bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of the Template in Prosthetically Guided Implantology
Authors: Annibali Susanna , La Monaca Gerardo , Tantardini Marco , Cristalli Maria Paola
Published: February 2009

In prosthetically guided implantology, where ideal placement of implants is determined by the definitive restoration, the use of a radiographic/surgical template plays an essential role. This article describes how to fabricate a radiographic/surgical template to be used for radiographic diagnosis of the selected implant sites and as a guide during surgery for the insertion of the implant with correct angulation.
Treatment of Edentulism: Optimizing Outcomes with Tissue Management and Impression Techniques
Authors: Salinas Thomas J.
Published: February 2009

Significant numbers of patients throughout the world seek treatment for edentulism. The trend toward tissue‐integrated prostheses has been a monumental step in restoring edentulous patients to function; however, this treatment can be out of reach for those who fail to qualify or those who do not have sufficient resources to afford it. In these cases, conventional dentures remain an important primary course of treatment. Attention to detail when diagnosing, treatment planning, and performing treatment for these patients is still a prime consideration for the best possible outcome. In particular, many experienced denture wearers are afflicted with chronically inflamed denture‐bearing mucosa. Clinicians must recognize the need for tissue conditioning, choices of impression materials, and accepted fabrication techniques that can have favorable outcomes when matched with patients who are philosophical and realistic in their expectations. The purpose of this article is to review impression philosophies, associated materials, and methods of tissue conditioning. Retention and stability of the denture bases can be augmented by the routine use of denture adhesive, and indications for use of denture adhesive will be discussed.
Contemporary Techniques for Denture Fabrication
Authors: McCord J. Fraser
Published: February 2009

This article reviews the fabrication of complete dentures and presents findings of recent technological studies that have relevance to current complete denture practice. In addition, summaries of two recent randomized controlled studies demonstrate the need for more deliberate prescription of impression materials.
The Current and Future Treatment of Edentulism
Authors: Cooper Lyndon F.
Published: February 2009

The purpose of this review and summary is to focus the clinician's attention on existing potential limitations regarding the management of edentulism. The current published data and opinions concerning the need for treating edentulism, the quality of dentures, related morbidity, and alternative or related therapeutics (e.g., dental implants) suggest there are opportunities for improvement in the treatment of the edentulous population. This may be achieved by adopting a broader therapeutic strategy focused not solely on technical aspects of an oral prosthesis. Instead, a wider array of clinical features of the edentulous patient should be addressed. A contemporary strategy may include concerns for prevention of tooth loss, evaluation of residual alveolar ridge resorption, and related issues of denture function, continual evaluation of oral mucosal health, compassionate management of maladaptive patients, a rationale for timely replacement of dentures, and continued development of dental implant therapies. The importance of therapeutic technical quality can be underscored, but should not overwhelm the broader concerns for assuring the overall health and well‐being of the edentulous population.
1. Globalization and Violence: The Challenge to Ethics
Authors: Demenchonok Edward , Peterson Richard
Published: February 2009

Despite its many benefits, globalization has proven to harbor a good deal of violence. This is not only a matter of the proliferation of weapons of mass destruction inaugurated by the atomic bombing of Hiroshima, but includes many forms of indirect or “structural violence” resulting from the routine of economic and political institutions on the global scale. In this essay, the multifaceted phenomena of violence are approached from the standpoint of ethics. The prevailing political thinking associated with “realism” fails to address the problems of militarism and of hegemonic unilateralism. In contrast, many philosophers are critically rethinking the problem of global violence from different ethical perspectives. Despite sharing similar concerns, philosophers nevertheless differ over the role of philosophical reflection and the potentials of reason. These differences appear in two contrasting approaches associated with postmodern philosophy and discourse ethics. In the analysis of discourse ethics, attention is paid to Karl‐Otto Apel's attempt of philosophically grounding a macroethics of planetary co‐responsibility. At the heart of the essay is the analysis of the problem of violence, including terrorism, by Jürgen Habermas, who explains the phenomenon of violence in terms of the theory of communicative action as the breakdown of communication. Jacques Derrida's deconstruction of the notion of “terrorism” also is analyzed. According to the principle of discourse ethics, all conflicts between human beings ought to be settled in a way free of violence, through discourses and negotiations. These philosophers conclude that the reliance on force does not solve social and global problems, including those that are the source of violence. The only viable alternative is the “dialogical” multilateral relations of peaceful coexistence and cooperation among the nations for solving social and global problems. They emphasize the necessity of strengthening the international rule of law and institutions, such as a reformed United Nations.
3. The Holocaust Sublime: Singularity, Representation, and the Violence of Everyday Life
Authors: Sanbonmatsu John
Published: February 2009

The world of the concentration camps . . . was not an exceptionally monstrous society. What we saw there was the image, and in a sense the quintessence, of the infernal society in which we are plunged every day.

—Ionesco1

Abstract

It has become common to view mass historical traumas like the atomic bombings of Hiroshima and Nagasaki or the Holocaust as singularities—in other words, events of such transcendent, almost metaphysical significance that they exceed intelligibility. Siding with “realist” intellectuals who instead emphasize the rootedness of genocide in the structures of modernity and everyday life, I argue that the discourse of singularity aestheticizes historical trauma in problematic ways. Drawing on Kant's analytic of the sublime, in which the subject, in confronting an awesome or terrifying phenomenon from a position of safety, comes to realize his or her own powers of transcendence and moral superiority, I argue that the holocaust sublime encourages the viewing subject to “face” overwhelming horrors of the past, but without having to confront the subject's actual responsibility for the atrocities of the present. By pitting the extraordinary or “singular” against the banal and everyday, the holocaust sublime thus obscures, rather than reveals, the habits of thought and social structures that make genocidal practices inevitable.
5. The Project of Reconciliation and the Road to Redemption: Hegel's Social Philosophy and Nietzsche's Critique
Authors: Hicks Steven V.
Published: February 2009

Abstract

Arthur Schopenhauer once observed: “A Philosophy in between the pages of which one does not hear the tears, the weeping and gnashing of teeth and the terrible din of mutual universal murder is no [genuine] philosophy.”1Certainly, the unforgettable events of the twentieth and early twenty‐first centuries, which bear the names Auschwitz, Hiroshima, Rwanda, and Darfur, pose a challenge for philosophical thinking to prove itself equal to what emerges from these horrific events. To that end, my paper looks back to the philosophies of G. W. F. Hegel and Friedrich Nietzsche—in particular to their vision of a social reconciliation and cultural redemption—as a source of inspiration in our efforts to meet the challenges posed for a philosophy of the future by the global scale of violence, human suffering, and alienation. In what follows, I first offer a comparative analysis of Hegel's “project of reconciliation” with Nietzsche's “project of redemption.” I then consider whether or not either philosopher can provide us with a coherent and attractive ethical/sociopolitical alternative for our postmodern world—a world still characterized by global violence, injustice, genocide, ecological degradation, and the prospect of nuclear annihilation.
9. Human Rights: Historical Learning in the Shadow of Violence
Authors: Peterson Richard T.
Published: February 2009

Abstract

This paper emphasizes the historical dimension of human rights understood as a social ethic. Rather than timeless principles, human rights and the universality proper to them emerge in a process of suffering, conflict, political assertion, and institutional change. We can understand them as historical yet also universal by seeing that human rights arise in processes of social learning that take place in an increasingly globalized world. Such learning often has advanced in the face of dramatic violence, for example, the bombing of Hiroshima. But the demands on a global social ethic today are not only a matter of responding to threats and acts of dramatic violence in isolation. Attention to the example of Hiroshima suggests that the problem of violence is bound up with other questions about the regulation of emerging technical powers in a context of inequality and social conflict. To what extent can an ethic centered on human rights provide an ethics that can inform effective responses to these problems? To consider the promise of human rights, we look more closely at the kind of social learning they involve and explore in particular the role of social movements in forging new identities and reciprocities along with normative claims proper to a global public sphere (the anti‐apartheid movement provides an example). We go on to see that these political experiences can inform interpretations of historical experience that can inform a widened sense of historical possibilities, both those missed in the past and those that confront us today. While this argument may thicken our sense of the promise of a human rights ethic, it remains speculative, not least because of the limited effectiveness of these norms in practice today. We close with the suggestion that nonetheless a coherent ethical response is possible, one that in the wealthy parts of the globe might take the form of an ethic of democratic responsibility. This would both represent a distinctive kind of learning and perhaps contribute to a wider advance of human rights.
Revisiting the Phylogenetic Position of Synchroma grande
Authors: PATIL VISHWANATH , BRÅTE JON , SHALCHIAN‐TABRIZI KAMRAN , JAKOBSEN KJETILL S.
Published: February 2009

ABSTRACT. Two new classes Synchromophyceae and Picophagea, belonging to the heterokonts, have been proposed recently in separate studies of 18S rRNA phylogenies. Here we revise the 18S phylogeny of these classes by including all available sequenced species and applying Bayesian and maximum likelihood methods; Synchroma grande groups with the photophagotrophic Chlamydomyxa labyrinthuloides with high statistical support. This clade is sister to Chrysophyceae, together they share a common ancestry. Our results show that the creation of class Synchromophyceae by Horn et al. was premature, because they did not include data from the closely related C. labyrinthuloides and Picophagus flagellatus species. A revision of these classes should include additional species and most likely multigene phylogenies.
Tetramitus thermacidophilus n. sp., an Amoeboflagellate from Acidic Hot Springs
Authors: BAUMGARTNER MANUELA , EBERHARDT SILVIA , DE JONCKHEERE JOHAN F. , STETTER KARL O.
Published: February 2009

ABSTRACT. Tetramitus thermacidophilus n. sp. is a novel thermophilic and acidophilic amoeboflagellate isolated from acidic hot springs in the Caldera Uzon (Kamchatka, Russia) and in Pisciarelli Solfatara (Naples, Italy). We describe it based on physiological, morphological, and sequence data. It was grown in monoxenic culture on the archaeon Acidianus brierleyi as food. Tetramitus thermacidophilus multiplies in a pH range from 1.2 to 5 and in a temperature range from 28 °C to 54 °C. The shortest doubling time was 4.5 h at pH 3 at 45 °C. Its spindle‐shaped biflagellated stage was only rarely found in culture. The amoeboid stage shows the typical locomotive form of vahlkampfiid amoebae. Sequence comparisons of the internal transcribed spacer sequences and the small subunit rRNA genes confirm that T. thermacidophilus is a novel species within the genus Tetramitus and that both isolates belong to that species.
The Secondary Metabolite Euplotin C Induces Apoptosis‐Like Death in the Marine Ciliated Protist Euplotes vannus
Authors: CERVIA DAVIDE , DI GIUSEPPE GRAZIANO , RISTORI CHIARA , MARTINI DAVIDE , GAMBELLINI GABRIELLA , BAGNOLI PAOLA , DINI FERNANDO
Published: February 2009

ABSTRACT. The sesquiterpenoid euplotin C is a secondary metabolite produced by the ciliated protist Euplotes crassus and provides a mechanism for damping populations of potential competitors. Indeed, E. crassus is virtually resistant to its own product while different non‐producer species representing an unbiased sample of the marine, interstitial, ciliate diversity are sensitive. For instance, euplotin C exerts a marked disruption of different homeostatic mechanisms in Euplotes vannus. We demonstrate by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay that euplotin C quickly decreases viability and mitochondrial function of E. vannus with a very high efficacy and at micromolar potency. In addition, euplotin C induces apoptosis in E. vannus as 4,6‐diamino‐2‐phenylindole and terminal transferase dUTP nick end labeling staining show the rapid condensation and fragmentation of nuclear material in cells treated with euplotin C. These effects occur without detectable permeabilisation or rupture of cell membranes and with no major changes in the overall morphology, although some traits, such as vacuolisation and disorganized microtubules, can be observed by transmission electron microscopy. In particular, E. vannus show profound changes of the mitochondrial ultrastructure. Finally, we also show that caspase activity in E. vannus is increased by euplotin C. These data elucidate the pro‐apoptotic role of euplotin C and suggest a mechanism for its impact on natural selection.
Ontogenesis of Dileptus terrenus and Pseudomonilicaryon brachyproboscis (Ciliophora, Haptoria)
Authors: VĎAČNÝ PETER , FOISSNER WILHELM
Published: February 2009

ABSTRACT. Dileptids are haptorid ciliates with a conspicuous proboscis belonging to the oral apparatus and carrying a complex, unique ciliary pattern. We studied development of body shape, ciliary pattern, and nuclear apparatus during and after binary fission of Dileptus terrenus using protargol impregnation. Additional data were obtained from a related species, Pseudomonilicaryon brachyproboscis. Division is homothetogenic and occurs in freely motile condition. The macronucleus is homomeric and condenses to a globular mass in mid‐dividers. The proboscis appears in late mid‐dividers as a small convexity in the opisthe's dorsal brush area and maturates post‐divisionally. The oral and dorsal brush structures develop by three rounds of basal body proliferation. The first round generates minute anarchic fields that will become circumoral kinetofragments, while the second round produces the perioral kinety on the right and the preoral kineties on the dorsal opisthe's side. The dorsal brush is formed later by a third round of basal body production. The formation of various Spathidium‐like body shapes and ciliary patterns during ontogenesis and conjugation of Dileptus shows a close relationship between spathidiids and dileptids. On the other hand, the peculiarities of the dileptid morphology and ontogenesis indicate a long, independent evolution.
Acanthamoeba Interaction with Extracellular Matrix Glycoproteins: Biological and Biochemical Characterization and Role in Cytotoxicity and Invasiveness
Authors: ROCHA‐AZEVEDO BRUNO DA , JAMERSON MELISSA , CABRAL GUY A. , SILVA‐FILHO FERNANDO C. , MARCIANO‐CABRAL FRANCINE
Published: February 2009

ABSTRACT. Acanthamoeba are free‐living amoebae that are dispersed in most environments. Occasionally, Acanthamoeba cause serious human infections, such as keratitis and encephalitis. During the infection process, amoebic adhesion to, and degradation of, host cells and their extracellular matrix (ECM) appear to be important requirements. We examined the interaction of Acanthamoeba with the ECM, and related this event to host cell destruction and tissue invasion. Pathogenic Acanthamoeba culbertsoni differentially attached on the ECM glycoproteins laminin‐1, collagen‐I, and fibronectin, as compared with non‐pathogenic Acanthamoeba astronyxis. Binding to collagen‐I and laminin‐1 induced A. culbertsoni to become flattened and elongated. Because attachment on laminin‐1 was higher in A. culbertsoni, laminin‐1 was chosen for further analysis. A 55‐kDa laminin‐binding protein was identified in pathogenic amoebae, but it was not found in non‐pathogenic amoebae. No differential cytotoxicity against distinct cell types was observed between A. culbertsoni incubated with or without ECM. On the other hand, binding on collagen‐I or matrigel scaffolds induced a differential effect where A. culbertsoni invaded collagen‐I matrices more rapidly. These results indicate that ECM recognition, as an antecedent to tissue invasion, may be a trait characteristic of pathogenic Acanthamoeba.
Length and Sequence Heterogeneity in the Mitochondrial Internal Transcribed Spacer of Acanthamoeba spp.
Authors: LEDEE DOLENA R. , BYERS THOMAS J.
Published: February 2009

ABSTRACT. The internal transcribed spacer (ITS) between the mitochondrial large (23S rRNA; rnl) and small (16S rRNA; rns) subunit ribosomal RNA genes of Acanthamoeba castellanii strain Neff was sequenced previously and was uniquely interesting because it contained tRNA genes with acceptor stem mismatches that underwent RNA editing repair. Our interest in this ITS region was to determine its phylogenetic potential in differentiating between closely related isolates. We analyzed the mitochondrial ITS region for 17 Acanthamoeba isolates and observed extensive sequence and length variability, making this region difficult to align. Acanthamoeba griffini strain S‐7 had the shortest ITS (i.e. 559 base pairs [bp]) compared with Acanthamoeba palestinensis strain Reich, which had the longest (i.e. 1,360 bp). The length disparity occurred predominantly between the spacer region of the aspartic acid (trnD) and methionine (trnM) tRNA genes. Unexpectedly, this region in A. palestinensis Reich was found to contain a duplication of the trnM gene. Additionally, like A. castellanii strain Neff, all isolates examined had tRNAs with mismatches in their acceptor stem. Also, the potential for an additional type of editing not described previously for Acanthamoeba, involving purine to pyrimidine transversions was observed.
4‐Aminoethylamino‐emodin – a novel potent inhibitor of GSK‐3β– acts as an insulin‐sensitizer avoiding downstream effects of activated β‐catenin
Authors: Gebhardt Rolf , Lerche Katja S. , Götschel Frank , Günther Robert , Kolander Jens , Teich Lars , Zellmer Sebastian , Hofmann Hans‐Jörg , Eger Kurt , Hecht Andreas , Gaunitz Frank
Published: February 2009

Glycogen synthase kinase‐3β (GSK‐3β) is a key target and effector of downstream insulin signalling. Using comparative protein kinase assays and molecular docking studies we characterize the emodin‐derivative 4‐[N‐2‐(aminoethyl)‐amino]‐emodin (L4) as a sensitive and potent inhibitor of GSK‐3β with peculiar features. Compound L4 shows a low cytotoxic potential compared to other GSK‐3β inhibitors determined by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide assay and cellular ATP levels. Physiologically, L4 acts as an insulin‐sensitizing agent that is able to enhance hepatocellular glycogen and fatty acid biosynthesis. These functions are particularly stimulated in the presence of elevated concentrations of glucose and in synergy with the hormone action at moderate but not high insulin levels. In contrast to other low molecular weight GSK‐3β inhibitors (SB216763 and LiCl) or Wnt‐3α‐conditioned medium, however, L4 does not induce reporter and target genes of activated β‐catenin such as TOPflash, Axin2 and glutamine synthetase. Moreover, when present together with SB216763 or LiCl, L4 counteracts expression of TOPflash or induction of glutamine synthetase by these inhibitors. Because L4 slightly activates β‐catenin on its own, these results suggest that a downstream molecular step essential for activation of gene transcription by β‐catenin is also inhibited by L4. It is concluded that L4 represents a potent insulin‐sensitizing agent favouring physiological effects of insulin mediated by GSK‐3β inhibition but avoiding hazardous effects such as activation of β‐catenin‐dependent gene expression which may lead to aberrant induction of cell proliferation and cancer.
MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy
Authors: Jung Monika , Mollenkopf Hans‐Joachim , Grimm Christina , Wagner Ina , Albrecht Marco , Waller Tobias , Pilarsky Christian , Johannsen Manfred , Stephan Carsten , Lehrach Hans , Nietfeld Wilfried , Rudel Thomas , Jung Klaus , Kristiansen Glen
Published: February 2009

MicroRNAs are short single‐stranded RNAs that are associated with gene regulation at the transcriptional and translational level. Changes in their expression were found in a variety of human cancers. Only few data are available on microRNAs in clear cell renal cell carcinoma (ccRCC). We performed genome‐wide expression profiling of microRNAs using microarray analysis and quantification of specific microRNAs by TaqMan real‐time RT‐PCR. Matched malignant and non‐malignant tissue samples from two independent sets of 12 and 72 ccRCC were profiled. The microarray‐based experiments identified 13 over‐expressed and 20 down‐regulated microRNAs in malignant samples. Expression in ccRCC tissue samples compared with matched non‐malignant samples measured by RT‐PCR was increased on average by 2.7‐ to 23‐fold for the hsa‐miR‐16, −452*, −224, −155 and −210, but decreased by 4.8‐ to 138‐fold for hsa‐miR‐200b, −363, −429, −200c, −514 and −141. No significant associations between these differentially expressed microRNAs and the clinico‐pathological factors tumour stage, tumour grade and survival rate were found. Nevertheless, malignant and non‐malignant tissue could clearly be differentiated by their microRNA profile. A combination of miR‐141 and miR‐155 resulted in a 97% overall correct classification of samples. The presented differential microRNA pattern provides a solid basis for further validation, including functional studies.
Classically and alternatively activated macrophages contribute to tissue remodelling after myocardial infarction
Authors: Troidl C. , Möllmann H. , Nef H. , Masseli F. , Voss S. , Szardien S. , Willmer M. , Rolf A. , Rixe J. , Troidl K. , Kostin S. , Hamm C. , Elsässer A.
Published: February 2009

An important goal in cardiology is to minimize myocardial necrosis and to support a discrete but resilient scar formation after myocardial infarction (MI). Macrophages are a type of cells that influence cardiac remodelling during MI. Therefore, the goal of the present study was to investigate their transcriptional profile and to identify the type of activation during scar tissue formation. Ligature of the left anterior descending coronary artery was performed in mice. Macrophages were isolated from infarcted tissue using magnetic cell sorting after 5 days. The total RNA of macrophages was subjected to microarray analysis and compared with RNA from MI and LV‐control. mRNA abundance of relevant targets was validated by quantitative real‐time PCR 2, 5 and 10 days after MI (qRT‐PCR). Immunohistochemistry was performed to localize activation type‐specific proteins. The genome scan revealed 68 targets predominantly expressed by macrophages after MI. Among these targets, an increased mRNA abundance of genes, involved in both the classically (tumour necrosis factor α, interleukin 6, interleukin 1β) and the alternatively (arginase 1 and 2, mannose receptor C type 1, chitinase 3‐like 3) activated phenotype of macrophages, was found 5 days after MI. This observation was confirmed by qRT‐PCR. Using immunohistochemistry, we confirmed that tumour necrosis factor α, representing the classical activation, is strongly transcribed early after ligature (2 days). It was decreased after 5 and 10 days. Five days after MI, we found a fundamental change towards alternative activation of macrophages with up‐regulation of arginase 1. Our results demonstrate that macrophages are differentially activated during different phases of scar tissue formation after MI. During the early inflammatory phase, macrophages are predominantly classically activated, whereas their phenotype changes during the important transition from inflammation to scar tissue formation into an alternatively activated type.
Computer‐aided analysis of cell interactions under dynamic flow conditions
Authors: Giegold Oliver , Ludwig Ralf J. , Hardt Katja , Will Jutta , Schön Michael P. , Oostingh Gertie J. , Pfeilschifter Josef M. , Boehncke Wolf‐Henning , Radeke Heinfried H.
Published: February 2009

Abstract:  Experimentally, initial steps of leucocyte extravasation, including tethering and rolling, are analysed in endothelial cell flow chambers. Given the complexity and speed of endothelial‐immune cell interaction, computer‐aided advances of this analysis are highly desirable. Herein, we compared two established methods, hand counting and tracking software, with novel analysis software using defined movies recorded at standard conditions of endothelial‐leucocyte interactions. As a first validation, cell counts and velocity parameters determined by seven experienced experts revealed no statistic differences to both semi‐automated tracking and fully computerized analyses. Nevertheless, interindividual variations were substantial for hand counting. In additional experiments, velocity distributions between 1 and 800 μm/s picked up by the fully computerized analysis matched well with the tracking software as indicated by speed vector histograms. With respect to the time consumed for a defined set of movies, hand counting took 3.6 ± 1.6 h, tracking software 4.5 ± 1.2 h, whereas fully automated analysis consumed less than 15 min, reaching real‐time mode. Thus, a validated and fully computerized method yielded functional flow chamber data unbiased, independent from an examiner, and reaching high‐throughput level, which in turn will allow a substantial progress in understanding this process central for skin inflammation.
Nitric oxide enhances expression of raf kinase inhibitor protein in keratinocytes
Authors: Tsao Der‐An , Yu Hsin‐Su , Chang Huoy‐Rou
Published: February 2009

Abstract: Several reports have focused on the potential of nitric oxide (NO) to influence the proliferation and differentiation cascade in a number of mammalian cells. The purpose of this study was to determine the relationship between expression of raf kinase inhibitor protein (RKIP) and proliferation in keratinocyte with NO treatment. Normal human keratinocytes were treated with SNAP (NO donor) doses of 10−7, 10−6, 10−5, 10−4and 0 m(control group) separately. Expression of protein and mRNA of RKIP, cell proliferation and apoptosis have been measured. These results showed that elevated expression of RKIP in keratinocyte with NO treatment may contribute to the pathological and physiological features of NO‐inhibited proliferation.
VEGFR1 (Flt1) Regulates Rab4 Recycling to Control Fibronectin Polymerization and Endothelial Vessel Branching
Authors: Jones Matthew C. , Caswell Patrick T. , Moran‐Jones Kim , Roberts Marnie , Barry Simon T. , Gampel Alexandra , Mellor Harry , Norman Jim C.
Published: February 2009

The cell's main receptor for VEGF, VEGFR2 (Kdr) is one of the most important positive regulators of new blood vessel growth and its downstream signalling is well characterized. By contrast, VEGFR1 (Flt1) and the mechanisms by which this VEGF receptor promotes branching morphogenesis in angiogenesis remain relatively unclear. Here we report that engagement of VEGFR1 activates a Rab4A‐dependent pathway that transports αvβ3 integrin from early endosomes to the plasma membrane, and that this is required for VEGF‐driven fibronectin polymerization in endothelial cells. Furthermore, VEGFR1 acts to promote endothelial tubule branching in an organotypic model of angiogenesis via a mechanism that requires Rab4A and αvβ3 integrin. We conclude that a recycling pathway regulated by Rab4A is a critical effector of VEGFR1 during branching morphogenesis of the vasculature.
How Location Governs Toll‐Like Receptor Signaling
Authors: Chaturvedi Akanksha , Pierce Susan K.
Published: February 2009

Toll‐like receptors (TLRs) are a family of innate immune system receptors responsible for recognizing conserved pathogen‐associated molecular patterns (PAMPs). PAMP binding to TLRs initiates intracellular signaling pathways that lead to the upregulation of a variety of costimulatory molecules and the synthesis and secretion of various cytokines and interferons by cells of the innate immune system. TLR‐induced innate immune responses are a prerequisite for the generation of most adaptive immune responses, and in the case of B cells, TLRs directly regulate signaling from the antigen‐specific B‐cell receptor. The outcome of TLR signaling is determined, in part, by the cells in which they are expressed and by the selective use of signaling adaptors. Recent studies suggest that, in addition, both the ligand recognition by TLRs and the functional outcome of ligand binding are governed by the subcellular location of the TLRs and their signaling adaptors. In this review we describe what is known about the intracellular trafficking and compartmentalization of TLRs in innate system's dendritic cells and macrophages and in adaptive system's B cells, highlighting how location regulates TLR function.
Cell‐Specific Trafficking Suggests a new role for Renal ATP7B in the Intracellular Copper Storage
Authors: Barnes Natalie , Bartee Mee Y. , Braiterman Lita , Gupta Arnab , Ustiyan Vladimir , Zuzel Vesna , Kaplan Jack H. , Hubbard Ann L. , Lutsenko Svetlana
Published: February 2009

Human Cu‐ATPases ATP7A and ATP7B maintain copper homeostasis through regulated trafficking between intracellular compartments. Inactivation of these transporters causes Menkes disease and Wilson disease, respectively. In Menkes disease, copper accumulates in kidneys and causes tubular damage, indicating that the renal ATP7B does not compensate for the loss of ATP7A function. We show that this is likely due to a kidney‐specific regulation of ATP7B. Unlike ATP7A (or hepatic ATP7B) which traffics from the TGN to export copper, renal ATP7B does not traffic and therefore is unlikely to mediate copper export. The lack of ATP7B trafficking is not on account of the loss of a kinase‐mediated phosphorylation or simultaneous presence of ATP7A in renal cells. Rather, the renal ATP7B appears 2–3 kDa smaller than hepatic ATP7B. Recombinant ATP7B expressed in renal cells is similar to hepatic protein in size and trafficking. The analysis of ATP7B mRNA revealed a complex behavior of exon 1 upon amplification, suggesting that it could be inefficiently translated. Recombinant ATP7B lacking exon 1 traffics differently in renal and hepatic cells, but does not fully recapitulate the endogenous phenotype. We discuss factors that may contribute to cell‐specific behavior of ATP7B and propose a role for renal ATP7B in intracellular copper storage.
Prenatal diagnosis of Holt‐Oram syndrome: Role of 3‐D ultrasonography
Authors: Sunagawa Sorahiro , Kikuchi Akihiko , Sano Yoko , Kita Mariko , Ono Kyoko , Horikoshi Tsuguhiro , Takagi Kimiyo , Kawame Hiroshi
Published: February 2009

Holt‐Oram syndrome (HOS) is an autosomal dominant disorder consisting of a congenital heart defect in combination with upper limb abnormalities. This report presents the ultrasonographic follow‐up of a fetus at risk for this syndrome. An abnormal four‐chamber view of the heart and slight shortening of the forearm were found by prenatal ultrasound performed at 16 weeks of gestation. At 25 weeks of gestation, detailed sonographic examination clearly revealed abnormalities in the upper limbs and heart of the fetus. At 39 weeks of gestation, spontaneous labor and delivery produced a female infant weighting 2940 g. Postnatal examination of the infant confirmed the prenatal sonographic findings. 3‐D ultrasound has an important role in prenatal diagnosis of HOS, which is essential for proper genetic counseling.
Further delineation of 9q22 deletion syndrome associated with basal cell nevus (Gorlin) syndrome: Report of two cases and review of the literature
Authors: Yamamoto Kayono , Yoshihashi Hiroshi , Furuya Noritaka , Adachi Masanori , Ito Susumu , Tanaka Yukichi , Masuno Mitsuo , Chiyo Hideaki , Kurosawa Kenji
Published: February 2009

Basal cell nevus syndrome (BCNS; Gorlin syndrome) is an autosomal dominant disorder, characterized by a predisposition to neoplasms and developmental abnormalities. BCNS is caused by mutations in the human homolog of the Drosophila patched gene‐1, PTCH1, which is mapped on chromosome 9q22.3. Nonsense, frameshift, in‐frame deletions, splice‐site, and missense mutations have been found in the syndrome. Haploinsufficiency of PTCH1, which is caused by interstitial deletion of 9q22.3, is also responsible for the syndrome. To date, 19 cases with interstitial deletion of long arm of chromosome 9 involving the region of q22 have been reported. We describe two unrelated patients with some typical features of BCNS associated with deletion of 9q21.33‐q31.1 and determined the boundary of the deletion by fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones. The results showed that the size of deletions is between 15.33 and 16.04 Mb in patient 1 and between 18.08 and 18.54 Mb in patient 2. Although the size and breakpoints were different from those of previously reported cases, the clinical features are common to patients with 9q22 deletion associated with BCNS. Delineation of the 9q22 deletions and further consideration of the genes responsible for the characteristic manifestations may provide insight into this newly recognized deletion syndrome.
Myocardial infarction in a neonate with left‐sided congenital diaphragmatic hernia
Authors: Verlaak René , Backx Ad P. , Van Heijst Arno F. J.
Published: February 2009

We present a case study of a newborn girl with a left‐sided congenital diaphragmatic hernia and a myocardial infarction (MI). The occurrence of MI in newborns has been associated with cardiac malformations and abnormalities of the coronary arteries or thromboembolization. In our patient, echocardiography revealed left ventricular dysfunction, persistent pulmonary hypertension and an inferolateral MI. Within 24 hours cardiac function and oxygenation did not improve and the baby died. Autopsy showed massive MI, a small aortic valve and ascending aorta, and hypoplasia of the distal aortic arch and isthmus. An accessory spleen was also present. The present report underlines the importance of cardiac evaluation in patients with congenital diaphragmatic hernia.
How would Australian hospital staff react to an avian influenza admission, or an influenza pandemic?
Authors: Martinese Franco , Keijzers Gerben , Grant Steven , Lind James
Published: February 2009

Objective:  To estimate the expected staff absentee rates and work attitudes in an Australian tertiary hospital workforce in two hypothetical scenarios: (i) a single admission of avian influenza; and (ii) multiple admissions of human pandemic influenza.

Methods:  A survey conducted at hospital staff meetings between May and August 2006.

Results:  Out of 570 questionnaires distributed, 560 were completed. For scenario one, 72 (13%) indicated that they would not attend work, and an additional 136 (25%) would only work provided that immunizations and/or antiviral medications were immediately available, so that up to 208 (38%) would not attend work. For scenario two, 196 (36%) would not attend work, and an additional 95 (17%) would work only if immunizations and/or antiviral medications were immediately available, so that up to 291 (53%) staff would not attend work. Staff whose work required them to be in the ED (odds ratios 2.2 and 1.6 for each scenario respectively) or on acute medical wards (odds ratios 2.2 and 2.0 respectively) were more likely to work.

Conclusion:  High absenteeism among hospital staff should be anticipated if patients are admitted with either avian or pandemic influenza, particularly if specific antiviral preventative measures are not immediately available. Measures to maximize the safety of staff and their families would be important incentives to attend work. Education on realistic level of risk from avian and pandemic influenza, as well as the effectiveness of basic infection control procedures and personal protective equipment, would be useful in improving willingness to work.
Does emergency department workload adversely influence timely analgesia?
Authors: Mitchell Rob , Kelly Anne‐Maree , Kerr Debra
Published: February 2009

Objective:  The impact of ED overcrowding on delay to analgesia has not been well studied. Our objective was to determine if ED workload influenced time to analgesia (TTA).

Methods:  An observational, retrospective study (May 2006 to March 2007) was conducted. Adult patients with diagnoses of acute biliary pain, renal colic, wrist and femoral neck fractures were identified and assigned to an ED workload group based on total patient care time – a validated measure of ED workload. The groups were defined by low, middle and high quartiles of total patient care time. The high quartile was defined as overcrowded – equating to average ED occupancy/24 h of 85–140%. Data collected included demographics, pain score and analgesia data. The primary outcome was comparison of TTA between workload groups. Data were analysed using Cox regression and multivariate analyses. Sample size required was 50 per group.

Results:  A total of 254 patients were studied (52% male; median age 57 years). Demographics were similar between groups. Ninety‐three per cent received analgesia with median TTA of 53 min (interquartile range 30.5–114.5). No significant association was found between workload and TTA (hazard ratio [HR] 1.02, 95% CI 0.99–1.02). On multivariate analysis, factors associated with delay to analgesia included advanced age (HR 0.35, P= 0.006), language other than English (HR 0.55, P= 0.010), lower triage acuity (HR 0.20, P= 0.000) and delay to pain assessment (HR 0.16, P= 0.000). Those with higher pain scores received analgesia more quickly (HR 1.12, P= 0.003).

Conclusion:  No relationship between workload and TTA was observed; however, there were delays to analgesia associated with age, non‐English‐speaking background and delay to pain assessment.
Paediatric emergency guidelines: Could one size fit all?
Authors: Dalton Sarah , Babl Franz E
Published: February 2009

Objectives:  The development of clinical practice guidelines (CPG) is a core task in EDs and CPGs are widely used. The process of CPGs development in Australian and New Zealand ED is unknown. We aim to describe this process in paediatric EDs and examine the feasibility of developing collaborative guidelines.

Methods:  A piloted questionnaire regarding CPG development, dissemination, implementation and evaluation was circulated to all 13 Paediatric Research in Emergency Departments International Collaborative (PREDICT) sites. Specific questions regarding feasibility of combined guidelines were included.

Results:  All PREDICT EDs participated in the survey. All used CPGs in EDs and 12/13 had ED‐specific guidelines. EDs had an average of 77 guidelines with approximately 5 new guidelines generated annually. Staff at most sites (10/13) also accessed guidelines from external sources. Most hospitals (10/13) had a guideline committee, generally comprising of senior ED and general paediatric staff. Guidelines were usually written by committee members and 10/13 hospitals adopted modified external guidelines. An average committee met six times a year for 90 min and involved seven clinicians. Most sites did not have a project manager or dedicated secretarial support. Few hospitals included literature references (3/13) or levels of evidence (1/13) in their guidelines. Most did not consider implementation, evaluation or teaching packages. Most sites (10/13) supported the development of collaborative guidelines.

Conclusions:  Paediatric EDs expend significant resources to develop CPGs. Collaborative guidelines would likely decrease duplication of effort and increase the number of available, current and evidence‐based CPGs.
Improving adherence to asthma clinical guidelines and discharge documentation from emergency departments: Implementation of a dynamic and integrated electronic decision support system†
Authors: Kwok Raymond , Dinh Michael , Dinh David , Chu Matthew
Published: February 2009

Objective:  The authors previously developed a dynamic and integrated electronic decision support system called ACAFE (Asthma Clinical Assessment Form and Electronic decision support). The objective of this present study was to evaluate the effectiveness of this system on asthma management and documentation in an ED.

Method:  Observational study using a pre‐ and post‐intervention design, comparing patients managed using ACAFE after its implementation with historical controls. A systematic data abstraction process was used to compare patient records.

Results:  A total of 50 patients were enrolled in the study group. These were compared with 50 historical controls. Use of ACAFE was associated with significantly higher rates of documentation of asthma severity (98% vs 18%, P < 0.01), as well as other clinically important variables, such as asthma precipitants, intensive care admission history and smoking history. ACAFE was also associated with significantly higher rate of asthma discharge plan documentation (76% vs 16%, P < 0.01), and this remained significant after adjustment for triage category and seniority of treating doctor in a regression model.

Conclusion:  The use of this decision support system in patients presenting to emergency with asthma was associated with improvements in clinical documentation and discharge management plans. Electronic decision support systems developed collaboratively with clinicians should play an important part of system‐wide efforts to improve guideline adherence and compliance in ED.
Leech on the eye: A novel use for hypertonic saline
Authors: Partyka Christopher , Fogg Toby
Published: February 2009

Although human interaction with leeches is common in Australia, there is little documented literature on ocular injuries as a result of contact with a leech. We report a case of ocular leech attachment and a previously undocumented method of removal with hypertonic saline solution.
Molecular data reveals California as the potential source of an invasive leafhopper species, Macrosteles sp. nr. severini, transmitting the aster yellows phytoplasma in Hawaii
Authors: Le Roux J.J. , Rubinoff D.
Published: February 2009

A species of aster leafhopper (Macrosteles sp.) became established in 2001 on Oahu, Hawaii, and through the transmission of the aster yellows phytoplasma, caused devastating losses to the island’s watercress industry. DNA sequence data were analysed from two mitochondrial genes [cytochrome oxidase subunit 1(CO1) and nicotinamide adenine dinucleotide 1 (NADH1)] and one nuclear gene (wingless, Wg) (combined total of 1874 bp) to reconstruct phylogenetic relationships between putative US mainland source populations of aster leafhoppers and those introduced to Hawaii. These data were applied to elucidate the origin(s) and identity of Hawaiian infestations and the amount of genetic diversity within introduced invasive populations. Both phylogenetic search criteria (Bayesian and maximum likelihood models) converged onto similar tree topologies for all three gene regions and suggested that Hawaii infestations represent a single undescribed leafhopper species unrelated to the common aster leafhopper, Macrosteles quadrilineatus. An exact haplotype match was found from a specimen intercepted from watercress shipped to Hawaii from Los Angeles, California, suggesting this region as the potential source for Hawaiian infestations. Two mitochondrial haplotypes were identified in Hawaii suggesting two or perhaps just a single introduction of more than one female.
Optical pulsations from the anomalous X-ray pulsar 1E 1048.1–5937
Authors: Dhillon V. S. , Marsh T. R. , Littlefair S. P. , Copperwheat C. M. , Kerry P. , Dib R. , Durant M. , Kaspi V. M. , Mignani R. P. , Shearer A.
Published: February 2009

We present high-speed optical photometry of the anomalous X-ray pulsar 1E 1048.1-5937 obtained with ULTRACAM on the 8.2-m Very Large Telescope in 2007 June. We detect 1E 1048.1-5937 at a magnitude of i′= 25.3 ± 0.2, consistent with the values found by Wang et al. and hence confirming their conclusion that the source was approximately 1 mag brighter than in 2003–06 due to an on-going X-ray flare that started in 2007 March. The increased source brightness enabled us to detect optical pulsations with an identical period (6.458 s) to the X-ray pulsations. The root-mean-square (rms) pulsed fraction in our data is 21 ± 7 per cent, approximately the same as the 2–10 keV X-ray rms pulsed fraction. The optical and X-ray pulse profiles show similar morphologies and appear to be approximately in phase with each other, the latter lagging the former by only 0.06 ± 0.02 cycles. The optical pulsations in 1E 1048.1-5937 are very similar in nature to those observed in 4U 0142+61. The implications of our observations for models of anomalous X-ray pulsars are discussed.
EFFECTS OF STAPHYLOCOCCUS CONDIMENTI AND MICROCOCCUS CASEOLYTICUS ON THE VOLATILE COMPOUNDS OF CANTONESE SAUSAGE
Authors: WU YANTAO , CUI CHUN , SUN WEIZHENG , YANG BAO , ZHAO MOUMING
Published: February 2009

Two strains, Staphylococcus condimenti and Micrococcus caseolyticus, were screened and isolated from Cantonese sausage in this study. The effects of these two strains on the flavor of Cantonese sausage were also investigated. Three Cantonese sausage samples were prepared: control, sausage inoculated with S. condimenti (SC) and sausage inoculated with M. caseolyticus (MC). The volatile compounds were extracted by a headspace solid‐phase microextraction method, quantified and identified by gas chromatography–mass spectrometry. A total of 22, 22 and 25 volatile compounds were identified from the three samples, respectively. Larger amounts of volatile compounds (alcohols, aldehydes, ketones and esters) were detected in SC and MC, particularly for aldehydes and ethyl esters, whereas the amounts of hydrocarbons and heterocyclic compounds decreased. The results showed that both strains could accelerate the degradation and oxidation of lipids and proteins, and improve the flavor characteristics of Cantonese sausage.

PRACTICAL APPLICATIONS

Cantonese sausage is a traditional Chinese meat product that is well accepted by consumers over the world. In order to improve the flavor characteristics of this sausage, two strains, Staphylococcus condimenti and Micrococcus caseolyticus, were used as starter cultures for Cantonese sausage preparation in this work. The volatile compounds were identified by gas chromatography–mass spectrometry. The results showed that these two strains could be good flavor enhancers of Cantonese sausage. Therefore, application of S. condimenti or M. caseolyticus on the Cantonese sausage will be of great significance in improving the quality of this traditional food.