bluuebunny/crossref_metadata_2025 huggingface dataset:
Infant sporotrichosis in northeast China: a report of 15 cases
Authors: Song Yang , Yao Lei , Zhong Shu‐Xia , Tian Ya‐Ping , Liu Yuan‐Yuan , Li Shan‐Shan
Published: April 2011

Background  Sporotrichosis is a deep mycosis caused by Sporothrix schenckii. It is not uncommon in adults and children but is very rare in infants.

Methods  We collated a series of case reports. Clinical data and laboratory and therapeutic results in 15 infants with cutaneous sporotrichosis were analyzed.

Results  A total of 15 cases of sporotrichosis in infants aged <10 months (mean age: 5.2 months; 10 male, five female) were diagnosed at the Department of Dermatology and Venereology, First Hospital of Jilin University, Changchun, Jilin, China, between May 2007 and May 2009. The mean duration of the disease was 2.07 months (range: 1–4 months). All the patients had facial involvement. Fixed cutaneous and lymphocutaneous sporotrichosis were seen in 11 (73.3%) and four (26.7%) patients, respectively. All patients lived in rural areas and had not experienced prior trauma or had contact with soil, plants, animals, or other sporotrichosis patients. Sporothrix schenckii was isolated in all cases, and pathological findings showed suppurative granuloma, tuberculoid granuloma, or mixed inflammatory reaction. One of the 15 patients achieved a spontaneous resolution after biopsy. Fourteen were treated with oral agents, including potassium iodide (KI) alone in two cases, itraconazole alone in three cases, terbinafine alone in four cases, and a combination of KI and terbinafine in five cases. Twelve cases were followed for 4–24 months and were cured with a mean of 2.96 months of treatment (range: 2–4 months) without adverse effects.

Conclusions  Infant sporotrichosis usually presents as a solitary lesion on the face. This is the largest series of infant sporotrichosis to be reported in the literature.
TNF alpha antagonist‐induced lupus‐like syndrome: report and review of the literature with implications for treatment with alternative TNF alpha antagonists
Authors: Williams Victoria L. , Cohen Philip R.
Published: April 2011

Background  In patients with various autoimmune and rheumatic diseases, a drug‐induced lupus‐like syndrome (DILS) has been reported with the use of adalimumab, cerrolizumab pegol, etanercept, and infliximab.

Objective  To review clinical characteristics of patients who develop tumor necrosis factor (TNF) alpha antagonist‐induced lupus‐like syndrome (TAILS) and review implications for further TNF alpha antagonist therapy.

Materials and methods  We describe a 62‐year‐old woman with rheumatoid arthritis who developed a pruritic photo‐distributed rash two months after the initiation of etanercept therapy. Her skin biopsy showed lupus erythematosus, and she had positive serum ANA, anti‐Sjogren's syndrome A (SSA)/Ro, and anti‐Sjogren’s syndrome B (SSB)/La antibodies. Her symptoms resolved after discontinuation of the drug, topical and systemic corticosteroids, and hydroxychloroquine sulfate. Subsequently, her rheumatoid arthritis was treated with golimumab for six months without recurrence of skin lesions. Published reports of individuals who have developed TAILS and those who have continued treatment with alternative TNF alpha antagonists are reviewed.

Results  TAILS is most commonly associated with the use of etanercept and infliximab. It occurs most often in women in the fifth decade of life. Onset of symptoms ranges from less than one month to more than four years. Syndrome‐associated cutaneous lesions and induction of autoantibodies are common. There is no definitively established mechanism of pathogenesis. Treatment can include discontinuation of the drug, corticosteroids, immunosuppressives, and hydroxychloroquine sulfate. To date, 10 patients with TAILS have continued therapy with an alternative TNF alpha antagonist without recurrence of lupus symptoms.

Conclusions  Development of a DILS after one TNF alpha antagonist does not preclude continued treatment with an alternative TNF alpha antagonist.
The assessment of dermatological needs in resource‐poor regions
Authors: Hay Roderick James , Fuller Lucinda Claire
Published: April 2011

The assessment of health needs is a key step in determining the nature and level of health service provision required in any global region. In dermatology, information on needs has provided information on the scale and impact of skin conditions in poor rural and urban populations. In such areas, additional problems in providing adequate services are access to trained health care professionals and cost to families and individuals, set against the background of a village‐mixed economy. A further problem is health literacy, which may limit the use of services. However, some of the most comprehensive surveys of the prevalence of skin disease have been carried out in resource‐poor countries, and attempts have been made to assess these along with their impact on individual disability. These studies and their outcomes are described in this article.
The contribution of the nursing service worldwide and its capacity to benefit within the dermatology field
Authors: Ersser Steven J. , Kaur Vineet , Kelly Pat , Langøen Arne , Maguire Susan A. , Nicol Noreen H. , Page Barbara , Ward Corrine
Published: April 2011

The nursing service is a significant element in the dermatological capacity to respond to skin care and dermatological needs worldwide. Although it is an area of development often neglected by dermatologists, it is one that is undergoing rapid and substantial evolution. This paper outlines the initiatives undertaken by nurses to enhance their contribution, and examines the development of nursing within the dermatology field. It argues for the need to develop a service delivery model in dermatology care that utilizes specialist‐nursing expertise to cascade dermatological knowledge and skill through primary care. The paper summarizes the strategic importance of nursing in dermatology care delivery, whether in resource‐rich or ‐poor countries, and its unmet potential in the capacity to benefit and meet skin care and dermatological care needs. The paper specifically focuses on the development work led by the International Skin Care Nursing Group (ISNG) to stimulate and develop the capacity of nursing to respond to these widespread needs through promoting service delivery models that operate interdependently with dermatologist‐led care.
Prospective monitoring of BK virus reactivation in renal transplant recipients in North India
Authors: Thakur R. , Arora S. , Nada R. , Minz M. , Joshi K.
Published: April 2011

R. Thakur, S. Arora, R. Nada, M. Minz, K. Joshi. Prospective monitoring of BK virus reactivation in renal transplant recipients in North India. Transpl Infect Dis 2011: 13: 575–583. All rights reserved

Abstract:
Background. BK nephropathy (BKN) is an important complication of renal transplantation with a reported incidence between 1% and 10% in different parts of the world. Early diagnosis is important to plan early therapeutic strategies. The epidemiology and evolution of BKN is relatively unknown in India and hence, the present study has been designed to prospectively monitor the activation of BK virus (BKV) in renal transplant recipients in India.

Patients and methods. In this study, 32 renal allograft recipients were prospectively monitored with protocol biopsies of allografts, BKV DNA load in plasma, and viral particles in urine by electron microscopy (EM) on day 1, and at 1, 3, and 6 months. Additionally, the baseline BKV DNA load in plasma was quantitated in 21 corresponding donors.

Results. On follow‐up in 32 recipients, 9.7%, 23.8%, 19.2%, and 13.3% of patients showed viral profiles by EM at day 1, 1 month, 3 months, and 6 months, respectively. BKV DNA positivity in plasma was 25.8%, 42.9%, 15.4%, and 20% at day 1, 1 month, 3 months, and 6 months, respectively, with mean BKV copy number/mL plasma of 1796, 1029, 2611, and 3318, respectively. A total of 15.7% (17/108) urine samples of 32 renal recipients were positive by urine EM. Out of 100 protocol biopsies, none developed histologically demonstrable cytopathic effects of BKN, although 8% biopsies were SV‐40 large  T  antigen (SV‐40 T Ag) positive. By quantitative real‐time polymerase chain reaction assay, 27/108 (25%) of recipients' plasma samples were positive for BKV. Peak viremia and viruria occurred at 1–3 months post transplantation. The baseline viremia in donors was predictive of viremia positivity in the post‐transplantation period at 1 month. Twenty‐four episodes of graft dysfunction were attributed mainly to rejection.

Conclusion. The study shows a total of 15.7% and 25% urine and plasma samples were positive for BKV at any time during a 6‐month follow‐up. The highest incidence of BK viruria and viremia occurred at 1 month. In protocol biopsies, focal positivity of SV‐40 T Ag was seen in 8% biopsies.
Social influence on age and reproduction: reduced lifespan and fecundity in multi‐queen ant colonies
Authors: SCHREMPF A. , CREMER S. , HEINZE J.
Published: April 2011

Evolutionary theories of ageing predict that life span increases with decreasing extrinsic mortality, and life span variation among queens in ant species seems to corroborate this prediction: queens, which are the only reproductive in a colony, live much longer than queens in multi‐queen colonies. The latter often inhabit ephemeral nest sites and accordingly are assumed to experience a higher mortality risk. Yet, all prior studies compared queens from different single‐ and multi‐queen species. Here, we demonstrate an effect of queen number on longevity and fecundity within a single, socially plastic species, where queens experience the similar level of extrinsic mortality. Queens from single‐ and two‐queen colonies had significantly longer lifespan and higher fecundity than queens living in associations of eight queens. As queens also differ neither in morphology nor the mode of colony foundation, our study shows that the social environment itself strongly affects ageing rate.
Planning Sustainability: Intergenerational and Intragenerational Justice in Spatial Planning Strategies
Authors: Manderscheid Katharina
Published: April 2011

Abstract:  Subsequent to the Brundtland Report (World Commission on Environment and Development 1987, Our Common Future), sustainability has been set up in many countries as a mission statement of cross‐sectoral policies. Sustainable development carries the normative notions of equity, empowerment and environmentally sensitive economic development. Thus, it seems to suggest a fundamentally different vision to neoliberal dogma, which is at the same time described as dominating all socio‐political processes. This paper intends to explore the relation between these two discursive framings of contemporary policies through the example of German spatial planning guidelines. More precisely, it addresses social justice as one pillar of sustainability and how it is operationalised in spatial planning policies in Germany. This may exemplify how the seemingly opposing discourses interact in policy practices. The empirical analysis suggests that the ways in which the German spatial planning report focused on social space in territorial terms promotes an economistic and truncated view of social justice, one which fosters the neoliberal idea of regional competition for global capital and reduces socio‐spatial justice to territorially equally distributed economic inclusion.
Community Volunteering as Neoliberal Strategy? Green Space Production in Berlin
Authors: Rosol Marit
Published: April 2011

Abstract:  The task for critical urban research is to analyze processes of neoliberalization “on the ground”. This paper examines—based on original empirical research—in how far the outsourcing of former local state responsibilities for public services and urban infrastructure is expressed in the promotion of community gardening in Berlin (Germany). It shows the contradictory outcomes: on the one hand, a failing strategy of outsourcing towards residents and the opening up of opportunity structures for other interests. On the other hand it shows how far the emergence of open green spaces maintained by volunteers can only be understood against the background of “roll‐back” neoliberal urban politics and that their rationality cannot be separated from “roll‐out neoliberalism”.
Visual Analysis of Large Graphs: State‐of‐the‐Art and Future Research Challenges
Authors: von Landesberger T. , Kuijper A. , Schreck T. , Kohlhammer J. , van Wijk J.J. , Fekete J.‐D. , Fellner D.W.
Published: April 2011

The analysis of large graphs plays a prominent role in various fields of research and is relevant in many important application areas. Effective visual analysis of graphs requires appropriate visual presentations in combination with respective user interaction facilities and algorithmic graph analysis methods. How to design appropriate graph analysis systems depends on many factors, including the type of graph describing the data, the analytical task at hand and the applicability of graph analysis methods. The most recent surveys of graph visualization and navigation techniques cover techniques that had been introduced until 2000 or concentrate only on graph layouts published until 2002. Recently, new techniques have been developed covering a broader range of graph types, such as time‐varying graphs. Also, in accordance with ever growing amounts of graph‐structured data becoming available, the inclusion of algorithmic graph analysis and interaction techniques becomes increasingly important. In this State‐of‐the‐Art Report, we survey available techniques for the visual analysis of large graphs. Our review first considers graph visualization techniques according to the type of graphs supported. The visualization techniques form the basis for the presentation of interaction approaches suitable for visual graph exploration. As an important component of visual graph analysis, we discuss various graph algorithmic aspects useful for the different stages of the visual graph analysis process. We also present main open research challenges in this field.
INCOME TAXES AND THE COMPOSITION OF PAY: EVIDENCE FROM THE BRITISH HOUSEHOLD PANEL SURVEY
Authors: Brunello Giorgio , Comi Simona , Sonedda Daniela
Published: April 2011

According to the standard principal‐agent model, the optimal composition of pay should balance the provision of incentives with the individual demand for insurance. Do income taxes alter this balance? We show that the relative share of Performance‐related pay (PRP), on total pay is reduced by higher average and marginal income taxes. Empirical evidence based on the British Household Panel Survey is consistent with the theoretical predictions of the tax–augmented principal‐agent model. Our estimates suggest that a 10% reduction in the marginal income tax rate, holding the average tax rate constant, increases the share of PRP in total pay by 2.25–3.02%, depending on the empirical specification. Similarly, a 10% reduction in the average income tax rate, holding the marginal tax rate constant, increases the share of PRP in total pay by 5.10–5.27%.
WHAT CREATES ABNORMAL PROFITS?
Authors: Griffiths William , Jensen Paul H. , Webster Elizabeth
Published: April 2011

In this paper, we re‐examine the debate regarding the determinants of persistent abnormal profits. Abnormal profits are estimated using data on tangible and intangible capital for 2689 Australian firms over a 17‐year period. The determinants of abnormal profits are then estimated using variables collated from accounting and survey data on innovation and management practices. We find that market share, use of lead‐time strategies, and industry concentration all affect abnormal profits.
Contact, the feature pool and the speech community: The emergence of Multicultural London English
Authors: Cheshire Jenny , Kerswill Paul , Fox Sue , Torgersen Eivind
Published: April 2011

In the multilingual centres of Northern Europe's major cities, new varieties of the host languages are emerging. While some analyse these ‘multiethnolects’ as youth styles, we take a variationist approach to an emerging ‘Multicultural London English’ (MLE), asking: (1) what features characterise MLE; (2) at what age(s) are they acquired; (3) is MLE vernacularised; and (4) when did MLE emerge, and what factors enabled this? We argue that innovations in the diphthongs and the quotative system are generated from the specific sociolinguistics of inner‐city London, where at least half the population is undergoing group second‐language acquisition and where high linguistic diversity leads to a heterogeneous feature pool to select from. We look for incrementation (Labov 2001) in the acquisition of the features, but find this only for two ‘global’ changes, BE LIKE and goose‐fronting, for which adolescents show the highest usage. Community‐internal factors explain the age‐related variation in the remaining features.
Space‐time modelling of trends in temperature series
Authors: Craigmile Peter F. , Guttorp Peter
Published: April 2011

Classical assessments of temperature trends are based on the analysis of a small number of time series. Considering trend to be only smooth changes of the mean value of a stochastic process through time is limiting, because it does not provide a mechanism to study changes of the mean that could also occur over space. Thus, in studies of climate there is a substantial interest in being able to jointly characterize temperature trends over time and space. In this article we build wavelet‐based space‐time hierarchical Bayesian models that can be used to simultaneously model trend, seasonality, and error, allowing for the possibility that the error process may exhibit space‐time long‐range dependence. We demonstrate how these statistical models can be used to assess the significance of trend over time and space. We motivate and apply our methods to the analysis of space‐time temperature trends, based on data collected in the last five decades from central Sweden.
Union Bargaining in Economies with Constant Returns to Scale
Authors: Cardona Daniel , Sánchez‐Losada Fernando
Published: April 2011

Although the presence of unions is hard to justify when considering steady‐state relationships in an economy with constant returns to scale and constant savings rate, transitions might explain its creation and persistence.
ic1/ic5 Interaction in the Music of Shostakovich
Authors: BROWN STEPHEN C.
Published: April 2011

Several analysts have observed in Shostakovich's later works a particular focusing of pitch resources – namely, a frequent emphasis on interval classes 1 and 5. In fact, pitch structures highlighting these interval classes occur in music from throughout his career, although no one has considered this phenomenon in depth. The present study does so by exploring the interaction of ic1 and ic5 within the context of Shostakovich's multi‐faceted tonal language, interpreting passages from the Piano Sonatas Nos. 1 and 2, the Viola Sonata, the Symphonies Nos. 14 and 15, the String Quartet No. 12, the ‘Funeral March’ from the Aphorisms and the song ‘Noch'‐Dialog’ (‘Night Dialog’) from the Suite on Verses of Michelangelo. Drawing on the methodology of dual interval space, the article demonstrates that a focus on ic1/ic5 relationships offers a compelling perspective on much of Shostakovich's music, one that engages both local detail and large‐scale organization. Not only can ic1/ic5 interaction shape a piece on its own, but it can also connect to other aspects of design, even to relationships between music and text. Moreover, an ic1/ic5 approach sheds new light on previous Shostakovich analyses, most notably those by Russian theorists on modality in Shostakovich.
In touch with psoriasis: topical treatments and current guidelines
Authors: Murphy G , Reich K
Published: April 2011

This article describes topical therapies and treatment guidelines for psoriasis and is based on a presentation given by the authors at a satellite symposium held during the 19th Congress of the European Academy of Dermatology and Venereology, 6–10 October, 2010, in Gothenburg, Sweden. The highly variable nature of psoriasis and its individual presentation in patients can make it difficult to choose the most appropriate treatment. There are many treatment options, from topical treatment with emollients for very mild psoriasis, to systemic therapy with fumaric acid esters, methotrexate or biologics for severe disease. For the treatment of mild‐to‐moderate psoriasis, topical therapy is generally the most appropriate and a variety of options, both historical and recent, are available. Newer therapies offer greater convenience and fewer side‐effects. Of the more recently available therapies, vitamin D analogues and topical corticosteroids are the two with the greatest proven efficacy in randomized clinical trials. A recent Cochrane review showed the highest efficacy overall with the fixed combination vitamin D analogue (calcipotriol) and corticosteroid (betamethasone dipropionate). Indeed, clinical trials have shown that two‐compound calcipotriol/betamethasone dipropionate ointment has higher efficacy than calcipotriol or betamethasone dipropionate alone. With regard to safety, two‐compound calcipotriol/betamethasone dipropionate was shown to be suitable for intermittent long‐term treatment of mild‐to‐moderate psoriasis. The findings of the Cochrane review are reflected in the current treatment guidelines from the USA and Germany regarding the treatment of mild‐to‐moderate psoriasis. In both these guidelines, which will be discussed in this article, the recommended treatments for this patient group are vitamin D analogues and corticosteroids, particularly when used in combination.
Folate is related to phosphorylated neurofilament‐H and P‐tau (Ser396) in rat brain
Authors: Obeid Rima , Schlundt Jennifer , Umanskaya Natalia , Herrmann Wolfgang , Herrmann Markus
Published: April 2011

J. Neurochem.(2011)117, 1047–1054.

Protein phosphatase PP2A dephosphorylates phosphorylated tau (P‐tau) and neurofilaments (pNFs). PP2A isS‐adenosylmethionine (SAM)‐dependent and might thus link methylation with neurodegeneration. Low SAM and increasedS‐adenosylhomocysteine (SAH) can enhance the risk of dementia. We studied the effect of hyperhomocysteinemia on P‐tau (Ser396), pNF‐H (heavy chain), and PP2A‐activity and level (the C subunit) in rat brain. Wistar rats (totaln = 55) were fed either on a standard, a homocystine 1.7% or a methionine 2.4%‐rich diet for 5 months. P‐tau was tested in 21 frontal cortex tissue slices using immuno‐fluorescence. Concentrations of pNF‐H and the activity and level of PP2A were measured in brain extracts. Concentrations of homocysteine, SAM and SAH strongly increased in plasma of rats on the modified diets. The diets caused lowering of plasma folate and vitamin B12 and a significant increase in P‐tau (Ser396) in brain tissues but PP2A activity and level were unchanged. Plasma folate correlated to brain tissue PP2A activity (r = 0.28), pNF‐H (r = −0.30), and P‐tau (Ser396) staining (r = −0.57) allp < 0.05. Phosphorylation of brain functional proteins was related to folate. The effect of the diet on P‐tau and pNF‐H seemed not to be explained by a lower activity or protein level of PP2A. Folate might prove protective against multiple steps in the process of neurodegeneration.
Glycogen synthase kinase 3β in the nucleus accumbens core is critical for methamphetamine‐induced behavioral sensitization
Authors: Xu Chun‐mei , Wang Jun , Wu Ping , Xue Yan‐xue , Zhu Wei‐li , Li Qian‐qian , Zhai Hai‐feng , Shi Jie , Lu Lin
Published: April 2011

J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07281.x

As a ubiquitous serine/threonine protein kinase, glycogen synthase kinase 3β (GSK‐3β) has been considered to be important in the synaptic plasticity that underlies dopamine‐related behaviors and diseases. We recently found that GSK‐3β activity in the nucleus accumbens (NAc) core is critically involved in cocaine‐induced behavioral sensitization. The present study further explored the association between the changes in GSK‐3β activity in the NAc and the chronic administration of methamphetamine. We also examined whether blocking GSK‐3β activity in the NAc could alter the initiation and expression of methamphetamine (1 mg/kg, i.p.)‐induced locomotor sensitization in rats using systemic administration of lithium chloride (LiCl, 100 mg/kg, i.p) and brain region‐specific administration of the GSK‐3β inhibitor SB216763 (1 ng/side). We found that GSK‐3β activity increased in the NAc core, but not NAc shell, after chronic methamphetamine administration. The initiation and expression of methamphetamine‐induced locomotor sensitization was attenuated by systemic administration of LiCl and direct infusion of SB216763 into the NAc core, but not NAc shell. These results indicate that GSK‐3β activity in the NAc core mediates the initiation and expression of methamphetamine‐induced locomotor sensitization, suggesting that GSK‐3β may be a potential target for the treatment of psychostimulant addiction.
Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2‐oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels
Authors: Parkhomenko Yulia M. , Kudryavtsev Pavel A. , Pylypchuk Svetlana Yu. , Chekhivska Lilia I. , Stepanenko Svetlana P. , Sergiichuk Andrej A. , Bunik Victoria I.
Published: April 2011

J. Neurochem. (2011) 117, 1055–1065.

Thiamine‐dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono‐ and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2‐oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2‐oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability.
Systemic administration of neuregulin‐1β1 protects dopaminergic neurons in a mouse model of Parkinson’s disease
Authors: Carlsson Thomas , Schindler Friederike R. , Höllerhage Matthias , Depboylu Candan , Arias‐Carrión Oscar , Schnurrbusch Stefan , Rösler Thomas W. , Wozny Wojciech , Schwall Gerhard P. , Groebe Karlfried , Oertel Wolfgang H. , Brundin Patrik , Schrattenholz André , Höglinger Günter U.
Published: April 2011

J. Neurochem. (2011) 117, 1066–1074.

Neuregulin‐1 (Nrg1) is genetically linked to schizophrenia, a disease caused by neurodevelopmental imbalance in dopaminergic function. The Nrg1 receptor ErbB4 is abundantly expressed on midbrain dopaminergic neurons. Nrg1 has been shown to penetrate blood‐brain barrier, and peripherally administered Nrg1 activates ErbB4 and leads to a persistent hyperdopaminergic state in neonatal mice. These data prompted us to study the effect of peripheral administration of Nrg1 in the context of Parkinson’s disease, a neurodegenerative disorder affecting the dopaminergic system in the adult brain. We observed that systemic injections of the extracellular domain of Nrg1β1 (Nrg1β1‐ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1β1‐ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6‐hydroxydopamine‐induced toxicity in vivo. Moreover, Nrg1β1‐ECD also protected human dopaminergic neurons in vitro against 6‐hydroxydopamine. In conclusion, we have identified Nrg1β1‐ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for Parkinson’s disease patients.
Historic speciation and recent colonization of Eurasian monkey gobies (Neogobius fluviatilis and N. pallasi) revealed by DNA sequences, microsatellites, and morphology
Authors: Neilson Matthew E. , Stepien Carol A.
Published: April 2011

Aim  Hidden diversity within an invasive ‘species’ can mask both invasion pathways and confound management goals. We assessed taxonomic status and population structure of the monkey goby Neogobius fluviatilis across Eurasia, comparing genetic variation across its native and invasive ranges.

Location  Native populations were analysed within the Black and Caspian Sea basins, including major river drainages (Dnieper, Dniester, Danube, Don and Volga rivers), along with introduced locations within the upper Danube and Vistula river systems.

Methods  DNA sequences and 10 nuclear microsatellite loci were analysed to test genetic diversity and divergence patterns of native and introduced populations; phylogenetic analysis of mtDNA cytochrome b and nuclear RAG‐1 sequences assessed taxonomic status of Black and Caspian Sea lineages. Multivariate analysis of morphology was used to corroborate phylogenetic patterns. Population genetic structure within each basin was evaluated with mtDNA and microsatellite data using FST analogues and Bayesian assignment tests.

Results  Phylogenetic analysis of mitochondrial and nuclear sequences discerned a pronounced genetic break between monkey gobies in the Black and Caspian Seas, indicating a long‐term species‐level separation dating to c. 3 million years. This pronounced separation further was confirmed from morphological and population genetic divergence. Bayesian inference showed congruent patterns of population structure within the Black Sea basin. Introduced populations in the Danube and Vistula River basins traced to north‐west Black Sea origins, a genetic expansion pattern matching that of other introduced Ponto‐Caspian gobiids.

Main conclusions  Both genetic and morphological data strongly supported two species of monkey gobies that were formerly identified as subspecies: N. fluviatilis in the Black Sea basin, Don and Volga Rivers, and the Kumo‐Manych Depression, and Neogobius pallasi in the Caspian Sea and Volga River delta. Genetic origins of introduced N. fluviatilis populations indicated a common invasion pathway shared with other introduced Ponto‐Caspian fishes and invertebrates.
Assessing invasion risk across taxa and habitats: life stage as a determinant of invasion success
Authors: Briski Elizabeta , Ghabooli Sara , Bailey Sarah A. , MacIsaac Hugh J.
Published: April 2011

Aim  Many aquatic invertebrates produce dormant life‐history stages as a means to endure inhospitable environments and to facilitate natural long‐distance dispersal, yet we have little understanding of the role of dormant stages as a mechanism for human‐mediated introductions of non‐indigenous species. We explore the survival of invertebrate dormant eggs in collected ships’ ballast sediment over a 1‐year period to determine relative invasion potential across taxa (i.e. rotifers, copepods, cladocerans and bryozoans) and different habitats (freshwater, marine).

Location  Canadian Atlantic and Pacific coasts and Laurentian Great Lakes.

Methods  During 2007 and 2008, 19 ballast samples were collected as a part of a larger study. The degradation rate of dormant eggs was assessed by enumerating dormant eggs and by conducting viability hatching experiments.

Results  Taxa examined included rotifers, copepods, anomopods, onychopods and bryozoans. Dormant eggs of rotifers degraded at the highest rate of all taxa examined, with no viable eggs remaining within 10 months. Copepods showed a less rapid degradation rate than rotifers. The degradation rate of anomopod dormant eggs was significantly slower than that of both rotifers and copepods. Onychopods and bryozoans did not visibly degrade at all over 12 months. Viability hatching experiments were successful for rotifers, copepods, and anomopods. Onychopods and bryozoans did not hatch during any of the three hatching trials.

Main conclusions  Dormancy is not equally beneficial to all invertebrate taxa. Our results indicate that dormant eggs of rotifers and copepods degrade at a rapid rate and may not pose high invasion risk. In contrast, the slow degradation rate of anomopod dormant eggs and the lack of degradation of onychopod and bryozoan dormant eggs could result in high invasion risk because of their accumulation in ballast tanks. Species having resistant dormant eggs mostly belong to freshwater taxa making freshwater habitats at higher invasion risk by dormant invertebrates than marine habitats.
Population Preferences for Health Care in Liberia: Insights for Rebuilding a Health System
Authors: Kruk Margaret E. , Rockers Peter C. , Tornorlah Varpilah S. , Macauley Rose
Published: April 2011

Objective. To quantify the influence of health system attributes, particularly quality of care, on preferences for health clinics in Liberia, a country with a high burden of disease that is rebuilding its health system after 14 years of civil war.

Data Sources/Study Setting. Informed by focus group discussions, a discrete choice experiment (DCE) was designed to assess preferences for structure and process of care at health clinics. The DCE was fielded in rural, northern Liberia as part of a 2008 population‐based survey on health care utilization.

Data Collection. The survey response rate was 98 percent with DCE data available for 1,431 respondents. Mixed logit models were used to estimate the influence of six attributes on choice of hypothetical clinics for a future illness.

Principal Findings. Participants' choice of clinic was most influenced by provision of a thorough physical exam and consistent availability of medicines. Respectful treatment and government (versus NGO) management marginally increased utility, whereas waiting time was not significant.

Conclusions. Liberians value technical quality of care over convenience, courtesy, and public management in selecting clinics for curative care. This suggests that investments in improved competence of providers and availability of medicines may increase population utilization of essential services as well as promote better clinical outcomes.
2‐(4‐(Biphenyl‐4‐ylamino)‐6‐chloropyrimidin‐2‐ylthio)octanoic acid (HZ52) – a novel type of 5‐lipoxygenase inhibitor with favourable molecular pharmacology and efficacy in vivo
Authors: Greiner C , Hörnig C , Rossi A , Pergola C , Zettl H , Schubert‐Zsilavecz M , Steinhilber D , Sautebin L , Werz O
Published: April 2011

BACKGROUND AND PURPOSE 5‐Lipoxygenase (5‐LO) is the key enzyme in the biosynthesis of pro‐inflammatory leukotrienes (LTs) representing a potential target for pharmacological intervention with inflammation and allergic disorders. Although many LT synthesis inhibitors are effective in simple in vitro test systems, they frequently fail in vivo due to lack of efficacy. Here, we attempted to assess the pharmacological potential of the previously identified 5‐LO inhibitor 2‐(4‐(biphenyl‐4‐ylamino)‐6‐chloropyrimidin‐2‐ylthio)octanoic acid (HZ52).

EXPERIMENTAL APPROACH We evaluated the efficacy of HZ52 in vivo using carrageenan‐induced pleurisy in rats and platelet‐activating factor (PAF)‐induced lethal shock in mice. We also characterized 5‐LO inhibition by HZ52 at the cellular and molecular level in comparison with other types of 5‐LO inhibitor, that is, BWA4C, ZM230487 and hyperforin.

KEY RESULTS HZ52, 1.5 mg·kg−1 i.p., prevented carrageenan‐induced pleurisy accompanied by reduced LTB4 levels and protected mice (10 mg·kg−1, i.p.) against PAF‐induced shock. Detailed analysis in cell‐based and cell‐free assays revealed that inhibition of 5‐LO by HZ52 (i) does not depend on radical scavenging properties and is reversible; (ii) is not impaired by an increased peroxide tone or by elevated substrate concentrations; and (iii) is little affected by the cell stimulus or by phospholipids, glycerides, membranes or Ca2+.

CONCLUSIONS AND IMPLICATIONS HZ52 is a promising new type of 5‐LO inhibitor with efficacy in vivo and with a favourable pharmacological profile. It possesses a unique 5‐LO inhibitory mechanism different from classical 5‐LO inhibitors and seemingly lacks the typical disadvantages of former classes of LT synthesis blockers.
Significant systemic and mucosal immune response induced on oral delivery of diphtheria toxoid using nano‐bilosomes
Authors: Shukla Anshuman , Singh Bhupinder , Katare O P
Published: April 2011

BACKGROUND AND PURPOSE Over the last decade apprehension has been growing over the effectiveness of existing parenteral vaccines for diphtheria and has created an interest in the development of a mucosally active vaccine. Oral immunization appears to be an effective alternative, but is not without the inherent disadvantages of antigen destruction and tolerance. Therefore, our objective was to investigate the incorporation of diphtheria toxoid (DTx) into bilosomes, which could provide protection as well as aid transmucosal uptake and subsequent immunization. Another objective was to determine the oral dose that will produce serum antibody titres comparable with those produced by i.m. doses of DTx.

EXPERIMENTAL APPROACH Bilosomes containing DTx were prepared by thin film hydration and characterized in vitro for their shape, size, percent antigen entrapment and stability. In the in vivo study the anti‐DTx IgG and anti‐DTx sIgA response was estimated using elisa, in serum and in various body secretions, respectively, following oral immunization with different doses of DTx entrapped in nano‐bilosomes.

KEY RESULTS High dose loaded nano‐bilosomes (DTxNB3, 2Lf) produced comparable anti‐DTx IgG levels in serum to those induced by i.m. alum‐adsorbed DTx (0.5Lf). In addition, all the nano‐bilosomal preparations elicited a measurable anti‐DTx sIgA response in mucosal secretion, whereas i.m. alum‐adsorbed DTx (0.5Lf) was unable to elicit this response.

CONCLUSIONS AND IMPLICATIONS The orally administered nano‐bilosomal DTx formulation produced comparable serum antibody titres to i.m.alum‐adsorbed DTx, at a fourfold higher dose and without the induction of tolerance. This approach will provide an effective and comprehensive immune protection against diphtheria with better patient compliance.
Radiotherapy‐induced myelosuppression in dogs: 103 cases (2002–2006)
Authors: Clermont T. , LeBlanc A. K. , Adams W. H. , LeBlanc C. J. , Bartges J. W.
Published: April 2011

Definitive radiotherapy refers to delivery of large doses, typically 48–62 Gray, of ionizing radiation over several weeks using a daily or alternate‐day fractionation schedule. The impact of definitive radiotherapy alone on haematopoiesis in tumour‐bearing dogs is unknown. Medical records from 103 dogs receiving definitive 60Cobalt teletherapy for cancer over a 5‐year period were reviewed for signalment, tumour type and location, total radiotherapy dose and fractionation scheme. Complete blood count data were collected before, halfway through, and at the end of radiation treatment, and analysed for changes associated with patient variables. The results demonstrate significant reductions in haematocrit, total white blood cell count, neutrophils, eosinophils, monocytes, lymphocytes and platelets occurred during definitive radiotherapy but remained within laboratory reference intervals. These data are important for anticipation of toxicity associated with combinations of radiotherapy and chemotherapy in dogs but do not support the routine monitoring of haematology parameters during definitive radiotherapy.
Small leucine‐rich proteoglycans, decorin and fibromodulin, are reduced in postburn hypertrophic scar
Authors: Honardoust Dariush , Varkey Mathew , Hori Keijiro , Ding Jie , Shankowsky Heather A. , Tredget Edward E.
Published: April 2011

Small leucine‐rich proteoglycans (SLRPs) are extracellular matrix molecules that regulate collagen fibrillogenesis and inhibit transforming growth factor‐β activity; thus, they may play a critical role in wound healing and scar formation. Hypertrophic scarring is a dermal form of fibroproliferative disorders, which occurs in over 70% of burn patients and leads to disfigurement and limitations in function. By understanding the cellular and molecular mechanisms that lead to scarring after injury, new clinical therapeutic approaches can by developed to minimize abnormal scar formation in hypertrophic scarring and other fibroproliferative disorders. To study the expression and localization of SLRPs with connective tissue cells in tissue immunohistochemistry, immunofluorescence staining, immunoblotting, and reverse‐transcription polymerase chain reaction were used in normal skin and hypertrophic scar (HTS). In normal skin, there was more decorin and fibromodulin accumulation in the superficial layers than in the deeper dermal layers. The levels of decorin and fibromodulin were significantly lower in HTS, whereas biglycan was increased when compared with normal skin. There was an increased expression of biglycan, fibromodulin, and lumican in the basement membrane and around basal epithelial cells. In contrast, these proteoglycans were absent or weakly expressed in HTS. The findings suggest that down‐regulation of SLRPs after wound healing in deep injuries to the skin plays an important role in the development of fibrosis and HTS.
Keratinocytes stimulate fibroblast hyaluronan synthesis through the release of stratifin: A possible role in the suppression of scar tissue formation
Authors: Edward Michael , Quinn Jean A. , Sands William
Published: April 2011

Scar tissue formation during healing of extensive skin wounds may be related to delayed reepithelialization, while elevated levels of hyaluronan may suppress scar tissue formation. This study investigates the expression of hyaluronan by human skin fibroblasts in response to keratinocyte‐conditioned medium (KCM), and attempts to identify any active factors within the conditioned medium. Serum‐free KCM was assessed for its ability to stimulate the incorporation of 3H‐glucosamine into fibroblast glycosaminoglycans, and hyaluronan synthesis. Conditioned medium was concentrated with an ultrafiltration membrane with a 30 kDa cutoff. Stratifin was assessed for its ability to stimulate hyaluronan synthesis and its role in KCM. KCM stimulated fibroblast glycosaminoglycan synthesis up to a 3.3‐fold increase and a 6.5‐fold increase in hyaluronan synthesis compared with serum‐free controls. Preliminary characterization of the active factors showed that they are retained by a >30 kDa ultrafiltration membrane, and are protease sensitive and heat resistant. Emmprin and stratifin were shown to stimulate fibroblast hyaluronan synthesis, and the hyaluronan‐stimulating activity of KCM was removed following stratifin depletion and to a lesser extent by emmprin depletion. Keratinocytes release soluble factors, including stratifin, that stimulate fibroblast hyaluronan synthesis, and this stimulation of fibroblast hyaluronan may contribute to the suppression of scar tissue formation.
How to assess scar hypertrophy—a comparison of subjective scales and Spectrocutometry: A new objective method
Authors: Kaartinen Ilkka S. , Välisuo Petri O. , Bochko Vladimir , Alander Jarmo T. , Kuokkanen Hannu O.
Published: April 2011

Scar hypertrophy is a significant clinical problem involving both linear scars from elective surgery and scars caused by trauma or burns. The treatment of hypertrophic scars is often time consuming, and patients may need to be followed up for months or even years. The methods for reliable quantification of scar hypertrophy are at present unsatisfying. We have developed a new, objective method, Spectrocutometry, for documentation and quantification of scar hypertrophy. The instrument is based on standardized digital imaging and spectral modeling and calculates the estimated concentration change of hemoglobin and melanin from the entire scar and also provides standardized images for documentation. Three plastic surgeons have assessed 37 scars from melanoma surgery using Spectrocutometry, the Vancouver scar scale, and the patient and observer scar assessment scale. The intraclass correlation coefficient for the Vancouver scar scale and the patient and observer scar assessment scale was lower than required for reliable assessment (r=0.66 and 0.60, respectively). The intraclass correlation coefficient for Spectrocutometry was high (r=0.89 and 0.88). A Bayesian network analysis revealed a strong dependency between the estimated concentration change of hemoglobin and scar pain. Spectrocutometry is a feasible method for measuring scar hypertrophy. It is shown to be more reliable than subjective rating in assessing linear surgical scars.
Transforming growth factor‐β1 suppresses the up‐regulation of matrix metalloproteinase‐2 by lung fibroblasts in response to tumor necrosis factor‐α
Authors: Ye Hong , Cai Peng‐Cheng , Zhou Qiong , Ma Wan‐Li
Published: April 2011

Exposed to inflammatory factors or cytokines, fibroblasts appear to play additional roles beyond the deposition of extracellular matrix. It has been reported that tumor necrosis factor‐α (TNF‐α) induces the production of matrix metalloproteinase‐2 (MMP‐2) and transforming growth factor‐β1 (TGF‐β1) in fibroblasts. In this study, we demonstrated that the active MMP‐2 secreted by lung fibroblasts reached the peak level at 12 hours after TNF‐α treatment, whereas, by adding anti‐TGF‐β1 antibody in the culture medium, the MMP‐2 production in response to TNF‐α was maintained at high levels after 24 hours of treatment. We also confirmed that TNF‐α induced up‐regulation of active TGF‐β1 and exogenous TGF‐β1 induced down‐regulation of MMP‐2 synthesis in lung fibroblasts. Moreover, an increased MMP‐2 level was observed in a rat model with pulmonary inflammation and fibrosis induced by bleomycin‐A5. This revealed that MMP‐2 in the lung reached the peak level when TNF‐α reached the peak level at the 7th day, and then MMP‐2 decreased along with an increase in the TGF‐β1 level. Taken together, our results demonstrate that TNF‐α induced an increase of MMP‐2 and TGF‐β1 in lung fibroblasts, and the TGF‐β1 attenuated the up‐regulation of MMP‐2. This suggests that MMP‐2 secreted from fibroblasts modulated by TNF‐α/TGF‐β1 might play an important role in pulmonary inflammation and fibrosis.