bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the World Social Forum a Transnational Public Sphere?
Authors: Conway Janet , Singh Jakeet
Published: August 2009

In a number of recent articles, Nancy Fraser attempts to understand the World Social Forum within the framework of critical democratic theory. In this article, we examine the descriptive and normative aspects of Fraser’s theoretical framework, and explore the effects of projecting it upon the World Social Forum. We argue that while this theory may elucidate some features of the Forum, many of the Forum’s most challenging and innovative aspects are obscured and limited by Fraser’s framework. Not only, then, does the World Social Forum elude Fraser’s conceptualization of it, but we suggest that the praxis of the Forum poses a number of serious challenges to Fraser’s critical theory of democracy and social justice.
Being-with
Authors: Pyyhtinen Olli
Published: August 2009

The article discusses Georg Simmel’s theorizing on the social in the light of his treatment of the ‘dyad’ and the ‘triad’, constellations of two and three elements. What makes the dyad and the triad particularly interesting is the fact that they express the difference between the primary intersubjectivity immanent to the individuals and the objectified social forms in numerical terms, as quantitatively determined. In the article, it is argued that in its basic, methodologically simplest form, the social amounts for Simmel to dyadic interaction between I and you, that can be conceptualized as ‘beingwith’. Nevertheless, a third element is always included also in the dyad, be it only as an excluded third. Therefore, it is claimed that in order to fully understand the dynamics of social relationships, one must look at the interplay of two socio-logics, bivalent and trivalent. The ‘third’ not only interrupts the supposedly immediate relation between the two elements of the dyad, but it is also capable of transforming it into a completely new figure: a social whole, a ‘we’, which obtains a supra-individual life independent of the individuals.
What is a Pipe?
Authors: Cetina Karin Knorr
Published: August 2009

This article is an attempt to make sociological sense of the 2008 American election — particularly of the phenomenological observation of extraordinary enchantment and almost amorous attraction which unlikely members of the American population displayed for Obama, from the early days of the campaign onward. I draw on charisma theory to argue that sociology has something surprising to say on the phenomenon, and on the metaphor of the pipe to add detail about the technology of attraction that was in play.
Active Living Among Older Residents of a Rural Naturally Occurring Retirement Community
Authors: Grant-Savela Stacey D.
Published: August 2009

This cross-sectional single case study of older residents ( N = 197, mean age = 71.5 years) of a Midwestern rural naturally occurring retirement community (NORC) investigates patterns of active living and how they relate to sociophysical NORC characteristics and individual factors. The study uses a self-administered questionnaire (mailed to participants), which includes the Physical Activity Scale for the Elderly (PASE), and the study findings reveal that most respondents engaged in at least one leisure (93.9%) or household (94.4%) activity in the preceding 7 days and walking was the most prevalent activity; respondents who walked, as part of their routine activities (during the 7 days prior to study), had higher self-efficacy scores than nonparticipants ( U = 563.5, p < .05); and self-efficacy was positively correlated with the frequency ( rs = .22, p < .01) and duration ( rs = .26, p < .01) of walking.
Chronic prenatal exposure to the 900 megahertz electromagnetic field induces pyramidal cell loss in the hippocampus of newborn rats
Authors: Bas O , Odaci E , Mollaoglu H , Ucok K , Kaplan S
Published: August 2009

Widespread use of mobile phones which are a major source of electromagnetic fields might affect living organisms. However, there has been no investigation concerning prenatal exposure to electromagnetic fields or their roles in the development of the pyramidal cells of the cornu ammonis in postnatal life. Two groups of pregnant rats, a control group and an experimental group, that were exposed to an electromagnetic field were used. For obtaining electromagnetic field offspring, the pregnant rats were exposed to 900 megahertz electromagnetic fields during the 1–19th gestation days. There were no actions performed on the control group during the same period. The offspring rats were spontaneously delivered—control group ( n = 6) and electromagnetic field group ( n = 6). Offspring were sacrificed for stereological analyses at the end of the 4th week. Pyramidal cell number in rat cornu ammonis was estimated using the optical fractionator technique. It was found that 900 megahertz of electromagnetic field significantly reduced the total pyramidal cell number in the cornu ammonis of the electromagnetic field group ( P < 0.001). Therefore, although its exact mechanism is not clear, it is suggested that pyramidal cell loss in the cornu ammonis could be due to the 900 megahertz electromagnetic field exposure in the prenatal period.
Follicle-stimulating hormone levels in male workers exposed to urban chemical, physical, and psychosocial stressors
Authors: Tomei G , Tomao E , Ciarrocca M , Rosati MV , Caciari T , Gamberale D , Palermo P , Sio S De , Tria M , Panfili A , Tomei F
Published: August 2009

The aim of this study is to evaluate whether occupational exposure to urban stressors could cause alterations in the follicle-stimulating hormone (FSH) levels in traffic policemen compared to a control group. After excluding the subjects with main confounding factors, traffic policemen and male controls were matched by age, working life, body mass index (BMI), drinking habit, cigarette smoking history, and daily consumption of Italian coffee, 166 traffic policemen and 166 controls were included into the study. FSH levels were significantly higher in traffic policemen compared to male controls ( P < 0.05). The distribution of FSH values in traffic policemen and controls was significant ( P < 0.05). Our results suggest that occupational exposure to low doses of chemical and psychosocial stressors may alter plasma levels of FSH in traffic policemen more than in the control group. If the results obtained are confirmed by further research, the plasma levels of FSH may be used as early biological markers, valuable for the group, used in occupational set even before the appearance of disorders of male fertility.
Phylogenetic analysis of ALAD and MGP genes related to lead toxicity
Authors: Shaik AP , Khan M , Jamil K
Published: August 2009

Experimental studies in our laboratory have established the role of δ-aminolevulinic acid dehydratase (ALAD) and matrix γ-carboxyglutamic acid (MGP) gene polymorphisms in the etiology of lead toxicity. Polymorphisms in these genes influenced the levels of lead in subjects exposed to this metal. In extension to our studies, we aimed to investigate the possible role of these proteins in evolution by studying the phylogenetic relationship and divergence of ALAD and MGP genes using computational phylogenetic methods. The human ALAD and MGP protein sequences from various species were retrieved from Swiss-Prot database and were compared using Basic Local Alignment Search Tool. Multiple sequence alignment was carried out using ClustalW with defaults, and phylogenetic trees for both the genes were built using neighbor-joining method as in Mega software. Our study indicated that ALAD is a highly conserved protein with the same metal binding site distributed in all the phyla (from archaea to chordates). Phylogenetic analysis of MGP gene revealed that it had an important role in the evolution of endogenous skeleton in contrast to exoskeleton of insects. Occurrence of these genes in evolution with conserved metal binding sites strengthens the role of ALAD and MGP genes in regulating heme biosynthesis and mineralization, respectively, in evolution and helps in better understanding of lead poisoning.
European registry of babies born to mothers with antiphospholipid syndrome: a result update
Authors: Boffa M-C , Lachassinne E , Boinot C , De Carolis S , Rovere-Querini P , Avcin T , Biasini-Rebaioli C , Le Toumelin P , Aurousseau MH , Tincani A
Published: August 2009

The registry is a prospective, European, multicentric, longitudinal study, which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). It was started in 2003. In this report, we update the results obtained from the study of 110 mothers and 112 children (two twin births). Eighty per cent of the mothers ( n = 86) had primary APS. Purely obstetrical, thrombotic and mixed (obstetrical and thrombotic) APS represent 65.5 %, 21.8 % and 12.7 % of the whole cohort respectively. Isolated antiphospholipid antibodies and isolated anticardiolipin antibodies positivity were present in 50 of 109 (46%) and in 34 of 109 (31%) of the pregnant women, respectively. In the babies, in spite of a high rate of prematurity (14.3%) with four (3.6%) of the premature babies born before 33 weeks of gestation and an increased number of newborns small for gestational age (17%), the large majority of the neonates were healthy. Thirty-one infants are now older than 24 months. Among them, three displayed behavioural abnormalities before 3 years of age. After completing data, there will be the possibility to evaluate the newborn status in relation to the mothers’ diseases, treatments and antibodies and to follow the neuropsychological development and immunological evolution of the babies during the next 5 years.
Registered Nurses’ Perceptions of Moral Distress and Ethical Climate
Authors: Pauly Bernadette , Varcoe Colleen , Storch Janet , Newton Lorelei
Published: August 2009

Moral distress is a phenomenon of increasing concern in nursing practice, education and research. Previous research has suggested that moral distress is associated with perceptions of ethical climate, which has implications for nursing practice and patient outcomes. In this study, a randomly selected sample of registered nurses was surveyed using Corley’s Moral Distress Scale and Olson’s Hospital Ethical Climate Survey (HECS). The registered nurses reported moderate levels of moral distress intensity. Moral distress intensity and frequency were found to be inversely correlated with perceptions of ethical climate. Each of the HECS factors (peers, patients, managers, hospitals and physicians) was found to be significantly correlated with moral distress. Based on these findings, we highlight insights for practice and future research that are needed to enhance the development of strategies aimed at improving the ethical climate of nurses’ workplaces for the benefit of both nurses and patients.
Ethical Problems Observed By Student Nurses
Authors: Erdil Fethiye , Korkmaz Fatoş
Published: August 2009

This descriptive study was conducted to determine nursing students’ observation of ethical problems encountered in their clinical practice. Data were collected through a questionnaire from 153 volunteer nursing students at a university-based nursing school in Ankara, Turkey. The students reported that some patients are either physically or psychologically mistreated by doctors and nurses; they were not given appropriate information; they were subjected to discrimination according to their socio-economic situation; and their privacy was ignored. The findings reveal that nurses’ own unethical behaviors contribute to a rise in ethical problems. It is argued that nurses should internalize their professional and ethical roles in order to provide safe and ethical care and be good role models for students.
Contemplating the Presence of Third Party Observers and Facilitators in Psychological Evaluations
Authors: Otto Randy K. , Krauss Daniel A.
Published: August 2009

Significant controversy surrounds how psychologists should balance competing interests when considering whether and under what conditions third parties should be permitted to be present during psychological evaluations. This is especially true in forensic contexts where much is often at stake for those being assessed. Unfortunately, existing professional statements on this issue provide limited guidance to practitioners on how to think about this issue. In this article, the authors (a) distinguish between different types of third party participants, (b) highlight the competing interests that underlie third party presence decisions, and (c) offer a framework for psychologists to employ when considering third party presence.
A Brief Assessment of the Interpersonal Circumplex
Authors: Markey Patrick M. , Markey Charlotte N.
Published: August 2009

Three studies are presented that demonstrate the psychometric properties and initial validation of the International Personality Item Pool—Interpersonal Circumplex (IPIP-IPC). The IPIP-IPC is a brief 32-item assessment of the interpersonal cirucmplex designed to be used when time is limited or when participants have difficulty understanding the adjective items used in more traditional assessments of the interpersonal circumplex. In Study 1, 501 participants were examined to develop the IPIP-IPC and demonstrate the circular structure of the IPIP-IPC scales and their relation to the five-factor model of personality. Study 2 included 274 participants to reconfirm the circular structure of the IPIP-IPC scales. Finally, in Study 3, 100 participants again reconfirm the circular structure of the IPIP-IPC scales and demonstrate the overlap of the IPIP-IPC with a commonly used assessment of the circumplex: the 64-item Interpersonal Adjective Scale. Overall, the results suggest that the IPIP-IPC provides a relatively short, quick, and valid assessment of the interpersonal circumplex while maintaining many of the psychometric properties of longer assessment tools.
Unexplained Discrepancies in the Activity—Antigen Ratio in Congenital FX Deficiencies With Defects in the Catalytic Domain
Authors: Girolami A. , Scarparo P. , Vettore S. , Candeo N. , Scandellari R. , Lombardi A.M.
Published: August 2009

Studies on molecular biology have considerably enhanced our understanding of congenital coagulation disorders but have failed so far to supply tools for an adequate classification of defects. In fact, mutations in the same domain may give rise to different phenotypes. Conversely, mutations in different domains, controlled by different exons, may cause similar patterns. The 37 kindreds with congenital factor X (FX) deficiency, known to have a defect in the catalytic domain, have been evaluated in an attempt to investigate the genotype—phenotype relation. Discrepant results were obtained because about half kindreds showed a type I pattern, namely a concomitant decrease in FX activity and antigen. The other half showed a type II pattern, namely a decrease in FX activity with a normal or near normal FX antigen. In a few instances, the allocation of the kindred either to type I or to type II defect could not be reached, due to the lack of information about the antigen.

The comparison of the kindreds in which the same mutation has been discovered by different investigations is not always possible also for lack of information.

The study analyzes the need to have a multipronged approach to the study of congenital FX deficiency. The indication of a mutation in a given domain does not provide clear information about the phenotype.
Use (and Misuse) of the Responsible Drinking Message in Public Health and Alcohol Advertising: A Review
Authors: Barry Adam E. , Goodson Patricia
Published: August 2009

The objective is to present a comparative analysis examining the alcohol industry’s and scholarly researchers’ use of the concept “responsible drinking.” Electronic databases associated with health, education, sociology, psychology, and medicine were the date sources. Results were limited to English, peer-reviewed articles and commentaries specifically addressing “responsible drinking.” Search descriptors included responsible, responsibility, drinking, alcohol, brewer, and campaign. Eighteen articles constituted the final sample. The matrix method was utilized to organize and abstract pertinent information. Misunderstanding stemming from the inconsistency and counterintuitive nature of brewer-sponsored “responsible drinking” campaigns is further compounded by researchers’ use of the term and concept of “responsible drinking” in their scholarly reports. In articulating the definition of “responsible drinking,” researchers employ subjective notions and personal ideas, thus not differentiating the construct’s meaning from the one acquired in brewer-sponsored campaigns. Researchers are consistently inconsistent when identifying specific health measures that promote and/or contradict responsible alcohol consumption. To evade the subjective notions of researchers and restrictive impressions attached by the alcohol industry, the manner in which individuals interpret, perceive, and practice responsible drinking must be systematically explored and examined using theoretically based constructs.
Parties’ Responses to Economic Globalization
Authors: Haupt Andrea B.
Published: August 2009

Do parties adjust their economic policy positions in response to the international economy? I explore how international economic conditions affect Western Europe’s welfare states by quantitatively analysing parties’ ideological dynamics over time. Considering the convergence—divergence argument of the globalization literature, I evaluate the hypothesis that economic openness motivates parties to adjust their economic policies. My empirical analyses reveal that both left-wing and right-wing parties do indeed systematically adjust their positions in response to economic changes associated with globalization. However, the results contradict the neoliberal convergence argument, as parties shift in varying directions in response to different indicators of openness. Importantly, the differences between left-wing and right-wing parties’ responses are not statistically significant, pointing to the importance of including right-wing parties in the globalization literature.
Archaeological record of the Adriatic offshore islands as an indicator of long-distance interaction in prehistory
Authors: Forenbaher Stašo
Published: August 2009

This article explores the proposition that the archaeological record of small, remote islands with scarce resources reflects the intensity of long-distance interaction in prehistory, taking as an example the Adriatic offshore islands. The best represented periods, the early Neolithic and the end of the Copper Age, correspond to the times of large-scale stylistic unity, the former, of the Mediterranean Impressed Wares, and the latter, of Bell Beakers. During those periods, radical innovations were introduced over vast areas of Europe, first, a new subsistence economy, and second, a different kind of social organization. In both cases, long-distance interaction would have played a crucial role.
Early Neolithic communities in southern Dalmatia: Farming seafarers or seafaring farmers?
Authors: Bass Bryon
Published: August 2009

Palaeoenvironmental data and vegetation histories derived from local datasets are examined in the light of Early Neolithic agro-pastoral activities and resource exploitation in the southeastern Adriatic Sea. Palynological evidence is summarized from three locations within the study area and compared to contemporaneous archaeological evidence. Coastal marine archaeological assemblages in the study area indicate that Early Neolithic inhabitants expended significant energy on terrestrial and marine hunting and gathering, and long distance maritime travel, well after the regional introduction of agro-pastoralism.
Transgastric and Transperineal Natural Orifice Translumenal Endoscopic Surgery (NOTES) in an Appendectomy Test Bed
Authors: Jayaraman Shiva , Schlachta Christopher M.
Published: August 2009

Introduction. Our purpose was to establish a NOTES appendectomy test bed to evaluate whether the transgastric or transperineal (transvaginal) approach is most efficient. Methods. Using the uterine horns of female pigs as a model for appendectomy, 18 NOTES appendectomies were performed in 2 arms: 9 transgastric and 9 transvaginal. The primary outcome was mean total operative time for each technique excluding access closure. Secondary outcomes were peritoneal access and resection times. Means were compared using Student’s t-test. Results. Transgastric cases were faster than transperineal (46.5 ± 14.5 vs 60.0 ± 20.2 minutes, P = .02). Most of the improvement in transgastric times was due to faster resection (37.9 ± 17.4 vs 51.3 ± 16.5 minutes, P = .03). Neither approach was faster for peritoneal access (8.2 ± 3.4 vs 8.3 ± 4.5 minutes, nonsignificant). A significant learning curve was not demonstrated for the transgastric approach (53.0 vs 40.3 minutes, nonsignificant). A significant learning curve was demonstrated for the transperineal approach (76.0 vs 46.7 minutes, P = .02). Transperineal times improved over the study and approached transgastric; however, the last three transgastric cases were still significantly faster than the last three transperineal (40.3 vs 46.7 minutes, P = .02). No complications occurred in either group. Conclusions. The transgastric as compared with transperineal approach to NOTES appendectomy resulted in improved operative time in this model. The transperineal approach demonstrated a significant learning curve with operative times between techniques converging over time. This NOTES appendectomy test bed is suitable for evaluating NOTES innovations.
Room temperature hardness of carbide strengthened cast alloys in relation to their carbon content and aging temperature Part 3 – Case of iron alloys
Authors: Berthod P.
Published: August 2009

Vickers macroindentation was performed on seven cast and aged Fe–30Cr based alloys with carbon contents varying from 0 to 2·0 wt-%. The measured hardness was studied versus the carbon content and the aging temperature (1000, 1100 and 1200°C). The hardness increases with the carbon content, first slowly but much faster when the carbides fraction reaches 30 vol.-%. A hardness of 600 HV or more can then be achieved. For low carbon contents, the hardness increases slower than a law of mixture of the volume fractions and of the hardness of carbides and matrix. This is due to the great difference in hardness between the two phases, which leads to the deformation of the matrix only. Beyond the critical value of 30 vol.-% of carbides, i.e. when the carbon content approaches 2 wt-%, hardness drastically increases since the main role in resistance against indentation is then played by the hard carbides skeleton, which has become continuous enough.
Production of FMDV virus-like particles by a SUMO fusion protein approach in Escherichia coli
Authors: Lee Chien-Der , Yan Yao-Pei , Liang Shu-Mei , Wang Ting-Fang
Published: August 2009

Virus-like particles (VLPs) are formed by the self-assembly of envelope and/or capsid proteins from many viruses. Some VLPs have been proven successful as vaccines, and others have recently found applications as carriers for foreign antigens or as scaffolds in nanoparticle biotechnology. However, production of VLP was usually impeded due to low water-solubility of recombinant virus capsid proteins. Previous studies revealed that virus capsid and envelope proteins were often posttranslationally modified by SUMO in vivo, leading into a hypothesis that SUMO modification might be a common mechanism for virus proteins to retain water-solubility or prevent improper self-aggregation before virus assembly. We then propose a simple approach to produce VLPs of viruses, e.g., foot-and-mouth disease virus (FMDV). An improved SUMO fusion protein system we developed recently was applied to the simultaneous expression of three capsid proteins of FMDV in E. coli. The three SUMO fusion proteins formed a stable heterotrimeric complex. Proteolytic removal of SUMO moieties from the ternary complexes resulted in VLPs with size and shape resembling the authentic FMDV. The method described here can also apply to produce capsid/envelope protein complexes or VLPs of other disease-causing viruses.
Phylogenetic detection of horizontal gene transfer during the step-wise genesis of Mycobacterium tuberculosis
Authors: Veyrier Frédéric , Pletzer Daniel , Turenne Christine , Behr Marcel A
Published: August 2009

Background

In the past decade, the availability of complete genome sequence data has greatly facilitated comparative genomic research aimed at addressing genetic variability within species. More recently, analysis across species has become feasible, especially in genera where genome sequencing projects of multiple species have been initiated. To understand the genesis of the pathogenMycobacterium tuberculosiswithin a genus where the majority of species are harmless environmental organisms, we have used genome sequence data from 16 mycobacteria to look for evidence of horizontal gene transfer (HGT) associated with the emergence of pathogenesis. First, using multi-locus sequence analysis (MLSA) of 20 housekeeping genes across these species, we derived a phylogeny that serves as the basis for HGT assignments. Next, we performed alignment searches for the 3989 proteins ofM. tuberculosisH37Rv against 15 other mycobacterial genomes, generating a matrix of 59835 comparisons, to look for genetic elements that were uniquely found inM. tuberculosisand closely-related pathogenic mycobacteria. To assign when foreign genes were likely acquired, we designed a bioinformatic program called mycoHIT (mycobacterial homologue investigation tool) to analyze these data in conjunction with the MLSA-based phylogeny.

Results

The bioinformatic screen predicted that 137 genes had been acquired by HGT at different phylogenetic strata; these included genes coding for metabolic functions and modification of mycobacterial lipids. For the majority of these genes, corroborating evidence of HGT was obtained, such as presence of phage or plasmid, and an aberrant GC%.

Conclusion

M. tuberculosisemerged through vertical inheritance along with the step-wise addition of genes acquired via HGT events, a process that may more generally describe the evolution of other pathogens.
Differential proteomic analysis of Clostridium perfringens ATCC13124; identification of dominant, surface and structure associated proteins
Authors: Alam Syed Imteyaz , Bansod Sunita , Kumar Ravi Bhushan , Sengupta Nabonita , Singh Lokendra
Published: August 2009

Background

Clostridium perfringens is a medically important clostridial pathogen causing diseases in man and animals. To invade, multiply and colonize tissues of the host, a pathogen must be able to evade host immune system, and obtain nutrients essential for growth. The factors involved in these complex processes are largely unknown and of crucial importance to understanding microbial pathogenesis. Many of the virulence determinants and putative vaccine candidates for bacterial pathogens are known to be surface localized.

Results

Using 2-DE mass spectrometry strategy, we identified major surface (22) and cell envelope (10) proteins from Clostridium perfringens ATCC13124 and those differentially expressed (11) in cells grown on cooked meat medium (CMM) in comparison with cells grown in reference state (tryptose-yeast extract-glucose medium). Riboflavin biosynthesis protein, ornithine carbamoyltransferase, cystathionine beta-lyase, and threonine dehydratase were the predominant proteins that exhibited 2.19 to 8.5 fold increase in the expression level in cells growing on CMM.

Conclusion

Ornithine carbamoyltransferase and cystathionine beta-lyase were over-expressed in cells grown on cooked meat medium and also identified in the surface protein fraction and the former was immunogenic; making them potential vaccine candidates. Based upon bioinformatic analysis; choloylglycine hydrolase family protein, cell wall-associated serine proteinase, and rhomboid family protein were predicted as surface protein markers for specific detection of C. perfringens from the environment and food. Most of the proteins over-expressed in CMM were shown to have putative function in metabolism, of which seven were involved in amino acid transport and metabolism or lipid metabolism.
In vitro antimicrobial effects of aztreonam, colistin, and the 3-drug combination of aztreonam, ceftazidime and amikacin on metallo-β-lactamase-producing Pseudomonas aeruginosa
Authors: Oie Shigeharu , Fukui Yumi , Yamamoto Masaya , Masuda Yuki , Kamiya Akira
Published: August 2009

Background

There are limited choice of antimicrobial agents to treat infection with metallo-β-lactamase-producing Pseudomonas aeruginosa. We evaluate the antimicrobial effects of aztreonam alone, colistin alone and the 3-drug combination of aztreonam, ceftazidime and amikacin on 23 strains of metallo-β-lactamase-producing P. aeruginosa by time-killing tests.

Methods

Strains used were from different hospitals in Japan and had different pulse-field gel electrophoresis patterns by restriction with SpeI. The minimum inhibitory concentrations of 11 antimicrobial agents (piperacillin, piperacillin/tazobactam, imipenem, meropenem, aztreonam, ceftazidime, amikacin, tobramycin, arbekacin, ciprofloxacin and colistin) were determined using the agar dilution test. The effects of aztreonam, colistin and the combination of aztreonam, ceftazidime and amikacin were determined by time-killing studies.

Results

Bacteriostatic effects after 6 hours of drug exposure were observed in 12 strains (52.2%) of 23 strains of metallo-β-lactamase-producing P. aeruginosa with 48 mg/l aztreonam, in 19 strains (82.6%) with the 3-drug combination of 16 mg/l aztreonam, 16 mg/l ceftazidime, and 4 mg/l amikacin, and in 23 strains (100%) with 2 mg/l colistin. Bactericidal effects after 6 h drug exposure were observed in 1 strain (4.3%) with 48 mg/l aztreonam, in 8 strains (30.4%) with the 3-drug combination and in all 23 strains (100%) with 2 mg/l colistin.

Conclusion

Evaluation of in vitro antimicrobial effects on metallo-β-lactamase-producing P. aeruginosa revealed relatively good effects of the 3-drug combination of aztreonam, ceftazidime and amikacin and marked effects of colistin.
Disappearance of myocardial perfusion defects on prone SPECT imaging: Comparison with cardiac magnetic resonance imaging in patients without established coronary artery disease
Authors: Hedén Bo , Persson Eva , Carlsson Marcus , Pahlm Olle , Arheden Håkan
Published: August 2009

Background

It is of great clinical importance to exclude myocardial infarction in patients with suspected coronary artery disease who do not have stress-induced ischemia. The diagnostic use of myocardial perfusion single-photon emission computed tomography (SPECT) in this situation is sometimes complicated by attenuation artifacts that mimic myocardial infarction. Imaging in the prone position has been suggested as a method to overcome this problem.

Methods

In this study, 52 patients without known prior infarction and no stress-induced ischemia on SPECT imaging were examined in both supine and prone position. The results were compared with cardiac magnetic resonance imaging (CMR) with delayed-enhancement technique to confirm or exclude myocardial infarction.

Results

There were 63 defects in supine-position images, 37 of which disappeared in the prone position. None of the 37 defects were associated with myocardial infarction by CMR, indicating that all of them represented attenuation artifacts. Of the remaining 26 defects that did not disappear on prone imaging, myocardial infarction was confirmed by CMR in 2; the remaining 24 had no sign of ischemic infarction but 2 had other kinds of myocardial injuries. In 3 patients, SPECT failed to detect small scars identified by CMR.

Conclusion

Perfusion defects in the supine position that disappeared in the prone position were caused by attenuation, not myocardial infarction. Hence, imaging in the prone position can help to rule out ischemic heart disease for some patients admitted for SPECT with suspected but not documented ischemic heart disease. This would indicate a better prognosis and prevent unnecessary further investigations and treatment.
The German MultiCare-study: Patterns of multimorbidity in primary health care – protocol of a prospective cohort study
Authors: Schäfer Ingmar , Hansen Heike , Schön Gerhard , Maier Wolfgang , Höfels Susanne , Altiner Attila , Fuchs Angela , Gerlach Ferdinand M , Petersen Juliana J , Gensichen Jochen , Schulz Sven , Riedel-Heller Steffi , Luppa Melanie , Weyerer Siegfried , Werle Jochen , Bickel Horst , Barth Kerstin , König Hans-Helmut , Rudolph Anja , Wiese Birgitt , Prokein Jana , Bullinger Monika , von dem Knesebeck Olaf , Eisele Marion , Kaduszkiewicz Hanna , Wegscheider Karl , van den Bussche Hendrik
Published: August 2009

Background

Multimorbidity is a highly frequent condition in older people, but well designed longitudinal studies on the impact of multimorbidity on patients and the health care system have been remarkably scarce in numbers until today. Little is known about the long term impact of multimorbidity on the patients' life expectancy, functional status and quality of life as well as health care utilization over time. As a consequence, there is little help for GPs in adjusting care for these patients, even though studies suggest that adhering to present clinical practice guidelines in the care of patients with multimorbidity may have adverse effects.

Methods/Design

The study is designed as a multicentre prospective, observational cohort study of 3.050 patients aged 65 to 85 at baseline with at least three different diagnoses out of a list of 29 illnesses and syndromes. The patients will be recruited in approx. 120 to 150 GP surgeries in 8 study centres distributed across Germany. Information about the patients' morbidity will be collected mainly in GP interviews and from chart reviews. Functional status, resources/risk factors, health care utilization and additional morbidity data will be assessed in patient interviews, in which a multitude of well established standardized questionnaires and tests will be performed.

Discussion

The main aim of the cohort study is to monitor the course of the illness process and to analyse for which reasons medical conditions are stable, deteriorating or only temporarily present. First, clusters of combinations of diseases/disorders (multimorbidity patterns) with a comparable impact (e.g. on quality of life and/or functional status) will be identified. Then the development of these clusters over time will be analysed, especially with regard to prognostic variables and the somatic, psychological and social consequences as well as the utilization of health care resources. The results will allow the development of an instrument for prediction of the deterioration of the illness process and point at possibilities of prevention. The practical consequences of the study results for primary care will be analysed in expert focus groups in order to develop strategies for the inclusion of the aspects of multimorbidity in primary care guidelines.
Antisense gapmers selectively suppress individual oncogenic p73 splice isoforms and inhibit tumor growth in vivo
Authors: Emmrich Stephan , Wang Weiwei , John Katja , Li Wenzhong , Pützer Brigitte M
Published: August 2009

Background

Differential mRNA splicing and alternative promoter usage of the TP73 gene results in the expression of multiple NH2-truncated isoforms that act as oncogenes. Abundant levels of these p73 variants in a variety of human cancers correlated with adverse clinical prognosis and response failure to conventional therapies, underscoring their relevance as marker for disease severity and target for cancer intervention. With respect to an equally important role for amino-truncated p73 splice forms (ΔTAp73) and ΔNp73 (summarized as DNp73) in the tumorigenic process, we designed locked nucleic acid (LNA) antisense oligonucleotide (ASO) gapmers against individual species that were complementary to ΔEx2 and ΔEx2/3 splice junctions and a region in exon 3B unique for ΔN' and ΔN.

Results

Treatment of cancer cells with these ASOs resulted in a strong and specific reduction of tumorigenic p73 transcripts and proteins, importantly, without abolishing the wild-type p73 tumor suppressor form as observed with p73-shRNA. The specific antisense oligonucleotides rescued cells from apoptosis inhibition due to overexpression of their corresponding amino-truncated p73 isoform and decreased tumor cell proliferation. Furthermore, ASO-116 against ΔEx2/3 coupled to magnetic nanobead polyethyleneimine (MNB/PEI) carriers significantly inhibited malignant melanoma growth, which correlated with a shift in the balance between endogenous TAp73 and ΔEx2/3 towards apoptotic full-length p73.

Conclusion

Our study demonstrates the successful development of LNA-ASOs that selectively differentiate between the closely related p73 oncoproteins, and provide new tools to further delineate their biological properties in different human malignancies and for therapeutic cancer targeting.
Mechanism of HIV-1 Tat RNA translation and its activation by the Tat protein
Authors: Charnay Nicolas , Ivanyi-Nagy Roland , Soto-Rifo Ricardo , Ohlmann Théophile , López-Lastra Marcelo , Darlix Jean-Luc
Published: August 2009

Background

The human immunodeficiency virus type 1 (HIV-1) Tat protein is a major viral transactivator required for HIV-1 replication. In the nucleus Tat greatly stimulates the synthesis of full-length transcripts from the HIV-1 promoter by causing efficient transcriptional elongation. Tat induces elongation by directly interacting with the bulge of the transactivation response (TAR) RNA, a hairpin-loop located at the 5'-end of all nascent viral transcripts, and by recruiting cellular transcriptional co-activators. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. Thus, Tat plays a central role in the regulation of HIV-1 gene expression both at the level of mRNA and protein synthesis. The requirement of Tat in these processes poses an essential question on how sufficient amounts of Tat can be made early on in HIV-1 infected cells to sustain its own synthesis. To address this issue we studied translation of the Tat mRNA in vitro and in human cells using recombinant monocistronic and dicistronic RNAs containing the 5' untranslated region (5'-UTR) of Tat RNA.

Results

This study shows that the Tat mRNA can be efficiently translated both in vitro and in cells. Furthermore, our data suggest that translation initiation from the Tat mRNA probably occurs by a internal ribosome entry site (IRES) mechanism. Finally, we show that Tat protein can strongly stimulate translation from its cognate mRNA in a TAR dependent fashion.

Conclusion

These results indicate that Tat mRNA translation is efficient and benefits from a feedback stimulation by the Tat protein. This translational control mechanism would ensure that minute amounts of Tat mRNA are sufficient to generate enough Tat protein required to stimulate HIV-1 replication.
Essential role for Argonaute2 protein in mouse oogenesis
Authors: Kaneda Masahiro , Tang Fuchou , O'Carroll Dónal , Lao Kaiqin , Surani M Azim
Published: August 2009

Background

Argonaute2 protein (Ago2) is a key component of RNA-induced gene silencing complex, which is crucial for microRNA-mediated repression of target genes. The function of Ago2 in the mouse oocyte and early embryonic development is less well characterized but it is likely to have an important role in regulating maternally inherited mRNA. We have examined the role of Ago2 by conditional deletion of the gene in developing oocytes.

Results

Ago2 was deleted specifically in the growing oocytes. Although the Ago2-deficient oocytes are able to develop to mature oocytes, they have abnormal spindles and chromosomes that are unable to cluster together properly. This phenotype is very similar to the phenotype of Dicer-deficient oocytes. We examined the microRNA expression profile in the Ago2-deficient oocyte and found that the expression of most microRNAs was reduced by more than 80%. To determine the downstream genes that are regulated by Ago2, we used microarray analysis on Ago2-deficient oocytes and found that 512 genes were upregulated and 1,073 genes were downregulated (FC > 2, P < 0.05).

Conclusion

Our study shows that Ago2 has a key function in the mouse oocyte through global regulation of microRNA stability, and through this mechanism it affects gene expression in developing oocytes.
Subcellular localization of APMCF1 and its biological significance of expression pattern in normal and malignant human tissues
Authors: Zhang Yaqing , Li Qinlong , Zhu Feng , Cui Jihong , Li Kainan , Li Qing , Wang Ruian , Wang Wenyong , Wang Weihua , Yan Wei
Published: August 2009

Background

APMCF1 is a novel human gene first cloned from apoptotic MCF-7 cells. Our previous study found ectogenic APMCF1 could induce G1 arrest in hepatocarcinoma cell line HHCC. In order to search its broad expression profile for further understanding of its mechanism in tumor, we investigated a subcellular location of APMCF1 and performed an immunohistochemistry study including various tumor and normal tissues. Discovery from the expression characterization of AMPCF1 may have applicability in the analysis of its biological function in tumor.

Methods

We investigated subcellular localization of APMCF1 by transient transfection in green monkey kidney epithelial cells (COS-7) with a fusion protein vector pEGFP-APMCF1 and detected expression profile in a broad range of normal and malignant human tissues via tissue microarray (TMA) by immunohistochemistry with polyclonal antibody first produced in our laboratory.

Results

EGFP-APMCF1 was generally localized in the cytoplasm of COS-7 cell. Positive staining of APMCF1 was found in liver, lung, breast, colon, stomach, esophagus and testis, exhibited a ubiquitous expression pattern while its expression was up-regulated in tumor tissues compared with corresponding normal tissues. Normal brain neuron cells also showed expression of APMCF1, but negative in gliocyte cells and glioma. Both the normal and tumor tissues of ovary were absent of APMCF1 expression. Positive immunostaining for APMCF1 with large samples in liver, colon, esophagus, lung and breast carcinomas were 96% (51/53), 80% (44/55), 57% (30/53), 58% (33/57) and 34% (16/47) respectively.

Conclusion

These results revealed a cytoplastic expression pattern of APMCF1 and up-regulated in tumour tissues suggesting APMCF1 may have potential relationship with oncogenesis. The data presented should serve as a useful reference for further studies of APMCF1 functions in tumorigenesis and might provide a potential anti-tumor target.
Type I interferon receptor controls B-cell expression of nucleic acid-sensing Toll-like receptors and autoantibody production in a murine model of lupus
Authors: Thibault Donna L , Graham Kareem L , Lee Lowen Y , Balboni Imelda , Hertzog Paul J , Utz Paul J
Published: August 2009

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of high-titer IgG autoantibodies directed against nuclear autoantigens. Type I interferon (IFN-I) has been shown to play a pathogenic role in this disease. In the current study, we characterized the role of the IFNAR2 chain of the type I IFN (IFN-I) receptor in the targeting of nucleic acid-associated autoantigens and in B-cell expression of the nucleic acid-sensing Toll-like receptors (TLRs), TLR7 and TLR9, in the pristane model of lupus.

Methods

Wild-type (WT) and IFNAR2-/- mice were treated with pristane and monitored for proteinuria on a monthly basis. Autoantibody production was determined by autoantigen microarrays and confirmed using enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation. Serum immunoglobulin isotype levels, as well as B-cell cytokine production in vitro, were quantified by ELISA. B-cell proliferation was measured by thymidine incorporation assay.

Results

Autoantigen microarray profiling revealed that pristane-treated IFNAR2-/- mice lacked autoantibodies directed against components of the RNA-associated autoantigen complexes Smith antigen/ribonucleoprotein (Sm/RNP) and ribosomal phosphoprotein P0 (RiboP). The level of IgG anti-single-stranded DNA and anti-histone autoantibodies in pristane-treated IFNAR2-/- mice was decreased compared to pristane-treated WT mice. TLR7 expression and activation by a TLR7 agonist were dramatically reduced in B cells from IFNAR2-/- mice. IFNAR2-/- B cells failed to upregulate TLR7 as well as TLR9 expression in response to IFN-I, and effector responses to TLR7 and TLR9 agonists were significantly decreased as compared to B cells from WT mice following treatment with IFN-α.

Conclusions

Our studies provide a critical link between the IFN-I pathway and the regulation of TLR-specific B-cell responses in a murine model of SLE.
Implementation of a delirium assessment tool in the ICU can influence haloperidol use
Authors: van den Boogaard Mark , Pickkers Peter , van der Hoeven Hans , Roodbol Gabriel , van Achterberg Theo , Schoonhoven Lisette
Published: August 2009

Introduction

In critically ill patients, delirium is a serious and frequent disorder that is associated with a prolonged intensive care and hospital stay and an increased morbidity and mortality. Without the use of a delirium screening instrument, delirium is often missed by ICU nurses and physicians. The effects of implementation of a screening method on haloperidol use is not known. The purpose of this study was to evaluate the implementation of the confusion assessment method-ICU (CAM-ICU) and the effect of its use on frequency and duration of haloperidol use.

Methods

We used a tailored implementation strategy focused on potential barriers. We measured CAM-ICU compliance, interrater reliability, and delirium knowledge, and compared the haloperidol use, as a proxy for delirium incidence, before and after the implementation of the CAM-ICU.

Results

Compliance and delirium knowledge increased from 77% to 92% and from 6.2 to 7.4, respectively (both, P < 0.0001). The interrater reliability increased from 0.78 to 0.89. More patients were treated with haloperidol (9.9% to 14.8%, P < 0.001), however with a lower dose (18 to 6 mg, P = 0.01) and for a shorter time period (5 [IQR:2–9] to 3 [IQR:1–5] days, P = 0.02).

Conclusions

With a tailored implementation strategy, a delirium assessment tool was successfully introduced in the ICU with the main goals achieved within four months. Early detection of delirium in critically ill patients increases the number of patients that receive treatment with haloperidol, however with a lower dose and for a shorter time period.