Hong‐Jo , Park Ki‐Jae , Lee Hyung‐Sik , Roh Mee Sook , Kim Hyo‐Jin
Published: March 2010

Nuclear factor‐κB (NF‐κB), hypoxia‐inducible factor 1α (HIF‐1α), and vascular endothelial growth factor (VEGF) are involved in cell proliferation, invasion, angiogenesis, and metastases. The principal objective of this study was to assess the prognostic significance of NF‐κB, HIF‐1α, and VEGF expression in stage III colorectal cancer. Tumor tissues from 148 patients with stage III colorectal carcinoma, all of whom underwent potentially curative resection, were immunohistochemically evaluated using monoclonal antibodies against NF‐κB, HIF‐1α, and VEGF. Positivity rates of NF‐κB, HIF‐1α, and VEGF were 47.3%, 42.6%, and 61.5%, respectively. NF‐κB expression in tumor tissues was correlated significantly with HIF‐1α expression (P < 0.001), VEGF expression (P = 0.044), and the presence of vascular invasion (P = 0.013). Univariate analysis demonstrated that NF‐κB expression was associated with poor 5‐year overall survival (55.8 months vs 76.9 months, P = 0.012). Multivariate analysis verified that NF‐κB was independently associated with adverse outcomes (relative risk: 1.92, P = 0.049). However, HIF‐1α and VEGF did not appear to be related to clinical outcomes. NF‐κB expression in tumor tissue is associated with angiogenesis and poor 5‐year overall survival in stage III colorectal cancer patients. (Cancer Sci 2010; 00: 000–000)
Studies in Glycoproteins
Authors: BLIX GUNNAR
Published: March 2010

A short review is given of the results of recent investigations on the chemistry of the glycoproteins and especially of the present state of the question concerning the relations between carbohydrate and protein in these substances.

Hyalomucoid, synovial mucin and submaxillary mucin were investigated with the aid of electrophoresis. In approximately neutral solutions the hyalomucoid and the synovial mucin proved each to contain two electrophoretically well‐defined components. In both cases the faster migrating component was found to consist of a pure polysaccharide acid (hyaluronic acid). The slower components were simple proteins. In native synovial fluid and native vitreous body fluid the hyaluronic acid in all probability is in no way combined with protein but exists solely in the form of salts of the inorganic bases present. The glycoproteins precipitated from neutral synovial fluid or vitreous body fluid on addition of acetic acid are to be regarded as purely artificial products.

Neutral solutions of submaxillary mucin were, on electrophoresis, found to contain two distinct components, both proteins. The main component, which was the faster migrating one, amounted to about 90 % of the whole and was a glycoprotein containing 27 % carbohydrate. The other component probably ought to be regarded as a contaminant.

Pure water extracts from cartilage contain chondroitin sulphuric acid exclusively in the free form. This confirms the old opinion of Mörner that the chondroitin sulphuric acid in the cartilage is partly present as alkali salt.

A chemical classification of the glycoproteins is suggested.
Saulfapyridine in Secretin Stimulated Pancreatic Juice and Bile of Cats
Authors: TAYLOR A. , ÅGREN G.
Published: March 2010

The combined treatment of cats with sulfapyridine and secretin is described. In conformance with other investigations, in which secretin was not used, the concentration of sulfapyridine in pancreatic juice was found to be just lower than that of blood, but an extremely high concentration of the drug was found in the bile. The drug is not diluted by the increased flow of juice either from pancreas or liver and tends to be independent of rate of flow. Blood concentration of sulfapyridine is more important. While there was no change in the percentage of free drug excreted in the pancreatic juice, 30 % of the free drug had been bound when excreted in the bile, indicating acetylation by the liver.
Meta‐analysis: proton pump inhibitor use and the risk of community‐acquired pneumonia
Authors: JOHNSTONE J. , NERENBERG K. , LOEB M.
Published: March 2010

Aliment Pharmacol Ther 31, 1165–1177

Background  Observational studies examining the association between proton pump inhibitor (PPI) use and risk of community‐acquired pneumonia are conflicting.

Aim  To assess systematically the association between risk of community‐acquired pneumonia and PPI use in adults.

Methods  We searched MEDLINE, EMBASE and CINAHL databases between 1988 and January 2010. Two reviewers independently selected studies based on eligibility criteria and extracted data. Included studies evaluated adults (≥18 years) who took PPIs as an out‐patient. The primary outcome was community‐acquired pneumonia. Only observational studies with a comparison arm were included.

Results  Over 2600 citations were reviewed. Six studies were included. All were nested case‐control studies. Meta‐analysis found an increased risk of community‐acquired pneumonia associated with PPI use [OR 1.36 (95% CI 1.12–1.65)]; significant heterogeneity remained (I2 92%, P < 0.001). In exploratory subgroup analysis, short duration of use was associated with an increased odds of community‐acquired pneumonia [OR 1.92 (95% CI 1.40–2.63), I2 75%, P = 0.003], whereas chronic use was not [OR 1.11 (95% CI 0.90–1.38), I2 91%, P < 0.001], a significant interaction (P < 0.005).

Conclusions  Heterogeneity precluded interpretation of the summary statistic. Exploratory analysis revealed that duration of PPI use may impact the risk of community‐acquired pneumonia, a finding that should be explored in future studies.
Single nucleotide polymorphism‐arrays provide new insights in the pathogenesis of post‐transplant diffuse large B‐cell lymphoma
Authors: Rinaldi Andrea , Capello Daniela , Scandurra Marta , Greiner Timothy C. , Chan Wing C. , Bhagat Govind , Rossi Davide , Morra Enrica , Paulli Marco , Rambaldi Alessandro , Rancoita Paola M. V. , Inghirami Giorgio , Ponzoni Maurilio , Moreno Santiago M. , Piris Miguel A. , Mian Michael , Chigrinova Ekaterina , Zucca Emanuele , Favera Riccardo D. , Gaidano Gianluca , Kwee Ivo , Bertoni Francesco
Published: March 2010

Post‐transplant lymphoproliferative disorders (PTLD) are complications of solid organ transplantation associated with severe morbidity and mortality. Diffuse large B‐cell lymphoma (DLBCL) represents the most common form of monomorphic PTLD. We studied 44 cases of post‐transplant DLBCL (PT‐DLBCL) with high‐density genome wide single nucleotide polymorphism‐based arrays, and compared them with 105 cases of immunocompetent DLBCL (IC‐DLBCL) and 28 cases of Human Immunodeficiency Virus‐associated DLBCL (HIV‐DLBCL). PT‐DLBCL showed a genomic profile with specific features, although their genomic complexity was overall similar to that observed in IC‐ and HIV‐DLBCL. Among the loci more frequently deleted in PT‐DLBCL there were small interstitial deletions targeting known fragile sites, such as FRA1B, FRA2E and FRA3B. Deletions at 2p16.1 (FRA2E) were the most common lesions in PT‐DLBCL, occurring at a frequency that was significantly higher than in IC‐DLBCL. Genetic lesions that characterized post‐germinal center IC‐DLBCL were under‐represented in our series of PT‐DLBCL. Two other differences between IC‐DLBCL and PT‐DLBCL were the lack of del(13q14.3) (MIR15/MIR16) and of copy neutral LOH affecting 6p [major histocompatibility complex (MHC) locus] in the latter group. In conclusion, PT‐DLBCL presented unique features when compared with IC‐DLBCL. Changes in PT‐DLBCL were partially different to those in HIV‐DLBCL, suggesting different pathogenetic mechanisms in the two conditions linked to immunodeficiency.
Active survival in the lives of unaccompanied minors: coping strategies, resilience, and the relevance of religion
Authors: Ní Raghallaigh Muireann , Gilligan Robbie
Published: March 2010

Asylum‐seeking unaccompanied minors contend with numerous challenges as they adjust to living in a new country. Although increasing attention has been paid to their capacity for resilience, little research has been done on the exact manner in which they cope. This paper describes some of the insights gleaned from a qualitative study undertaken with unaccompanied minors living in Ireland. Six different coping strategies are identified, namely: (1) Maintaining continuity in a changed context, (2) Adjusting by learning and changing, (3) Adopting a positive outlook, (4) Suppressing emotions and seeking distraction, (5) Acting independently, and (6) Distrusting. These are described in turn. Particular attention is paid to the role of religion in relation to the participants' coping strategies.
Transforming growth factor‐β stimulates the expression of eotaxin/CC chemokine ligand 11 and its promoter activity through binding site for nuclear factor‐κB in airway smooth muscle cells
Authors: Matsukura S. , Odaka M. , Kurokawa M. , Kuga H. , Homma T. , Takeuchi H. , Notomi K. , Kokubu F. , Kawaguchi M. , Schleimer R. P. , Johnson M. W. , Adachi M.
Published: March 2010

Background
Chemokines ligands of CCR3 including eotaxin/CC chemokine ligand 11 (CCL11) may contribute to the pathogenesis of asthma. These chemokines and a growth factor (TGF‐β) may be involved in the process of airway remodelling.

Objective
We analysed the effects of TGF‐β on the expression of CCR3 ligands in human airway smooth muscle (HASM) cells and investigated the mechanisms.

Methods
HASM cells were cultured and treated with TGF‐β and Th2 cytokines IL‐4 or IL‐13. Expression of mRNA was analysed by real‐time PCR. Secretion of CCL11 into the culture medium was analysed by ELISA. Transcriptional regulation of CCL11 was analysed by luciferase assay using CCL11 promoter–luciferase reporter plasmids.

Results
IL‐4 or IL‐13 significantly up‐regulated the expression of mRNAs for CCL11 and CCL26. TGF‐β alone did not increase the expression of chemokine mRNAs, but enhanced the induction of only CCL11 by IL‐4 or IL‐13 among CCR3 ligands. Activity of the CCL11 promoter was stimulated by IL‐4, and this activity was enhanced by TGF‐β. Activation by IL‐4 or IL‐4 plus TGF‐β was lost by mutation of the binding site for signal transducers and activators of transcription‐6 (STAT6) in the promoter. Cooperative activation by IL‐4 and TGF‐β was inhibited by mutation of the binding site for nuclear factor‐κB (NF‐κB) in the promoter. Pretreatment with an inhibitor of NF‐κB and glucocorticoid fluticasone propionate significantly inhibited the expression of CCL11 mRNA induced by IL‐4 plus TGF‐β, indicating the importance of NF‐κB in the cooperative activation of CCL11 transcription by TGF‐β and IL‐4.

Conclusion
These results indicate that Th2 cytokines and TGF‐β may contribute to the pathogenesis of asthma by stimulating expression of CCL11. The transcription factors STAT6 and NF‐κB may play pivotal roles in this process.

Cite this as: S. Matsukura, M. Odaka, M. Kurokawa, H. Kuga, T. Homma, H. Takeuchi, K. Notomi, F. Kokubu, M. Kawaguchi, R. P. Schleimer, M. W. Johnson and M. Adachi, Clinical & Experimental Allergy, 2010 (40) 763–771.
Hypertrophic cardiomyopathy: from genetics to treatment
Authors: Marian Ali J.
Published: March 2010

Eur J Clin Invest 2010; 40 (4): 360–369

Background  Hypertrophic cardiomyopathy (HCM) is the prototypic form of pathological cardiac hypertrophy. HCM is an important cause of sudden cardiac death in the young and a major cause of morbidity in the elderly.

Design  We discuss the clinical implications of recent advances in the molecular genetics of HCM.

Results  The current diagnosis of HCM is neither adequately sensitive nor specific. Partial elucidation of the molecular genetic basis of HCM has raised interest in genetic‐based diagnosis and management. Over a dozen causal genes have been identified. MYH7 and MYBPC3 mutations account for about 50% of cases. The remaining known causal genes are uncommon and some are rare. Advances in DNA sequencing techniques have made genetic screening practical. The difficulty, particularly in the sporadic cases and in small families, is to discern the causal from the non‐causal variants. Overall, the causal mutations alone have limited implications in risk stratification and prognostication, as the clinical phenotype arises from complex and often non‐linear interactions between various determinants.

Conclusions  The clinical phenotype of ‘HCM’ results from mutations in sarcomeric proteins and subsequent activation of multiple cellular constituents including signal transducers. We advocate that HCM, despite its current recognition and management as a single disease entity, involves multiple partially independent mechanisms, despite similarity in the ensuing phenotype. To treat HCM effectively, it is necessary to delineate the underlying fundamental mechanisms that govern the pathogenesis of the phenotype and apply these principles to the treatment of each subset of clinically recognized HCM.
Using Principal Components and Factor Analysis in Animal Behaviour Research: Caveats and Guidelines
Authors: Budaev Sergey V.
Published: March 2010

Principal component (PCA) and factor analysis (FA) are widely used in animal behaviour research. However, many authors automatically follow questionable practices implemented by default in general‐purpose statistical software. Worse still, the results of such analyses in research reports typically omit many crucial details which may hamper their evaluation. This article provides simple non‐technical guidelines for PCA and FA. A standard for reporting the results of these analyses is suggested. Studies using PCA and FA must report: (1) whether the correlation or covariance matrix was used; (2) sample size, preferably as a footnote to the table of factor loadings; (3) indices of sampling adequacy; (4) how the number of factors was assessed; (5) communalities when sample size is small; (6) details of factor rotation; (7) if factor scores are computed, present determinacy indices; (8) preferably they should publish the original correlation matrix.
Interleukin‐1β and ‐10 polymorphisms influence erosive reflux esophagitis and gastritis in Taiwanese patients
Authors: Cheng Hsin‐Hung , Chang Chi‐Sen , Wang Hung‐Jung , Wang Wen‐Ching
Published: March 2010

Background and Aims:  Helicobacter pylori (H. pylori) infection induces cytokine production and is associated with gastrointestinal diseases. This study examined the relationship of gene polymorphisms, including interleukin (IL)‐1β, ‐10, ‐8, and tumor necrosis factor‐α (TNF‐α), H. pylori infection, and susceptibility to gastrointestinal disorders in Taiwanese patients.

Methods:  IL‐1β−511/−31/+3953, ‐10−1082/−819/−592, ‐8−251, and TNF‐α−308 polymorphisms were assessed in 628 gastrointestinal disease patients, and 176 healthy controls were analyzed using the polymerase chain reaction−restriction fragment length polymorphism method.

Results:  IL‐1β−511 T/T and −31 C/C genotypes, and IL‐1β−511 T and −31 C alleles were associated with an increased risk of reflux esophagitis (P = 0.034, odds ratio [OR] = 1.384, 95% confidence interval [CI]: 1.023–1.871; P = 0.031, OR = 1.388, 95% CI: 1.028–1.873; P = 0.044, OR = 1.342, 95% CI: 1.008–1.786; and P = 0.040, OR = 1.349, 95% CI: 1.014–1.796, respectively). No relationship was found between H. pylori infection and the risk of reflux esophagitis. IL‐10−819 C/T and ‐10−592 A/C genotypes and IL‐10−1082/−819/−592 ATA/ACC and ATA/GCC haplotypes were associated with an increased risk of gastritis (P = 0.021, OR = 1.721, 95% CI: 1.084–2.733; P = 0.016, OR = 1.766, 95% CI: 1.112–2.805; P = 0.039, OR = 1.662, 95% CI: 1.024–2.697; and P = 0.035, OR = 1.600, 95% CI: 1.024–2.499, respectively).

Conclusion:  Among Taiwanese patients, IL‐1β and ‐10 polymorphisms were associated with an increased risk of erosive reflux esophagitis and gastritis, respectively.
Is irritable bowel syndrome associated with chronic hepatitis C?
Authors: Fouad Yasser M , Makhlouf Madeha M , Khalaf Hanna , Mostafa Zainab , Raheem Ehab Abdel , Meneasi Wesam
Published: March 2010

Background and Aim:  Hepatitis C virus (HCV) is a common chronic infection that is widely associated with symptoms of fatigue and abdominal pain. The aim of the present study was to determine the prevalence of irritable bowel syndrome (IBS) among patients with hepatitis C compared to controls.

Methods:  This study included 258 patients with chronic hepatitis C, 36 patients with chronic hepatitis B, and 160 healthy volunteers. Clinical and laboratory data were recorded for every patient. All patients and controls were administered a questionnaire of IBS according to Rome III criteria.

Results:  The percentage of patients with IBS was significantly higher in patients with chronic HCV (66%, 170/258) than chronic hepatitis B virus (HBV; 22%, 8/36) and normal controls (18%, 28/160 patients; P < 0.001 and P < 0.001, respectively). There was no significant difference between chronic HBV and normal controls. In chronic HCV patients, IBS with constipation was the predominant type (51%, 86/170) followed by mixed IBS (73/170, 43%). In patients with chronic HCV, the percentage of females with IBS (91%) was significantly higher than those without IBS (9%; P < 0.001), and the percentage of patients with a high fibrosis score (F2–3) was significantly higher in patients with IBS (45%) than in patients without IBS (6%; P < 0.001). There was no difference regarding age, alanine aminotransferase level, or HCV viremia. A multivariate regression analysis revealed a significant association between sex, fibrosis score, and IBS.

Conclusion:  IBS is more prevalent in patients with chronic hepatitis C. Female patients with chronic HCV and those with higher fibrosis scores are more likely to have IBS.
Phenotypic and metabolic profiling of colony morphology variants evolved from Pseudomonas fluorescens biofilms
Authors: Workentine Matthew L. , Harrison Joe J. , Weljie Aalim M. , Tran Vy A. , Stenroos Pernilla U. , Tremaroli Valentina , Vogel Hans J. , Ceri Howard , Turner Raymond J.
Published: March 2010

Colony morphology variants isolated from natural and laboratory‐grown biofilms represent subpopulations of biofilm cells that may be important for multiple aspects of the sessile lifestyle, from surface colonization to stress resistance. There are many genetic and environmental factors that determine the frequency at which colony morphology variants are recovered from biofilms. One of these factors involves an increased selection for variants in biofilms of Pseudomonas species bearing inactivating mutations in the global activator of cyanide biosynthesis/regulator of secondary metabolism (gac/rsm) signal transduction pathway. Here we characterize two distinct colony morphology variants isolated from biofilms of Pseudomonas fluorescens missing the gacS sensor kinase. These variants produced more biofilm cell mass, and in one case, this was likely due to overproduction of the exopolysaccharide cellulose. Nuclear magnetic resonance (NMR) metabolomics revealed distinct metabolic changes for each of the two phenotypic variants, and these changes involved amino acids and metabolites produced through glutathione biochemistry. Some of these metabolites are hypothesized to play a role in redox and metal homeostasis, and corresponding to this, we show that biofilm populations grown from each of these variants had a different ability to survive when exposed to toxic doses of metal ions. These data suggest that colony morphology variants that evolve during growth of P. fluorescens as a biofilm may have distinct metabolic capacities that contribute to their individual abilities to withstand environmental stress.
Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight
Authors: Zhang L. , Feng Y. , List J. , Kasichayanula S. , Pfister M.
Published: March 2010

Aim: Dapagliflozin is a stable, competitive, reversible, and highly selective inhibitor of sodium‐glucose co‐transporter 2, the major transporter responsible for renal glucose reabsorption. With an insulin‐independent mechanism of action, dapagliflozin is currently being developed for the treatment of type 2 diabetes mellitus (T2DM). This work aims to compare the efficacy of dapagliflozin, as measured by the change in hemoglobin A1c concentration (A1c) and body weight, and to determine the pharmacodynamic effects of dapagliflozin, as measured by urinary glucose excretion in early‐stage and late‐stage T2DM patient populations.

Methods: A total of 151 early‐stage patients and 58 late‐stage patients with T2DM randomly assigned 10 or 20 mg once daily (QD) dapagliflozin treatment or placebo for 12 weeks from two phase 2 studies were included in the analysis. A1c, body weight, and urinary glucose were compared between the two patient populations.

Results: Compared with the early‐stage population, patients in the late‐stage population had a longer duration of T2DM and higher baseline levels of A1c, body weight, fasting plasma glucose, and urinary glucose excretion. After 12 weeks of dapagliflozin treatment, A1c reduction, weight loss, and increased urinary glucose excretion from baseline were observed in both populations. Baseline A1c level impacted the A1c reduction after dapagliflozin treatment with a comparable effect in patients with early and late stage disease. Late‐stage patients had greater reduction in body weight. There was no statistically significant difference in the amount of urinary glucose excretion between the early‐stage and late‐stage patients.

Conclusions: Dapagliflozin treatment at 10 and 20 mg QD for 12 weeks resulted in significant improvement in glycaemic control and body weight reduction in both early‐stage and late‐stage patients with T2DM. The findings suggest that dapagliflozin could be a promising treatment option for a wide range of patients with T2DM.
Urinary fistulae after partial nephrectomy
Authors: Kundu Shilajit D. , Thompson R. Houston , Kallingal George J. , Cambareri Gina , Russo Paul
Published: March 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To report the risk factors and natural history of urinary fistula (UF) after partial nephrectomy (PN), as their incidence has been reported to be 3–6% in large series of PN but there are few reports of the risk factors associated with the development of UF after PN, and the natural history of UF in a large group of patients.

PATIENTS AND METHODS

This was a retrospective review of 1118 PN at one tertiary‐care institution. Most patients had a drain placed in the perinephric space after surgery. Fifty‐two patients were identified as having a UF if they had persistent flank drainage for >14 days after surgery, or presented with evidence of a UF after the drain had been removed. Risk factors for development and the course of the UF are reported.

RESULTS

Fifty‐two patients developed a UF after PN (4.4%, 95% confidence interval, CI, 3.5–6.1%) The rate of a persistent urine leak (defined as drain fluid consistent with urine for >2 weeks after surgery) was 4.0 (95% CI 2.9–5.3)%. The overall rate of delayed UF presentation was only 0.4 (0.09–0.9)%. Patients who developed a UF had larger tumours (3.5 vs 2.6 cm, P= 0.03), a higher estimated blood loss (400 vs 300 mL, P < 0.001), and longer ischaemia time (50 vs 39 min, P < 0.001) than patients who did not develop a UF. Differences in tumour histology, laterality, multifocality, type of surgery (laparoscopic vs open), and intraoperative collecting system entry were not statistically different in patients who did or did not develop a UF. Patients with tumours of >2.5 cm were twice as likely to develop a UF than patients with tumours of <2.5 cm (P= 0.02). Most patients were managed conservatively with a percutaneous drain until the UF resolved, if they were asymptomatic. Overall, in 36 patients (69%) the fistula resolved with no intervention, while 16 (31%) required intervention. Stenting was the commonest intervention (15%). No patient required re‐operative open surgery.

CONCLUSION

The rate of development of UF after PN is low. Tumour size, blood loss and ischaemia time were all associated with the development of a UF. In most patients with a urine leak immediately after surgery the UF will resolve with no intervention, and can be managed conservatively with patience, in the absence of clinical symptoms.
Dorsal urethroplasty with labia minora skin graft for female urethral strictures
Authors: Rehder Peter , Glodny Bernhard , Pichler Renate , Exeli Lukas , Kerschbaumer Andrea , Mitterberger Michael Josef
Published: March 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To report a new dorsal labia minora skin‐graft urethroplasty as a simple, safe and effective therapeutic alternative for female urethral strictures, as although distal urethral strictures can be treated by meatoplasty, proximal and mid‐urethral strictures need appropriate urethroplasty.

PATIENTS AND METHODS

Eight women with a confirmed proximal or mid‐urethral stricture had indications for urethroplasty with the use of a thin free labia minora skin graft using a dorsal (6 o’clock position) urethroplasty technique. Full informed consent was obtained. From the inner aspect of one labium minora a thin free skin flap was prepared. The strictured urethra and the anterior vaginal wall were transected and the graft sutured into the defect. All scar tissue was removed and the anterior vaginal wall closed in two layers over the area of the urethroplasty. Continence was evaluated by a stress test with a full bladder.

RESULTS

All patients were operated on with no complications during or after surgery. After 1 and 2 years of follow‐up seven and six of the eight patients had no recurrence of stricture disease. All patients remained continent.

CONCLUSION

The urethroplasty using an inlay of free thin genital skin graft was safe, uncomplicated and effective.
Gibrat's Law in the “Third Italy”: Firm Growth in the Veneto Region
Authors: PIERGIOVANNI ROBERTA
Published: March 2010

According to Gibrat's Law of Proportionate Effect, the growth rate of a given firm is independent of its size at the beginning of the period examined. While earlier studies tended to confirm the Law, more recent research generally rejects it. The aim of this paper is to test whether Gibrat's Law is confirmed, for the 1995–2005 period, for a large sample of firms active in the Veneto region of Italy. Controlling for firm age and size, findings show that the Law is not confirmed in the early stages of a firm's life cycle, with younger firms growing faster than established ones, whereas it cannot be rejected once a given threshold in terms of age is reached. These findings are consistent with the life cycle theory of the firm and with the hypothesis that fast growing small and medium‐sized enterprises may have played a role in the evolution and the structural transformation of local systems in the “Third Italy” during the 1990s and early 2000s.
The employment effects of labour legislation in India: a critical essay
Authors: D'Souza Errol
Published: March 2010

Job security regulations have been central to government interventions in the labour market in India. These have been criticised for restricting employment growth. We argue that job security regulation has not had the negative effects its critics make a case out for. Firms have changed work practices and reorganised job boundaries as the import substituting industrialisation regime was dismantled. Weak enforcement of laws has supported this restructuring effort, with firms resorting to voluntary retirement of workers and increasingly hiring on the basis of flexible contracts. A two‐tier system of employment currently prevails, with job security for the employed insiders and no protection to newly hired outsiders. Unorganised workers' employment prospects have been furthered in this emerging scenario, and their alliance with firms and the state results in an atrophying of job security regulations.
Globalisation and outsourcing: confronting new human resource challenges in India's business process outsourcing industry
Authors: Kuruvilla Sarosh , Ranganathan Aruna
Published: March 2010

In this article, we argue that the rapid growth of the outsourcing industry has resulted in both high turnover and labour shortages and at the same time provided employment opportunities to a new group of employees: young upwardly mobile college graduates. We argue that this particular demographic profile is prone to high turnover and presents new managerial challenges. We then examine the variety of recruitment and retention strategies that companies in the business process outsourcing industry are experimenting with and show that many novel HR strategies are being crafted to address the needs of this young middle‐class workforce. We also examine macro efforts by state and central governments and the industry association to help resolve some of these problems.
Evidence‐based recommendations to assess psoriasis severity: systematic literature review and expert opinion of a panel of dermatologists
Authors: Paul C , Gourraud P‐A , Bronsard V , Prey S , Puzenat E , Aractingi S , Aubin F , Bagot M , Cribier B , Joly P , Jullien D , Le Maitre M , Richard‐Lallemand M‐A , Ortonne J‐P
Published: March 2010

Background  Severity of psoriasis appears to be multidimensional and its assessment in everyday clinical practice requires a complex holistic approach.

Objectives  To develop evidence‐based recommendations to assess severity of plaque‐type psoriasis in adult patients in everyday clinical practice.

Methods  A scientific committee (10 members identified on the basis of their expertise in psoriasis) using Delphi methodology selected eight questions in three domains: severity, health‐related quality of life (HR‐QoL) and comorbidities. Three systematic literature reviews (one per domain) of all studies published between January 1980 and June 2009 were performed based on Pub‐Med, Cochrane and Embase database. Selected articles were systematically reviewed and evidence appraised according to the Oxford Levels of Evidence. On June 2009, a group of 44 French dermatologists both hospital and office based participated in a meeting including three separate rounds of discussions, plenary sessions, and modified Delphi technique votes. Recommendations for clinical practice based on systematic review and clinical experience were formulated by the group. Subsequently, agreements among the participants regarding these recommendations as well as potential impact on clinical practice were evaluated.

Results  A total of 10 642 references were identified, of which 154 articles were analysed. Ten key recommendations on the assessment of psoriasis severity were formulated: three recommendations relating to severity assessment, three recommendations relating to HR‐QoL (including the use of the Dermatology Life Quality Index [DLQI] in clinical practice) and four recommendations relating to comorbidities (including systematic screening for peripheral or axial inflammatory joint damage, regardless of psoriasis severity).

Conclusions  Ten recommendations to assess the severity of plaque‐type psoriasis in adult patients in daily practice were developed. The recommendations are based on systematic appraisal of available evidence. They were developed and supported by a panel of dermatologists, which enhances their validity and practical relevance.
Assessment of risk of psoriatic arthritis in patients with plaque psoriasis: a systematic review of the literature
Authors: Prey S , Paul C , Bronsard V , Puzenat E , Gourraud P‐A , Aractingi S , Aubin F , Bagot M , Cribier B , Joly P , Jullien D , Maitre M Le , Richard‐Lallemand M‐A , Ortonne J‐P
Published: March 2010

Objective  The aim of this study was to determine the prevalence of psoriatic arthritis (PsA) in the patients with plaque psoriasis and to give recommendation for the diagnosis of PsA for dermatologists.

Methods  A systematic search was performed in Pubmed, Cochrane and Embase databases. The key‐words used from the Medical Searching Heading (MeSH) were: ‘Psoriasis’, ‘Arthritis, Psoriatic’, ‘Uveitis’ and ‘Dactylitis’. We selected cross‐sectional epidemiological studies written in English or French between January 1980 and October 2009.

Results  The initial literature search identified 2171 references. Based on abstract reading and exclusion of studies not written in English or French, and without control group, the final selection included 20 epidemiological studies. With the eight studies using rheumatologically validated criteria, the prevalence of PsA among psoriasis patient spanned a wide range from 7% to 26%.

Conclusion  Psoriasis arthritis may affect up to 24% of psoriasis patients. Dermatologist should be aware of main clinical sign of PsA to promote earlier recognition and treatment of PsA.
Analysis of the STS gene in 40 patients with recessive X‐linked ichthyosis: a high frequency of partial deletions in a Spanish population
Authors: Cañueto J , Ciria S , Hernández‐Martín A , Unamuno P , González‐Sarmiento R
Published: March 2010

Background  Recessive X‐linked ichthyosis (RXLI) (OMIM 308100) is a genodermatosis characterized by polygonal, dark, adherent and mild‐to‐moderate scales that normally improve during summer. RXLI is caused by a deficiency in steroid sulphatase (STS), whose gene has been located on the X chromosome (locus Xp22.3). Up to 90% of the mutations described in this gene are complete deletions.

Objectives  Previous reports of partial deletion of STS gene in cases of RXLI prompted us to determine the incidence of these abnormalities in a Spanish population.

Methods  We have studied exons 1, 5 and 10 of the STS gene by polymerase chain reaction in 40 patients with clinical features of RXLI.

Results  Our results revealed that 30 patients presented complete deletions (75%) while 10 patients had partial deletions (25%) a rate higher than that reported in the previous studies.

Conclusions  Amplification of exons 1, 5 and 10 is reliable in screening RXLI in the population studied here. No correlation was found between phenotype and the extent of the deletions.
Paederus dermatitis in Egypt: a clinicopathological and ultrastructural study
Authors: Assaf M , Nofal E , Nofal A , Assar O , Azmy A
Published: March 2010

Background  Outbreaks of paederus dermatitis (PD) have been observed in different parts of the world, yet the histopathological and ultrastructural changes and their relationship to pederin toxin have not been described.

Objective  To describe the clinical presentations of PD in Egypt and to study the effects of pederin toxin on the skin by evaluating the histopathological and ultrastructural changes of some representative cases.

Methods  One hundred and thirteen patients with PD were studied clinically and epidemiologically. Skin biopsies were taken from 40 patients for histopathological examination and from 20 patients for electron microscopic (EM) examination.

Results  Clinically, the most common presentation comprised erythematous plaques with micropustules. Blisters exhibited a linear configuration in 40% of the patients and kissing lesions were observed in 13%. Multiple lesions occurred in 78% of the patients and the face was the most commonly involved site (48%). The insect was identified as Paederus alfierii. Histopathological examination revealed features of acute irritant dermatitis in the upper epidermis. Mitotic figures and apoptotic changes such as chromatin condensation and DNA fragmentation were identified in the basal and suprabasal layers. These features were confirmed by EM.

Conclusions  Clinical, histopathological and, for the first time, ultrastructural characteristics of paederus dermatitis are described. The pathological abnormalities of the upper epidermis are caused by the irritant effect of pederin toxin. The presence of apoptosis within the lower epidermis can be related to this toxin, a point that needs further research, hoping for its future implications in the management of hyperproliferative disorders.
Heterogeneous mutations of the ATP2C1 gene causing Hailey–Hailey disease in Hong Kong Chinese
Authors: Cheng TS , Ho KM , Lam CW
Published: March 2010

Background  Hailey–Hailey disease (HHD) is a rare autosomal dominant dermatosis. It causes suprabasilar acantholysis leading to vesicular and crusted erosions affecting the flexures. Mutation of ATP2C1 gene encoding the human secretory pathway Ca2+/Mn2+‐ATPase (hSPCA1) was identified to be the cause of this entity.

Objective  The aim of this study was to study the mutational profile of the ATP2C1 gene in Hong Kong Chinese patients with HHD.

Methods  Patients with the clinical diagnosis of HHD proven by skin biopsy were included in this study. Mutation analysis was performed in 17 Hong Kong Chinese patients with HHD.

Results  Ten mutations in the ATP2C1 gene were found. Six of these were novel mutations. The novel mutations included a donor splice site mutation (IVS22+1G>A); a missense mutation (c.1049A>T); two deletion mutations (c.185_188delAGTT and c.923_925delAAG); an acceptor splice site mutation (IVS21‐1G>C) and an insertion mutation (c.2454dupT).

Conclusion  The six novel mutations provide additions to the HHD mutation database. No hot‐spot mutation was found and high allelic heterogeneity was demonstrated in the Hong Kong Chinese patients.
Probable trigeminal autonomic cephalgia in a 3‐month‐old male infant
Authors: VAZ IRENE
Published: March 2010

To my knowledge trigeminal autonomic cephalgias (TACs) have not previously been reported in infancy. The diagnosis is dependent on an accurate history, including parents noting any physical signs at the time of the episode. Obtaining a clear history can be challenging when such symptoms occur in preverbal children. Similarly, physical signs, being transient, may have resolved by the time the parents take the child to a doctor. In addition, the investigations may also be normal. In such circumstances, taking a photograph during an episode can confirm the diagnosis. I describe a case of probable trigeminal autonomic cephalgia starting in a 3‐month‐old male infant who presented with screaming episodes associated with characteristic changes seen on his face. Investigations, including cranial magnetic resonance imaging, electroencephalography, and urinary catecholamines, were normal. The diagnosis was confirmed from a photograph taken by the parents at the time of the attack. As the condition is very rare in young children, there is little information available in the literature on using treatment for prophylaxis or for aborting acute episodes in this age group.
Ubiquitin/proteasome‐dependent down‐regulation following clathrin‐mediated internalization of histamine H1‐receptors in Chinese hamster ovary cells
Authors: Hishinuma Shigeru , Komazaki Hiroshi , Fukui Hiroyuki , Shoji Masaru
Published: March 2010

J. Neurochem.(2010)113, 990–1001.

We investigated the regulatory pathways responsible for agonist‐induced internalization and down‐regulation of Gqprotein‐coupled histamine H1‐receptors in Chinese hamster ovary cells. Histamine‐induced internalization and down‐regulation of H1‐receptors were detected as the loss of [3H]mepyramine binding sites on intact cells accessible to hydrophilic and hydrophobic H1‐receptor antagonists, pirdonium and mepyramine, respectively. Pretreatment of cells with 0.1 mM histamine for 30 min at 37°C induced internalization as well as down‐regulation of H1‐receptors, both of which were inhibited either in the presence of an inhibitor against G protein‐coupled receptor kinases (ZnCl2) or under hypertonic conditions where clathrin‐dependent endocytosis is known to be inhibited, but were not affected by inhibitors against caveolae/raft‐dependent endocytosis (filipin and nystatin). Down‐regulation of H1‐receptors, but not their internalization, was inhibited by protein kinase C inhibitors (chelerythrin or GF109203X), a ubiquitin E1 inhibitor (UBEI‐41) and proteasome inhibitors (lactacystin and MG‐132). Neither a Ca2 + /calmodulin‐dependent protein kinase II inhibitor (KN‐62) nor lysosomal protease inhibitors (E‐64, leupeptin, chloroquine and NH4Cl) affected the internalization and down‐regulation of H1‐receptors. These results suggest that H1‐receptors internalize upon agonist stimulation via G protein‐coupled receptor kinase/clathrin‐dependent but caveolae/raft‐independent mechanisms and are delivered to proteasomes, preferentially to lysosomes, for their prompt down‐regulation.