bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial dynamics of the 1918 influenza pandemic in England, Wales and the United States
Authors: Eggo Rosalind M. , Cauchemez Simon , Ferguson Neil M.
Published: June 2010

There is still limited understanding of key determinants of spatial spread of influenza. The 1918 pandemic provides an opportunity to elucidate spatial determinants of spread on a large scale.

To better characterize the spread of the 1918 major wave, we fitted a range of city-to-city transmission models to mortality data collected for 246 population centres in England and Wales and 47 cities in the US. Using a gravity model for city-to-city contacts, we explored the effect of population size and distance on the spread of disease and tested assumptions regarding density dependence in connectivity between cities. We employed Bayesian Markov Chain Monte Carlo methods to estimate parameters of the model for population, infectivity, distance and density dependence. We inferred the most likely transmission trees for both countries.

For England and Wales, a model that estimated the degree of density dependence in connectivity between cities was preferable by deviance information criterion comparison. Early in the major wave, long distance infective interactions predominated, with local infection events more likely as the epidemic became widespread. For the US, with fewer more widely dispersed cities, statistical power was lacking to estimate population size dependence or the degree of density dependence, with the preferred model depending on distance only. We find that parameters estimated from the England and Wales dataset can be applied to the US data with no likelihood penalty.
Optimal viral strategies for bypassing RNA silencing
Authors: Rodrigo Guillermo , Carrera Javier , Jaramillo Alfonso , Elena Santiago F.
Published: June 2010

The RNA silencing pathway constitutes a defence mechanism highly conserved in eukaryotes, especially in plants, where the underlying working principle relies on the repressive action triggered by the intracellular presence of double-stranded RNAs. This immune system performs a post-transcriptional suppression of aberrant mRNAs or viral RNAs by small interfering RNAs (siRNAs) that are directed towards their target in a sequence-specific manner. However, viruses have evolved strategies to escape from silencing surveillance while promoting their own replication. Several viruses encode suppressor proteins that interact with different elements of the RNA silencing pathway and block it. The different suppressors are not phylogenetically nor structurally related and also differ in their mechanism of action. Here, we adopt a model-driven forward-engineering approach to understand the evolution of suppressor proteins and, in particular, why viral suppressors preferentially target some components of the silencing pathway. We analysed three strategies characterized by different design principles: replication in the absence of a suppressor, suppressors targeting the first protein component of the pathway and suppressors targeting the siRNAs. Our results shed light on the question of whether a virus must opt for devoting more time into transcription or into translation and on which would be the optimal step of the silencing pathway to be targeted by suppressors. In addition, we discussed the evolutionary implications of such designing principles.
A first integral of Navier–Stokes equations and its applications
Authors: Scholle Markus , Haas André , Gaskell Philip H.
Published: June 2010

Although it is well known that Bernoulli's equation is obtained as the first integral of Euler's equations in the absence of vorticity and that in the case of non-vanishing vorticity a first integral of them can be found using the Clebsch transformation for inviscid flow, generalization of the procedure for viscous flow has remained elusive. Accordingly, in this paper, a first integral of the Navier–Stokes equations for steady flow is constructed. In the case of a two-dimensional flow, this is made possible by formulating the governing equations in terms of complex variables and introducing a new scalar potential. Associated boundary conditions are considered, and an extension of the theory to three dimensions is proposed. The capabilities of the new approach are demonstrated by calculating a Reynolds number correction to the laminar shear flow generated in the narrow gap between a flat moving and a stationary wavy wall, as is often encountered in lubrication problems. It highlights the first integral as a suitable tool for the development of new analytical and numerical methods in fluid dynamics.
Diet and hormonal manipulation reveal cryptic genetic variation: implications for the evolution of novel feeding strategies
Authors: Ledón-Rettig Cris C. , Pfennig David W. , Crespi Erica J.
Published: June 2010

When experiencing resource competition or abrupt environmental change, animals often must transition rapidly from an ancestral diet to a novel, derived diet. Yet, little is known about the proximate mechanisms that mediate such rapid evolutionary transitions. Here, we investigated the role of diet-induced, cryptic genetic variation in facilitating the evolution of novel resource-use traits that are associated with a new feeding strategy—carnivory—in tadpoles of spadefoot toads (genusSpea). We specifically asked whether such variation in trophic morphology and fitness is present inScaphiopus couchii, a species that serves as a proxy for ancestralSpea. We also asked whether corticosterone, a vertebrate hormone produced in response to environmental signals, mediates the expression of this variation. Specifically, we compared broad-sense heritabilities of tadpoles fed different diets or treated with exogenous corticosterone, and found that novel diets can expose cryptic genetic variation to selection, and that diet-induced hormones may play a role in revealing this variation. Our results therefore suggest that cryptic genetic variation may have enabled the evolutionary transition to carnivory inSpeatadpoles, and that such variation might generally facilitate rapid evolutionary transitions to novel diets.
Pre-exposure to context affects learning strategy selection in mice
Authors: Tunur Tumay , Dohanich Gary P. , Schrader Laura A.
Published: June 2010

The multiple memory systems hypothesis proposes that different types of learning strategies are mediated by distinct neural systems in the brain. Male and female mice were tested on a water plus-maze task that could be solved by either a place or response strategy. One group of mice was pre-exposed to the same context as training and testing (PTC) and the other group was pre-exposed to a different context (PDC). Our results show that the PTC condition biased mice to place strategy use in males, but this bias was dependent on the presence of ovarian hormones in females.
Chronic idiopathic urticaria: prevalence and clinical course
Authors: KULTHANAN Kanokvalai , JIAMTON Sukhum , THUMPIMUKVATANA Narumol , PINKAEW Sumruay
Published: June 2010

The purpose of our study was to assess the prevalence and clinical course of patients with chronic idiopathic urticaria (CIU), as well as possible causes or associated findings, laboratory findings and the duration of the disease in patients with chronic urticaria (CU). We retrospectively reviewed the 450 case record forms of patients with CU and/or angioedema who attended the Department of Dermatology, Siriraj Hospital, during the period 2000–2004. Of 450 patients with CU, 337 patients (75%) were diagnosed as CIU. Forty‐three patients (9.5%) had physical urticaria, while 17 patients (3.8%) had infectious causes. Other possible causes were food, thyroid diseases, atopy, drugs, dyspepsia and collagen vascular diseases. In eighty‐nine percent of patients, no abnormalities were detected at the time of physical examination. The most common abnormal laboratory finding was minimal elevation of the erythrocyte sedimentary rate (42%). In 61 patients, autologous serum skin tests had been done. Fifteen patients (24.5%) had positive results i.e. autoimmune urticaria. Anti‐thyroglobulin and anti‐microsomal antibodies were positive in 16 % and 12% of CIU patients respectively. After 1 year from the onset of the symptoms, 34.5% of CIU patients were free of symptoms and after 1.2 years from the onset of the symptoms, 56.5% of autoimmune urticaria patients were free of symptoms. The median disease duration of CIU and autoimmune urticaria were 390 days and 450 days respectively. Our study provided an overview of CU and CIU in a large series of Thai patients, based on etiological aspects and clinical courses.
WASP and WAVE family proteins: Friends or foes in cancer invasion?
Authors: Kurisu Shusaku , Takenawa Tadaomi
Published: June 2010

Wiskott–Aldrich syndrome protein (WASP) and WASP family verprolin‐homologous protein (WAVE) family proteins activate cells’ major actin nucleating machinery, the actin‐related protein 2/3 (Arp2/3) complex, leading to the formation and remodeling of cortical actin filament networks. Cortical actin regulation is critical in many aspects of cell physiology including cell–cell adhesion and cell motility, whose dysregulation is directly associated with cancer invasion and metastasis. In line with this association, the WASP and WAVE family proteins have been reported to be involved in cancer malignancies. What is puzzling, however, is that they can act as either enhancers or suppressors of cancer malignancies depending on the type of cancer and its pathological stage. We are still far from understanding the roles of the WASP and WAVE family proteins in cancer progression. Here, we summarize the recent advances of studies of the WASP and WAVE family proteins with respect to cancer invasion and we offer a model that can account for the diverse outcomes originating from dysregulated WASP and WAVE family proteins in cancer development. (Cancer Sci 2010.)
Identification of acute myeloid leukaemia associated microRNA expression patterns
Authors: Isken Fabienne , Steffen Björn , Merk Sylvia , Dugas Martin , Markus Birgit , Tidow Nicola , Zühlsdorf Michael , Illmer Thomas , Thiede Christian , Berdel Wolfgang E. , Serve Hubert , Müller‐Tidow Carsten
Published: June 2010

MicroRNAs (miRNAs) play an important role in cellular differentiation and cancer pathogenesis. This study analysed the expression of 154 human miRNAs in acute myeloid leukaemia (AML) and control samples using a stem‐loop real‐time reverse transcription polymerase chain reaction approach. Global patterns of miRNA expression in AML, normal bone marrow (NBM) and CD34+ progenitor cells allowed correct class predictions similar to whole genome microarray expression analyses that were performed at the same time. At single miRNA species level, MIRN23B was repressed in AML specimens compared to NBM and purified CD34+ haematopoietic progenitor cells. In contrast, the MIRN221/MIRN222 cluster and MIRN34A were expressed at significantly higher levels in AML blasts. Patients with high MIRN221/MIRN222 expression showed low levels of KIT RNA and protein expression but the correlation between kit protein and KIT mRNA was significantly stronger than the correlation of either one with MIRN221/MIRN222. A global analysis between miRNA expression levels and mRNA expression of predicted target genes revealed only weak associations in the majority of miRNA species. Nonetheless, the presence of two or more miRNA binding sites within the mRNA was usually associated with a decrease in mRNA levels. Taken together, these findings provide evidence that specific miRNA expression patterns exist in AML.
Parathyroid hormone stimulates the endothelial expression of vascular endothelial growth factor
Authors: Rashid G. , Bernheim J. , Green J. , Benchetrit S.
Published: June 2010

Background  We showed previously that parathyroid hormone (PTH) may stimulate the endothelial expression of pro‐atherosclerotic and pro‐inflammatory markers. Considering the impact of PTH on vasculature, we decided to evaluate its effect on mRNA and intra‐cellular protein expressions of endothelial vascular endothelial growth factor (VEGF) taking into account that VEGF may play a role in the pathogenesis of endothelial dysfunctions.

Materials and methods  Human umbilical vein cords endothelial cells (HUVEC) were stimulated for 24 h with 10−12–10−10 mol L−1 PTH. The VEGF‐165 mRNA expression (critical in stimulating endothelial cell proliferation) was evaluated by RT/PCR and the intra‐cellular VEGF protein expression by flow cytometry. The pathways by which PTH may have an effect on VEGF expression were also evaluated.

Results  PTH (10−10 mol L−1) significantly increased VEGF‐165 mRNA expression (P < 0·05). The addition of 50 nmol L−1 protein kinase C (PKC) and 10 µmol L−1 protein kinase A (PKA) inhibitors significantly reduced the VEGF‐165 mRNA expression (P = 0·01). We also examined whether nitric oxide (NO) may be involved in the PTH‐induced stimulation of VEGF‐165 expression. Pre‐treatment of the cells with 200 µmol L‐nitro arginine methyl ester (L‐NAME, NO synthase inhibitor) was found to inhibit VEGF‐165 mRNA expression (P = 0·006). VEGF protein could not be detected in the medium of HUVEC but it was present in the cell cytoplasm. PTH had no significant effect on cytoplasmatic VEGF protein expression.

Conclusion  The stimulatory effect of PTH on endothelial VEGF‐165 mRNA expression is partly through PKC and PKA pathways and is also NO dependent.
Treatment responses to cladribine and dasatinib in rapidly progressing aggressive mastocytosis
Authors: Aichberger K. J. , Sperr W. R. , Gleixner K. V. , Kretschmer A. , Valent P.
Published: June 2010

Background  Systemic mastocytosis (SM) is a mast cell neoplasm in which neoplastic cells usually display the D816V‐mutated variant of KIT. Cladribine (2CdA) and dasatinib are two drugs that counteract the in vitro growth of neoplastic mast cells in SM. However, only little is known about the in vivo effects of these drugs in SM.

Patient and methods  We report on a patient with highly aggressive interferon‐alpha‐resistant SM who was treated with 2CdA and dasatinib. In vitro pretesting revealed a response of neoplastic mast cells to both compounds with reasonable IC50 values.

Results  The patient was treated with six cycles of 2CdA (0·13 mg kg−1 intravenously daily on 5 consecutive days). Despite a short‐lived major clinical response and a decrease in serum tryptase, the patient progressed to mast cell leukaemia after the sixth cycle of 2CdA. The patient then received two further courses of 2CdA followed by treatment with dasatinib (100 mg per os daily). However, no major response was obtained and the patient died from disease progression after 2 months.

Conclusions  In a patient with rapidly progressing aggressive SM, neither 2CdA nor dasatinib produced a long‐lasting response in vivo, despite encouraging in vitro results. For such patients, alternative treatment strategies have to be developed.
Role of glucocorticoid receptor polymorphism in adrenal incidentalomas
Authors: Morelli Valentina , Donadio Francesca , Eller‐Vainicher Cristina , Cirello Valentina , Olgiati Luca , Savoca Chiara , Cairoli Elisa , Salcuni Antonio Stefano , Beck‐Peccoz Paolo , Chiodini Iacopo
Published: June 2010

Eur J Clin Invest 2010; 40 (9): 803–811

Background  Adrenal incidentalomas (AI) have been associated with and an increased prevalence of metabolic and bone complications. The N363S and BclI polymorphisms of the glucocorticoid receptor (GR) have been associated with an increased sensitivity to glucocorticoid (GC). This observational study aims to evaluate whether BclI and N363S polymorphisms play a role in the development of complications in AI.

Materials and methods  We enrolled 100 patients with AI (66 F; 34M). The presence of diabetes, arterial hypertension (AH), dyslipidaemia, osteoporosis and vertebral fracture (Fx), waist circumference and the Body Mass Index (BMI) were assessed. DNA samples were genotyped. Patients with wild‐type BclI, wild‐type N363S and heterozygous BclI polymorphism were classified as carriers of haplotype 1 (H1; n = 86), patients with homozygous BclI and heterozygous N363S polymorphism of GR of haplotype 2 (H2; n = 14).

Results  We found no clinical or biochemical differences between haplotype 1 and 2 groups, but a higher prevalence of the simultaneous presence of Fx plus AH in H2 patients (H2 n = 7, H1 n = 16, P = 0·01). Logistic regression analysis showed that the presence of Fx and of AH and the combination of the presence of Fx plus AH were associated with the H2 genotype regardless of the degree of cortisol secretion, age, BMI and BMD (OR 4·88, 95%CI 1·47–18·40, P = 0·05; OR 8·25, 95%CI 0·98–69·52, P = 0·05; OR 7·25, 95%CI 1·57–35·78, P = 0·011; respectively).

Conclusions  In AI patients, the presence of the haplotype 2 of BclI and N363S is associated with the presence of AH, Fx and with the combination of Fx and AH.
Secondary vascular changes in pulmonary sequestrations
Authors: Desai Saral , Dusmet Michael , Ladas George , Pomplun Sabine , Padley Simon P G , Griffin Nyree , Badreddine Jamal , Goldstraw Peter , Nicholson Andrew G
Published: June 2010

Desai S, Dusmet M, Ladas G, Pomplun S, Padley S P G, Griffin N, Badreddine J, Goldstraw P & Nicholson A G (2010) Histopathology 57, 121–127 Secondary vascular changes in pulmonary sequestrations

Aims:  Whilst parenchymal changes in pulmonary sequestrations are well described, there are comparatively little data on associated vascular changes and their extent. The aim of this study was to retrospectively review morphological changes within sequestrations, concentrating on vascular changes and associations with clinical parameters.

Methods and results:  Twenty‐seven resected cases of sequestrations (intralobar n = 20, extralobar n = 7) showed a male predominance (n = 16) and an age range of 2 months–60 years (average 13 years). Plexogenic vascular changes (medial hypertrophy and intimal fibrosis) were seen in 15 of 27 cases, as well as plexiform lesions in seven cases. Patients with plexogenic changes had a higher mean age compared with those lacking vascular changes (19 versus 6 years) and were more commonly female. Respiratory tract infections were associated solely with intralobar sequestrations. No other associations between presenting symptoms and histopathological parameters were identified. Adjacent lung showed lesser plexogenic changes in six of 22 intralobar cases. There were features of type 2 congenital cystic adenomatoid lesions in 63% of cases. Dissection of the supplying systemic artery (n = 1), intralesional aspergilloma (n = 1) and coexistent lymphangiomatosis (n = 1) were also identified.

Conclusions:  Hypertensive vascular changes are not uncommon in both intrapulmonary and extrapulmonary sequestrations, although their relative severity seems unrelated to presenting symptoms.
Expression of the reversion‐inducing cysteine‐rich protein with Kazal motifs and matrix metalloproteinase‐14 in neuroblastoma and the role in tumour metastasis
Authors: Dong Qian , Yu Dan , Yang Chuan‐Min , Jiang Buxian , Zhang Hong
Published: June 2010

Neuroblastoma is the most common malignant tumour in infancy; the reversion‐inducing cysteine‐rich protein with Kazal motifs gene (RECK) is a tumour suppressor gene. Previous studies show that RECK inhibits tumour invasion and metastasis through negative regulation of the matrix metalloproteinase (MMP)‐2, MMP‐9 and MMP‐14. Therefore, we wanted to detect the expression of RECK and MMP‐14 in neuroblastomas to assess the correlation between the expression levels of these proteins, and to investigate the roles in the metastasis and development of the tumour. PV‐6000 immunohistochemistry method was used to detect the expression levels of RECK and MMP‐14 in 36 samples of neuroblastoma tissue. Samples from paraffin wax‐embedded specimens and the complete clinicopathological data of 36 neuroblastoma and 10 ganglioneuroma patients were collected. The rate of expression of the RECK protein in the neuroblastoma was low (16.7%). Furthermore, it reduced with the increase in the invasive depth and distant metastasis (P = 0.015; P < 0.05). The rate of expression of the MMP‐14 protein in the neuroblastoma was high (58.3%) and increased with the increase in the extent of invasive depth and distant metastasis (P = 0.002; P < 0.05). The expression of the RECK protein correlated negatively with that of MMP‐14 (r = −0.418; P < 0.05). Low levels of the RECK protein are expressed in the neuroblastoma, while the MMP‐14 protein is expressed at high levels. The RECK and MMP‐14 proteins may serve as markers in the estimation of the extent of metastasis and dissemination of the neuroblastoma.
Leptin Resistance During Pregnancy in the Rat
Authors: Ladyman S. R.
Published: June 2010

The adipose‐derived hormone leptin primarily acts in the hypothalamus to decrease appetite and increase energy expenditure, thereby maintaining body fat levels around a set point. Pregnancy is a physiological state where this feedback mechanism is not beneficial. Successful reproductive efforts are highly demanding on the resources of the mother; thus, it is imperative that the maternal body can increase energy stores without restraint. Food intake, fat mass and serum leptin concentrations increase during pregnancy in the rat, suggesting that the feedback loop between adipose tissue and appetite is disrupted and a state of leptin resistance exists. In support of this, there is an attenuation of the satiety response to exogenous leptin administration in pregnant rats. This state of leptin resistance is associated with impaired activation of the leptin‐induced Janus activating kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the ventromedial nucleus of the hypothalamus (VMH) and arcuate nucleus, and reduced expression of leptin receptor mRNA in the VMH. Furthermore, pregnant rats do not show a satiety response to exogenous alpha‐melanocyte stimulating hormone. This model offers the possibility of examining how hypothalamic leptin signalling can be modified in response to changes in physiological conditions.
Co‐Expression of Leptin and Oestrogen Receptors in the Preoptic‐Hypothalamic Area
Authors: Del Bianco‐Borges B. , Cabral F. J. , Franci C. R.
Published: June 2010

The interaction between the reproductive axis and energy balance suggests that leptin acts as a possible mediator. This hormone acts in the regulation of metabolism, feeding behaviour and reproduction. Animals homozygous for the gene ‘ob’ (ob/ob) are obese and infertile, and these effects are reversed after systemic administration of leptin. Thus, the present study aimed to determine: (i) whether cells that express leptin also express oestrogen receptors of type‐α (ER‐α) or ‐β (ER‐β) in the medial preoptic area (MPOA) and in the arcuate (ARC), dorsomedial (DMH) and ventromedial hypothalamic nucleus and (ii) whether there is change in the gene and protein expression of leptin in these brain areas in ovariectomised (OVX) animals when oestrogen‐primed. Wistar female rats with normal oestrous cycles or ovariectomised oestrogen‐primed or vehicle (oil)‐primed were utilised. To determine whether there was a co‐expression, immunofluorescence was utilised for double staining. Confocal microscopy was used to confirm the co‐expression. The technique of real‐time polymerase chain reaction and western blotting were employed to analyse gene and protein expression, respectively. The results obtained showed co‐expression of leptin and ER‐α in the MPOA and in the DMH, as well as leptin and ER‐β in the MPOA, DMH and ARC. However, we did not detect leptin in the MPOA, ARC and DMH using western blotting and there was no statistical difference in leptin gene expression in the MPOA, DMH, ARC, pituitary or adipose tissue between OVX rats treated with oestrogen or vehicle. In conclusion, the results obtained in the present study confirm that the brain is also a source of leptin and reveal co‐expression of oestrogen receptors and leptin in the same cells from areas related to reproductive function and feeding behaviour. Although these data corroborate the previous evidence obtained concerning the interaction between the action of brain leptin and reproductive function, the physiological relevance of this interaction remains uncertain and additional studies are necessary to elucidate the exact role of central leptin.
Occupational allergy to bell pepper pollen in greenhouses in the Netherlands, an 8‐year follow‐up study
Authors: Patiwael J. A. , Jong N. W. , Burdorf A. , Groot H. , Gerth van Wijk R.
Published: June 2010

To cite this article: Patiwael JA, Jong NW, Burdorf A, Groot H, Gerth van Wijk R. Occupational allergy to bell pepper pollen in greenhouses in the Netherlands, an 8‐year follow‐up study. Allergy 2010; 65: 1423–1429.

Background:  Pollen from bell pepper plants cultivated in greenhouses are known to cause occupational allergic disease. A cross‐sectional study among 472 bell pepper employees in 1999 estimated prevalences for sensitization to bell pepper pollen of 28% and for work‐related allergic symptoms of 54%. There is scarce information on the incidence of work‐related allergy and its risk factors. Aims of the present study were to estimate the cumulative incidence of work‐related symptoms and sensitization to bell pepper pollen, and to determine risk factors for the onset of these symptoms and sensitization.

Methods:  Bell pepper employees who participated in a cross‐sectional survey in 1999 were asked to take part in a follow‐up study in 2007. Information on demographic characteristics, job characteristics and allergic symptoms was gathered by means of a questionnaire. Furthermore, skin tests were performed with a.o. bell pepper pollen.

Results:  In total, 280 of 472 employees were available for questionnaires and in 250 employees allergy tests were performed. During the 8‐year follow‐up, the cumulative incidence of sensitization to bell pepper pollen was 9% and of work‐related rhinitis 19%. Atopy [odds ratio (OR) 5.60] and smoking (OR 3.53) were significantly associated with development of rhinitis. The cumulative incidence of work‐related asthma symptoms was 8%. Again atopy (OR 5.03) and smoking (OR 11.85) were significant risk factors.

Conclusion:  Cumulative incidences for sensitization to bell pepper pollen, work‐related rhinitis and asthma symptoms were 9%, 19% and 8%, respectively. Atopy and smoking are risk factors for developing work‐related symptoms among workers in bell pepper horticulture.
Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review
Authors: Choo K. J. L. , Simons E. , Sheikh A.
Published: June 2010

To cite this article: Choo KJL, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy 2010; 65: 1205–1211.

Background:  Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis.

Objectives:  We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis.

Methods:  We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI‐EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi‐randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion.

Results:  None of the 2496 reports identified satisfied the inclusion criteria.

Conclusions:  We conclude that there is no evidence from high‐quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose.
Early markers for protective mechanisms during rush venom immunotherapy
Authors: Bussmann C. , Xia J. , Allam J.‐P. , Maintz L. , Bieber T. , Novak N.
Published: June 2010

To cite this article: Bussmann C, Xia J, Allam J‐P, Maintz L, Bieber T, Novak N. Early markers for protective mechanisms during rush venom immunotherapy. Allergy 2010; 65: 1558–1565.

Background:  Allergen‐specific venom immunotherapy (VIT) represents the only rational‐based option to treat allergic sensitizations against bee and wasp venom. So far, there is not much knowledge about early induction of protective and tolerogenic pathways during VIT.

Objectives:  To identify the earliest markers for protective mechanisms against allergic reactions in the peripheral blood during the build‐up phase of VIT.

Methods:  PBMC and monocytes were isolated, and serum samples were taken before and during a five day build‐up phase from 65 hymenoptera venom allergic patients. Expression level of tolerogenic markers was analyzed on mRNA and protein level. Serum levels of different soluble tolerogenic factors were measured.

Results:  We observed significantly enhanced tryptophan degradation, elevated ILT4 expression of monocytes as well as IL‐10 production of CD3+ T cells only a few hours after the first injection on day 1, followed by increased IL‐10 serum levels, monocyte apoptosis and elevated intracellular cAMP levels of monocytes on day 3 combined with a higher ILT3 protein expression and IL‐10 secretion of monocytes on day 5.

Conclusion:  From these data, we conclude that tryptophan depletion, ILT3/4‐mediated inhibition, higher IL‐10 production as well as intracellular cAMP might contribute to early induction of protective mechanisms against allergic reactions during the build‐up phase of VIT.
Root System Size Influences Water‐Nutrient Uptake and Nitrate Leaching Potential in Wheat
Authors: Ehdaie B. , Merhaut D. J. , Ahmadian S. , Hoops A. C. , Khuong T. , Layne A. P. , Waines J. G.
Published: June 2010

Environmental and economic considerations require the effective use of water and nutrients to elevate grain production in bread wheat (Triticum aestivumL.) with concomitant reduction in nitrate leaching to minimize contamination of underground water. We determined the effect of the root system on leaching fraction, leachate N concentration, and N, P and K uptake using bread wheat ‘Pavon 76’ and its three near‐isogenic translocation lines: Pavon 1RS.1AL, Pavon 1RS.1BL and Pavon 1RS.1DL. These genotypes were grown in sand‐tube experiments under optimum and low level of nutrients for 2 years. Root, stem and leaves, and grain N, P, and K content, and agronomic characters were measured. Leaching fraction and leachate nitrate concentration were measured at early tillering, booting and early grain filling. Significant main effects for year, nutrient level and genotype were found for the characters. Genotype × N interaction was significant only for root P content. Genotype × year interaction was significant only for plant N content, root P content and plant P content. Genotype × year × N interaction was significant only for root N uptake efficiency. Thus, genotypic means averaged across years and nutrient levels are reported. Low levels of nutrients (1330, 235 and 793 mg vs. 1915, 375 and 1268 mg N, P and K, respectively) reduced mean root biomass, plant biomass and grain yield by 27 %, 25 %, and 19 %, respectively. The translocation lines produced 31–46 % more root biomass, 11–14 % heavier grains and 6–8 % greater grain yield than Pavon 76. Leaching fraction was higher under low level of nutrient at booting and grain filling. Leaching fraction at tillering, booting, and grain filling was 67%, 42% and 25%, respectively. Leaching fraction at early tillering was lower for Pavon 1RS.1AL (39 %) and Pavon 1RS.1DL (40.5 %) than for Pavon 76 (45.3 %). Leachate nitrate concentration was lower for two translocation lines at all three stages of plant growth compared to Pavon 76. The correlation coefficient between plant N content and root biomass, between plant N content and plant biomass, and between grain yield and root biomass was positive and significant. Significant positive correlation was found between root biomass and P and K uptake. Multiple small applications of N fertilizer during early plant growth with adequate irrigation water are recommended. Wheat genotypes with superior root characteristics for efficient nutrient uptake, especially during tillering and booting, should be developed in breeding programmes to increase grain yield and to minimize the nitrate leaching.
Dendrochronological assessment of the time since death of dead wood in an old growth Magellan's beech forest, Navarino Island (Chile)
Authors: LOMBARDI FABIO , COCOZZA CLAUDIA , LASSERRE BRUNO , TOGNETTI ROBERTO , MARCHETTI MARCO
Published: June 2010

The present study investigated the relationship between time since death and the morphological characteristics of fallen dead trees in a Nothofagus betuloides forest stand located on the island of Navarino (Chile). In this unmanaged forest, there were 399 m3 ha−1 of dead wood, which represented about half of the living tree volume. At the investigation site, 18 living trees were selected and increment cores were collected from them to build master ring‐width chronologies. Cross sections were also collected from 48 fallen dead trees. The samples collected were then assigned to observable decay classes and their death date was determined dendrochronologically. Cross‐dating techniques were used and it was found that the fallen dead trees cross‐dated significantly with standard chronologies. A year of death was successfully determined for 75% of the sampled fallen dead trees. However, this study demonstrated that, in the standard classification, the transition rate from one class of decay to another was highly variable. Furthermore, the inconsistencies found in the decay rates of the fallen dead trees demonstrated that the existing decay classification schemes were unsuitable for this type of forest stand and that the relationship between qualitatively assessed decay classes and the time since death of trees in this extreme environment was rather weak. In addition, the analysis of the time since death, in this old growth forest, was indicative of the persistence of dead wood on the forest floor in austral cold ecosystems and of its contribution to long‐term carbon storage.
Local‐scale spatial dynamics of ants in a temperate agroecosystem
Authors: CHONG CHEE‐SENG , HOFFMANN ARY A. , THOMSON LINDA J.
Published: June 2010

At the local scale, spatial aggregations in ant distribution are often thought to be driven by competitive interactions among dominant ant species, although niche preferences and habitat heterogeneity might also lead to patchiness. Nevertheless, competitive interactions might be particularly important in agroecosystems that are structurally more homogeneous than natural habitats. The spatial patterns of ants in two Australian vineyards were investigated by intensive pitfall trapping to examine if non‐random patterns occur and whether these might be the result of competitive species interactions as well as the influence of woody vegetation adjacent to the vineyards. Null model analyses suggested competitive species interactions within ant assemblages that might have been driven by numerically dominant species, even though both positive and negative associations between these were found. Consistent spatial aggregations indicated significant spatial overlap in distributions of some species. Such overlap suggests that potential coexistence might be attributed to temporal partitioning or differences in foraging strategies. The presence of woody vegetation had a marked influence on ant assemblage structure and competitive interactions, and might facilitate coexistence by increasing resource heterogeneity. The implications of these findings for sampling strategies and ecological processes within vineyards are discussed.
Grassland restoration after afforestation: No direction home?
Authors: ZALOUMIS NICHOLAS P. , BOND WILLIAM J.
Published: June 2010

The coastal grasslands in north‐eastern South Africa are a severely threatened vegetation type rich in plant species, particularly forbs. Many of the forbs have underground storage organs which allow them to resprout rapidly after fires. A significant portion of this land was placed under commercial pine afforestation in the 1950s. The pine plantations have since been removed starting 17 years ago and restored to grasslands within a conservation area. We assessed the effects of plantations on grassland plant diversity and functional trait composition by sampling 64 circular quadrats of 5 m radius distributed equally in restored versus natural grasslands. The difference in plant diversity was dramatic with the natural grassland supporting 221 species of which 163 were forbs compared with 144 and only 73 forb species in restored grasslands. Major differences in species composition were recorded, especially for forb species. Natural grasslands were dominated by resprouters (130 species) but these were rare in the restored grasslands (36 species). Differences in plant species response to fire were also evident for the two grassland states. In contrast to coastal forest restoration studies in the same area which have shown near linear increases in woody species with time, restored grasslands showed no increase in forb species richness with increasing time since clear‐felling of pines. Our results indicate that current methods for restoring these grasslands are inadequate and that restoring grasslands may be a lot harder than previously thought. Considerable effort should be made in conserving what is left of natural grasslands.
Marked gestational edema as a clinical sign of life‐threatening condition
Authors: Koyama Takahiro , Yamada Takashi , Morikawa Mamoru , Tanaka Rieko , Yamamura Mie , Araki Naoto , Yamada Takahiro , Shimada Shigeki , Minakami Hisanori
Published: June 2010

A 35‐year‐old Japanese nulliparous woman exhibited rapid weight gain (6 kg/7 days), reduced antithrombin activity and platelet count at 37 weeks of gestation without hypertension or proteinuria, and underwent cesarean section. Postnatally, pulmonary edema developed for 7 days, with transient hypertension and proteinuria, and bodyweight loss (14.6 kg) by 14 days postpartum. Platelet count and antithrombin activity normalized promptly postpartum. Despite a life‐threatening clinical condition due to enhanced vascular permeability, neither hypertension nor proteinuria appeared antenatally. Determining antithrombin activity and platelet count may be useful for distinguishing between women with pathological edema and physiological edema.
Recent trends in the prevalence of and factors associated with maternal smoking during pregnancy in Japan
Authors: Suzuki Kohta , Sato Miri , Tanaka Taichiro , Kondo Naoki , Yamagata Zentaro
Published: June 2010

Aim:  To compare the prevalence of maternal smoking during pregnancy and the correlations between maternal smoking and other maternal lifestyle or pregnancy factors between the years 1996–2001 and 2001–2006.

Methods:  The participants were pregnant women who responded to questionnaires while registering their pregnancies between 1 April 1996 and 31 March 2001 (Group 1), and between 1 April 2001 and 31 March 2006 (Group 2). The odds ratios were calculated with a 95% confidence interval for maternal smoking during early pregnancy by using a logistic multivariate regression analysis based on maternal factors.

Results:  In Group 1, 1051 pregnant women responded to the questionnaire administered at pregnancy registration, and 86 (8.2%) mothers reported smoking during early pregnancy. In Group 2, 1022 pregnant women responded, and 91 (8.9%) mothers reported smoking during early pregnancy. There was no significant difference between the groups. In both groups, partner smoking and skipping breakfast were significantly associated with maternal smoking. In Group 2, unintended pregnancy was significantly associated with maternal smoking.

Conclusions:  To prevent maternal smoking during pregnancy, it is necessary to carefully monitor pregnant women who report partner smoking, skipping breakfast, and unintended pregnancy.
Are heterochromatin polymorphisms associated with recurrent miscarriage?
Authors: Caglayan Ahmet Okay , Ozyazgan Isılay , Demiryilmaz Fatma , Ozgun Mahmut Tuncay
Published: June 2010

Aim:  Recurrent miscarriage is a multifactorial problem associated with genetic abnormalities reflected by inherited disorders. The aim of the present study was to investigate the contribution of chromosomal abnormalities and the frequency of a particular type of aberration in couples of Turkish origin with recurrent miscarriages compared with patients without miscarriages.

Methods:  A total of 336 patients with recurrent miscarriages and 427 patients without miscarriages were analyzed.

Results:  In the recurrent miscarriage group, a structural chromosomal abnormality was found in four patients (1%). Twelve patients had mosaic karyotype (3%) and the total rate of chromosomal abnormalities was 4% in this group. The karyotypes were composed of polymorphisms in 8% of patients with recurrent miscarriages compared with 4% in the control group (P < 0.05).

Conclusion:  The overall high incidence of chromosome polymorphisms in patients with recurrent miscarriages compared to the normal population needs to be confirmed with additional investigations including larger populations in order to delineate the role of ‘harmless’ chromosomal aberrations in the etiology of recurrent spontaneous abortions.
Four weeks administration of Liraglutide improves memory and learning as well as glycaemic control in mice with high fat dietary‐induced obesity and insulin resistance
Authors: Porter D. W. , Kerr B. D. , Flatt P. R. , Holscher C. , Gault V. A.
Published: June 2010

Aim: Liraglutide is a long‐acting glucagon‐like peptide‐1 (GLP‐1) mimetic which is a treatment option for type 2 diabetes. GLP‐1 peptides, including Liraglutide, cross the blood‐brain barrier and may additionally act to improve brain function. The present study tested the hypothesis that, in addition to its antihyperglycaemic actions, peripheral administration of Liraglutide exerts positive actions on cognitive function in mice with high fat dietary‐induced obesity and insulin resistance.

Methods: Young Swiss TO mice maintained on high fat diet for 20 weeks received twice‐daily injections of Liraglutide (200 µg/kg bw; sc) or saline vehicle over 28 days. An additional group of mice on standard diet received twice‐daily saline injections. Energy intake, bodyweight, non‐fasting plasma glucose and insulin concentrations were monitored at regular intervals. Glucose tolerance, open field assessment, object recognition testing and electrophysiological long‐term potentiation (LTP) were performed at termination of the study.

Results: Liraglutide treatment resulted in significant time‐dependent reduction in bodyweight and energy intake, whilst improving non‐fasting glucose and normalizing glucose tolerance. Although Liraglutide did not alter general behaviour, treated mice exhibited marked increase in recognition index (RI) during object recognition testing, indicative of enhanced learning and memory ability. Furthermore, Liraglutide rescued the deleterious effects of high fat diet on hippocampal LTP of neurotransmission following both chronic and direct intracerebroventricular (icv) administration.

Conclusion: Liraglutide administered peripherally not only improves metabolic parameters but exerts additional beneficial effects on cognitive function and hippocampal synaptic plasticity. Whether therapy with GLP‐1 mimetics has similar effects in humans with type 2 diabetes needs to be established.
Nicorandil‐induced penile ulcerations: a case series
Authors: Yap Tet , Philippou Prodromos , Perry Matthew , Lam Wayne , Corbishley Cathy , Watkin Nick
Published: June 2010

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

What’s known on the subject? and What does the study add?

Nicorandil is used as a vasodilator for the prevention and long‐term treatment of angina. However, ulceration induced by nicorandil has been reported in the past, involving the mouth, anus and other parts of the gastrointestinal system.

We herein report the largest to‐date series of external genitalia ulceration, related to treatment with nicorandil.

OBJECTIVE

To report on the largest series to date of ulceration of the external genitalia, related to treatment with nicorandil – a vasodilator for the prevention and long‐term treatment of angina – and to review the literature on the subject, focusing on the clinical features and the pathogenesis of this rare, yet marked, side‐effect.

PATIENTS AND METHODS

Three patients (aged 71–83 years) were referred for severe ulceration of the penis. A complete work‐up was performed to exclude potential underlying causes, including malignancy and sexually transmitted diseases. After a careful review of the patients’ medical history, a potentially causal relationship was noted; all patients had been taking nicorandil for at least 2 years before the development of penile ulceration.

RESULTS

Penile ulcers associated with nicorandil are characteristically large, deep, painful and have punched‐out edges. They usually involve the prepuce or the penile shaft skin. Higher doses of nicorandil (at least 40 mg daily) and surgical procedures seem to increase the risk for nicorandil‐related ulceration. Response to topical steroids is poor, but complete healing is achieved by discontinuation of nicorandil, while surgical treatment should be discouraged.

CONCLUSION

The growing body of literature showing the link between treatment with nicorandil and ulceration at multiple sites has led to the recognition of this side‐effect by the World Health Organization. Nicorandil‐related ulcers rarely involve the penile skin and constitute a diagnostic and therapeutic challenge. The pathogenesis of this rare side‐effect is largely unknown, but mechanisms such as the ‘vascular steal phenomenon’ and the direct toxic effect of the drug or its metabolites have been implicated.
Early oncological outcomes of robot‐assisted radical prostatectomy for high‐grade prostate cancer
Authors: Wambi Chris O. , Siddiqui Sameer A. , Krane L. Spencer , Agarwal Piyush K. , Stricker Hans J. , Peabody James O.
Published: June 2010

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

OBJECTIVE

To evaluate the oncological outcomes of patients with specimen Gleason 8 and 9 prostate cancers and to determine factors that predict biochemical recurrence‐free survival (BCRFS) after robot‐assisted radical prostatectomy (RARP).

PATIENTS AND METHODS

Of 4156 patients who underwent RARP from January 2001 to 2009, we identified 368 men with Gleason 8 or 9 tumours who met the inclusion criteria. BCR was defined as a PSA level of ≥0.2 ng/mL with a second rising value. The Kaplan–Meier method and log‐rank test were used to compare BCRFS while factors that predict BCRFS were determined by Cox proportional hazards modelling.

RESULTS

The median age and PSA level were 62 years and 6.4 ng/mL for men with Gleason 8, and 63 years and 6.7 ng/mL for Gleason 9 cancers. The median (interquartile range, IQR) overall follow‐up was 23 (10–46) months and 19 (7–37) months for Gleason 8 and 9 tumours, respectively. At 60 months the mean (se) overall BCRFS was 36 (5)% and for Gleason 8 it was 47 (6)% and for Gleason 9 it was 21 (7)% (P < 0.001). At 5 years, extraprostatic extension (pT3a) resulted in BCRFS of 52 (9)% for Gleason 8 tumours and 21 (11)% for Gleason 9 (P= 0.012). On multivariable analysis, lymph node invasion, specimen Gleason score, pathological stage and tumour volume predicted BCRFS.

CONCLUSIONS

Early results suggest RARP monotherapy performs comparably to RP for BCRFS in men with high‐grade prostate cancer. There are significant oncological differences between Gleason 8 and 9 tumours.