bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Epidemiology of Acquired-Metallo-β-Lactamase-Producing Bacteria in Poland
Authors: Fiett Janusz , Baraniak Anna , Mrówka Agnieszka , Fleischer Małgorzata , Drulis-Kawa Zuzanna , Naumiuk Łukasz , Samet Alfred , Hryniewicz Waleria , Gniadkowski Marek
Published: February 2006

We have analyzed 40 metallo-β-lactamase (MBL)-producing isolates of
Pseudomonas aeruginosa
(
n
= 38),
Pseudomonas putida
(
n
= 1), and
Acinetobacter
genospecies 3 (
n
= 1) from 17 hospitals in 12 cities in Poland that were identified in 2000 to 2004. Pulsed field gel electrophoresis typing classified the
P. aeruginosa
isolates into eight types, with two types differentiated further into subtypes. Each of the types was specific either to a given center or to several hospitals of the same or neighboring geographic area. Almost all of the organisms produced β-lactamase VIM-2; the only exceptions were several
P. aeruginosa
isolates from two centers which expressed VIM-4. The
bla
VIM
genes resided exclusively within class 1 integrons, and these were located in either chromosomal or plasmid DNA. PCR-restriction fragment length polymorphism study of the variable regions of the integrons, followed by DNA sequencing, revealed the presence of eight different, mostly novel gene cassette arrays, six of which contained
bla
VIM-2
and two of which contained
bla
VIM-4
. The occurrence of the integron variants correlated well with the geographic distribution of the MBL-producing organisms, and this suggested that their emergence in particular parts of the country had been likely due to a number of independent events. The following regional dissemination of MBL producers could be attributed to various phenomena, including their clonal spread, horizontal transmission of resistance determinants, or both. All of the data collected in this study revealed that even at this early stage of detection, the epidemiological situation concerning MBL producers in Poland has already been complex and very dynamic.
Head-to-Head Comparison of the Activities of Currently Available Antifungal Agents against 3,378 Spanish Clinical Isolates of Yeasts and Filamentous Fungi
Authors: Cuenca-Estrella Manuel , Gomez-Lopez Alicia , Mellado Emilia , Buitrago Maria J. , Monzon Araceli , Rodriguez-Tudela Juan Luis
Published: February 2006

We have compared the activities of posaconazole and other currently available antifungal agents against a collection of 3,378 clinical isolates of yeasts and filamentous fungi. A total of 1,997 clinical isolates of
Candida
spp., 359 of other yeast species, 697 strains of
Aspergillus
spp., and 325 nondermatophyte non-
Aspergillus
spp. were included. The average geometric means of the MICs of agents that were tested against
Candida
spp. were 0.23 μg/ml for amphotericin B, 0.29 μg/ml for flucytosine, 0.97 μg/ml for fluconazole, 0.07 μg/ml for itraconazole, 0.04 μg/ml for voriconazole, 0.15 μg/ml for caspofungin, and 0.03 μg/ml for posaconazole. Voriconazole and posaconazole were active in vitro against the majority of isolates, with resistance to fluconazole and itraconazole, and against
Cryptococcus neoformans
and other
Basidiomycota
yeasts. Posaconazole was the most active of antifungal agents tested against
Aspergillus
spp., with an average geometric mean of 0.10 μg/ml. It was active against
Paecilomyces
spp.,
Penicillium
spp.,
Scedosporium apiospermum
, and some black fungi, such as
Alternaria
spp. Multiresistant filamentous fungi, such as
Scedosporium prolificans
,
Scopulariopsis brevicaulis
, and
Fusarium solani
, were also resistant to voriconazole, caspofungin, and posaconazole. Amphotericin B and posaconazole were found to be active against most of the
Mucorales
strains tested. Posaconazole and currently available antifungal agents exhibit a potent activity in vitro against the majority of pathogenic fungal species.
Fluoroquinolone Resistance in InvasiveStreptococcus pyogenesIsolates Due to Spontaneous Mutation and Horizontal Gene Transfer
Authors: Pletz M. W. R. , McGee L. , Van Beneden C. A. , Petit S. , Bardsley M. , Barlow M. , Klugman K. P.
Published: February 2006

Fluoroquinolone resistance inStreptococcus pyogeneshas been described only anecdotally. In this study we describe two invasive ciprofloxacin-resistantS. pyogenesisolates (ciprofloxacin MICs, 8 mg/liter), one of which shows evidence of interspecies recombination. The quinolone resistance-determining regions ofgyrAandparCwere sequenced. In both isolates, there was no evidence for an efflux pump and no mutation ingyrA. Both isolates had an S79F mutation inparCthat is known to confer fluoroquinolone resistance. In addition, a D91N mutation inparC, which is not related to fluoroquinolone resistance but is a feature of theparCsequence ofStreptococcus dysgalactiae, was found in one isolate. TheparCnucleotide sequence of that isolate showed greater diversity than that ofS. pyogenes. A GenBank search and phylogenetic analysis suggest that this isolate acquired resistance by horizontal gene transfer fromS. dysgalactiae. Statistical testing for recombination confirmed interspecies recombination of a 90-bp sequence containing the S79F mutation fromS. dysgalactiae. For the other isolate, we could confirm that it acquired resistance by spontaneous mutation by identifying the susceptible ancestor in an outbreak setting.
Involvement of Reactive Oxygen Species in the Action of Ciprofloxacin againstEscherichia coli
Authors: Goswami M. , Mangoli S. H. , Jawali N.
Published: February 2006

Ciprofloxacin is an important and commonly used member of the fluoroquinolone group of antibiotics. Ciprofloxacin inhibits DNA topoisomerase II and DNA topoisomerase IV activities, eventually leading to bacterial cell death. In addition, an increase of reactive oxygen species in the bacterial cells in response to ciprofloxacin has been shown. We investigated the role of reactive oxygen species in the antibacterial action of ciprofloxacin by studying the effects of different antioxidant compounds on ciprofloxacin susceptibility ofEscherichia coli. Among the antioxidants checked, glutathione and ascorbic acid provided substantial protection against ciprofloxacin. The involvement of superoxide anion (O2−) and hydrogen peroxide (H2O2) in the antibacterial action of ciprofloxacin was analyzed using superoxide dismutase, catalase, and alkyl hydroperoxide reductase knockout strains ofE. coli. The effects of multicopysodgenes on ciprofloxacin susceptibility ofE. coliwere also analyzed. On the basis of our results, we conclude that O2−and H2O2may be involved in antibacterial action of ciprofloxacin. Our findings that glutathione gave protection against other fluoroquinolones and not against nonfluoroquinolone antibiotics imply that reactive oxygen species may have a similar role in the antibacterial action of all these fluoroquinolones and that glutathione-mediated protection is not a general phenomenon but specific to fluoroquinolones. These observations are of significance, as fluoroquinolones are important antibiotics with immense therapeutic value, and the effectiveness of treatment by these drugs may be affected by dietary intake and cellular levels of these antioxidants.
In Vitro Characterization of the Anti-Hepatitis B Virus Activity and Cross-Resistance Profile of 2′,3′-Dideoxy-3′-Fluoroguanosine
Authors: Jacquard A.-C. , Brunelle M.-N. , Pichoud C. , Durantel D. , Carrouée-Durantel S. , Trepo C. , Zoulim F.
Published: February 2006

The fluorinated guanosine analog 2′,3′-dideoxy-3′-fluoroguanosine (FLG) was shown to inhibit wild-type (wt) hepatitis B virus (HBV) replication in a human hepatoma cell line permanently expressing HBV. Experiments performed in the duck model of HBV infection also showed its in vivo antiviral activity. In this study, we investigated the mechanism of inhibition of FLG on HBV replication and its profile of antiviral activity against different HBV or duck hepatitis B virus (DHBV) drug-resistant mutants. We found that FLG-triphosphate inhibits weakly the priming of the reverse transcription compared to adefovir-diphosphate in a cell-free system assay allowing the expression of an enzymatically active DHBV reverse transcriptase. It inhibits more potently wt DHBV minus-strand DNA synthesis compared to lamivudine-triphosphate and shows a similar activity compared to adefovir-diphosphate. FLG-triphosphate was most likely a competitive inhibitor of dGTP incorporation and a DNA chain terminator. In Huh7 cells transiently transfected with different HBV constructs, FLG inhibited similarly the replication of wt, lamivudine-resistant, adefovir-resistant, and lamivudine-plus-adefovir-resistant HBV mutants. These results were consistent with those obtained in the DHBV polymerase assay using the same drug-resistant polymerase mutants. In conclusion, our data provide new insights in the mechanism of action of FLG-triphosphate on HBV replication and demonstrate its inhibitory activity on drug-resistant mutant reverse transcriptases in vitro. Furthermore, our results provide the rationale for further clinical evaluation of FLG in the treatment of drug-resistant virus infection and in the setting of combination therapy to prevent or delay drug resistance.
Efficacy and Potential for Resistance Selection of Antipseudomonal Treatments in a Mouse Model of Lung Infection by HypermutablePseudomonas aeruginosa
Authors: Maciá M. D. , Borrell N. , Segura M. , Gómez C. , Pérez J. L. , Oliver A.
Published: February 2006

HypermutablePseudomonas aeruginosastrains are found with high frequency in the lungs of patients with chronic infections and are associated with high antibiotic resistance rates. The in vivo consequences of hypermutation for treatment in a mouse model of lung infection using strain PAO1 and its hypermutable derivative PAOΔmutSare investigated. Groups of 30 mice were treated for 3 days with humanized regimens of ciprofloxacin (CIP), tobramycin (TOB), CIP plus TOB, or placebo, and mortality, total lung bacterial load, and 4×- and 16×-MIC mutants were recorded. The rates of mutation and the initial in vivo frequencies of mutants (at the onset of treatment) were also estimated and the in vitro- and in vivo-selected mutants characterized. Since both strains had identical MICs, the same pharmacokinetic/pharmacodynamic (PK/PD) parameters were obtained: area under the 24-h concentration-time curve (fAUC)/MIC = 385 for CIP and maximum concentration of drug in serum (fCmax)/MIC = 19 for TOB. Despite adequate PK/PD parameters, persistence of high bacterial numbers and amplification (50,000-fold) of resistant mutants (MexCD-OprJ hyperexpression) were documented with CIP treatment for PAOΔmutS, in contrast to complete resistance suppression for PAO1 (P< 0.01), showing that conventional PK/PD parameters may not be applicable to infections by hypermutable strains. On the other hand, the efficacy of TOB monotherapy in terms of mortality reduction and bacterial load was very low regardless of the strain but not due to resistance development, since mutants were not selected for PAO1 and were only modestly amplified for PAOΔmutS. Finally, the CIP-plus-TOB combination was synergistic, further reducing mortality and bacterial load and completely preventing resistance even for PAOΔmutS(P< 0.01 compared to monotherapy), showing that it is possible to suppress resistance selection in infections by hypermutableP. aeruginosausing appropriate combined regimens.
Pharmacokinetic-Pharmacodynamic Relationships Describing the Efficacy of Oritavancin in Patients with
Staphylococcus aureus
Bacteremia
Authors: Bhavnani Sujata M. , Passarell Julie A. , Owen Joel S. , Loutit Jeffrey S. , Porter Steven B. , Ambrose Paul G.
Published: February 2006

Bloodstream infections due to antimicrobial-resistant
Staphylococcus aureus
occur with increasing frequency and represent an important cause of morbidity and mortality. To date, the evaluation of pharmacokinetic-pharmacodynamic relationships for efficacy among patients with bacteremia has been limited. The objectives of these analyses were to evaluate relationships between microbiological and clinical responses for patients with
S. aureus
bacteremia and exposures for oritavancin, a novel bactericidal glycopeptide in development. Bayesian oritavancin exposure predictions, following treatment with 5, 6.5, 8, or 10 mg/kg of body weight/day, were derived using a validated population pharmacokinetic model for 55 patients with
S. aureus
bacteremia. Using classification and regression tree analysis, a breakpoint of the percentage of the dosing interval duration for which free-drug concentrations were above the MIC (free-drug % time > MIC) of 22% was identified for microbiological response; the probabilities of success greater than or equal to and less than this value were 93% and 76%, respectively. Using logistic regression, a relationship was found between microbiological response and free-drug % time > MIC (odds ratio = 4.42,
P
= 0.09, and odds ratio = 8.84,
P
= 0.05, when one patient, a medical outlier, was excluded). A similar relationship was found for clinical response. These results will be valuable in supporting dose selection of oritavancin for patients with
S. aureus
bacteremia.
ANALYSIS AND IMPLEMENTATION OF A NEURAL EXTENDED KALMAN FILTER FOR TARGET TRACKING
Authors: KRAMER KATHLEEN A. , STUBBERUD STEPHEN C.
Published: February 2006

Having a better motion model in the state estimator is one way to improve target tracking performance. Since the motion model of the target is not known a priori, either robust modeling techniques or adaptive modeling techniques are required. The neural extended Kalman filter is a technique that learns unmodeled dynamics while performing state estimation in the feedback loop of a control system. This coupled system performs the standard estimation of the states of the plant while estimating a function to approximate the difference between the given state-coupling function model and the behavior of the true plant dynamics. At each sample step, this new model is added to the existing model to improve the state estimate. The neural extended Kalman filter has also been investigated as a target tracking estimation routine. Implementation issues for this adaptive modeling technique, including neural network training parameters, were investigated and an analysis was made of the quality of performance that the technique can have for tracking maneuvering targets.
CLASSIFICATION OF MENTAL TASKS FROM EEG SIGNALS USING EXTREME LEARNING MACHINE
Authors: LIANG NAN-YING , SARATCHANDRAN PARAMASIVAN , HUANG GUANG-BIN , SUNDARARAJAN NARASIMHAN
Published: February 2006

In this paper, a recently developed machine learning algorithm referred to as Extreme Learning Machine (ELM) is used to classify five mental tasks from different subjects using electroencephalogram (EEG) signals available from a well-known database. Performance of ELM is compared in terms of training time and classification accuracy with a Backpropagation Neural Network (BPNN) classifier and also Support Vector Machines (SVMs). For SVMs, the comparisons have been made for both 1-against-1 and 1-against-all methods. Results show that ELM needs an order of magnitude less training time compared with SVMs and two orders of magnitude less compared with BPNN. The classification accuracy of ELM is similar to that of SVMs and BPNN. The study showed that smoothing of the classifiers' outputs can significantly improve their classification accuracies.
THE FORECAST OF THE POSTOPERATIVE SURVIVAL TIME OF PATIENTS SUFFERED FROM NON-SMALL CELL LUNG CANCER BASED ON PCA AND EXTREME LEARNING MACHINE
Authors: HAN FEI , HUANG DE-SHUANG , ZHU ZHI-HUA , RONG TIE-HUA
Published: February 2006

In this paper, a new effective model is proposed to forecast how long the postoperative patients suffered from non-small cell lung cancer will survive. The new effective model which is based on the extreme learning machine (ELM) and principal component analysis (PCA) can forecast successfully the postoperative patients' survival time. The new model obtains better prediction accuracy and faster convergence rate which the model using backpropagation (BP) algorithm and the Levenberg-Marquardt (LM) algorithm to forecast the postoperative patients' survival time can not achieve. Finally, simulation results are given to verify the efficiency and effectiveness of our proposed new model.
A NOVEL CONNECTIONIST FRAMEWORK FOR COMPUTATION OF AN APPROXIMATE CONVEX-HULL OF A SET OF PLANAR POINTS, CIRCLES AND ELLIPSES
Authors: PAL SRIMANTA , BHATTACHARYA SABYASACHI , PAL NIKHIL R.
Published: February 2006

We propose a two layer neural network for computation of an approximate convex-hull of a set of points or a set of circles/ellipses of different sizes. The algorithm is based on a very elegant concept — shrinking of a rubber band surrounding the set of planar objects. Logically, a set of neurons is placed on a circle (rubber band) surrounding the objects. Each neuron has a parameter vector associated with it. This may be viewed as the current position of the neuron. The given set of points/objects exerts a force of attraction on every neuron, which determines how its current position will be updated (as if, the force determines the direction of movement of the neuron lying on the rubber band). As the network evolves, the neurons (parameter vectors) approximate the convex-hull more and more accurately. The scheme can be applied to find the convex-hull of a planar set of circles or ellipses or a mixture of the two. Some properties related to the evolution of the algorithm are also presented.
CONSTRUCTION OF A 3-D FINITE ELEMENT MODEL OF THE HUMAN FOREARM COMPLEX USING A SERIES OF 2-D COLOR IMAGES
Authors: Kim Kyu-Jung , Hwang Il-Kyu
Published: February 2006

A simple yet efficient paradigm for geometric mesh generation using the Visible Human Project Male dataset for further finite element analysis was presented. The minimum distance classifier was used for the discriminant function between the class centers classified by the fuzzy c-means clustering method in the RGB space. Furthermore, based on two major geometric assumptions on the boundary curves, star-shaped polygon and geometric conformity, a points-on-line search technique was devised for efficient computation of the boundary points of the contours for each anatomical component of the human forearm complex. The computed boundary points in each slice were fitted to a closed spline curve and resampled and then refitted for correct alignment with the consecutive boundary curves in order to improve geometric fidelity. By using the refitted contours, a 3-D geometric model of the human radius, ulna, and surrounding soft tissue was generated in a commercial computer–aided design system and exported to a commercial finite element analysis package for meshing with its built-in automatic mesh generator. The proposed method can be applied to geometric mesh generation of other long bones, which allows easy handling, storage, and exchange of the model.
LASER MICRODISSECTION OF PLANT TISSUE: What You See Is What You Get
Authors: Nelson Timothy , Tausta S. Lori , Gandotra Neeru , Liu Tie
Published: February 2006

Laser microdissection (LM) utilizes a cutting or harvesting laser to isolate specific cells from histological sections; the process is guided by microscopy. This provides a means of removing selected cells from complex tissues, based only on their identification by microscopic appearance, location, or staining properties (e.g., immunohistochemistry, reporter gene expression, etc.). Cells isolated by LM can be a source of cell-specific DNA, RNA, protein or metabolites for subsequent evaluation of DNA modifications, transcript/protein/metabolite profiling, or other cell-specific properties that would be averaged with those of neighboring cell types during analysis of undissected complex tissues. Plants are particularly amenable to the application of LM; the highly regular tissue organization and stable cell walls of plants facilitate the visual identification of most cell types even in unstained tissue sections. Plant cells isolated by LM have been the starting point for a variety of genomic and metabolite studies of specific cell types.
Mechanisms for Chromosome and Plasmid Segregation
Authors: Ghosh Santanu Kumar , Hajra Sujata , Paek Andrew , Jayaram Makkuni
Published: February 2006

The fundamental problems in duplicating and transmitting genetic information posed by the geometric and topological features of DNA, combined with its large size, are qualitatively similar for prokaryotic and eukaryotic chromosomes. The evolutionary solutions to these problems reveal common themes. However, depending on differences in their organization, ploidy, and copy number, chromosomes and plasmids display distinct segregation strategies as well. In bacteria, chromosome duplication, likely mediated by a stationary replication factory, is accompanied by rapid, directed migration of the daughter duplexes with assistance from DNA-compacting and perhaps translocating proteins. The segregation of unit-copy or low-copy bacterial plasmids is also regulated spatially and temporally by their respective partitioning systems. Eukaryotic chromosomes utilize variations of a basic pairing and unpairing mechanism for faithful segregation during mitosis and meiosis. Rather surprisingly, the yeast plasmid 2-micron circle also resorts to a similar scheme for equal partitioning during mitosis.
ECONOMIC DEVELOPMENT AND DEMOCRACY
Authors: Robinson James A.
Published: February 2006

▪ Abstract  In this essay, I review recent research on the effects of economic development on democracy. On the theoretical side, for the first time there has been a systematic attempt to bring the types of formal models developed by economists and political scientists outside of comparative politics to bear on the origins of democracy. I present a simple analytical framework that captures some of the results in this literature. On the empirical side, the issue of identifying causal relationships in the data is finally receiving attention. However, the application of techniques adopted from best-practice econometrics shows no evidence that economic development has a causal effect on democracy. Neither does it support the idea that economic development influences the probability of coups but not democratizations. More likely, and in line with the model I develop, income per capita and democracy are correlated because the same features of a society simultaneously determine how prosperous and how democratic it is. There is still a lot to learn on this topic.
Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells
Authors: Wei Yuren , Wang Dong , Topczewski Farran , Pagliassotti Michael J.
Published: February 2006

Accumulation of lipids in nonadipose tissues can lead to cell dysfunction and cell death, a phenomenon known as lipotoxicity. However, the signaling pathways and mechanisms linking lipid accumulation to cell death are poorly understood. The present study examined the hypothesis that saturated fatty acids disrupt endoplasmic reticulum (ER) homeostasis and promote apoptosis in liver cells via accumulation of ceramide. H4IIE liver cells were exposed to varying concentrations of saturated (palmitate or stearate) or unsaturated (oleate or linoleate) fatty acids. ER homeostasis was monitored using markers of the ER stress response pathway, including phosphorylation of IRE1α and eIF2α, splicing of XBP1 mRNA, and expression of molecular chaperone (e.g., GRP78) and proapoptotic (CCAAT/enhancer-binding protein homologous protein) genes. Apoptosis was monitored using caspase activity and DNA laddering. Palmitate and stearate induced ER stress, caspase activity, and DNA laddering. Inhibition of caspase activation prevented DNA laddering. Unsaturated fatty acids did not induce ER stress or apoptosis. Saturated fatty acids increased ceramide concentration; however, inhibition of de novo ceramide synthesis did not prevent saturated fatty acid-induced ER stress and apoptosis. Unsaturated fatty acids rescued palmitate-induced ER stress and apoptosis. These data demonstrate that saturated fatty acids disrupt ER homeostasis and induce apoptosis in liver cells via mechanisms that do not involve ceramide accumulation.
Calcium wave of tubuloglomerular feedback
Authors: Peti-Peterdi János
Published: February 2006

ATP release from macula densa (MD) cells into the interstitium of the juxtaglomerular (JG) apparatus (JGA) is an integral component of the tubuloglomerular feedback (TGF) mechanism that controls the glomerular filtration rate. Because the cells of the JGA express a number of calcium-coupled purinergic receptors, these studies tested the hypothesis that TGF activation triggers a calcium wave that spreads from the MD toward distant cells of the JGA and glomerulus. Ratiometric calcium imaging of in vitro microperfused isolated JGA-glomerulus complex dissected from rabbits was performed with fluo-4/fura red and confocal fluorescence microscopy. Activation of TGF by increasing tubular flow rate at the MD rapidly produced a significant elevation in intracellular Ca2+ concentration ([Ca2+]i) in extraglomerular mesangial cells (by 187.6 ± 45.1 nM) and JG renin granular cells (by 281.4 ± 66.6 nM). Subsequently, cell-to-cell propagation of the calcium signal at a rate of 12.6 ± 1.1 μm/s was observed upstream toward proximal segments of the afferent arteriole and adjacent glomeruli, as well as toward intraglomerular elements including the most distant podocytes (5.9 ± 0.4 μm/s). The same calcium wave was observed in nonperfusing glomeruli, causing vasoconstriction and contractions of the glomerular tuft. Gap junction uncoupling, an ATP scavenger enzyme cocktail, and pharmacological inhibition of P2 purinergic receptors, but not adenosine A1 receptor blockade, abolished the changes in [Ca2+]i and propagation of the calcium wave. These studies provided evidence that both gap junctional communication and extracellular ATP are integral components of the TGF calcium wave.
Prefrontal Cortex–Projecting Glutamatergic Thalamic Paraventricular Nucleus-Excited by Hypocretin: A Feedforward Circuit That May Enhance Cognitive Arousal
Authors: Huang Hao , Ghosh Prabhat , van den Pol Anthony N.
Published: February 2006

The paraventricular thalamic nucleus (PVT) receives one of the most dense innervations by hypothalamic hypocretin/orexin (Hcrt) neurons, which play important roles in sleep-wakefulness, attention, and autonomic function. The PVT projects to several loci, including the medial prefrontal cortex (mPFC), a cortical region involved in associative function and attention. To study the effect of Hcrt on excitatory PVT neurons that project to the mPFC, we used a new line of transgenic mice expressing green fluorescent protein (GFP) under the control of the vesicular glutamate-transporter-2 promoter. These neurons were retrogradely labeled with cholera toxin subunit B that had been microinjected into the mPFC. Membrane characteristics and responses to hypocretin-1 and -2 (Hcrt-1 and -2) were studied using whole cell recording ( n > 300). PVT neurons showed distinct membrane properties including inward rectification, H-type potassium currents, low threshold spikes, and spike frequency adaptation. Cortically projecting neurons were depolarized and excited by Hcrt-2. Hcrt-2 actions were stronger than those of Hcrt-1, and the action persisted in TTX and in low calcium/high magnesium artificial cerebrospinal fluid, consistent with direct actions mediated by Hcrt receptor-2. Two mechanisms of Hcrt excitation were found: an increase in input resistance caused by closure of potassium channels and activation of nonselective cation channels. The robust excitation evoked by Hcrt-2 on cortically projecting glutamate PVT neurons could generate substantial excitation in multiple layers of the mPFC, adding to the more selective direct excitatory actions of Hcrt in the mPFC and potentially increasing cortical arousal and attention to limbic or visceral states.
Hemispheric Specialization for the Visual Control of Action Is Independent of Handedness
Authors: Gonzalez Claudia L. R. , Ganel Tzvi , Goodale Melvyn A.
Published: February 2006

The idea that visually guided action is independent of visual perception has been supported by neurological, neuropsychological, and behavioral studies. In healthy subjects, evidence for this distinction has come from psychophysical studies of the effects of visual illusions on perceptual judgments and object-directed grasping. This evidence is limited, however, by the fact that virtually all studies have involved right-handed subjects using their dominant hand, which is presumably controlled by the left hemisphere. There is tentative evidence from earlier neurological studies that the left hemisphere may in fact play a special role in the integration of visual and motor information during grasping. We designed two experiments to test this idea. The first experiment involved pictorial illusions, which are known to have robust effects on perceptual judgments but little influence on grasping. Right- and left-handed subjects reached out and grasped objects embedded in two different visual illusions with either their dominant or their nondominant hand. For both right- and left-handed subjects, precision grasping with the left hand, but not with the right, was affected by the illusions. In a follow-up experiment, we examined precision grasping in a more natural setting and showed that left-handed subjects use their nondominant (right) hand significantly more as compared with right-handed subjects. We conclude that visuomotor mechanisms encapsulated in the left hemisphere play a crucial role in the visual control of action and that this hemispheric specialization evolved independently of handedness.
Transcriptome profiling the gills of amoebic gill disease (AGD)-affected Atlantic salmon (Salmo salarL.): a role for tumor suppressor p53 in AGD pathogenesis?
Authors: Morrison Richard N. , Cooper Glenn A. , Koop Ben F. , Rise Matthew L. , Bridle Andrew R. , Adams Mark B. , Nowak Barbara F.
Published: February 2006

Neoparamoeba spp. are amphizoic amoebae with the capacity to colonize the gills of some marine fish, causing AGD. Here, the gill tissue transcriptome response of Atlantic salmon ( Salmo salar L.) to AGD is described. Tanks housing Atlantic salmon were inoculated with Neoparamoeba spp. and fish sampled at time points up to 8 days postinoculation (pi.). Gill tissues were taken from AGD-affected fish, and a DNA microarray was used to compare global gene expression against tissues from AGD-unaffected fish. A total of 206 genes, representing 190 unique transcripts, were reproducibly identified as up- or downregulated in response to Neoparamoeba spp. infection. Informative transcripts having GO biological process identifiers were grouped according to function. Although a number of genes were placed into each category, no distinct patterns were observed. One Atlantic salmon cDNA that was upregulated in infected gill relative to noninfected gill at 114 and 189 h pi. showed significant identity with the Xenopus, mouse, and human anterior gradient-2 (AG-2) homologs. Two Atlantic salmon AG-2 mRNA transcripts, designated asAG-2/1 and asAG-2/2, were cloned, sequenced, and shown to be predominantly expressed in the gill, intestine, and brain of a healthy fish. In AGD-affected fish, differential asAG-2 expression was confirmed in samples used for microarray analyses as well as in AGD-affected gill tissue taken from fish in an independent experiment. The asAG-2 upregulation was restricted to AGD lesions relative to unaffected tissue from the same gill arch, while p53 tumor suppressor protein mRNA was concurrently downregulated in AGD lesions. Differential expression of p53-regulated transcripts, proliferating cell nuclear antigen and growth arrest and DNA damage-inducible gene-45β (GADD45β) in AGD lesions, suggests a role for p53 in AGD pathogenesis. Thus AGD may represent a novel model for comparative analysis of p53 and p53-regulated pathways.
National Hospital Infection Surveillance on Methicillin-Resistant Staphylococcus aureus
Authors: Kobayashi Hiroyoshi
Published: February 2006

National hospital infection surveillances on methicillin-resistant Staphylococcus aureus (MRSA) had been carried out in 1995 and 1996. Recently, in the UK and the USA, the prevalence of MRSA has increased and strict precautions against MRSA are recommended. In Japan, hospital infection rates of MRSA have appeared to be stable in recent years, but a reevaluation is required to confirm this assumption. In a nationwide surveillance, the incidences of MRSA hospital infections per 100 admissions remained stable at between 0.7 and 0.8 from 1999 to 2003, with a tendency towards a slight decline being observed. This study shows that the precautions against MRSA infection in Japan may prove to be an effective preventive measure.
The Efficacy of Povidone-Iodine Products against Periodontopathic Bacteria
Authors: Nakagawa Taneaki , Hosaka Yasuo , Ishihara Kazuyuki , Hiraishi Toru , Sato Soh , Ogawa Tomohisa , Kamoi Kyuichi
Published: February 2006

A total of 8 strains of 6 bacterial species, Porphyromonas gingivalis ATCC33277 and TDC286, Actinobacillus actinomycetemcomitans ATCC29523 and JP2, Fusobacterium nucleatum No. 2, Tannerella forsythensis ATCC43937, Prevotella intermedia ATCC25611 and Streptococcus anginosus ATCC33397, were treated with povidone-iodine (PVP-I) gargle (PVP-I: 0.47 and 0.23% w/v) or chlorhexidine gluconate (CHG) gargle (CHG: 0.002% w/v) for 15, 30 or 60 s, after which they were inoculated into various media, cultured and counted for residual bacteria. At both concentrations, PVP-I gargle reduced the viable cell count of all 8 bacterial strains to below the measurable limit within 15 s. By contrast, there were more than 1,000 viable colonies 60 s following treatment with the CHG gargle. The results demonstrate that povidone-iodine gargle has rapid bactericidal activity against the causative bacteria of periodontal disease.
Bacterial Vaginosis and Group B Streptococcal Colonization and Preterm Delivery in a Low-Risk Population
Authors: Daskalakis George , Papapanagiotou Angeliki , Mesogitis Spyros , Papantoniou Nikolaos , Mavromatis Konstantinos , Antsaklis Aris
Published: February 2006

Objective: To evaluate the relationship between bacterial vaginosis (BV) and group B streptococcal (GBS) colonization in the 2nd trimester of pregnancy and preterm delivery. Methods: 1,197 pregnant women between 22 and 25 weeks’ gestation had a high vaginal swab for assessment of BV and GBS. Exclusion criteria were: previous preterm delivery, or mid-trimester abortion or termination of pregnancy, multiple gestation, oligo- or polyhydramnios, placenta previa, fetal abnormalities, uterine malformations, cervical incompetence, cervical cerclage, or receipt of an antibiotic effective against BV or GBS following the screening. All women had no risk factors for preterm delivery. The primary outcome measure in this analysis was spontaneous preterm delivery before 37 weeks’ gestation. Results: The preterm delivery rate was 8.7%, while the maternal BV and GBS colonization rates were 7.9 and 12.5%, respectively. Following adjustment for potential confounders BV was associated with an increased risk of preterm delivery (RR 2.19; CI: 1.21–3.98) (p = 0.01). On the contrary, GBS colonization was found to have a negative correlation with preterm birth (RR 0.43; 95% CI: 0.19–1.00). Conclusions: Although BV is a risk factor for preterm delivery, GBS colonization in the 2nd trimester of pregnancy has an inverse correlation with preterm delivery.
Prenatal Catheter Placement for Fetal Cystic Adenomatoid Pulmonary Malformation: A Case Report
Authors: Viggiano Marcello Braga , Naves do Amaral Waldemar , Peres Fonseca Paulo Sérgio , Hamú Zacarias Calil , Damasceno de Castro Juliane , Pulcinelli Francielle
Published: February 2006

Introduction: Fetal congenital cystic adenomatoid malformation is a pulmonary developmental anomaly arising from an overgrowth of the terminal respiratory bronchioles. This is such a rare malformation that it is not always thought of as a diagnostic possibility. Case: In the present case, after a large pulmonary cyst started deviating the mediastinum and following an increase in amniotic fluid volume in the fetus at 28 weeks of gestation, the placement of a catheter for continuous drainage was performed. Subsequent follow-up with ultrasounds and serial echocardiograms revealed normalization of the position of mediastinum, normal amniotic fluid levels, and the correct position of the catheter. The size of the cyst was decreasing daily, but 8 weeks after fetal invasive procedure, there was concern about the stabilization of its size, with the suspicion of obstruction of the catheter. Cesarean delivery was performed at 38 weeks’ gestation. The size of the cyst on the day of C-section was 3.0 × 2.9 × 2.1 cm. At delivery, the infant weighed 3,030 g, with no evidence of respiratory distress, revealing the correct location of catheter. At day 4 after delivery a superior right pulmonary lobe resection was performed. Conclusion: Large pulmonary cysts may produce deviation of mediastinum and can lead to cardiac tamponade, nonimmune hydrops and pulmonary hypoplasia. Precise prenatal imaging and different fetal therapeutic strategies may allow survival of affected fetuses.
Which Phototherapy System Is Most Effective in Lowering Serum Bilirubin in Very Preterm Infants?
Authors: Romagnoli Costantino , Zecca Enrico , Papacci Patrizia , Vento Giovanni , Girlando Pietro , Latella Caterina
Published: February 2006

Objective: To compare the effectiveness of various phototherapy systems in lowering serum bilirubin levels in preterm infants. Methods: This randomized clinical trial enrolled 140 preterm infants with gestational age ≤30 weeks and presenting nonhemolytic hyperbilirubinemia. When total serum bilirubin level reached 6.0 mg/dl (102.6 µmol/l), eligible infants were randomly assigned to four study groups: conventional, fiberoptic Wallaby, fiberoptic Biliblanket, and combined phototherapy. Efficacy was assessed by comparing highest serum bilirubin levels, duration of treatment, and number of infants requiring exchange transfusion. Results: Our results confirm that fiberoptic phototherapy, both Wallaby and Biliblanket, had the same effectiveness of conventional phototherapy. The best results have been obtained using combined phototherapy, which allowed to reach lower serum bilirubin levels, a shorter duration of treatment and a significant reduction of exchange transfusions. Conclusion: Our data suggest that combined phototherapy should be the method of choice in treating hyperbilirubinemia in very preterm infants.
Disseminated Intravascular Coagulation following Selective Termination in a Twin Pregnancy
Authors: Hackney D.N. , Williams M. , Landon M.B. , Samuels P. , O’Shaughnessy R.W.
Published: February 2006

Objective: Coagulation abnormalities after single fetal demise are well described, but similar cases had not been previously reported following therapeutic selective termination. Case: A 23-year-old G3 P2001 with a monochorionic-diamnionic twin pregnancy underwent selective termination at 20 4/7 weeks for severe twin-twin transfusion syndrome. Her fibrinogen thereafter decreased and she developed disseminated intravascular coagulopathy with pathological bleeding during a cesarean section. The maternal coagulopathy resolved postpartum. Conclusion: Coagulation disorders can follow selective termination. Recommendations to serially follow coagulation parameters after these procedures, however, cannot be based upon a single case.
Probiotics and Prebiotics in Human Health
Authors: Saier Jr. Milton H. , Mansour Nahla M.
Published: February 2006

Probiotic bacteria are found in the intestines of humans and other mammals where they provide health benefits to the host. They do so by (1) providing nutrients and cofactors, (2) successfully competing with pathogens, and (3) stimulating host immune responses by producing specific polysaccharides. These bacteria can also alleviate the symptoms of disease-related metabolic disorders. Prebiotics are substances, usually poorly met- abolized polysaccharides and oligosaccharides, that cannot be ingested effectively by the animal. They stimulate the growth of intestinal probiotic bacteria, which can utilize these carbohydrates, thereby promoting health of the organism. Genetic engineering has proven useful for the design of probiotic bacteria that counteract the symptoms of genetic and age-related diseases. Can these bacteria be engineered, through human-promoted accelerative evolution, so that they stimulate their own growth and that of other probiotic bacteria so as to crowd pathogens out of the intestine?
Focal Palmoplantar Keratoderma Caused by an Autosomal Dominant Inherited Mutation in the Desmoglein 1 Gene
Authors: Milingou M. , Wood P. , Masouyé I. , McLean W.H. , Borradori L.
Published: February 2006

Background: Palmoplantar keratodermas (PPK) encompass a large genetically heterogeneous group of diseases associated with hyperkeratosis of the soles and/or palms that occur either isolated or in association with other cutaneous and extracutaneous manifestations. Pathogenic mutations in the desmoglein 1 gene (DSG1) have recently been identified in a subset of patients with the striate type of PPK. Observation: We have identified a patient with a focal non-striated form of PPK associated with discrete troubles of keratinisation at sites exposed to mechanical trauma, such as the knees, ankles or finger knuckles, and with mild nail dystrophy. Genetic analyses disclosed a novel dominantly inherited heterozygous single base insertion in exon 3 of DSG1, 121insT, leading to a premature termination codon. The mutation was also present in the father and in a sister. Conclusion: Our observation extends the spectrum of clinical features associated with genetic defects in DSG1 and provides further evidence that perturbation of desmoglein 1 expression has a critical impact on the integrity of tissues experiencing strong mechanical stress.
Cost of Moderate to Severe Plaque Psoriasis in Germany: A Multicenter Cost-of-Illness Study
Authors: Sohn S. , Schoeffski O. , Prinz J. , Reich K. , Schubert E. , Waldorf K. , Augustin M.
Published: February 2006

Background: There is little information concerning the costs of psoriasis and patients’ quality of life (QoL) in Germany. Objective: To obtain data on the annual costs and QoL(to follow in a further publication) of patients with moderate to severe plaque psoriasis. Methods: Between October 2003 and February 2004, six office-based dermatologists and eight dermatology outpatient departments retrospectively documented cost-of-illness data from a societal cost perspective in 184 patients over a 12-month period. Patients were stratified into three subgroups according to their treatment scheme. Results: Mean total costs amounted to € 6,709 per patient and year. The mean PASI score was 18.2 and PBSA 28.9%. Annual costs were highest with € 8,831 in high-need patients. They also showed the highest PASI score (22.2). Conclusion: Moderate to severe plaque psoriasis is associated with tremendous costs, particularly in patients not adequately controlled by conventional therapies, while the outcomes of patients were unsatisfactory.
Prolonged Clinical Remission of Patients with Severe Pemphigus upon Rapid Removal of Desmoglein-Reactive Autoantibodies by Immunoadsorption
Authors: Eming Rüdiger , Rech Jürgen , Barth Sandra , Kalden Joachim R. , Schuler Gerold , Harrer Thomas , Hertl Michael
Published: February 2006

Background: In pemphigus, loss of epidermal adhesion is induced by binding of circulating autoantibodies to the desmosomal cadherins desmoglein 3 (Dsg3) in pemphigus vulgaris (PV) and desmoglein 1 (Dsg1) in pemphigus foliaceus (PF), respectively. Therapeutic removal of Dsg-reactive autoantibodies by immunoadsorption (IA) has been demonstrated to exert clinical remission of the disease. Objectives: The aim of this intervention study was to evaluate the efficacy and safety of the peptide-based Globaffin® adsorber system in the treatment of severe pemphigus cases. Patients and Methods: We applied IA in 4 PV and 2 PF patients with severe chronic disease resistant to conventional immunosuppressive therapy. IA was performed on 4 consecutive days, representing 1 treatment cycle, followed by a 4-week treatment-free interval. Serum samples for determining serum IgG and anti-Dsg1/Dsg3 IgG autoantibodies were drawn daily before and after IA, respectively. During follow-up, patients were examined carefully, and laboratory parameters were controlled monthly for up to 1 year. Results: IA led to excellent clinical responses. Skin and mucosal lesions cleared almost completely within weeks. One IA cycle reduced anti-Dsg1 and anti-Dsg3 autoantibodies by an average of 50–70% as determined by ELISA. Conclusions: Using the Globaffin adsorber system, IA represents an effective and safe treatment opportunity in severe and therapy-resistant pemphigus.
Public Health Genetics and Social Justice
Authors: Dabrock Peter
Published: February 2006

This article deals with societal challenges of Public Health Genetics and reflects on social justice as its fundamental norm. Accordingly, the first emphasis is put on the difference between the idea of the good and the right. Then the capabilities approach is introduced as the adequate concept of justice in Public Health Genetics. Considering the conflict between respect for autonomy and common welfare in this field of discussion, the author finally presents an ethical grading.
Effects of Prenatal Flutamide on Testicular Development, Androgen Production and Fertility in Rats
Authors: Okur Hamit , Muhtaroglu Sabahattin , Bozkurt Ali , Kontas Olgun , Kücükaydin Nursel , Kücükaydin Mustafa
Published: February 2006

Introduction: To investigate the effects of blocking prenatal androgen with the anti-androgen flutamide on testicular weight (TW), seminiferous tubular diameter (STD), testicular biopsy score (TBS), testicular testosterone (TT), and fertility. Materials and Methods: Ten pregnant Wistar albino rats were injected with flutamide (100 mg/kg) on gestational days 16 and 19. Rats injected with the solvent were used as controls. Male pups from these dams were evaluated for testicular descent on postnatal day 22. The ability of each male to produce offspring was tested when the animals were aged 130 days. The rats were killed when 180 days old, and the testes were removed. Results: Sixteen of the 24 male rats (66.6%) exhibited cryptorchidism (6 unilateral, 10 bilateral) in the flutamide-treated group. Three of the rats with normally descended testicles were fertile, but none of the cryptorchid rats was fertile in flutamide-treated group. The average TW, mean STD, TBS and TT levels of the flutamide-treated rats was significantly lower than in the solvent-injected rats. However, there was no significant difference in these values between descended and undescended testes in flutamide-treated rats. Conclusion: Blocking of prenatal androgen with flutamide interferes with testicular development by inhibiting testicular descent, and also effects testicular morphology and function in both the descended and undescended testes of rats.