bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual learning intervention to reduce bullying victimization in primary school: a controlled trial
Authors: Sapouna Maria , Wolke Dieter , Vannini Natalie , Watson Scott , Woods Sarah , Schneider Wolfgang , Enz Sibylle , Hall Lynne , Paiva Ana , André Elisabeth , Dautenhahn Kerstin , Aylett Ruth
Published: August 2009

Background:  Anti‐bullying interventions to date have shown limited success in reducing victimization and have rarely been evaluated using a controlled trial design. This study examined the effects of the FearNot! anti‐bullying virtual learning intervention on escaping victimization, and reducing overall victimization rates among primary school students using a nonrandomized controlled trial design. The program was designed to enhance the coping skills of children who are known to be, or are likely to be, victimized.

Methods:  One thousand, one hundred twenty‐nine children (mean age 8.9 years) in 27 primary schools across the UK and Germany were assigned to the FearNot! intervention or the waiting control condition. The program consisted of three sessions, each lasting approximately 30 minutes over a three‐week period. The participants were assessed on self‐report measures of victimization before and one and four weeks after the intervention or the normal curriculum period.

Results:  In the combined sample, baseline victims in the intervention group were more likely to escape victimization at the first follow‐up compared with baseline victims in the control group (adjusted RR, 1.41; 95% CI, 1.02–1.81). A dose–response relationship between the amount of active interaction with the virtual victims and escaping victimization was found (adjusted OR, 1.09; 95% CI, 1.003–1.18). Subsample analyses found a significant effect on escaping victimization only to hold for UK children (adjusted RR, 1.90; CI, 1.23–2.57). UK children in the intervention group experienced decreased victimization rates at the first follow‐up compared with controls, even after adjusting for baseline victimization, gender and age (adjusted RR, .60; 95% CI, .36–.93).

Conclusions:  A virtual learning intervention designed to help children experience effective strategies for dealing with bullying had a short‐term effect on escaping victimization for a priori identified victims, and a short‐term overall prevention effect for UK children.
454 Pyrosequencing analyses of forest soils reveal an unexpectedly high fungal diversity
Authors: Buée M. , Reich M. , Murat C. , Morin E. , Nilsson R. H. , Uroz S. , Martin F.
Published: August 2009

DOI: 10.1111/j.1469-8137.2009.03042.xCommentary p 279
Vernacularization on the ground: local uses of global women's rights in Peru, China, India and the United States
Authors: LEVITT PEGGY , MERRY SALLY
Published: August 2009

The articles published in this special journal issue examine how global ideas about women's rights actually get used in four contexts – China, India, Peru and the United States. Our findings result from collaborative research conducted by teams in each country. We call the process of appropriation and local adoption of globally generated ideas and strategies vernacularization. In each country, vernacularization differed depending on the contents of the global women's rights packages at play, the work of vernacularizers and the different social positions they occupy, how human rights ideas are framed, the channels and technologies of transmission, and the local geographies of history and culture within which circulation and vernacularization take place. We find that vernacularization is a widespread practice that takes different forms in different kinds of organizations and in different cultural and historical contexts. Ongoing tensions between global and national rights ideas are quite common. Finally, our work brings to light two dilemmas in the way human rights are appropriated and used – a resonance dilemma and an advocacy dilemma – both arising from the disparity between human rights as law and human rights as a social movement.
INVESTIGATING MATERIAL DECAY OF HISTORIC BUILDINGS USING VISUAL ANALYTICS WITH MULTI‐TEMPORAL INFRARED THERMOGRAPHIC DATA
Authors: DANESE MARIA , DEMŠAR URŠKA , MASINI NICOLA , CHARLTON MARTIN
Published: August 2009

This paper shows how visual analytics methodology can be used to facilitate interpretation of multi‐temporal thermographic imagery for the purpose of restoration of cultural heritage. We explore thermographic data in a visual environment from the unifying spatio‐temporal perspective in an attempt to identify spatial and spatio‐temporal patterns that could provide information about the structure and the level of decay of the material, and the presence of other physical phenomena in the wall. The approach is tested on a thermographic dataset captured on the façade of a Romanesque building from the 13th century—the Cathedral in Matera (Italy).
Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF‐I receptor signalling pathway
Authors: Xu Li , Chen Wen‐Fang , Wong Man‐Sau
Published: August 2009

Background and purpose:  We have shown that ginsenoside Rg1 is a novel class of potent phytoestrogen and activates insulin‐like growth factor‐I receptor (IGF‐IR) signalling pathway in human breast cancer MCF‐7 cells. The present study tested the hypothesis that the neuroprotective actions of Rg1 involved activation of the IGF‐IR signalling pathway in a rat model of Parkinson's disease, induced by 6‐hydroxydopamine (6‐OHDA).

Experimental approach:  Ovariectomized rats were infused unilaterally with 6‐OHDA into the medial forebrain bundle to lesion the nigrostriatal dopamine pathway and treated with Rg1 (1.5 h after 6‐OHDA injections) in the absence or presence of the IGF‐IR antagonist JB‐1 (1 h before Rg1 injections). The rotational behaviour induced by apomorphine and the dopamine content in the striatum were studied. Protein and gene expression of tyrosine hydroxylase, dopamine transporter and Bcl‐2 in the substantia nigra were also determined.

Key results:  Rg1 treatment ameliorated the rotational behaviour induced by apomorphine in our model of nigrostriatal injury. This effect was partly blocked by JB‐1. 6‐OHDA significantly decreased the dopamine content of the striatum and treatment with Rg1 reversed this decrease. Treatment with Rg1 of 6‐OHDA‐lesioned rats reduced neurotoxicity, as measured by tyrosine hydroxylase, dopamine transporter and Bcl‐2 protein and gene level in the substantia nigra. These effects were abolished by JB‐1.

Conclusions and implications:  These data provide the first evidence that Rg1 has neuroprotective effects on dopaminergic neurons in the 6‐OHDA model of nigrostriatal injury and its actions might involve activation of the IGF‐IR signalling pathway.
British Association of Critical Care Nurses position statement on prescribing in critical care
Authors: Bray Kate , Dawson Deborah , Gibson Vanessa , Howells Heather , Cooper Heather , McCormick Joanna , Plowright Catherine
Published: August 2009

Background: Nurses in the UK are now one group of non‐medical staff who can prescribe. This practice is evolving for critical care nursing staff who care for critically ill patients during their stay in hospital through ward and outpatient follow‐up after admission to critical care.

Aim: The purposes of this paper were to present existing information regarding prescribing to support nurses in critical care currently prescribing and to inform those who are intending to prescribe.

Methods: To develop the position statement, a search of the literature was conducted using key databases. To ascertain the current level and type of prescribing in critical care, a short questionnaire was sent by email to British Association of Critical Care Nursing members, and the results of this are presented in Appendix A.

Outcomes/Results: Evidence was found in relation to the history, context in critical care, educational requirements and issues of consent related to non‐medical prescribing.

Conclusions: The position statement is based upon evidence from the literature, National Health Service policy and the Nursing and Midwifery Council regulations. It takes account of the critical care patient pathway before, during and after an admission to critical care.
Interacting with relatives in intensive care unit. Nurses' perceptions of a challenging task
Authors: Ågård Anne Sophie , Maindal Helle Terkildsen
Published: August 2009

Aims: To describe how Danish intensive care unit (ICU)‐nurses perceive personal knowledge and skills (self‐efficacy) and outcome expectations to interacting with relatives. Moreover, to explore relationships between self‐efficacy and outcome expectations and the nurses' attitude towards involving relatives in care‐related tasks and allowing relatives to be with the patient during critical situations.

Background: Interacting with relatives can be a challenging task, and nurses play a leading role in integrating relatives in ICU. Little is known about how ICU‐nurses cope with this part of nursing

Design: Cross‐sectional

Method: Sixty‐eight ICU‐nurses responded to a self‐administered questionnaire based on Bandura's self‐efficacy theory adjusted to critical care.

Results: The nurses' perceptions of personal knowledge, skills and expectations to the outcome of interacting with relatives were positive. There were disparities in nurses' level of agreement on when to involve relatives in caring activities. Generally, the nurses did not support the presence of relatives in critical situations. Nurses' outcome expectations were correlated to their attitude towards involving relatives in caring activities. No other statistically significant correlations were found between general attitude, knowledge, skills, and attitude of nurses towards involving relatives in caring activities or allowing them to be with the patient at cardiac arrest or acute intubation.

Conclusion: The nurses' outcome expectations and self‐efficacy in terms of knowledge and skills interacting with relatives were high. There was considerable variation in the nurses' agreement on when to involve relatives in caring activities or allowing them to be with the patient in critical situations. The self‐efficacy theory was not supported as a result of lack of correlation between nurses' self‐efficacy and outcome expectations and their attitude towards involving relatives in ICU.

Relevance to clinical practice: The study provides important knowledge to clinicians, educators and managers on how to educate and supervise ICU‐nurses to support their efforts to interact proficiently with relatives.
PROGRESS IN UREMIC TOXIN RESEARCH: Guanidino Compounds as Uremic (Neuro)Toxins
Authors: De Deyn Peter Paul , Vanholder Raymond , Eloot Sunny , Glorieux Griet
Published: August 2009

Neurological and vascular impairment are important sources of morbidity in patients with renal failure. A portion of patients still suffers from uremic encephalopathy or other signs of nervous system impairment. Several reports demonstrate increased incidence of cardiac infarction and cerebrovascular accidents in chronic renal failure patients, even in those otherwise adequately dialyzed. Epileptic and cognitive symptoms are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be substantially increased as well in serum, cerebrospinal fluid, and brain of uremic patients. These compounds, “uremic” GCs, are creatinine, guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine. All four compounds are experimental convulsants in concentrations similar to those found in uremic brain. We described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. It was demonstrated that the excitatory effects of uremic GCs on the central nervous system can be explained by the activation of N‐methyl‐d‐aspartate receptors by GSA, concomitant inhibition of γ‐aminobutyric acid type A receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy. In this article, we review the uremic GCs with particular attention to their neurotoxicity. We elaborate in detail on the mechanisms of action of the neurotoxic uremic GCs and summarize the kinetics of these toxins.
PROGRESS IN UREMIC TOXIN RESEARCH: Phosphate Metabolism in Chronic Kidney Disease: From Pathophysiology to Clinical Management
Authors: Spasovski Goce , Massy Ziad , Vanholder Raymond
Published: August 2009

Hyperphosphatemia is considered as an independent risk factor for surrogate clinical endpoints like vascular calcification (VC) and bone disease, or hard clinical outcomes like cardiovascular events. To date, various treatment options for phosphate removal or reduction are available. The great expectations put into calcium‐based phosphate binders were mitigated because of their possible contribution to progressive VC, particularly in patients treated simultaneously with active vitamin D derivatives. Thus, a paradigm change occurred whereby the main clinical concern shifted from the avoidance of hypocalcemia to that of the consequences of inducting a positive calcium balance. Sevelamer‐HCl treatment allowed a comparable control of hyperphosphatemia with a lower risk of hypercalcemia than calcium‐based phosphate binders, and a slower progression of VC; however, convincing evidence of improved clinical outcomes in dialysis patients is lacking. Although data on the safety and efficacy of lanthanum carbonate in the treatment of hyperphosphatemia have been provided in long‐term clinical studies, there is still an ongoing scientific debate about its possible long‐term toxicity. Moreover, there are no data from randomized clinical trials demonstrating beneficial effects of La carbonate treatment on VC or cardiovascular outcomes. In the absence of convincing clinical trials testing the effects of non‐metal‐based phosphate binders on cardiovascular and global outcomes it appears reasonable to maintain bone health and mineral homeostasis by mainly relying on adaptations of standard therapies. Noncalcium, non‐aluminum‐based binders might be reserved for patients with major mineral metabolism abnormalities and a high risk of VC.
PROGRESS IN UREMIC TOXIN RESEARCH: Parathyroid Hormone, A Uremic Toxin
Authors: Rodriguez Mariano , Lorenzo Victor
Published: August 2009

Despite the innovations in the treatment of secondary hyperparathyroidism, there are uremic patients with marked elevation in PTH levels. Uremic toxicity is in part attributable to the excess of circulating PTH. It has been known for many years that PTH may induce changes in cell calcium, a key intracellular signal required for normal cell function. The effect of PTH in dialysis patients is not limited to bone; the diversity of biologic effects of PTH is summarized in this review. In addition, the present review addresses other issues: (i) the presence of different circulating PTH fragments in uremic patients, (ii) the PTH assays currently utilized to measure circulating PTH, and (iii) the fact that some of the PTH effects seen in uremic patients may be due to the interaction of C‐terminal PTH fragment with putative C‐terminal PTH receptors.
PROGRESS IN UREMIC TOXIN RESEARCH: Resistin as a Cardiovascular and Atherosclerotic Risk Factor and Uremic Toxin
Authors: Cohen Gerald , Hörl Walter H.
Published: August 2009

Resistin is a 12.5 kDa protein originally found to be secreted by mouse adipocytes. Whereas in rodents adipose tissue is the main source of resistin, in humans resistin is expressed primarily in macrophages. In a variety of pathophysiologic states, particularly in type 2 diabetes mellitus and in chronic kidney disease, the serum concentration of resistin is increased. Resistin reduces the glucose uptake in adipose tissue and skeletal muscle cells and may be involved in insulin resistance. A positive correlation between resistin levels and inflammatory markers has been described. Resistin has a potential role in cardiovascular disease and may contribute to an increased atherosclerotic risk by modulating the activity of endothelial cells. We recently found that resistin in concentrations measured in uremia is able to interfere with the chemotactic movement and the oxidative burst of neutrophils, cells of the first‐line nonspecific immune defense. Therefore, resistin may also contribute to the disturbed immune response and as a consequence to the increased risk of infections in uremic and diabetic subjects.
PROGRESS IN UREMIC TOXIN RESEARCH: Dinucleoside Polyphosphates and Uremia
Authors: Jankowski Vera , Günthner Thomas , Herget‐Rosenthal Stefan , Zidek Walter , Jankowski Joachim
Published: August 2009

Dinucleoside polyphosphates constitute a group of endogenous vasoregulatory purines and pyrimidines with a strong impact on physiologic and pathophysiologic processes of the cardiovascular system. Recently, the importance of dinucleoside polyphosphates in chronic kidney disease (CKD) and uremia gained increasing interest. Although our knowledge about the impact of dinucleoside polyphosphates in CKD and uremia is just at the beginning, this article reviews the current knowledge of the physiologic and pathophysiologic role of dinucleoside polyphosphates in CKD and uremia.
PROGRESS IN UREMIC TOXIN RESEARCH: The Role of Oxidative Stress in Chronic Kidney Disease
Authors: Massy Ziad A. , Stenvinkel Peter , Drueke Tilman B.
Published: August 2009

New, reliable circulating oxidative stress markers have become available in chronic kidney disease (CKD) patients and have confirmed the long held belief that CKD is a pro‐oxidant state. However, several questions related to this state of oxidative stress remain largely unresolved. First, the relative importance of each type of oxidant involved has been insufficiently evaluated. Only two recent studies have addressed this issue, and both suggested that chlorinated stress played a central role. Second, as only few population‐based studies are available, the prevalence of oxidative stress among CKD patients remains undetermined. Third, although the link between oxidative stress and inflammation in CKD is emerging as a key process contributing to the genesis of oxidative stress in these patients, its pathogenesis remains poorly defined. Fourth, data favoring the involvement of oxidative stress in uremic toxicity are still limited. Finally, while two recent pilot studies have demonstrated that treatment of CKD patients with antioxidants is able to reduce cardiovascular events, information related to the pharmacokinetic characteristics of antioxidants, as well as their efficacy to prevent oxidative stress, is still limited in this patient group. Thus, although existing data suggest a prominent role of CKD‐associated oxidative stress in uremic toxicity, further studies are required to definitively prove this concept.
PROGRESS IN UREMIC TOXIN RESEARCH: Proteomics in Uremia and Renal Disease
Authors: Mischak Harald , Massy Ziad A. , Jankowski Joachim
Published: August 2009

Proteomics has emerged as a powerful technology to decipher biological processes. One of the main goals of proteomics is the identification of biomarkers for diseases from tissues and body fluids. However, the complexity and wide dynamic range of protein expression presents an enormous challenge. This review gives an overview of the different technologies used, their potentials and limitations, focusing on capillary electrophoresis coupled to mass spectrometry (CE‐MS). CE‐MS is discussed from an application point of view, evaluating its merits and vices for biomarker discovery and clinical applications in chronic kidney disease. Finally, several examples on the application of CE‐MS to determine biomarkers for disease diagnosis, prognosis, and therapy evaluation are presented.
PROGRESS IN UREMIC TOXIN RESEARCH: Platelet/Leukocyte Activation, Inflammation, and Uremia
Authors: Glorieux Griet , Cohen Gerald , Jankowski Joachim , Vanholder Raymond
Published: August 2009

Chronic kidney disease (CKD) is a state of chronic, low‐grade inflammation which contributes to the accelerated progression of chronic inflammatory disturbances of which atherosclerosis is a major example. Platelet and leukocyte activation and interaction, evoked by the uremic condition, play an important role in this process. The effect of specific uremic retention solutes, progressively retained in uremia, on important platelet and leukocytes functions is discussed and summarized. The main uremic toxins involved are molecules with a molecular weight above 500 Da (the so‐called “middle molecules”) and/or protein‐bound molecules. Classification of the molecules and elucidation of the pathophysiological pathways involved will result in new therapeutic strategies pursuing specific removal or pharmacological neutralization of molecular impact.
PROGRESS IN UREMIC TOXIN RESEARCH: Lipoprotein Lipase Disturbances Induced by Uremia and Hemodialysis
Authors: Stegmayr Bernd , Olivecrona Thomas , Olivecrona Gunilla
Published: August 2009

Factors such as malnutrition, physical inactivity, uremic toxins, and inflammation are known to influence the activity of lipoprotein lipase (LPL), an important enzyme in metabolism of blood lipids. In patients with chronic kidney disease these factors are common and may result in a decreased LPL activity. This is particularly so in patients on hemodialysis. Further, during each dialysis treatment, the use of heparin (or low molecular weight heparin) induces a release of LPL from its normal binding sites at the plasma membrane of endothelial cells. This results in an increased degradation of the enzyme and a relative lack of LPL activity for up to 10 hours from the start of the dialysis. Thus, the use of conventional anticoagulation for hemodialysis, in addition to the consequences of the uremic state, may cause a severe functional deficiency of LPL. This in turn may have deleterious effects on energy metabolism and may contribute to the increased risk for cardiovascular disease in this vulnerable group of patients.
PROGRESS IN UREMIC TOXIN RESEARCH: Should Dialysis Modalities be Designed to Remove Specific Uremic Toxins?
Authors: Baurmeister Ulrich , Vienken Joerg , Ward Richard A.
Published: August 2009

The definition of optimal dialysis therapy remains elusive. Randomized clinical trials have neither supported using urea as a surrogate marker for uremic toxicity nor provided clear cut evidence in favor of larger solutes. Thus, where to focus resources in the development of new membranes, and therapies remains unclear. Three basic questions remain unanswered: (i) what solute(s) should be used as a marker for optimal dialysis; (ii) should dialytic therapies be designed to remove a specific solute; and (iii) how can current therapies be modified to provide better control of uremic toxicity? Identification of a single, well‐defined uremic toxin appears to be unlikely as new analytical tools reveal an increasingly complex uremic milieu. As a result, it is probable that membranes and therapies should be designed for the nonspecific removal of a wide variety of solutes retained in uremia. Removal of the widest range of solutes can best be achieved using existing therapies that incorporate convection in conjunction with longer treatment times and more frequent treatments. Membranes capable of removing solutes over an expanded effective molecular size range can already be fabricated; however, their use will require novel approaches to conserve proteins, such as albumin.
Householder Status and Residence Type as Correlates of Radon Awareness and Testing Behaviors
Authors: Larsson Laura S. , Hill Wade G. , Odom‐Maryon Tamara , Yu Paul
Published: August 2009

ABSTRACT
Objectives: The primary aim of this research was to assess radon awareness and testing across 2 housing types.

Design and Sample: Cross‐sectional prevalence study with time trends. National, probabilistic sample of 18,138 and 29,632 respondents from the 1994 and 1998 National Health Interview Surveys, respectively.

Results: Odds ratio (OR) estimates confirmed that occupants of single family homes/townhomes were twice as likely to have ever heard of radon (1994: OR=2.18; confidence intervals [CI]=2.01–2.36) (1998: OR=2.26; CI=2.09–2.44) and also more likely to know if their household air had been tested for radon (1994: OR=2.04; CI=1.57–2.65) (1998: OR=1.38; CI=1.19–1.59) as occupants of apartments/condominiums. Time trend analyses revealed that radon awareness improved from 69.4% to 70.7% and home testing among those with knowledge of radon increased from 9.7% to 15.5% over the 4‐year period.

Conclusions: Housing type provided fairly stable estimates of radon awareness and testing. Findings demonstrate that housing status may be a useful variable to differentiate risk for radon awareness and testing. Public health nurses should consider their client's housing type when assessing families for environmental risks.
Work Setting, Community Attachment, and Satisfaction Among Rural and Remote Nurses
Authors: Kulig Judith C. , Stewart Norma , Penz Kelly , Forbes Dorothy , Morgan Debra , Emerson Paige
Published: August 2009

ABSTRACT
Objectives: To describe community satisfaction and attachment among rural and remote registered nurses (RNs) in Canada.

Design and Sample: Cross‐sectional survey of rural and remote RNs in Canada as part of a multimethod study.The sample consisted of a stratified random sample of RNs living in rural areas of the western country and the total population of RNs who worked in three northern regional areas and those in outpost settings. A subset of 3,331 rural and remote RNs who mainly worked in acute care, long‐term care, community health, home care, and primary care comprised the sample.

Measures: The home community satisfaction scale measured community satisfaction, whereas single‐item questions measured work community satisfaction and overall job satisfaction. Community variables were compared across practice areas using analysis of variance, whereas a thematic analysis was conducted of the open‐ended questions.

Results: Home care and community health RNs were significantly more satisfied with their work community than RNs from other practice areas. RNs who grew up in rural communities were more satisfied with their current home community. Four themes emerged from the open‐ended responses that describe community satisfaction and community attachment.

Conclusions: Recruitment and retention strategies need to include mechanisms that focus on community satisfaction, which will enhance job satisfaction.
“Our Usable Past”: A Historical Contextual Approach to Administrative Values
Authors: Moynihan Donald P.
Published: August 2009

In responding to Professor Lynn's criticism that the field of public administration has been insufficiently attentive to law, this article offers an alternative perspective on the source of administrative legitimacy. Leonard White understood that public administration is shaped by its broader context. It does not assert its own values but, in an effort to maintain legitimacy, reflects the political and cultural values of its environment. In White's time, the extraordinary challenges that the state faced, and its subsequent transformation, demanded a management capacity that previously had not existed. While the role of law as a formal means of control is generally accepted, it must take its place with management and other administrative values in the exercise of legal discretionary behavior. Asserting law, or any other single administrative value, as dominant undercuts other values that act as sources of legitimacy.
Living in the Past? Change and Continuity in the Norwegian Central Civil Service
Authors: Christensen Tom , Lægreid Per
Published: August 2009

In this article, the authors describe the changes that have taken place in the Norwegian civil service over the past 30 years, focusing on demographic changes in education and gender and on changes in civil servants' tasks, attitudes, and contact patterns. The changes are analyzed using tenure, structural, and demographic perspectives. The unique empirical database is provided by surveys conducted every 10 years of civil servants in the ministries since 1976. The main empirical findings are that there has been a combination of robustness and change. The findings show little support for the generational version of a tenure perspective, meaning that civil servants are not living in the past. The structural perspective, illustrated by the importance of formal position, best explains the variations in civil servants' contact patterns and attitudes, followed by the career version of a tenure perspective. Demography, as represented by different educational backgrounds and gender, also has an effect.
Methylation‐associated silencing of S100A4 expression in human epidermal cancers
Authors: Li Yan , Liu Zhi‐Li , Zhang Kai‐Li , Chen Xiao‐Yan , Kong Qing‐You , Wu Mo‐Li , Sun Yuan , Liu Jia , Li Hong
Published: August 2009

Abstract:  S100A4 appears important for cancer metastasis and its overexpression is common in a variety of human malignancies, but its status in epidermal cancers remains lesser known. Likewise, E‐cadherin downregulation and Wingless (Wnt) activation are frequent cancer‐associated alterations, whereas their potential correlations with S100A4 expression in skin lesions have not been characterized. These issues were addressed in the present study using tissue microarray‐based immunohistochemical staining, reverse transcriptase polymerase chain reaction and western blotting. Meanwhile, the underlying epigenetic mechanism leading to the altered S100A4 expression in epidermal tumors was elucidated. Immunohistochemistry revealed that S100A4 expression frequencies were 100% (8/8) in normal epidermis, 80.6% (25/31) in tumor‐surrounding non‐cancerous epidermis, 66.7% (10/15) in premalignant diseases, 8.3% (1/11) in Bowen’s disease and 7.7–26.3% in different cancer tissues. The incidence of S100A4 detection in the normal and non‐cancerous epidermis was significantly different from that of epidermal cancers (P = 0.000). Accordingly, human immortalized keratinocyte line HaCat but not skin squamous cell carcinoma (SCC) line colo16 was positive in S100A4 expression. S100A4 downregulation, E‐cadherin reduction and Wnt activation coexisted in most of epidermal cancers but unnecessarily overlapped. Methylation DNA sequencing revealed methylation of four critical (cytosine and guanine separated by a phosphate or ‐C‐phosphate‐G‐) CpG sites within S100A4 intron first in S100A4‐negative colo16 cells and skin SCCs, and demethylator/5‐aza‐2′‐deoxycytidine treatment efficiently recovered S100A4 expression in colo16 cells. Our findings demonstrate that S100A4 downregulation, as the consequence of DNA methylation, is closely correlated with skin tumor formation. Wnt activation and E‐cadherin reduction and S100A4 down‐regulation are paralleled molecular events in skin tumors, which may serve as the biomarkers for predicting epidermal cancer risk.
Tattooing of skin results in transportation and light‐induced decomposition of tattoo pigments – a first quantification in vivo using a mouse model
Authors: Engel Eva , Vasold Rudolf , Santarelli Francesco , Maisch Tim , Gopee Neera V. , Howard Paul C. , Landthaler Michael , Bäumler Wolfgang
Published: August 2009

Abstract:  Millions of people are tattooed with inks that contain azo pigments. The pigments contained in tattoo inks are manufactured for other uses with no established history of safe use in humans and are injected into the skin at high densities (2.5 mg/cm2). Tattoo pigments disseminate after tattooing throughout the human body and although some may photodecompose at the injection site by solar or laser light exposure, the extent of transport or photodecomposition under in vivo conditions remains currently unknown. We investigated the transport and photodecomposition of the widely used tattoo Pigment Red 22 (PR 22) following tattooing into SKH‐1 mice. The pigment was extracted quantitatively at different times after tattooing. One day after tattooing, the pigment concentration was 186 μg/cm2 skin. After 42 days, the amount of PR 22 in the skin has decreased by about 32% of the initial value. Exposure of the tattooed skin, 42 days after tattooing, to laser light reduced the amount of PR 22 by about 51% as compared to skin not exposed to laser light. A part of this reduction is as a result of photodecomposition of PR 22 as shown by the detection of corresponding hazardous aromatic amines. Irradiation with solar radiation simulator for 32 days caused a pigment reduction of about 60% and we again assume pigment decomposition in the skin. This study is the first quantitative estimate of the amount of tattoo pigments transported from the skin into the body or decomposed by solar or laser radiation.
Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function
Authors: Kim Minjeong , Jung Minyoung , Hong Seung‐Phil , Jeon Hyerin , Kim Min‐Jung , Cho Mee‐Yon , Lee Seung‐Hun , Man Mao‐Qiang , Elias Peter M. , Choi Eung‐Ho
Published: August 2009

Please cite this paper as: Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function. Experimental Dermatology 2010; 19: 501–510.

Background:  Topical calcineurin inhibitors (TCIs) such as pimecrolimus and tacrolimus have recently been used for dermatologic diseases including atopic dermatitis instead of topical glucocorticoids, because they display comparable efficacy, but less‐frequent side effects. Although even short‐term topical glucocorticoid compromise epidermal permeability barrier homeostasis, the effects of TCI on barrier function have not yet been reported. However, viral infections such as eczema herpeticum and molluscum contagiosum, which could indicate an impaired skin barrier, continue to occur with TCI use in atopic dermatitis.

Objectives:  We determined here whether TCIs disrupt epidermal permeability barrier and antimicrobial function, and whether these effects can be prevented.

Methods and results:  In normal humans, topical pimecrolimus and tacrolimus applied twice‐daily for 5 days, delay barrier recovery without an increase in basal transepidermal water loss was observed. Co‐application of physiologic lipid mixture (PLM) containing an equimolar ratio of ceramides, cholesterol and free fatty acids normalized barrier homeostasis in the face of topical TCIs. In hairless mice, 4 days of TCI treatment also disrupted barrier function significantly. TCIs‐treated epidermis showed the decrease of epidermal lipid content, lamellar body number and secretion, and lipid synthesis‐related enzymes such as 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) reductase, serine‐palmitoyl transferase and fatty acid synthase, implying decreased lipid synthesis. TCIs also suppressed expression of IL‐1α and antimicrobial peptides, CRAMP and mouse β‐defensin 3. However, these TCI‐induced abnormalities can be overridden by topical replacement with PLM.

Conclusions:  Our results demonstrate that TCIs induce negative effects on the skin barrier including permeability and antimicrobial functions, which are mediated by decreasing epidermal lipid synthesis, lamellar body secretion and antimicrobial peptides expression through suppression of cytokine such as IL‐1α, therefore co‐treatment with PLM would be helpful to overcome these negative effects.
Iliotibial band syndrome: an examination of the evidence behind a number of treatment options
Authors: Falvey E. C. , Clark R. A. , Franklyn‐Miller A. , Bryant A. L. , Briggs C. , McCrory P. R.
Published: August 2009

Iliotibial band (ITB) syndrome (ITBS) is a common cause of distal lateral thigh pain in athletes. Treatment often focuses on stretching the ITB and treating local inflammation at the lateral femoral condyle (LFC). We examine the area's anatomical and biomechanical properties. Anatomical studies of the ITB of 20 embalmed cadavers. The strain generated in the ITB by three typical stretching maneuvers (Ober test; Hip flexion, adduction and external rotation, with added knee flexion and straight leg raise to 30°) was measured in five unembalmed cadavers using strain gauges. Displacement of the Tensae Fasciae Latae (TFL)/ITB junction was measured on 20 subjects during isometric hip abduction. The ITB was uniformly a lateral thickening of the circumferential fascia lata, firmly attached along the linea aspera (femur) from greater trochanter up to and including the LFC. The microstrain values [median (IQR)] for the OBER [15.4(5.1–23.3)me], HIP [21.1(15.6–44.6)me] and SLR [9.4(5.1–10.7)me] showed marked disparity in the optimal inter‐limb stretching protocol. HIP stretch invoked significantly (Z=2.10, P=0.036) greater strain than the SLR. TFL/ITB junction displacement was 2.0±1.6 mm and mean ITB lengthening was <0.5% (effect size=0.04). Our results challenge the reasoning behind a number of accepted means of treating ITBS. Future research must focus on stretching and lengthening the muscular component of the ITB/TFL complex.
Cost‐utility of exercise therapy in adolescents and young adults suffering from the patellofemoral pain syndrome
Authors: Tan S. S. , Van Linschoten R. L. , Van Middelkoop M. , Koes B. W. , Bierma‐Zeinstra S. M. , Koopmanschap M. A.
Published: August 2009

The objective of this paper was to determine the cost effectiveness of exercise therapy (intervention group) compared with “usual care” (control group) in adolescents and young adults with the patellofemoral pain syndrome in primary care. This multicenter prospective randomized clinical trial with cost‐utility analysis was conducted at 38 general practices and three sport medical advice centers in the Netherlands for 2007. A total of 131 patients were included. The annual direct medical costs per patient were significantly higher for the intervention group (€434) compared with the control group (€299) mainly caused by additional physiotherapy visits. The average annual societal costs per patient were significantly lower in the intervention group (€1011 vs €1.166). Productivity costs were the largest cost component, in particular costs due to reduced efficiency at paid work which were responsible for 47% and 56% of the total costs in the intervention and control group respectively. Patients in the intervention group experienced a slightly, but not significantly, higher quality of life (0.8722 vs 0.8617). With a cost effectiveness ratio of −€14 738 per quality adjusted life year, exercise therapy appears to be cost effective as compared with “usual care.”
Extraction of skin lesion texture features based on independent component analysis
Authors: Tabatabaie Kaveh , Esteki Ali , Toossi Parviz
Published: August 2009

Background/purpose: During the recent years, many diagnostic methods have been proposed aiming at early detection of malignant melanoma. The texture of skin lesions is an important feature to differentiate melanoma from other types of lesions, and different techniques have been designed to quantify this feature. In this paper, we discuss a new approach based on independent component analysis (ICA) for extraction of texture features of skin lesions in clinical images.

Methods: After preprocessing and segmentation of the images, features that describe the texture of lesions and show high discriminative characteristics are extracted using ICA, and then these features, along with the color features of the lesions, are used to construct a classification module based on support vector machines for the recognition of malignant melanoma vs. benign nevus.

Results: Experimental results showed that combining melanoma and nevus color features with proposed ICA‐based texture features led to a classification accuracy of 88.7%.

Conclusion: ICA can be used as an effective tool for quantifying the texture of lesions.
ORIGINAL ARTICLE: Identification of Toll‐Like Receptors in the Rat (Rattus norvegicus): Messenger RNA Expression in the Male Reproductive Tract Under Conditions of Androgen Variation
Authors: Biswas Barnali , Narmadha Ganapathy , Choudhary Mithilesh , French Frank S. , Hall Susan H. , Yenugu Suresh
Published: August 2009

Problem  Although the majority of Toll‐like receptors (TLRs) are reported in many species, some of them are not yet described in the rat. Further, factors that govern Tlr expression in the male reproductive tract have received little attention. We attempt to identify and characterize Tlrs in the rat and determine the expression profile under conditions that affect male reproductive tract gene expression.

Method of study  Rat Tlr5, Tlr10, and Tlr11 transcript sequences were submitted to GenBank and in silico characterization carried out using bioinformatics tools. RT‐PCR analyses using gene specific primers for rat Tlr1–13 were carried out with RNA isolated from reproductive tract tissues of various experimental groups.

Results  Tlr5, Tlr10, and Tlr11 identified in this study share features that are characteristic of the known TLRs. Abundant Tlr expression was observed in the male reproductive tract of adult and developing rats. Further, Tlr expression was also observed in the epididymides of androgen ablated rats.

Conclusion  Tlr5, Tlr10, and Tlr11 are ubiquitously expressed in the rat. Tlrs seem to be expressed during male reproductive tract development and under conditions of androgen ablation, suggesting the preparedness of the male reproductive tract to detect an infection under all conditions of androgen status.
The bactericidal effect of a Genius® Nd:YAG laser
Authors: Kranendonk AA , Van Der Reijden WA , Van Winkelhoff AJ , Van Der Weijden GA
Published: August 2009

Abstract:  Purpose: To evaluate the ‘in vitro’ bactericidal effect of the Nd:YAG laser (Genius, MØlsgaard Dental, Copenhagen, Denmark) on six periodontal pathogens. Methods: Suspensions of six different periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum and Parvimonas micra) were prepared in small Eppendorff tubes, and exposed to a Nd:YAG laser for five different periods of time. Laser settings used: Power 6 Watt (on a scale of 1–12 W), Frequency 50 Hz, Pulse duration 250 μs. After exposure to the laser, aliquots of the suspensions were spread on blood agar plates for bacterial counting. Results: After 5 s of laser exposure, there was a decrease in total colony forming units for all six selected microorganisms. After 15, 30 and 45 s, no viable bacterial cells could be retrieved. Conclusion: In this ‘in vitro’ model, 15 s of Nd:YAG laser use was found to be effective for total killing of the six tested periodontal pathogens.
Grey Seals Red in Tooth and Claw: How Darwin Helps Model Their Population
Authors: Thomas Len
Published: August 2009

Grey seals in Britain are a conservation success, brought back from the brink of extinction by protection in the early 20th century. The public love them. Fishermen hate them. The resurgence of the “grey guzzlers” threatens their livelihood, they say. Len Thomas shows how Charles Darwin's ideas are used to determine seal numbers and population dynamics. Surprisingly, Darwin's theories have also influenced the statistical tools that are used.
The Completeness of the Fossil Record
Authors: Benton Michael
Published: August 2009

Fossils are the data for evolution. The fossil record was already well known 150 years ago, when Charles Darwin published On the Origin of Species, and it is central to Darwin's theories; yet it is commonly claimed that the fossil record is woefully incomplete. Creationists say that it does not show the missing links that evolution predicts. Michael Benton asks if the gaps are too big to fill in.
Take Five: Renaissance Literature and the Study of the Senses
Authors: Cahill Patricia A.
Published: August 2009

In recent years scholars of various critical stripes have shown a keen interest in Renaissance literature and the study of the senses. I offer an overview of such sensory scholarship, detailing the contributions of social historians, of those who work on Renaissance allegory, and of those engaged in scholarship on faculty psychology and early modern embodiment. As I trace the contours of work by literary and cultural critics on the individual senses, I note that critical explorations of vision, the sense that many Renaissance philosophers ranked at the top of the sensory hierarchy, no longer eclipse scholarship on the other senses. Rather, work on aurality has blossomed in the past decade as scholars have investigated the history of hearing and listening and have recognized the privileged position of aurality in Renaissance sensory hierarchies. Before ending, I discuss recent discussions of smell, taste, and touch, and I suggest some ways in which recent scholarship on tactility might reinvigorate the study of Renaissance drama.
In vitro characterization of Synechocystis CYP120A1 revealed the first nonanimal retinoic acid hydroxylase
Authors: Alder Adrian , Bigler Peter , Werck‐Reichhart Danièle , Al‐Babili Salim
Published: August 2009

Retinoids are C20 apocarotenoids that have various important functions in metazoans. In addition, several findings suggest their occurrence in eubacteria, including cyanobacteria. It has been shown that the Synechocystis cytochrome P450 enzyme CYP120A1 is a retinoic acid‐binding polypeptide. In this work, we determined the reaction catalyzed by CYP120A1 and investigated its substrate specificity in vitro. CYP120A1‐containing microsomes generated in yeast converted all‐trans‐retinoic acid into a compound exhibiting higher polarity in HPLC analysis. Liquid chromatography–MS analysis suggested the introduction of a single hydroxyl group, and NMR analysis of the purified product revealed C16 or C17 as the reaction site. Incubations with cis‐retinoic acids, retinal, 3(R)‐OH‐retinal, retinol, β‐apo‐13‐carotenone (C18) and β‐apo‐14′‐carotenal (C22) resulted in the formation of the corresponding hydroxyl derivatives, as suggested by HPLC and liquid chromatography–MS analyses. Comparisons of the relative product amounts revealed the highest conversion rate for all‐trans‐retinoic acid, followed by β‐apo‐13‐carotenone (C18). As shown by real‐time RT‐PCR, CYP120A1 is expressed under normal growth conditions and is slightly induced by high‐intensity light. Our work provides the first enzymatic study of a cyanobacterial cytochrome P450, showing it to be the first nonanimal retinoic acid‐metabolizing enzyme characterized so far. Moreover, the CYP120A1‐catalyzed reaction represents a novel modification of retinoids.
Confirmation of allele HLA‐A*3116 found in a family of a leukaemia patient with Caucasian and Caribbean origin
Authors: Skrablin P. S. , Brixner V. , Richter R. , Boehme A. , Seifried E. , Seidl C.
Published: August 2009

We confirm allele HLA‐A*3116 that we found in the family of a leukaemia patient of mixed Caucasian and Caribbean origin by sequence based typing. This allele is closest related to HLA‐A*310102 with one nucleotide replacement at position 221 (C>T) leading to an amino acid substitution at position 50 of the mature protein from proline to leucine. As the amino acid at position 50 in the alpha 1 domain is part of the peptide‐binding region, this change could be relevant for the functionality in peptide presentation.