bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating CD52 and CD20 levels at end of treatment predict for progression and survival in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab (FCR)
Authors: Alatrash Gheath , Albitar Maher , O’Brien Susan , Wang Xuemei , Manshouri Taghi , Faderl Stefan , Ferrajoli Alessandra , Burger Jan , Garcia‐Manero Guillermo , Kantarjian Hagop M. , Lerner Susan , Keating Michael J. , Wierda William G.
Published: November 2009

CD52 and CD20 antigens are important therapeutic targets for the monoclonal antibodies (mAbs) alemtuzumab and rituximab respectively. Circulating CD52 (cCD52) and CD20 (cCD20) have prognostic utility in lymphoid malignancies. The efficacy of mAb therapy in patients with chronic lymphocytic leukaemia (CLL) may be adversely affected by cCD52 or cCD20. In this report, blood and bone marrow (BM) cCD52 and cCD20 were measured at response assessment in previously treated (N = 235) patients with CLL who received fludarabine, cyclophosphamide, and rituximab (FCR). Univariate and multivariate statistical models evaluated correlations of pre‐ and response variables with progression‐free (PFS) and overall survival (OS). Response variables included 1996 National Cancer Institute‐Working Group (NCI‐WG) response, polymerase chain reaction (PCR) for immunoglobulin heavy chain (IGHV) in BM, and cCD52 and cCD20 levels (blood and BM) at response assessment. Using multivariate analysis, response blood and BM cCD52, blood cCD20, and NCI‐WG response were significant independent predictors of PFS. At the time of response assessment, BM cCD52 correlated with OS in univariate analysis. cCD52 and cCD20, therefore appear useful in predicting survival and may be important for monitoring patients following salvage FCR (fludarabine, cyclophosphamide, rituximab) therapy. These data further indicate that plasma may be a good target to evaluate for minimal residual disease using cCD52/cCD20 levels.
Antigen receptor gene rearrangements reflect on the heterogeneity of adult Acute Lymphoblastic Leukaemia (ALL) with implications of cell‐origin of ALL subgroups – a UKALLXII study
Authors: Rai Lena , Casanova Anouska , Moorman Anthony V. , Richards Sue , Buck Georgina , Goldstone Anthony H. , Fielding Adele K. , Foroni Letizia
Published: November 2009

Cytogenetic and molecular investigations of Acute Lymphoblastic Leukaemia (ALL) have identified the existence of distinct clinical subgroups. Molecular monitoring of clonal Immunoglobulin and T cell receptor (IG/TR) gene rearrangements has become an important tool in stratification of therapy of ALL. In order to determine whether certain features of the patient‐specific rearrangements could hold further prognostic clues or provide information on the cell of origin of ALL, a comprehensive analysis of structural and biological features (V gene usage, coding frame and mutational status and complementarity‐determining region ‐III length) of 473 IG/TR rearrangements identified in 229 adults with ALL was carried out. Distinct variable‐gene usage profiles were identified between ALL subgroups, particularly for patients positive for BCR‐ABL1 compared to MLL‐AFF1 positive leukaemias; suggesting that the former is derived from a more mature B progenitor. Interestingly, occurrence of TRGV1‐TRGV8 was prognostic for better event‐free survival (31% at 4 years with vs. 0% at 4 years without, P = 0·05). The heterogeneity in clinical outcome is suggested by the basic molecular processes of antigen receptor gene rearrangements as shown in this work.
The minimal clinically important difference in allergic rhinitis
Authors: Barnes M. L. , Vaidyanathan S. , Williamson P. A. , Lipworth B. J.
Published: November 2009

Background
When presented with results from clinical measurements or research findings, clinicians must first make an interpretation of their importance, not only in statistical terms, but also the ‘clinical importance’ given the size of the change observed. To do this, they require an understanding of the relationship between their outcome measures, and the patient's perception of change. The minimal clinically important difference (MCID) illustrates this relationship by calculating the smallest change in a given outcome that is meaningful to a patient. There are few reports of calculated MCIDs in the Rhinology literature.

Objective
To calculate MCIDs for common subjective and objective outcome measures in allergic rhinitis (AR).

Methods
Nine randomized, blinded, placebo‐controlled clinical trials in intermittent and persistent AR (pooled subjects, n=204) were analysed using anchor‐ and distribution‐based approaches, applying regression and meta‐analysis techniques.

Results
MCIDs were obtained for the Mini Rhinoconjunctivitis Quality of Life Questionnaire: 0.4 units, peak nasal inspiratory flow: 5 L/min and total nasal symptoms score: 0.55 units. Nasal NO measurement changes had no correlation with patient perceptions of benefit.

Conclusion
Estimates of MCIDs were obtained for common subjective and objective rhinological outcomes. MCIDs can and should be applied by physicians interpreting research findings, as well as researchers reporting their findings. We can then be confident that our changes in practice will be of perceptible benefit to the patient.

Cite this as: M. L. Barnes, S. Vaidyanathan, P. A. Williamson and B. J. Lipworth, Clinical & Experimental Allergy, 2010 (40) 242–250.
Moisture and vegetation controls on decadal‐scale accrual of soil organic carbon and total nitrogen in restored grasslands
Authors: O'BRIEN SARAH L. , JASTROW JULIE D. , GRIMLEY DAVID A. , GONZALEZ‐MELER MIQUEL A.
Published: November 2009

Revitalization of degraded landscapes may provide sinks for rising atmospheric CO2, especially in reconstructed prairies where substantial belowground productivity is coupled with large soil organic carbon (SOC) deficits after many decades of cultivation. The restoration process also provides opportunities to study the often‐elusive factors that regulate soil processes. Although the precise mechanisms that govern the rate of SOC accrual are unclear, factors such as soil moisture or vegetation type may influence the net accrual rate by affecting the balance between organic matter inputs and decomposition. A resampling approach was used to assess the control that soil moisture and plant community type each exert on SOC and total nitrogen (TN) accumulation in restored grasslands. Five plots that varied in drainage were sampled at least four times over two decades to assess SOC, TN, and C4‐ and C3‐derived C. We found that higher long‐term soil moisture, characterized by low soil magnetic susceptibility, promoted SOC and TN accrual, with twice the SOC and three times the TN gain in seasonally saturated prairies compared with mesic prairies. Vegetation also influenced SOC and TN recovery, as accrual was faster in the prairies compared with C3‐only grassland, and C4‐derived C accrual correlated strongly to total SOC accrual but C3‐C did not. High SOC accumulation at the surface (0–10 cm) combined with losses at depth (10–20 cm) suggested these soils are recovering the highly stratified profiles typical of remnant prairies. Our results suggest that local hydrology and plant community are critical drivers of SOC and TN recovery in restored grasslands. Because these factors and the way they affect SOC are susceptible to modification by climate change, we contend that predictions of the C‐sequestration performance of restored grasslands must account for projected climatic changes on both soil moisture and the seasonal productivity of C4 and C3 plants.
Volumetric analysis of root fillings using spiral computed tomography: an in vitro study
Authors: Anbu R. , Nandini S. , Velmurugan N.
Published: November 2009

Aim  To analyse volumetrically using spiral computed tomography (SCT) the efficacy of various techniques to fill root canals.

Methodology  Root canals in 40 maxillary central incisors were instrumented with K‐files to size 60 and the volume of the canal measured using SCT. The teeth were divided into four groups of 10 each and root filled by lateral compaction, Thermafil, Obtura II and System B techniques, respectively. AH plus was used as sealer with all techniques. The filled volume in each canal was measured using SCT and the percentage of obturated volume (POV) was calculated. The data were statistically analysed using Kruskal–Wallis test and Mann–Whitney U‐test.

Results  The four groups were comparable in canal volume. The overall POV was 80.4%, 93.3%, 84.8% and 93.7% for lateral compaction, Thermafil, Obtura II and System B, respectively (P < 0.05).

Conclusion  The greatest POV was obtained with System B and Thermafil. Voids were seen in all root fillings.
Influence of the shape of artificial canals on the fatigue resistance of NiTi rotary instruments
Authors: Plotino G. , Grande N. M. , Cordaro M. , Testarelli L. , Gambarini G
Published: November 2009

Aim  To investigate the influence of the trajectory of NiTi rotary instruments on the outcome of cyclic fatigue tests.

Methodology  Ten ProFile and Mtwo instruments tip size 20, taper 0.06 and tip size 25, taper 0.06 were tested in two simulated root canals with an angle of curvature of 60° and radius of curvature of 5 mm but with different shape. Geometrical analysis of the angle and radius of the curvature that each instrument followed inside the two different artificial canals was performed on digital images. The instruments were then rotated until fracture at a constant speed of 300 rpm to calculate the number of cycles to failure (NCF) and the length of the fractured fragment. Mean values were calculated and analysed using two different multivariate linear regression models and an independent sample t‐test.

Results  The shape of the artificial root canal used in cyclic fatigue studies influenced the trajectory of the instrument. This difference is reflected by the NCF measured for the same instrument in the different artificial root canals and by the impact of the type of canal on both the NCF (St.β = 0.514) and fragment length (St.β = −0.920).

Conclusions  Small variations in the geometrical parameters of the curvature of an instrument subjected to flexural fatigue could have a significant influence on the results of fatigue tests.
Functional traits of alien plants across contrasting climatic and land‐use regimes: do aliens join the locals or try harder than them?
Authors: Tecco Paula A. , Díaz Sandra , Cabido Marcelo , Urcelay Carlos
Published: November 2009

1 Two main views have been put forward to explain whether coexisting alien and resident plant species should show converging or diverging functional attributes. According to the ‘try‐harder’ hypothesis, successful aliens should differ from resident species with traits that allow them to deal better with the local conditions than resident species. On the other hand, the ‘join‐the‐locals’ hypothesis stresses the importance of filtering by environmental factors and predicts strong functional trait similarities between alien and native species, especially among the dominants.

2 On the basis of a functional trait comparison between native and alien species of central‐western Argentina across five contrasting ecosystems and four land‐use regimes, we tested these hypotheses over a broad range of habitats. We built a data set with common measurement methods and biogeographical factors but strongly varying environmental conditions, ranging from mesic to extremely dry, and from nearly pristine to heavily disturbed.

3 When considering all species together, the main trend of variation in trait syndromes was between acquisitive (tender, large leaves, with high specific area) and conservative (tough, small leaves, with low specific area and low nutrient content). Although both native and alien species appeared to be well spread across the whole range of trait variation, woody alien species showed a significantly more acquisitive set of attributes (higher specific leaf area, larger and thinner leaves, lower wood density) than native species. No significant difference was detected between herbaceous alien and native species. These general trends were maintained under contrasting climatic and land‐use conditions.

4 Synthesis. The patterns detected for herbaceous species were in line with the ‘join‐the‐locals’ hypothesis. In contrast, those found for woody species, with woody alien species showing more acquisitive attributes than native species in more resource‐rich habitats, provide partial support for the ‘try‐harder’ hypothesis. Overall, our findings reinforce the idea that a universal suit of attributes is unlikely to explain alien plant distribution. They also stress the need for caution when mixing major life‐forms in comparative plant trait analysis.
Drivers of lowland rain forest community assembly, species diversity and forest structure on islands in the tropical South Pacific
Authors: Keppel Gunnar , Buckley Yvonne M. , Possingham Hugh P.
Published: November 2009

1. Testing the comparative strength and influence of age and area of islands, proximity of source propagules and disturbances on community assembly, species diversity and vegetation structure has proved difficult at large scales. The little‐studied rain forests in the Tropical South Pacific (TSP) provide a unique study area to investigate determinants of community dynamics, with islands varying in age, isolation, area and cyclone frequency. We tested the effects of biogeographical factors and cyclone frequency on the species composition, species diversity and forest structure of old‐growth rain forest using 1‐ha inventory plots on 12 islands between New Guinea and the Solomon Islands.

2. As predicted by the General Dynamic Model of Oceanic Island Biogeography, the biogeographical variables of archipelago age and island area are the most important factors affecting species richness and diversity, with older and larger islands having higher richness and diversity. There is no significant effect of cyclone frequency on species diversity.

3. The theory that diversity drives endemism is not supported in this system as endemism is not correlated with species diversity. Instead, age and isolation of an island best explain patterns of endemism, with the latter suggesting dispersal limitations between archipelagos.

4. Proximity to source area influences species composition of lowland tropical rain forests in the TSP, which is also supported by a strong correlation between geographic distance and floristic similarity. Vector‐fitting onto non‐metric multidimensional scaling suggests that archipelago age and cyclone frequency may, in addition to proximity to source area, influence species composition. This implies that a species’ tolerance to cyclones affects its abundance at different cyclone frequencies.

5. Synthesis. Both biogeographical variables (island area and isolation) and cyclone frequency appear to affect community assembly in lowland rain forests in the TSP. While species are hence not ecologically equivalent, interspecific ecological differences do not seem to affect the overall patterns of species diversity, which are mostly determined by biogeographical variables, as predicted by the neutral theory.
Alternative community states maintained by fire in the Klamath Mountains, USA
Authors: Odion Dennis C. , Moritz Max A. , DellaSala Dominick A.
Published: November 2009

1. The earliest examples of alternative community states in the literature appear to be descriptions of natural vegetation said to both depend on and promote fire. Nonetheless, alternative community states determined by fire have rarely been documented at landscape scales and in natural vegetation. This is because spatial autocorrelation may confound analyses, experimental manipulations are difficult and a long‐term perspective is needed to demonstrate that alternative community states can persist for multiple generations.

2. We hypothesized that alternative community states occur in a largely forested landscape in the Klamath Mountains, north‐western California, USA, where shrub‐dominated sclerophyllous vegetation establishes after fire that is lethal to forests. Forests redevelop if succession is not arrested by fire. Our hypothesis would require that sclerophyll and forest vegetation states each be maintained by different self‐reinforcing relationships with fire.

3. To test this hypothesis, we examined pyrogenicity of forest and sclerophyll vegetation as a function of time since the previous fire, accounting for spatial autocorrelation. Fire exclusion served as ade factoexperimental treatment. Areas where fire had proceeded to occur served as controls.

4. Our findings are consistent with the occurrence of alternative community states established and maintained by different self‐reinforcing feedbacks with fire. Sclerophyll vegetation was more pyrogenic, especially where time‐since‐fire (TSF) was relatively short, a favourable relationship for this fire‐dependent vegetation. Forests were much less pyrogenic, especially where TSF was long, favouring their maintenance. Fire exclusion therefore has led to afforestation and rapid retreat of fire‐dependent vegetation.

5. Synthesis: We have documented how different self‐reinforcing combustion properties of forest and sclerophyll vegetation can naturally produce alternative states coexisting side‐by‐side in the same environment. Such fire‐mediated alternative states may be underappreciated, in part, because they are difficult to demonstrate definitively. In addition, the dynamics they exhibit contrast with common perceptions that fire hazard increases deterministically with TSF in forests and shrublands. Addressing the impacts of fire exclusion will probably require a management shift to better allow fire to perform its ecological role in shaping landscape diversity and maintaining fire‐dependent biota.
Making an informed choice in the catering environment: what do consumers want to know?
Authors: Mackison D. , Wrieden W. L. , Anderson A. S.
Published: November 2009

Background:  Eating outside the home is common in the UK, but it remains difficult for consumers to make informed choices based on menu information. The present study examines the reported preferences for the provision of nutrition (salt, fat and energy) and ingredient information in six types of UK catering outlets.

Methods:  Participants completed a short postal survey, assessing their frequency of dining at specific catering establishments as well as their desire to see nutrition and ingredient information.

Results:  The responses from 786 adults aged ≥18 years (of whom 65% claimed to be ‘motivated to eat a healthy diet’) indicated that over 40% reported eating at a catering outlet at least once a week. Over half said that they would wish to see information on ingredients and the salt content of menu items at all venues. Preference for information on energy and fat content was less popular and varied in the range 42–56% for energy and 47–59% for fat. It is notable that 43% of respondents said they would welcome information on energy content of menu items in restaurants.

Conclusion:  A significant proportion of consumers wish to see information on the ingredients and nutrition composition on menu items for sale in UK catering outlets. Such information is likely to raise an awareness and understanding of healthy food choices and assist the population in making informed choices about healthy eating.
Applying the quarter‐hour rule: can people with insomnia accurately estimate 15‐min periods during the sleep‐onset phase?
Authors: HARROW LISA , ESPIE COLIN
Published: November 2009

The ‘quarter‐hour rule’ (QHR) instructs the person with insomnia to get out of bed after 15 min of wakefulness and return to bed only when sleep feels imminent. Recent research has identified that sleep can be significantly improved using this simple intervention (Malaffo and Espie, Sleep, 27(s), 2004, 280; Sleep, 29 (s), 2006, 257), but successful implementation depends on estimating time without clock monitoring, and the insomnia literature indicates poor time perception is a maintaining factor in primary insomnia (Harvey, Behav. Res. Ther., 40, 2002, 869). This study expands upon previous research with the aim of identifying whether people with insomnia can accurately perceive a 15‐min interval during the sleep‐onset period, and therefore successfully implements the QHR. A mixed models anova design was applied with between‐participants factor of group (insomnia versus good sleepers) and within‐participants factor of context (night versus day). Results indicated no differences between groups and contexts on time estimation tasks. This was despite an increase in arousal in the night context for both groups, and tentative support for the impact of arousal in inducing underestimations of time. These results provide promising support for the successful application of the QHR in people with insomnia. The results are discussed in terms of whether the design employed successfully accessed the processes that are involved in distorting time perception in insomnia. Suggestions for future research are provided and limitations of the current study discussed.
Priming affects poor sleepers but not normal sleepers on an Insomnia Ambiguity Task
Authors: ELLIS JASON , GARDANI MARIA , HOGH HENRIETTE
Published: November 2009

With increasing importance being placed on the role of cognitive biases as a maintaining factor in insomnia, the influence of order effects on interpretative responses should be examined and subsequently accounted for. The aim of the present study was to examine whether asking participants about their sleep experiences, prior to testing for a perceptual bias, affects responses on a sleep‐related ambiguity task. One hundred and seventeen undergraduate students, blind to the aims of the experiment, were issued either the Dysfunctional Beliefs and Attitudes to Sleep scale (DBAS‐10) and Insomnia Severity Index (ISI) before, or following, completion of an Insomnia Ambiguity Task (IAT). As expected, a multivariate analysis of variance showed that the order in which participants completed the task affected the responses on the IAT with those given the DBAS‐10 and ISI first, showing greater insomnia‐related interpretations than those given the IAT first. However, on closer examination, this effect was evident only for those who were defined as poor sleepers, and that normal sleepers were largely unaffected by the order in which the tests are given. The results are discussed in terms of design and management of sleep‐related research protocols involving implicit cognitive tasks.
Mechanisms of Cl‐ transport contributing to salt tolerance
Authors: TEAKLE NATASHA L. , TYERMAN STEPHEN D.
Published: November 2009

Mechanisms of Cl‐ transport in plants are poorly understood, despite the importance of minimizing Cl‐ toxicity for salt tolerance. This review summarizes Cl‐ transport processes in plants that contribute to genotypic differences in salt tolerance, identifying key traits from the cellular to whole‐plant level. Key aspects of Cl‐ transport that contribute to salt tolerance in some species include reduced net xylem loading, intracellular compartmentation and greater efflux of Cl‐ from roots. We also provide an update on the biophysics of anion transport in plant cells and address issues of charge balance, selectivity and energy expenditure relevant to Cl‐ transport mechanisms. Examples are given of anion transport systems where electrophysiology has revealed possible interactions with salinity. Finally, candidate genes for anion transporters are identified that may be contributing to Cl‐ movement within plants during salinity. This review integrates current knowledge of Cl‐ transport mechanisms to identify future pathways for improving salt tolerance.
Complexity and coordination of root growth at low water potentials: recent advances from transcriptomic and proteomic analyses
Authors: YAMAGUCHI MINEO , SHARP ROBERT E.
Published: November 2009

Progress in understanding root growth regulation and adaptation under water‐stressed conditions is reviewed, with emphasis on recent advances from transcriptomic and proteomic analyses of maize and soybean primary roots. In both systems, kinematic characterization of the spatial patterns of cell expansion within the root elongation zone showed that at low water potentials, elongation rates are preferentially maintained towards the root apex but are progressively inhibited at more basal locations resulting in a shortened growth zone. This characterization provided an essential foundation for extensive research into the physiological mechanisms of growth regulation in the maize primary root at low water potentials. Recently, these studies were expanded to include transcriptomic and cell wall proteomic analyses of the maize primary root, and a proteomic analysis of total soluble proteins in the soybean primary root. This review focuses on findings related to protection from oxidative damage, the potential roles of increased apoplastic reactive oxygen species in regulation of wall extension properties and other processes, region‐specific phenylpropanoid metabolism as related to accumulation of (iso)flavonoids and wall phenolics and amino acid metabolism. The results provide novel insights into the complexity and coordination of the processes involved in root growth at low water potentials.
Effects of exogenous GABA on gene expression of Caragana intermedia roots under NaCl stress: regulatory roles for H2O2 and ethylene production
Authors: SHI SHENG‐QING , SHI ZHENG , JIANG ZE‐PING , QI LI‐WANG , SUN XIAO‐MEI , LI CHUN‐XIU , LIU JIAN‐FENG , XIAO WEN‐FA , ZHANG SHOU‐GONG
Published: November 2009

γ‐aminobutyric acid (GABA) is a four‐carbon non‐protein amino acid presented in a wide range of organisms. In this study, a suppression subtractive hybridization (SSH) library was constructed using roots of a legume shrub, Caragana intermedia, with the combined treatment of 300 mm NaCl and 300 mm NaCl + 10 mm GABA. We obtained 224 GABA‐regulated unique expressed sequence tags (ESTs) including signal transduction, transcriptional regulation, hormone biosynthesis, reactive oxygen species (ROS) and polyamine metabolism, etc. The key H2O2‐generated genes, NADPH oxidase (CaGR60), peroxidase (CaGR61) and amine oxidase (CaGR62), were regulated at the mRNA level by 10 mm GABA, which clearly inhibited H2O2 accumulation brought about by NaCl stress in roots and leaves with the observation of 3,3′‐diaminobenzidine (DAB) staining. Similarly, 10 mm GABA also regulated the expression of 1‐aminocyclopropane‐1‐carboxylic acid (ACC) oxidase (ACO) genes (CaGR30 and CaGR31) and ethylene production in NaCl‐treated roots. Surprisingly, these H2O2‐generated genes were enhanced at the mRNA level by a lower concentration of GABA, at 0.25 mm, but not other alternative nitrogen sources, and endogenous GABA accumulated largely just by the application of GABA at either concentration. Our results further proved that GABA, as a signal molecule, participates in regulating the expression of genes in plants under salt stress.
Mimosa pudica: Electrical and mechanical stimulation of plant movements
Authors: VOLKOV ALEXANDER G. , FOSTER JUSTIN C. , ASHBY TALITHA A. , WALKER RONALD K. , JOHNSON JON A. , MARKIN VLADISLAV S.
Published: November 2009

Thigmonastic movements in the sensitive plant Mimosa pudica L., associated with fast responses to environmental stimuli, appear to be regulated through electrical and chemical signal transductions. The thigmonastic responses of M. pudica can be considered in three stages: stimulus perception, electrical signal transmission and induction of mechanical, hydrodynamical and biochemical responses. We investigated the mechanical movements of the pinnae and petioles in M. pudica induced by the electrical stimulation of a pulvinus, petiole, secondary pulvinus or pinna by a low electrical voltage and charge. The threshold value was 1.3–1.5 V of applied voltage and 2 to 10 µC of charge for the closing of the pinnules. Both voltage and electrical charge are responsible for the electro‐stimulated closing of a leaf. The mechanism behind closing the leaf in M. pudica is discussed. The hydroelastic curvature mechanism closely describes the kinetics of M. pudica leaf movements.
The effect of BDNF gene variants on asthma in German children
Authors: Zeilinger S. , Pinto L. A. , Nockher W. A. , Depner M. , Klopp N. , Illig T. , Von Mutius E. , Renz H. , Kabesch M.
Published: November 2009

Background:  Allergic inflammation can trigger neuronal dysfunction and structural changes in the airways and the skin. Levels of brain‐derived neurotrophic factor (BDNF) are strongly up regulated at the location of allergic inflammation.

Aim:  We systematically investigated whether polymorphisms in the BDNF gene influence the development or severity of asthma and atopic diseases.

Methods:  The BDNF gene was screened for mutations in 80 chromosomes. Genotyping of six BDNF tagging polymorphisms was performed in a cross‐sectional study population of 3099 children from Dresden and Munich (age 9–11 years, ISAAC II). Furthermore, polymorphisms were also investigated in an additional 655 asthma cases analysed with a random sample of 767 children selected from ISAAC II. Associations were calculated via chi‐square test and anova using SAS Genetics and spss.

Results:  We identified nine polymorphisms with minor allele frequency ≥0.03, one of them leading to an amino acid change from Valine to Methionine. In the cross‐sectional study population, no significant association was found with asthma or any atopic disease. However, when more severe asthma cases from the MAGIC study were analysed, significant asthma effects were observed with rs6265 (odds ratio 1.37, 95% confidence interval 1.14–1.64, P = 0.001), rs11030101 (OR 0.82, 95%CI 0.70–0.95, P = 0.009) and rs11030100 (OR 1.19, 95%CI 1.00–1.42, P = 0.05).

Conclusions:  As in previous studies, effects of BDNF polymorphisms on asthma remain controversial. The data may suggest that BDNF polymorphisms contribute to severe forms of asthma.
Interleukin (IL)‐31 induces pro‐inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins
Authors: Kasraie S. , Niebuhr M. , Werfel T.
Published: November 2009

To cite this article: Kasraie S, Niebuhr M, Werfel T. Interleukin (IL)‐31 induces pro‐inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins. Allergy 2010; 65: 712–721.

Background:  IL‐31 is a cytokine expressed by T cells following activation with cytokines or staphylococcal exotoxins. A major function of IL‐31 in atopic dermatitis (AD) is the induction of pruritus in the skin via the IL‐31 receptor on sensory nerve cells. However, the regulation of the IL‐31 receptor and pro‐inflammatory functions of IL‐31 in human monocytes and monocyte‐derived cells are yet to be studied in detail.

Objective:  To investigate the regulation and function of IL‐31 receptors in resting and activated human monocytes, macrophages and dendritic cells.

Methods:  Human monocytes, macrophages and dendritic cells were stimulated with staphylococcal exotoxins (SEB, α‐toxin) or cytokines (IFN‐γ, IL‐13). IL‐31RA expression and regulation were then investigated at both the mRNA and the protein level. Subsequently, functional effects of IL‐31 stimulation on cytokine secretion were measured at the protein level.

Results:  Staphylococcal exotoxins significantly up‐regulated IL‐31RA expression on monocytes and macrophages but not on dendritic cells at both the mRNA and the protein level. IL‐31 enhanced the secretion of IL‐1β, IL‐6 and IL‐18 and up‐regulated CD86 expression. In patients with AD, functional IL‐31RA was also detected following stimulation of PBMC with IFN‐γ. However, this was not observed in healthy individuals.

Conclusion:  IL‐31 induces pro‐inflammatory effects in activated human monocytes and macrophages. This may have implications for cutaneous inflammation in eczema where an over‐expression of IL‐31 has been described previously. Moreover, our findings provide a new link between staphylococcal colonization and the worsening of inflammation via IL‐31. Further therapeutic considerations may include IL‐31 as a target in AD.
Congenital melanocytic naevi
Authors: Kovalyshyn Ivanka , Braun Ralph , Marghoob Ashfaq
Published: November 2009

Congenital melanocytic naevi, consisting of clusters of naevo‐melanocytes, develop in utero. Although many congenital naevi are visible at birth, some may not become evident until later in life. The timing of naevo‐melanocyte proliferation, senescence and melanogenesis may all contribute towards determining when a naevus will become clinically manifest on the skin. Besides the fact that congenital melanocytic naevi may be aesthetically displeasing, resulting in a multitude of psychosocial issues, they also increase the risk for developing cutaneous melanoma, leptomeningeal melanoma, neurocutaneous melanocytosis, malformations of the brain and, rarely, other tumours such as rhabdomyosarcoma and liposarcoma. Whereas the risk of developing malignancy in association with congenital naevi is dependent, to some extent, on the size of the naevus, the risk of developing neurocutaneous melanocytosis correlates best with the number of satellite naevi. Management of patients with congenital melanocytic naevi requires individualization, taking into account the naevus size and location, and the risk of developing cutaneous melanoma or neurocutaneous melanocytosis. When contemplating treatment options, it is important to set realistic expectations and to address the possible aesthetic and functional outcomes, while at the same time addressing the risk for developing cutaneous and/or extracutaneous melanoma.
Cutaneous invasive squamous cell carcinoma: 10‐year experience and recommendations for follow up
Authors: Yoong Corinne , De'Ambrosis Brian
Published: November 2009

Currently, the National Health and Medical Research Council do not have any recommendations about the frequency of follow up after treatment of primary cutaneous invasive squamous cell cancer (SCC), due to a lack of data. The present study aimed to establish appropriate follow‐up times and to determine the long‐term risk of subsequent non‐melanoma skin cancers and melanoma. Patients who had a primary invasive cutaneous SCC excised during 1996 were retrospectively identified from the databases of a dermatologist in private practice in south‐east Queensland. Data on size, site, depth, differentiation, perineural involvement, lymphovascular involvement of the index SCC were obtained. The patients were regularly followed up and lymph‐node involvement, patient immunocompetence, and the presence of local recurrences and subsequent SCC, basal cell carcinomas and melanoma were recorded. Forty patients were identified, comprising 25 men and 15 women with a mean age of 65 years. The majority (60%) of primary incident SCC were in the low‐risk category. The median follow‐up time was 7.5 years. One in two developed a second SCC within 5 years, a significant number had a second SCC detected only in 5–10 year follow up, and 72.5% had a BCC within 5 years, and 82.5% at 10 years. One in eight had a subsequent melanoma detected.
Topical diphencyprone immunotherapy for cutaneous metastatic melanoma
Authors: Damian Diona L , Shannon Kerwin F , Saw Robyn P , Thompson John F
Published: November 2009

Topical immunotherapy with contact sensitizers for metastatic melanoma was first reported more than 30 years ago. Diphencyprone (DPCP) immunotherapy is frequently used to treat cutaneous warts and alopecia areata, and we have previously reported the use of DPCP as a single agent to successfully treat extensive, radiotherapy‐resistant melanoma metastases on the scalp. We now report DPCP treatment of a further six patients with cutaneous metastatic melanoma. Of seven patients treated with DPCP thus far, four have demonstrated complete responses of their cutaneous lesions and three have had partial responses. The treatment was well‐tolerated by all patients. Topical immunotherapy with DPCP is inexpensive and relatively non‐invasive and should be considered in patients with locally advanced skin metastases that are unsuitable for other therapies.
Managing depression across the life cycle: new strategies for clinicians and their patients
Authors: Hickie I. B. , Naismith S. L. , Norrie L. M. , Scott E. M.
Published: November 2009

Depression is the leading cause of non‐fatal disease burden in Australia. Recently, increasing public recognition, together with the development of more integrated medical and psychological healthcare services has resulted in significant improvements. New pathophysiological models incorporate structural brain changes with established changes in neurotransmitter function. Further, recognition of predisposing factors and the salience of differential ages of onset have led to more pragmatic diagnostic systems. There is an ongoing need to promote early recognition, better information to inform treatment choices and more comprehensive treatment programmes that incorporate behavioural and lifestyle factors in addition to the wide range of pharmacological therapies that are now available.
Single incision laparoscopic left colectomy for carcinoma of distal transverse colon
Authors: Law W.‐L. , Fan J. K. M. , Poon J. T. C.
Published: November 2009

Objective  We report a single‐incision laparoscopic left colectomy for a patient with a distal transverse colon cancer.

Method  A 78‐year‐old man with carcinoma of the transverse colon close to the splenic flexure underwent a single‐incision laparoscopic left colectomy with full mobilization of splenic flexure using the TriPort™ Access System and ordinary laparoscopic instruments.

Results  The operation was successfully performed. The patient recovered uneventfully and was discharged after 3 days. Histopathological examination showed a T3N1 tumour with clear resection margins.

Conclusion  This case demonstrates that single‐incision laparoscopic colectomy can be applied safely to large bowel cancer close to the splenic flexure. The technique warrants further investigation.
Integrating educational and technological interventions to improve pregnancy outcomes in women with diabetes
Authors: Murphy Helen R.
Published: November 2009

A gap currently exists between our expectations of tight blood glucose control and the reality of safely achieving it before and during pregnancy. Technological and pharmaceutical advances will not in isolation prevent poor pregnancy outcomes without recognising the social, cultural and behavioural context of the women living with diabetes. Neither will behavioural and/or educational programmes completely overcome the fundamentally disordered metabolic pathways and physiological challenges of pregnancy. Improved integration of the technological, behavioural and educational aspects of diabetes care will pave the way for truly personalized, interdisciplinary diabetes management and ultimately improved pregnancy outcomes for women with diabetes and their infants.
Selective effects of PPARγ agonists and antagonists on human pre‐adipocyte differentiation
Authors: Leyvraz C. , Suter M. , Verdumo C. , Calmes J.‐M. , Paroz A. , Darimont C. , Gaillard R. C. , Pralong F. P. , Giusti V.
Published: November 2009

Aim: The insulin sensitizer rosiglitazone (RTZ) acts by activating peroxisome proliferator and activated receptor γ (PPAR γ), an effect accompanied in vivo in humans by an increase in fat storage. We hypothesized that this effect concerns PPARγ1 and PPARγ2 differently and is dependant on the origin of the adipose cells (subcutaneous or visceral). To this aim, the effect of RTZ, the PPARγ antagonist GW9662 and lentiviral vectors expressing interfering RNA were evaluated on human pre‐adipocyte models.

Methods: Two models were investigated: the human pre‐adipose cell line Chub‐S7 and primary pre‐adipocytes derived from subcutaneous and visceral biopsies of adipose tissue (AT) obtained from obese patients. Cells were used to perform oil‐red O staining, gene expression measurements and lentiviral infections.

Results: In both models, RTZ was found to stimulate the differentiation of pre‐adipocytes into mature cells. This was accompanied by significant increases in both the PPARγ1 and PPARγ2 gene expression, with a relatively stronger stimulation of PPARγ2. In contrast, RTZ failed to stimulate differentiation processes when cells were incubated in the presence of GW9662. This effect was similar to the effect observed using interfering RNA against PPARγ2. It was accompanied by an abrogation of the RTZ‐induced PPARγ2 gene expression, whereas the level of PPARγ1 was not affected.

Conclusions: Both the GW9662 treatment and interfering RNA against PPARγ2 are able to abrogate RTZ‐induced differentiation without a significant change of PPARγ1 gene expression. These results are consistent with previous results obtained in animal models and suggest that in humans PPARγ2 may also be the key isoform involved in fat storage.
Diabetes and obesity: therapeutic targeting and risk reduction – a complex interplay
Authors: Niswender Kevin
Published: November 2009

Obesity is a major risk factor for the development of diabetes and predisposes individuals to hypertension and dyslipidaemia. Together these pathologies increase the risk for cardiovascular disease (CVD), the major cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). Worsening trends in obesity and T2DM raise a serious conundrum, namely, how to control blood glucose, blood pressure, and lipids when many antidiabetic agents cause weight gain and thereby exacerbate other cardiovascular risk factors associated with T2DM. Further, evidence suggests that some established antihypertensive agents may worsen glucose intolerance. Many patients who are obese, hypertensive, and/or hyperlipidaemic fail to achieve blood pressure, lipid and glycaemic goals, and this failure may in part be explained by physician reluctance to utilize complex combination regimens for fear of off‐target effects. Thus, a clear need exists for clinicians to understand the risks and benefits of different pharmacologic, and indeed non‐pharmacologic, options in order to maximize treatment outcomes. While intensive lifestyle modification remains an elusive gold standard, newer diabetes targets, including the incretin axis, may offer greater cardiovascular risk reduction than other antidiabetes therapies, although definitive clinical trial data are needed. The glucagon‐like peptide‐1 (GLP‐1) receptor agonists exenatide and liraglutide and the dipeptidyl peptidase‐4 (DPP‐4) inhibitors sitagliptin and vildagliptin effectively lower HbA1c; exenatide and liraglutide reduce weight and blood pressure and improve lipid profiles. Sitagliptin and vildagliptin are weight neutral but also appear to improve lipid profiles. Integration of incretin therapies into the therapeutic armamentarium is a promising approach to improving outcomes in T2DM, and perhaps even in reducing complications of T2DM, such as co‐morbid hypertension and dyslipidaemia. Additional long‐term studies, including CVD end‐point studies, will be necessary to determine the appropriate places for incretin‐based therapies in treatment algorithms.
The role of integrins in corneal wound healing
Authors: Carter Renee T.
Published: November 2009

Integrins are cell adhesion molecules important in cell–cell and cell–extracellular matrix interactions. These interactions are vital to numerous physiological processes including corneal wound healing. This review discusses the structure of integrins as well as the various roles that integrins play in the corneal wound healing process. Integrin profile abnormalities identified in various corneal pathological conditions are also reviewed.
Equine immune‐mediated keratopathies
Authors: Matthews Andrew , Gilger Brian C.
Published: November 2009

Equine immune mediated keratopathies are common in both Europe and the USA. This review article will compare the clinical differences in horses with this disease and also review the current theories on pathogenesis and treatment of equine IMMK.
The use of amniotic membrane transplantation for ocular surface reconstruction: a review and series of 58 equine clinical cases (2002–2008)
Authors: Plummer Caryn E.
Published: November 2009

Amniotic membrane transplantation (AMT) is an effective clinical therapy for reconstruction of the ocular surface in human and veterinary patients. Amnion is avascular and strong, contains antiangiogenic and antiinflammatory properties and growth factors, and has properties that prevent or decrease fibrosis in healing tissue. Indications for its use are steadily growing and include grafting to replace diseased, missing or excised tissue, patching to support diseased tissue during the healing process and as a substrate for the expansion of epithelial cells for transplantation to the cornea. AMT through a combination of mechanical and biologic factors can preserve the integrity of the globe, optimize the visual outcome, and minimize scarring in severely diseased corneas.
Meet the corneal myofibroblast: the role of myofibroblast transformation in corneal wound healing and pathology
Authors: Myrna Kathern E. , Pot Simon A. , Murphy Christopher J.
Published: November 2009

In recent years the role of the myofibroblast in corneal wound healing has been extensively studied. The transformation of the corneal keratocyte to the fibroblast and myofibroblast phenotypes is a critical process in normal and pathologic corneal wound healing. This review will introduce this important transformation and its role in corneal wound healing and pathology.
The relevance of a hypoxic tumour microenvironment in prostate cancer
Authors: Stewart Grant D. , Ross James A. , McLaren Duncan B. , Parker Christopher C. , Habib Fouad K. , Riddick Antony C.P.
Published: November 2009

Research into the hypoxic tumour microenvironment is accelerating and the reversal of hypoxia is increasingly being suggested as a mechanism for improving cancer treatment. Recent studies have suggested that hypoxia is also a feature in prostate cancer and is associated with a poor prognosis. Hypoxia has been shown to cause radio‐resistance and hence hamper one of the major treatments for prostate cancer. However, unlike other solid tumours, such as cervical and head‐and‐neck cancer, there are inconsistencies and unanswered questions about the relevance of hypoxia in prostate cancer. This review outlines the role of low‐oxygen conditions in prostate cancer and the areas where further studies are required.