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Efficient gene replacement and direct hyphal transformation in Sclerotinia sclerotiorum.
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Homologous recombination is required for gene-targeted procedures such as gene disruption and gene replacement. Ku80 is part of the non-homologous end-joining DNA repair mechanism in many organisms. We identified and disrupted the Ku80 homologue in Sclerotinia sclerotiorum and generated heterokaryon mutants enriched with Ku80-deficient nuclei (ssku80). Sclerotial formation and pathogenicity of ssku80 mutants were normal on tomato fruits. The frequencies of homologous recombination in these strains were much higher than those of the wild type when transformed with a cna1 (encoding calcineurin) replacement construct. We coupled the increase in homologous recombination with a direct BIM-LAB-mediated transformation procedure, which utilizes compressed air to assist the transforming DNA in penetrating fungal hyphae of S. sclerotiorum. We found this method to be efficient and reproducible, and it did not alter the fitness of the mutants. We also demonstrated the first case of direct transformation of sclerotia. Nourseothricin was introduced as a selectable marker in S. sclerotiorum. The tools and procedures described will improve our ability to study gene function in S. sclerotiorum and are most likely to be adaptable for use in other plant pathogens.
| 19,019,000
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Electrochemical detection of neurotransmitters in the gut wall.
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Cells interact with each other by releasing signalling molecules, which can activate or inactivate target cells. In order to understand how coordination results from this communication, accurate measurements of these signalling molecules are prerequisite. Several different techniques exist to monitor and quantify these compounds, including enzymatic and histochemical assays, electrophysiological and optical recordings. However, there has been little use of electrochemical recordings in gastroenterological research, although these are very fast and sensitive. Electrochemical techniques rely on the simple fact that electroactive molecules can be oxidized at a given potential. The currents, elicited by the oxidation, are directly proportional to the concentration of the compound. In the current issue of Neurogastroenterology and Motility, electrochemical detection was successfully applied to measure nitric oxide (NO) from intestinal preparations. Although there are some important specificity, timing and spatial aspects to consider, this direct NO-probing technique is definitely a great asset to the field of gastrointestinal research and advances our understanding of NO signalling in the intestinal wall.
| 19,019,019
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Ink dispersion by sequential contractions in isolated segments of guinea pig ileum and duodenum.
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Conventional preparations that record the effect of contractions on intestinal flow assess primarily net propulsion and not flow events that like mixing are essential for digestion and absorption. Here we recorded the flow of an ink bolus in response to peristaltic contractions of segments of guinea pig intestine. It took three to four contraction/relaxation cycles to disperse a tiny and compact ink bolus throughout the intestinal segment. This was achieved by stretching, propulsion and separation of the bolus into portions during the contraction phase, and return and confluence of the bolus portions during the relaxation phase. As the contraction advanced through the intestinal segment, it generated rapid retrograde flow through its narrow lumen; eddies (flow vortices) formed at upstream shoulder of the contracting segment and dispersed the ink radially. The contraction cleared much of the fluid from the intestinal segment; during the subsequent relaxation, fluid returned into the segment, and carried portions of the ink upstream into the segment where it coalesced with residual portions. The current video observations of luminal flow confirm earlier predictions on luminal flow derived from computations. These flow events are likely an important mechanism through which intestinal contractions promote digestion and absorption.
| 19,019,034
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The relation between epinephrine concentration and the anesthetic effect of lidocaine iontophoresis.
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We assessed the effect of epinephrine at various concentrations on the anesthetic effect during lidocaine iontophoresis. A solution of 2% lidocaine with epinephrine in concentration of 1:80,000, 1:160,000, 1:320,000, 2% lidocaine plain and normal saline control was delivered to the medial antecubital skin for 10 minutes by iontophoresis with 1.0 mA of direct current. The pinprick test and the von Frey test were conducted to evaluate anesthetic effect. Pricking pain using visual analogue scale was significantly lower throughout the entire experiment compared with the baseline values and lasted for 60 minutes in groups with 1:80,000 and 1:160,000 epinephrine. The pressure pain thresholds (PPT) and the touch thresholds (TT) were significantly elevated in groups with 1:80,000 and 1:160,000 epinephrine compared with the baseline values. No significant elevations in the PPT and TT values were observed in the other groups. The present study revealed that the anesthetic effect was significantly enhanced in an epinephrine dose-related manner and the anesthetic effect of 2% lidocaine with 1:160,000 epinephrine was equivalent to the same anesthetic with 1:80,000 epinephrine.
| 19,019,048
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Liquid storage of goat semen in chemically defined extenders.
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The suitability of certain commercial and self-made chemically defined extenders for liquid storage of goat semen was tested and the effects of storage temperatures, dilution rates and sperm washing and pH of extenders on the goat sperm during liquid storage were observed. Semen was collected from nine goat bucks of the Lubei White and Boer breeds using an artificial vagina. Each ejaculate after initial evaluation was diluted with a specific extender, cooled and stored at a desired temperature. Stored semen was evaluated for sperm motility and other parameters every 24 or 48 h of storage. The ranking order of the existing milk- and yolk-free extenders in sustaining goat sperm motility was Androhep > Zorlesco > Beltsville thawing solution > the Tris-glucose medium. The new extender (mZA) which was formulated based on Zorlesco and Androhep was more suitable for goat sperm than Androhep. The mZAP extender with Bovine Serum Albumin (BSA) replaced with polyvinyl alcohol (PVA) worked as efficiently as the mZA in maintaining sperm motility, membrane integrity, acrosome intactness and capacitation status. Goat sperm motility was best maintained at 5 degrees C during liquid preservation, but decreased significantly as the temperature increased. When semen was sixfold diluted, sperm motility was maintained longer (p < 0.05) after centrifugation, but sperm motility did not differ between the centrifuged and non-centrifuged groups when semen was 11-fold diluted. When the extender pH was adjusted from 6.6 to 6.04, the efficiency increased significantly in both Androhep and mZAP. A forward sperm motility of 34% was maintained for 9 days when buck semen was 11-fold diluted and stored at 5 degrees C in mZAP, with pH adjusted to 6.04. It is concluded that for liquid storage of buck semen, the mZA extender was more suitable than other extenders; BSA can be replaced with PVA in mZA; centrifugation to remove seminal plasma can be omitted by adequate dilution; and the storage temperature and pH of extenders affected sperm motility significantly.
| 19,019,073
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Induction of lymphotoxin-alpha by interleukin-12 p40 homodimer, the so-called biologically inactive molecule, but not IL-12 p70.
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Interleukin-12 (IL-12) p70 (p40:p35) is a bioactive cytokine and its biological functions are becoming clear. On the other hand, the IL-12 p40 homodimer (p40(2)) was considered an inactive or inhibitory molecule and its functions are poorly understood. It has been reported that increased expression of lymphotoxin-alpha (Lt-alpha) in the central nervous system as well as in peripheral immune cells is associated with multiple sclerosis and experimental allergic encephalomyelitis. Here we describe that p40(2) induces the expression of Lt-alpha in primary mouse and human microglia, BV-2 microglial cells, splenic macrophages, RAW 264.7 cells and splenic T cells. Interestingly, IL-12 p70 was either unable to induce Lt-alpha or was a very weak inducer of Lt-alpha in these cell types. Consistently, p40(2), but not p70, induced Lt-alpha promoter-driven luciferase activity in microglial cells. Among various stimuli tested, p40(2) emerged as the most potent followed by IL-16, lipopolyaccharide and double-stranded RNA in inducing the activation of Lt-alpha promoter in microglial cells. Furthermore, an increase in Lt-alpha messenger RNA expression by overexpression of p40, but not p35, complementary DNA and induction of Lt-alpha expression by p40(2) in microglia isolated from IL-12p35(-/-) mice confirm that p40, but not p35, is responsible for the induction of Lt-alpha. Finally, by using primary microglia from IUL-12 receptor beta1 deficient (IL-12Rbeta1(-/-)) and IL-12Rbeta2(-/-) mice, we demonstrate that p40(2) induced the expression of Lt-alpha in microglia and macrophages via IL-12Rbeta1, but not IL-12Rbeta2. These studies delineate a novel biological function of p40(2) that is absent in IL-12.
| 19,019,087
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CD4+ CD25(high) Foxp3+ regulatory T cells downregulate human Vdelta2+ T-lymphocyte function triggered by anti-CD3 or phosphoantigen.
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Vdelta2+ T cells, the major circulating T-cell receptor-gammadelta-positive (TCR-gammadelta+) T-cell subset in healthy adults, are involved in immunity against many microbial pathogens including Mycobacterium tuberculosis. Vdelta2+ T cells recognize small phosphorylated metabolites (phosphoantigens), expand in response to whole M. tuberculosis bacilli, and complement the protective functions of CD4+ T cells. CD4+ CD25(high) Foxp3+ T cells (Tregs) comprise 5-10% of circulating T cells and are increased in patients with active tuberculosis (TB). We investigated whether, in addition to their known role in suppressing TCR-alphabeta+ lymphocytes, Tregs suppress Vdelta2+ T-cell function. We found that depletion of Tregs from peripheral blood mononuclear cells increased Vdelta2+ T-cell expansion in response to M. tuberculosis (H37Ra) in tuberculin-skin-test-positive donors. We developed a suppression assay with fluorescence-activated cell sorting-purified Tregs and Vdelta2+ T cells by coincubating the two cell types at a 1 : 1 ratio. The Tregs partially suppressed interferon-gamma secretion by Vdelta2+ T cells in response to anti-CD3 monoclonal antibody plus interleukin-2 (IL-2). In addition, Tregs downregulated the Vdelta2+ T-cell interferon-gamma responses induced by phosphoantigen (BrHPP) and IL-2. Under the latter conditions there was no TCR stimulus for Tregs and therefore IL-2 probably triggered suppressor activity. Addition of purified protein derivative (PPD) increased the suppression of Vdelta2+ T cells, suggesting that PPD activated antigen-specific Tregs. Our study provides evidence that Tregs suppress both anti-CD3 and antigen-driven Vdelta2+ T-cell activation. Antigen-specific Tregs may therefore contribute to the Vdelta2+ T-cell functional deficiencies observed in TB.
| 19,019,089
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Differential effects of tumour necrosis factor-alpha and interleukin-12 on isopentenyl pyrophosphate-stimulated interferon-gamma production by cord blood Vgamma9 T cells.
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Lower numbers of Vgamma9Vdelta2 T cells in cord blood (CB) than in adult peripheral blood (PB), as well as their impaired ability to produce interferon-gamma (IFN-gamma) in response to stimulation, are associated with functional deficiency in the immune system in newborns. In this study, we stimulated CB Vgamma9 T cells with their T-cell receptor-specific ligand, isopentenyl pyrophosphate (IPP), plus exogenous costimulatory cytokines such as interleukin-2 (IL-2), IL-12 and tumour necrosis factor-alpha (TNF-alpha), which are known to play important roles in the activation of PB gammadelta T cells. Our data show that CB Vgamma9 T cells are able to produce IFN-gamma at levels comparable to PB Vgamma9 T cells by the addition of TNF-alpha in the presence of IPP and IL-2; however, under the same culture conditions, IL-12 does not efficiently activate CB Vgamma9 T cells to produce IFN-gamma. The frequency of TNF-alpha receptor II-positive Vgamma9T cells and the expression levels of TNF-alpha receptor II are similar in CB and PB; in contrast, the frequency of IL-12 receptor betaI (IL-12RbetaI) -positive Vgamma9T cells and expression levels of IL-12RbetaI are significantly lower in CB than PB. TNF-alpha but not IL-12 increases the expression of IL-2Rbeta on CB Vgamma9 T cells. These results provide new insights into the role of TNF-alpha in the activation of CB Vgamma9 T cells.
| 19,019,091
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Signalling mechanisms for Toll-like receptor-activated neutrophil exocytosis: key roles for interleukin-1-receptor-associated kinase-4 and phosphatidylinositol 3-kinase but not Toll/IL-1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF).
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Lipopolysaccharide (LPS) stimulates exocytosis in neutrophils. The signalling molecules involved in the regulation of this mechanism are currently unknown. Using neutrophils from interleukin-1-receptor-associated kinase (IRAK)-4- and Toll/IL-1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-deficient mice, we dissected the signalling pathways that control exocytosis. We analysed exocytosis of peroxidase-negative and azurophilic granules by following the mobilization of the beta2-integrin subunit CD11b and myeloperoxidase (MPO)-containing granules, respectively. IRAK-4-null neutrophils showed marked defects in both peroxidase-negative and azurophilic granule exocytosis in response to LPS. In contrast, the exocytic response to LPS of TRIF-deficient neutrophils was not different from that of wild-type cells. No differences were observed in the exocytosis of secretory organelles between IRAK-4-null and wild-type neutrophils when they were stimulated with the phorbol ester phorbol 12-myristate 13-acetate (PMA). Electron microscopy analysis showed that no morphological abnormalities were present in the granules of IRAK-4-deficient neutrophils, suggesting that the lack of exocytic response to LPS is not attributable to developmental abnormalities. Using pharmacological inhibitors, we found that p38 mitogen-activated protein kinase (p38MAPK) is essential for the exocytosis of all neutrophil secretory organelles in response to LPS. Interestingly, we found that phosphatidylinositol 3-kinase (PI3K) is essential for azurophilic granule exocytosis but not for the mobilization of other neutrophil granules in response to LPS. Azurophilic granule exocytosis in response to Listeria monocytogenes was dependent on PI3K but not IRAK-4 activity, suggesting that alternative signalling pathways are activated in IRAK-4-deficient neutrophils exposed to whole bacteria. Our results identified IRAK-4, p38MAPK and PI3K as important regulatory components with different roles in the signalling pathways that control Toll-like receptor ligand-triggered neutrophil exocytosis.
| 19,019,092
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Selective induction of the Notch ligand Jagged-1 in macrophages by soluble egg antigen from Schistosoma mansoni involves ERK signalling.
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Soluble egg antigen (SEA) from the helminth Schistosoma mansoni promotes T helper type 2 (Th2) responses by modulating antigen-presenting cell function. The Jagged/Notch pathway has recently been implicated in driving Th2 development. We show here that SEA rapidly up-regulated mRNA and protein expression of the Notch ligand Jagged-1 in both murine bone marrow-derived macrophages (BMMs) and human monocyte-derived macrophages (HMDMs). Another potential Th2-promoting factor, interleukin (IL)-33, was not transcriptionally induced by SEA in BMMs. Up-regulation of Jagged-1 mRNA by SEA was also apparent in conventional dendritic cells (DCs), although the effect was less striking than in BMMs. Conversely, SEA-pulsed DCs, but not BMMs, promoted IL-4 production upon T-cell activation, suggesting that Jagged-1 induction alone is insufficient for instructing Th2 development. A comparison of the responses initiated in BMMs by SEA and the bacterial endotoxin lipopolysaccharide (LPS) revealed common activation of extracellular signal-regulated kinase-1/2 (ERK-1/2) and p38 phosphorylation, as well as induction of Jagged-1 mRNA. However, only LPS triggered IkappaB degradation, phosphorylation of c-Jun N-terminal kinase (Jnk) and signal transducer and activator of transcription 1 (Stat1) Tyr701, and IL-33 and IL-12p40 mRNA up-regulation. Inducible gene expression was modified by the presence of the macrophage growth factor colony-stimulating factor (CSF)-1, which inhibited Jagged-1 induction by SEA and LPS, but enhanced LPS-induced IL-12p40 expression. Unlike LPS, SEA robustly activated signalling in HEK293 cells expressing either Toll-like receptor 2 (TLR2) or TLR4/MD2. Pharmacological inhibition of the ERK-1/2 pathway impaired SEA- and LPS-inducible Jagged-1 expression in BMMs. Taken together, our data suggest that Jagged-1 is an ERK-dependent target of TLR signalling that has a macrophage-specific function in the response to SEA.
| 19,019,093
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The replication fork trap and termination of chromosome replication.
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Bacteria that have a circular chromosome with a bidirectional DNA replication origin are thought to utilize a 'replication fork trap' to control termination of replication. The fork trap is an arrangement of replication pause sites that ensures that the two replication forks fuse within the terminus region of the chromosome, approximately opposite the origin on the circular map. However, the biological significance of the replication fork trap has been mysterious, as its inactivation has no obvious consequence. Here we review the research that led to the replication fork trap theory, and we aim to integrate several recent findings that contribute towards an understanding of the physiological roles of the replication fork trap. Likely roles include the prevention of over-replication, and the optimization of post-replicative mechanisms of chromosome segregation, such as that involving FtsK in Escherichia coli.
| 19,019,156
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Elevated cerebrospinal fluid levels of prostaglandin E2 and 15-(S)-hydroxyeicosatetraenoic acid in multiple sclerosis.
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To test the hypothesis that the arachodinic acid metabolites prostaglandin E2 (PGE2) and 15-(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in cerebrospinal fluid (CSF) are elevated and reflect neuroinflammation and degenerative changes in multiple sclerosis (MS). We measured PGE2 and 15(S)-HETE concentrations, as well as markers of axonal and astroglial injury in CSF from 46 MS patients, 46 healthy siblings and 50 controls. We found elevated levels of both PGE2 and 15(S)-HETE in MS compared with the control and sibling groups. Siblings had lower PGE2 levels and higher 15(S)-HETE levels than controls. There were no correlations between either PGE2 or 15(S)-HETE and clinical scores of MS severity or biochemical markers of axonal or astroglial injury. These data suggest no direct involvement of PGE2 and 15(S)-HETE in the MS disease process. Rather, the elevated levels reflect a general up-regulation of arachidonic acid metabolism and neuroinflammation.
| 19,019,188
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Preferential allocation to beneficial symbiont with spatial structure maintains mycorrhizal mutualism.
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Mutualisms, beneficial interactions between species, are expected to be unstable because delivery of benefit likely involves fitness costs and selection should favour partners that deliver less benefit. Yet, mutualisms are common and persistent, even in the largely promiscuous associations between plants and soil microorganisms such as arbuscular mycorrhizal fungi. In two different systems, we demonstrate preferential allocation of photosynthate by host plants to the more beneficial of two AM fungal symbionts. This preferential allocation could allow the persistence of the mutualism if it confers sufficient advantage to the beneficial symbiont that it overcomes the cost of mutualism. We find that the beneficial fungus does increase in biomass when the fungi are spatially separated within the root system. However, in well-mixed fungal communities, non-beneficial fungi proliferate as expected from their reduced cost of mutualism. Our findings suggest that preferential allocation within spatially structured microbial communities can stabilize mutualisms between plants and root symbionts.
| 19,019,195
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Light responses in the mouse retina are prolonged upon targeted deletion of the HCN1 channel gene.
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Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels contribute to pacemaker activity, and co-determine the integrative behaviour of neurons and shape their response to synaptic stimulation. Four channel isoforms, HCN1-4, have been described in mammals. Recent studies showed particularly strong expression of HCN1 channels in rods and cones of the rat retina, suggesting that HCN1 channels are involved in the shaping of light responses in both types of photoreceptors. Therefore, the loss of HCN1 channels should lead to pronounced changes in light-induced electrical responses under both scotopic and photopic conditions. This was tested using a mouse transgenic approach. We used immunohistochemistry and patch-clamp recording to study the distribution of HCN1 channels in the mouse retina. HCN1 channels were strongly expressed in rod and cone photoreceptors, as well as in some bipolar, amacrine and ganglion cell types. In electroretinograms (ERGs) from animals in which the HCN1 channel gene had been knocked out, the b-wave amplitudes were unaltered (scotopic conditions) or somewhat reduced (photopic conditions), whereas the duration of both scotopic and photopic ERG responses was strikingly prolonged. Our data suggest that in visual information processing, shortening and shaping of light responses by activation of HCN1 at the level of the photoreceptors is an important step in both scotopic and photopic pathways.
| 19,019,198
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Visual mismatch negativity for changes in orientation--a sensory memory-dependent response.
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It remains unclear whether the mismatch negativity of event-related potentials (ERPs) in vision resembles its auditory counterpart in terms of memory relatedness. We recorded ERPs to visual bars in adult humans engaged in an auditory task. In one condition, a bar ('standard') repeated at 400- or 1100-ms non-stimulated intervals was rarely (P = 0.1) replaced by another bar of a different orientation ('deviant'). In the other condition (400-ms intervals), the occurrences of the standards were replaced by 10 (P = 0.1 each) bars of different orientations, including that of the deviant ('control-deviant'). Deviants shifted ERPs towards negative polarity relative to standards in occipital electrodes and towards positive polarity in frontal electrodes at 185-205 ms post-stimulus but only when 400-ms non-stimulated intervals were applied. Furthermore, the shift existed even relative to ERPs to control-deviants. The findings suggest that, as in audition, vision supports the detection of voluntarily unattended changes per se within the constraints of sensory memory. The findings also pave the way for the future exploration of both intact and impaired memory-based visual processing and memory capacity.
| 19,019,200
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Role of spinal 5-HT2 receptor subtypes in quipazine-induced hindlimb movements after a low-thoracic spinal cord transection.
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A role of serotonin receptors (5-HTRs) in spinal rhythmogenesis has been proposed several years ago based mainly upon data showing that bath-applied 5-HT could elicit locomotor-like rhythms in in vitro isolated spinal cord preparations. Such a role was partially confirmed in vivo after revealing that systemically administered 5-HTR(2) agonists, such as quipazine, could induce some locomotor-like movements (LM) in completely spinal cord-transected (Tx) rodents. However, given the limited binding selectivity of currently available 5-HTR(2) agonists, it has remained difficult to determine clearly if one receptor subtype is specifically associated with LM induction. In situ hybridization, data using tissues from L1-L2 spinal cord segments, where critical locomotor network elements have been identified in mice, revealed greater 5-HTR(2A) mRNA levels in low-thoracic Tx than non-Tx animals. This expression level remained elevated for several days, specifically in the lateral intermediate zone, where peak values were detected at 1 week post-Tx and returned to normal at 3 weeks post-Tx. Behavioral and kinematic analyses revealed quipazine-induced LM in 1-week Tx mice either non-pretreated or pretreated with selective 5-HTR(2B) and/or 5-HTR(2C) antagonists. In contrast, LM completely failed to be induced by quipazine in animals pretreated with selective 5-HTR(2A) antagonists. Altogether, these results provide strong evidence suggesting that 5-HTR(2A) are specifically associated with spinal locomotor network activation and LM generation induced by quipazine in Tx animals. These findings may contribute to design drug treatments aimed at promoting locomotor function recovery in chronic spinal cord-injured patients.
| 19,019,202
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Genome-wide survey of prokaryotic serine proteases: analysis of distribution and domain architectures of five serine protease families in prokaryotes.
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Serine proteases are one of the most abundant groups of proteolytic enzymes found in all the kingdoms of life. While studies have established significant roles for many prokaryotic serine proteases in several physiological processes, such as those associated with metabolism, cell signalling, defense response and development, functional associations for a large number of prokaryotic serine proteases are relatively unknown. Current analysis is aimed at understanding the distribution and probable biological functions of the select serine proteases encoded in representative prokaryotic organisms. A total of 966 putative serine proteases, belonging to five families, were identified in the 91 prokaryotic genomes using various sensitive sequence search techniques. Phylogenetic analysis reveals several species-specific clusters of serine proteases suggesting their possible involvement in organism-specific functions. Atypical phylogenetic associations suggest an important role for lateral gene transfer events in facilitating the widespread distribution of the serine proteases in the prokaryotes. Domain organisations of the gene products were analysed, employing sensitive sequence search methods, to infer their probable biological functions. Trypsin, subtilisin and Lon protease families account for a significant proportion of the multi-domain representatives, while the D-Ala-D-Ala carboxypeptidase and the Clp protease families are mostly single-domain polypeptides in prokaryotes. Regulatory domains for protein interaction, signalling, pathogenesis, cell adhesion etc. were found tethered to the serine protease domains. Some domain combinations (such as S1-PDZ; LON-AAA-S16 etc.) were found to be widespread in the prokaryotic lineages suggesting a critical role in prokaryotes. Domain architectures of many serine proteases and their homologues identified in prokaryotes are very different from those observed in eukaryotes, suggesting distinct roles for serine proteases in prokaryotes. Many domain combinations were found unique to specific prokaryotic species, suggesting functional specialisation in various cellular and physiological processes.
| 19,019,219
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Development of a fluorescence-based method for monitoring glucose catabolism and its potential use in a biomass hydrolysis assay.
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The availability and low cost of lignocellulosic biomass has caused tremendous interest in the bioconversion of this feedstock into liquid fuels. One measure of the economic viability of the bioconversion process is the ease with which a particular feedstock is hydrolyzed and fermented. Because monitoring the analytes in hydrolysis and fermentation experiments is time consuming, the objective of this study was to develop a rapid fluorescence-based method to monitor sugar production during biomass hydrolysis, and to demonstrate its application in monitoring corn stover hydrolysis. Hydrolytic enzymes were used in conjunction with Escherichia coli strain CA8404 (a hexose and pentose-consuming strain), modified to produce green fluorescent protein (GFP). The combination of hydrolytic enzymes and a sugar-consuming organism minimizes feedback inhibition of the hydrolytic enzymes. We observed that culture growth rate as measured by change in culture turbidity is proportional to GFP fluorescence and total growth and growth rate depends upon how much sugar is present at inoculation. Furthermore, it was possible to monitor the course of enzymatic hydrolysis in near real-time, though there are instrumentation challenges in doing this. We found that instantaneous fluorescence is proportional to the bacterial growth rate. As growth rate is limited by the availability of sugar, the integral of fluorescence is proportional to the amount of sugar consumed by the microbe. We demonstrate that corn stover varieties can be differentiated based on sugar yields in enzymatic hydrolysis reactions using post-hydrolysis fluorescence measurements. Also, it may be possible to monitor fluorescence in real-time during hydrolysis to compare different hydrolysis protocols.
| 19,019,221
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The inv dup (15) or idic (15) syndrome (Tetrasomy 15q).
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The inv dup(15) or idic(15) syndrome displays distinctive clinical findings represented by early central hypotonia, developmental delay and intellectual disability, epilepsy, and autistic behaviour. Incidence at birth is estimated at 1 in 30,000 with a sex ratio of almost 1:1. Developmental delay and intellectual disability affect all individuals with inv dup(15) and are usually moderate to profound. Expressive language is absent or very poor and often echolalic. Comprehension is very limited and contextual. Intention to communicate is absent or very limited. The distinct behavioral disorder shown by children and adolescents has been widely described as autistic or autistic-like. Epilepsy with a wide variety of seizure types can occur in these individuals, with onset between 6 months and 9 years. Various EEG abnormalities have been described. Muscle hypotonia is observed in almost all individuals, associated, in most of them, with joint hyperextensibility and drooling. Facial dysmorphic features are absent or subtle, and major malformations are rare. Feeding difficulties are reported in the newborn period.Chromosome region 15q11q13, known for its instability, is highly susceptible to clinically relevant genomic rearrangements, such as supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) results in tetrasomy 15p and partial tetrasomy 15q. The large rearrangements, containing the Prader-Willi/Angelman syndrome critical region (PWS/ASCR), are responsible for the inv dup(15) or idic(15) syndrome. Diagnosis is achieved by standard cytogenetics and FISH analysis, using probes both from proximal chromosome 15 and from the PWS/ASCR. Microsatellite analysis on parental DNA or methylation analysis on the proband DNA, are also needed to detect the parent-of-origin of the inv dup(15) chromosome. Array CGH has been shown to provide a powerful approach for identifying and detecting the extent of the duplication. The possible occurrence of double supernumerary isodicentric chromosomes derived from chromosome 15, resulting in partial hexasomy of the maternally inherited PWS/ASCR, should be considered in the differential diagnosis. Large idic(15) are nearly always sporadic. Antenatal diagnosis is possible. Management of inv dup(15) includes a comprehensive neurophysiologic and developmental evaluation. Survival is not significantly reduced.
| 19,019,226
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Comparison of quality control for trauma management between Western and Eastern European trauma center.
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Quality control of trauma care is essential to define the effectiveness of trauma center and trauma system. To identify the troublesome issues of the system is the first step for validation of the focused customized solutions. This is a comparative study of two level I trauma centers in Italy and Romania and it has been designed to give an overview of the entire trauma care program adopted in these two countries. This study was aimed to use the results as the basis for recommending and planning changes in the two trauma systems for a better trauma care. We retrospectively reviewed a total of 182 major trauma patients treated in the two hospitals included in the study, between January and June 2002. Every case was analyzed according to the recommended minimal audit filters for trauma quality assurance by The American College of Surgeons Committee on Trauma (ACSCOT). Satisfactory yields have been reached in both centers for the management of head and abdominal trauma, airway management, Emergency Department length of stay and early diagnosis and treatment. The main significant differences between the two centers were in the patients' transfers, the leadership of trauma team and the patients' outcome. The main concerns have been in the surgical treatment of fractures, the outcome and the lacking of documentation. The analyzed hospitals are classified as Level I trauma center and are within the group of the highest quality level centers in their own countries. Nevertheless, both of them experience major lacks and for few audit filters do not reach the mmum standard requirements of ACS Audit Filters. The differences between the western and the eastern European center were slight. The parameters not reaching the minimum requirements are probably occurring even more often in suburban settings.
| 19,019,230
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Dispensary level pilot implementation of rapid diagnostic tests: an evaluation of RDT acceptance and usage by providers and patients--Tanzania, 2005.
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Malaria rapid diagnostic tests (RDTs) may assist in diagnosis, improve prescribing practices and reduce potential drug resistance development. Without understanding operational issues or acceptance and usage by providers and patients, the costs of these tests may not be justified. To evaluate the impact of RDTs on prescribing behaviours, assess prescribers' and patients' perceptions, and identify operational issues during implementation. Baseline data were collected at six Tanzanian public dispensaries. RDTs were implemented for eight weeks and data collected on frequency of RDT use, results, malaria diagnoses and the prescription of antimalarials. Patients referred for RDTs completed a standardised exit interview. Qualitative methods assessed attitudes toward and satisfaction with RDTs, perceptions about the test and operational issues related to implementation. Of 595 patients at baseline, 200 (33%) were diagnosed clinically with malaria but had a negative RDT. Among the 2519 RDTs performed during implementation, 289 (11.5%) had a negative result and antimalarials prescribed. The proportion of "over-prescriptions" at baseline was 54.8% (198/365). At weeks four and eight this decreased to 16.1% (27/168) and 16.4% (42/256) respectively.A total of 355 patient or parent/caregiver and 21 prescriber individual interviews and 12 focus group discussions (FGDs) were conducted. Patients, caregivers and providers trusted RDT results, agreed that use of RDTs was feasible at dispensary level, and perceived that RDTs improved clinical diagnosis. Negative concerns included community suspicion and fear that RDTs were HIV tests, the need for additional supervision in interpreting the results, and increased work loads without added compensation. Overprescriptions decreased over the study period. There was a high degree of patient/caregiver and provider acceptance of and satisfaction with RDTs. Implementation should include community education, sufficient levels of training and supervision and consideration of the need for additional staff.
| 19,019,233
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Gamma probes and their use in tumor detection in colorectal cancer.
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The purpose of this article is to summarize the role of gamma probes in intraoperative tumor detection in patients with colorectal cancer (CRC), as well as provide basic information about the physical and practical characteristics of the gamma probes, and the radiopharmaceuticals used in gamma probe tumor detection. In a significant portion of these studies, radiolabeled monoclonal antibodies (Mabs), particularly 125I labeled B72.3 Mab that binds to the TAG-72 antigen, have been used to target tumor. Studies have reported that intraoperative gamma probe radioimmunodetection helps surgeons to localize primary tumor, clearly delineate its resection margins and provide immediate intraoperative staging. Studies also have emphasized the value of intraoperative gamma probe radioimmunodetection in defining the extent of tumor recurrence and finding sub-clinical occult tumors which would assure the surgeons that they have completely removed the tumor burden. However, intraoperative gamma probe radioimmunodetection has not been widely adapted among surgeons because of some constraints associated with this technique. The main difficulty with this technique is the long period of waiting time between Mab injection and surgery. The technique is also laborious and costly. In recent years, Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) use in gamma probe tumor detection surgery has renewed interest among surgeons. Preliminary studies during surgery have demonstrated that use of FDG in gamma probe tumor detection during surgery is feasible and useful.
| 19,019,238
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A second generation genetic map for rainbow trout (Oncorhynchus mykiss).
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Genetic maps characterizing the inheritance patterns of traits and markers have been developed for a wide range of species and used to study questions in biomedicine, agriculture, ecology and evolutionary biology. The status of rainbow trout genetic maps has progressed significantly over the last decade due to interest in this species in aquaculture and sport fisheries, and as a model research organism for studies related to carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. We constructed a second generation genetic map for rainbow trout using microsatellite markers to facilitate the identification of quantitative trait loci for traits affecting aquaculture production efficiency and the extraction of comparative information from the genome sequences of model fish species. A genetic map ordering 1124 microsatellite loci spanning a sex-averaged distance of 2927.10 cM (Kosambi) and having 2.6 cM resolution was constructed by genotyping 10 parents and 150 offspring from the National Center for Cool and Cold Water Aquaculture (NCCCWA) reference family mapping panel. Microsatellite markers, representing pairs of loci resulting from an evolutionarily recent whole genome duplication event, identified 180 duplicated regions within the rainbow trout genome. Microsatellites associated with genes through expressed sequence tags or bacterial artificial chromosomes produced comparative assignments with tetraodon, zebrafish, fugu, and medaka resulting in assignments of homology for 199 loci. The second generation NCCCWA genetic map provides an increased microsatellite marker density and quantifies differences in recombination rate between the sexes in outbred populations. It has the potential to integrate with cytogenetic and other physical maps, identifying paralogous regions of the rainbow trout genome arising from the evolutionarily recent genome duplication event, and anchoring a comparative map with the zebrafish, medaka, tetraodon, and fugu genomes. This resource will facilitate the identification of genes affecting traits of interest through fine mapping and positional cloning of candidate genes.
| 19,019,240
|
High prevalence of HIV infection among homeless and street-involved Aboriginal youth in a Canadian setting.
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Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth. We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline, 15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection (odds ratio = 2.87, 95%CI: 1.02-8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants (p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention among Aboriginal young people are urgently required.
| 19,019,253
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The relationship between population growth and elderly suicide rates: a cross-national study.
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Elderly suicide rates are associated with the elderly population size, the proportion of elderly in the general population and the elderly dependency ratio. A cross-national study examining the "a priori" hypothesis that the relationship between elderly suicide rates and average annual population growth rates would be curvilinear (U-shaped curve) fitting the quadratic equation y = a + bx + cx2 (where y is the elderly suicide rate, x is the population growth rate and a, b and c are constants) was conducted using data from the World Health Organization and the United Nations. There was a significant curvilinear (U-shaped curve) relationship between elderly suicide rates and average annual population growth rates fitting the above quadratic equation. A theoretical model with three sequential stages incorporating population growth, the elderly population size, the proportion of elderly in the general population, life expectancy and birth rates was proposed to explain the findings. Caution should be exercised in the application of this model because of the cross-sectional and ecological study design whereby the findings are subject to ecological fallacy and require rigourous testing in within-country longitudinal studies over time.
| 19,019,260
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Subjective memory impairment in a rural population with low education in the Amazon rainforest: an exploratory study.
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The high prevalence of subjective memory impairment (SMI) in the elderly living in developed countries may be partly dependent on greater demand placed on them by new technologies. As part of a comprehensive study on cognitive impairment in a population living in the Amazon rainforest, we evaluated the prevalence of SMI and investigated the features associated with it. We evaluated 163 subjects (82 females) with a mean age of 62.3 years (50-94 years), 110 of whom were illiterate, using the answer to a single question "Do you have memory problems?" to classify them into groups with or without SMI. The assessment involved application of the Mini-mental State Examination (MMSE), delayed recall from the Brief Cognitive Battery designed for the evaluation of low educated and illiterate individuals, the Patient Questionnaire (PQ) of the Primary Care Evaluation of Mental Disorders (PRIME-MD), and the Happiness Analogical Scale. A very high prevalence of SMI (70%) was observed, exceeding rates reported by similar studies conducted in developed countries. SMI was more frequent in women, whereas age and education did not impact on prevalence. Subjects with SMI had significantly more somatic and psychiatric symptoms on the PQ, as well as lower means on the MMSE, but not on the delayed recall test. Multiple logistic regressions showed that the most important factor associated with the presence of SMI was a high score on the PQ (OR: 3.84, p = 0.011). Psychological and somatic symptoms may be the principal cause of SMI in this population.
| 19,019,263
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ALS drug development: reflections from the past and a way forward.
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Tremendous advances in our understanding of pathogenesis of amyotrophic lateral sclerosis (ALS) have provided a rich pipeline of drugs for clinical trialists. At least 32 unique compounds have been tested. Nevertheless, riluzole is currently the only treatment that prolongs survival. We present a critical overview of past clinical trials, how therapies are selected for testing in people, challenges with ALS clinical trial design and conduct, and ways to best move forward.
| 19,019,302
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Idiopathic inflammatory myopathies: current and future therapeutic options.
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Idiopathic inflammatory myopathies (notably polymyositis and dermatomyositis) are relatively uncommon diseases with a heterogeneous clinical presentation. Only a few randomized, double-blind, placebo-controlled trials have been performed, measures to assess outcome and response to treatment have to be validated. Initial treatment options of first choice are corticosteroids, although rarely tested in randomized, controlled trials. Unfortunately, not all patients respond to them and many develop undesirable side effects. Thus, second line agents or immunosuppressants given in combination with corticosteroids are used. For dermatomyositis/polymyositis, combination with azathioprine is most common. In case this combination is not sufficient or applicable, intravenous immunoglobulins are justified. Alternative or stronger immunosuppressants, such as cyclosporine A, cyclophosphamide, methotrexate, or mycophenolate are also used. There are no defined guidelines or best treatment protocols agreed on internationally; therefore, the medical approach must be individualized based on the severity of clinical presentation, disease duration, presence of extramuscular features, and prior therapy and contraindications to particular agents. Approximately 25% of patients are nonresponders and continue to experience clinical relapses. Those are candidates for alternative treatment options and experimental therapies. New immunoselective therapies directed toward cytokine modulation, immune cell migration, or modification of certain immune subsets (B- and T-cells) are a promising avenue of research and clinical application. Possible future therapeutic options are presented and discussed.
| 19,019,306
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Therapeutic approaches in glycogen storage disease type II/Pompe Disease.
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Glycogen storage disease type II (GSDII)/Pompe disease is an autosomal recessive multi-system disorder due to a deficiency of the glycogen-degrading lysosomal enzyme, acid alpha-glucosidase. Without adequate levels of alpha-glucosidase, there is a progressive accumulation of glycogen inside the lysosome, resulting in lysosomal expansion in many tissues, although the major clinical manifestations are seen in cardiac and skeletal muscle. Pompe disease presents as a continuum of clinical phenotypes. In the most severe cases, disease onset occurs in infancy and death results from cardiac and respiratory failure within the first 1 or 2 years of life. In the milder late-onset forms, cardiac muscle is spared and muscle weakness is the primary symptom. Weakness of respiratory muscles is the major cause of mortality in these cases. Enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme; Genzyme Corp., Framingham, MA) is now available for all forms of glycogen storage disease type II. ERT has shown remarkable success in reversing pathology in cardiac muscle and extending life expectancy in infantile patients. However, skeletal muscle has proven to be a more challenging target for ERT. Although ERT is less effective in skeletal muscle than was hoped for, the lessons learned from both clinical and pre-clinical ERT studies have greatly expanded our understanding of the pathogenesis of the disease. A combination of fundamental studies and clinical follow-up, as well as exploration of other therapies, is necessary to take treatment for glycogen storage disease type II to the next level.
| 19,019,308
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Gender differences in global-local perception? Evidence from orientation and shape judgments.
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Direct examinations of gender differences in global-local processing are sparse, and the results are inconsistent. We examined this issue with a visuospatial judgment task and with a shape judgment task. Women and men were presented with hierarchical stimuli that varied in closure (open or closed shape) or in line orientation (oblique or horizontal/vertical) at the global or local level. The task was to classify the stimuli on the basis of the variation at the global level (global classification) or at the local level (local classification). Women's classification by closure (global or local) was more accurate than men's for stimuli that varied in closure on both levels, suggesting a female advantage in discriminating shape properties. No gender differences were observed in global-local processing bias. Women and men exhibited a global advantage, and they did not differ in their speed of global or local classification, with only one exception. Women were slower than men in local classification by orientation when the to-be-classified lines were embedded in a global line with a different orientation. This finding suggests that women are more distracted than men by misleading global oriented context when performing local orientation judgments, perhaps because women and men differ in their ability to use cognitive schemes to compensate for the distracting effects of the global context. Our findings further suggest that whether or not gender differences arise depends not only on the nature of the visual task but also on the visual context.
| 19,019,319
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Nanofluids droplets evaporation kinetics and wetting dynamics on rough heated substrates.
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The influence of aluminium nanoparticles on the evaporation and wetting dynamics of ethanol sessile droplets on a heated PTFE surface is investigated experimentally. The experimental technique uses a goniometer to measure the evolution in time of the shape of the droplets (contact angle, base diameter and volume). The evaporation rate is deduced from the measurements of the evolution of volume in time. During the "pinning" phase and contrary to what is expected, the presence of nanoparticles leads to a reduction of the evaporation rate compared to the base fluid. It is found that the deposition of nanoparticles into the triple contact line wedge during the evaporation of the droplet causes a greater pinning time for nanofluid droplets. The overall evaporation time for base fluid droplets is found to be longer than for nanofluid ones. The wetting dynamics of the droplets throughout the evaporation process shows major influence of nanoparticles. Depinning contact angles tend to be larger for nanofluid droplets than for base liquid ones. Over a range of imposed substrate temperatures, no effect on the nanofluids depinning contact angle is observed. The alteration of contact line behavior as well as wettability can have important implications in a wide range of applications, e.g. two phase boiling heat transfer [Kim, S. J. et al., Appl. Phys. Lett., 2006, 89, 153107].
| 19,019,321
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The recommendation for bed rest in the setting of arrested preterm labor and premature rupture of membranes.
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The objective of the study was to estimate practice patterns regarding bed rest in women with preterm premature rupture of membranes (PPROM) and arrested preterm labor. This was a mail-based survey of all Society for Maternal-Fetal Medicine members in the United States asking whether they would recommend bed rest in the setting of arrested preterm labor or PPROM at 26 weeks. Bed rest was defined as no more than 1-2 hours per day out of bed, with permitted activities including bathroom use, bathing, and brief ambulation inside the home/hospital. Seventy-one percent and 87% would recommend bed rest for women with cervical dilation and arrested preterm labor and women with PPROM, respectively, even though the majority believed bed rest was associated with minimal or no benefit. Female sex, nonacademic practice, and practice location in the South or West were independently associated with the recommendation for bed rest. Despite the belief that bed rest is associated with minimal or no benefit, most maternal-fetal medicine specialists recommend bed rest for arrested preterm labor and PPROM. Randomized, prospective trials are needed to evaluate the efficacy of bed rest in these settings.
| 19,019,329
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Postmenopausal hormone therapy and incident urinary incontinence in middle-aged women.
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The objective of the study was to examine the association of hormone therapy with incident urinary incontinence (UI) in postmenopausal women aged 37-54 years in the Nurses' Health Study II. Participants reported use of hormone therapy, including hormone type, on biennial questionnaires from 1989 to 2001. Among 7341 postmenopausal women reporting no UI in 2001, we identified 1026 women who developed UI at least monthly between 2001 and 2003. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Women currently using hormone therapy had 1.39-fold (95% CI, 1.16-1.67) increased odds of incident UI, compared with women who never used hormone therapy. ORs were similar in current users of oral estrogen alone (OR, 1.35, 95% CI, 1.03-1.78) and oral estrogen with progestin (OR, 1.37, 95% CI, 1.13-1.67). These findings suggest an increased risk of UI associated with use of postmenopausal hormone therapy in younger postmenopausal women.
| 19,019,333
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Activity of jaw muscles in unilateral cross-bite without mandibular shift.
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To evaluate and compare electromyographic activity of jaw muscles at rest and during maximal voluntary clenching in maximal intercuspation between growing individuals with unilateral posterior cross-bite without functional mandibular lateral shift during closure and matched individuals with normal occlusion. These findings may help elucidate the impact of this occlusal condition on jaw muscle function and the therapeutic implications. 30 growing children (10-12 years) with unilateral cross-bite without functional mandibular lateral shift during closure (cases) and 30 age- and sex-matched children with normal occlusion (controls) were consecutively selected applying highly restrictive criteria. Electromyographic activity coming from the areas of right and left anterior temporalis, posterior temporalis, masseter, and supra-hyoid muscles was evaluated at rest and during clenching. The asymmetry index was calculated for each muscle area to quantify the degree of asymmetry between sides. The masseter/anterior temporalis ratio during clenching was also recorded. No significant differences were found between groups at rest. During clenching, activity of the cross-bite side masseter area was significantly lower in cases versus controls but no difference was found between cross-bite and non-cross-bite sides of this muscle. Unilateral posterior cross-bite without functional mandibular lateral shift is associated with a lower electromyographic activity of masseter muscle area of the cross-bite side during maximal clenching in maximal intercuspation, compared to the children with normal occlusion. This result could suggest a functional adaptation that should be carefully considered. Long-term studies are needed to determine future repercussions and to evaluate the benefit of an early treatment.
| 19,019,348
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Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides.
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The aim of this study was to determine optimum biomarkers to detect fetal exposure to environmental pesticides by the simultaneous analysis of maternal (hair and blood) and infant (cord blood, infant hair or meconium) matrices and to determine if a combination of these biomarkers will further increase the detection rate. Pregnant women were prospectively recruited from an agricultural site in the Philippines with substantial use at home and in the farm of the following pesticides: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin. Maternal hair and blood were obtained at midgestation and at delivery and infant hair, cord blood and meconium were obtained after birth. All samples were analyzed by gas chromatography/mass spectrometry (GC/MS) for the above pesticides and some of their metabolites. A total of 598 mother/infant dyads were included in this report. The highest rates of pesticide exposure were detected in meconium (23.2% to propoxur, 2.0% to pretilachlor, 1.7% to cypermethrin, 0.8% to cyfluthrin, 0.7% to 1,1,1-trichloro-2,2-bis, p-chlorophenylethane (DDT) and 0.3% to malathion and bioallethrin) and in maternal hair (21.6% to propoxur, 14.5% to bioallethrin, 1.3% to malathion, 0.8% to DDT, 0.3% to chlorpyrifos and 0.2% to pretilachlor). Combined analysis of maternal hair and meconium increased detection rate further to 38.5% for propoxur and to 16.7% for pyrethroids. Pesticide metabolites were rarely found in any of the analyzed matrices. There is significant exposure of the pregnant woman and her fetus to pesticides, particularly to the home pesticides, propoxur and pyrethroids. Analysis of meconium for pesticides was the single most sensitive measure of exposure. However, combined analysis of maternal hair and meconium significantly increased the detection rate. A major advantage of analyzing maternal hair is that prenatal pesticide exposure in the mother can be detected and intervention measures can be initiated to minimize further exposure of the fetus to pesticides.
| 19,019,354
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Effect of 1-month war in Lebanon on sex ratio.
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Our study showed no effect of 33-day war in Lebanon on sex ratio. More research is needed to explore other modifying factors for a better understanding of the complex effect of wars on sex ratio changes.
| 19,019,356
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Wave intensity amplification and attenuation in non-linear flow: implications for the calculation of local reflection coefficients.
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Local reflection coefficients (R) provide important insights into the influence of wave reflection on vascular haemodynamics. Using the relatively new time-domain method of wave intensity analysis, R has been calculated as the ratio of the peak intensities (R(PI)) or areas (R(CI)) of incident and reflected waves, or as the ratio of the changes in pressure caused by these waves (R(DeltaP)). While these methods have not yet been compared, it is likely that elastic non-linearities present in large arteries will lead to changes in the size of waves as they propagate and thus errors in the calculation of R(PI) and R(CI). To test this proposition, R(PI), R(CI) and R(DeltaP) were calculated in a non-linear computer model of a single vessel with various degrees of elastic non-linearity, determined by wave speed and pulse amplitude (DeltaP(+)), and a terminal admittance to produce reflections. Results obtained from this model demonstrated that under linear flow conditions (i.e. as DeltaP(+)-->0), R(DeltaP) is equivalent to the square-root of R(PI) and R(CI) (denoted by R(PI)(p) and R(CI)(p)). However for non-linear flow, pressure-increasing (compression) waves undergo amplification while pressure-reducing (expansion) waves undergo attenuation as they propagate. Consequently, significant errors related to the degree of elastic non-linearity arise in R(PI) and R(CI), and also R(PI)(p) and R(CI)(p), with greater errors associated with larger reflections. Conversely, R(Delta)(P) is unaffected by the degree of non-linearity and is thus more accurate than R(PI) and R(CI).
| 19,019,371
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Influence of surface penetration on measured fluid force on a hand model.
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The purpose of this study was to quantify the effect of wave drag due to surface penetration on drag and lift forces (C(d) and C(l)) acting on a hand model. The values of C(d) and C(l) had been acquired to gain the hydrodynamic characteristics of the swimmer's hand and predict force on the swimmer's hand. These values have also been used to benchmark computational fluid dynamics analysis. Because the previous studies used a hand/forearm model which penetrated the water's surface, the values of C(d) and C(l) include the effect of the surface wave on the model. Wave formation causes pressure differences between the frontal and rear sides of a surface-penetrating model as a result of depressions and elevations in the water's surface. This may be considered as wave drag due to surface penetration. Fluid forces due to wave drag on the forearm should not be included in the measured C(d) and C(l) of a swimmer's hand that does not sweep near the water's surface. Two hand/forearm models are compared, one with the hand rigidly connected to the forearm. The other model was constructed to isolate the fluid forces acting on the hand from the influence of wave drag on the forearm. The measurements showed that the effect of wave drag on the hand model caused large increases in the values of C(d), up to 46-98% with lesser increases in C(l) of 2-12% depending on the hand orientation. The present study provides an improved method to determine the values of C(d) and C(l) that eliminates the effect of wave drag on a hand/forearm model by isolating the measurement of fluid forces on the forearm of the hand/forearm model in order to separately acquire the forces on the hand.
| 19,019,377
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Analysis of industrial contaminants in indoor air: part 1. Volatile organic compounds, carbonyl compounds, polycyclic aromatic hydrocarbons and polychlorinated biphenyls.
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This article reviews recent literature on the analysis of industrial contaminants in indoor air in the framework of the REACH project, which is mainly intended to improve protection of human health and the environment from the risks of more than 34 millions of chemical substances. Industrial pollutants that can be found in indoor air may be of very different types and origin, belonging to the volatile organic compounds (VOCs) and semivolatile organic compounds (SVOCs) categories. Several compounds have been classified into the priority organic pollutants (POPs) class such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/PCDFs) and related polychlorinated compounds, and polycyclic aromatic hydrocarbons (PAHs). Many of these compounds are partially associated to the air gas phase, but also to the suspended particulate matter. Furthermore, settled dust can act as a concentrator for the less volatile pollutants and has become a matrix of great concern for indoors contamination. Main literature considered in this review are papers from the last 10 years reporting analytical developments and applications regarding VOCs, aldehydes and other carbonyls, PCBs, PCDDs, PCDFs, and PAHs in the indoor environment. Sample collection and pretreatment, analyte extraction, clean-up procedures, determination techniques, performance results, as well as compound concentrations in indoor samples, are summarized and discussed. Emergent contaminants and pesticides related to the industrial development that can be found in indoor air are reviewed in a second part in this volume.
| 19,019,381
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Nitric oxide stimulates embryonic somatotroph differentiation and growth hormone mRNA and protein expression through a cyclic guanosine monophosphate-independent mechanism.
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In the pituitary gland, NO is locally synthesized by gonadotroph and folliculo-stellate cells. Many reports have shown that NO can modulate the growth hormone (GH) secretion. However, its role on mice embryo GH regulation remains unclear. In addition, it is unknown whether the regulation is associated with the proliferation of pituitary cells. In this study, we have investigated the regulatory effects of NO on somatotroph differentiation, proliferation and GH mRNA and protein expression using primary cell cultures of mice fetal pituitaries (embryonic days 16.5, ED 16.5). Our results show that incubation of pituitary cells in the presence of sodium nitroprusside (SNP; 1mM), a NO donor, for 4.5h resulted in a significant increase in GH mRNA and protein expression (P<0.05) and the stimulation of SNP can be inhibited by hemoglobin, a NO scavenger. But the addition of cyclic guanosine monophosphate (cGMP; 3.0mM), the second messenger of multiple NO actions cannot influence GH mRNA and protein expression. The cyclic nucleotide cellular efflux pumps existed in the pituitary cells can transport the majority of de novo-produced cGMP and effectively block cGMP accumulation. For maintaining intracellular concentration of cGMP, probenecid (0.5mM), a blocker of cGMP efflux pump, combined with cGMP (3.0mM) was used to treat the pituitary cells. This also cannot influence GH mRNA and protein expression. In addition, the ratio of GH-positive cells is increased significantly after the stimulation of SNP (P<0.05). However, SNP cannot modulate the pituitary cell proliferation. From these results we conclude that NO can increase GH mRNA and protein expression in fetal pituitary cells and cGMP is not involved in this hormonal regulation. Stimulation of NO on the somatotroph differentiation does not occur due to pituitary cell proliferation.
| 19,019,400
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Insights into adenovirus host cell interactions from structural studies.
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Human adenoviruses cause a significant number of acute respiratory, enteric and ocular infections, however they have also served as useful model systems for uncovering fundamental aspects of cell and molecular biology. In addition, replication-defective forms of adenovirus are being used in gene transfer and vaccine clinical trials. Over the past decade, steady advances in structural biology techniques have helped reveal important insights into the earliest events in the adenovirus life cycle as well as virus interactions with components of the host immune system. This review highlights the continuing use of structure-based approaches to uncover the molecular features of adenovirus-host interactions.
| 19,019,405
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Does chest CT matter in the staging of GTN?
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The term gestational trophoblastic neoplasia (GTN) encompasses a variety of uncommon neoplastic conditions arising from the placental trophoblast. Staging of GTN using the FIGO 2000 system divides patients into low and high risk groups and treatment of these patients depends on the risk score achieved. Chest x-ray (CXR) is recommended to assess lung metastases; however the significance of lung metastases seen on computed tomography (CT) scan of the chest is uncertain. The aim of this study is to determine whether or not CT scan significantly influences outcome of patients with GTN in terms of a need to change to second line chemotherapy or time to remission. 96 patients with low risk metastatic GTN and 102 patients with low risk non-metastatic GTN who had been staged at Weston Park Hospital, Sheffield were identified. Staging according to the FIGO 2000 system was retrospectively calculated to assess what impact using CT scan would have had on the scores of those patients. Rates of first line treatment failure and time to remission were assessed and comparisons made. There was no significant difference in the need to change to second line chemotherapy or in time to remission in those patients with metastatic GTN whose score or risk was changed when CT scan was used in place of CXR. Low risk patients with metastatic disease were, however, significantly more likely to need to change to second line chemotherapy than patients with non-metastatic GTN although there was no significant difference in time to remission between these groups. CT scan of the chest used instead of CXR in the staging of GTN does not alter outcome.
| 19,019,416
|
LPA receptor 2 mediates LPA-induced endometrial cancer invasion.
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We have previously shown that lysophosphatidic acid (LPA) promotes the ovarian cancer metastatic cascade. In this study, we evaluated the role of LPA on endometrial cancer invasion. Transient mRNA knockdown was accomplished using pre-designed siRNA duplexes against LPA receptor 2 (LPA2) and human matrix metalloproteinase-7 (MMP-7). RT-PCR was used to characterize LPA receptor and MMP-7 expression. Analysis of in vitro invasion was performed with rat-tail collagen type I coated Boyden chambers. Gelatin zymography was used to evaluate the MMP activity in cell culture conditioned media. Cell-cell and cell-matrix attachment was also assessed upon LPA2 knockdown to further illuminate the LPA2 cascade. LPA increases HEC1A cellular invasion at physiologic concentrations (0.1-1 muM). Of the four principle LPA receptors, LPA2 is predominantly expressed by HEC1A cells. Transient transfection of LPA2 siRNA reduced LPA2 mRNA expression in HEC1A cells by 93% (P<0.01). Silencing LPA2 eliminated the LPA-stimulated increase in invasion (P<0.05) and reduced LPA-induced MMP-7 secretion/activation, without significantly affecting cell-cell or cell-matrix adhesion. Silencing MMP-7 reduced overall invasion but did not eliminate LPA's pro-invasive effect on HEC1A cells, as compared to negative control (P<0.05). Gelatin zymography confirmed that LPA2 and MMP-7 knockdown reduced MMP-7 activation in HEC1A conditioned media. LPA2 mediates LPA-stimulated HEC1A invasion and the subsequent activation of MMP-7.
| 19,019,417
|
Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors.
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To evaluate factors associated with visual field (VF) progression, using all available follow-up through 9 years after treatment initiation, in the Collaborative Initial Glaucoma Treatment Study (CIGTS). Longitudinal follow-up of participants enrolled in a randomized clinical trial. Six hundred seven newly diagnosed glaucoma patients. In a randomized clinical trial, 607 subjects with newly diagnosed open-angle glaucoma initially were treated with either medication or trabeculectomy. After treatment initiation and early follow-up, subjects were evaluated clinically at 6-month intervals. Study participants in both arms of the CIGTS were treated aggressively in an effort to reduce intraocular pressure (IOP) to a level at or below a predetermined, eye-specific target pressure. Visual field progression was analyzed using repeated measures models. Visual field progression, measured by Humphrey 24-2 full-threshold testing and assessed by the change in the mean deviation (MD), and an indicator of substantial worsening of the VF (MD decrease of > or =3 dB from baseline), assessed at each follow-up visit. Follow-up indicated minimal change from baseline in each initial treatment group's average MD. However, at the 8-year follow-up examination, substantial worsening (> or =3 dB) of MD from baseline was found in 21.3% and 25.5% of the initial surgery and initial medicine groups, respectively. The effect of initial treatment on subsequent VF loss was modified by time (P<0.0001), baseline MD (P = 0.03), and diabetes (P = 0.01). Initial surgery led to less VF progression than initial medicine in subjects with advanced VF loss at baseline, whereas subjects with diabetes had more VF loss over time if treated initially with surgery. The CIGTS intervention protocol led to a lowering of IOP that persisted over time in both treatment groups. Progression in VF loss was seen in a subset, increasing to more than 20% of the subjects. The findings regarding initial surgery being beneficial for subjects with more advanced VF loss at presentation, but detrimental for patients with diabetes, are noteworthy and warrant independent confirmation. The author(s) have no proprietary or commercial interest in any materials discussed in this article.
| 19,019,444
|
Corpus callosum size and shape in individuals with current and past depression.
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The corpus callosum enables the efficient linking of the two cerebral hemispheres. Reductions in the size of the anterior callosum have been described in geriatric depression, although findings in young adults have been much more equivocal. Data was acquired in 26 currently depressed (mean age 32.15 years, 5/26 male) and 28 remitted non-geriatric adults (mean age 36.36 years, 7/28 male), and 32 control subjects (mean age 34.41 years, 11/32 male). The total area, length and curvature of the callosum, and regional thickness along 39 points, from a mid-sagittal T1-weighted magnetic resonance image were compared across the groups. Total area, length and curvature did not differ between the groups. The currently-depressed group showed expansions in the thickness of the posterior body and isthmus when compared to controls; this was not seen in remitted patients. Similar expansions were seen when comorbidly anxious patients were compared to depressed patients without anxiety. There was no difference between melancholic and non-melancholic patients, and medication status did not affect the results. Currently-depressed patients showed higher rates of co-morbid anxiety and medication usage than remitted patients, although in the depression group as a whole there was no difference between medicated and unmedicated patients. The corpus callosum shows expansions in regions connecting frontal, temporal and parietal regions in currently depressed patients only, suggestive of state-related changes in white matter in major depression that may reflect the effects of state-related factors on white matter structure.
| 19,019,454
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Cytokine expression by neutrophils of adult horses stimulated with virulent and avirulent Rhodococcus equi in vitro.
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Rhodococcus equi is an intracellular pathogen of macrophages that causes rhodococcal pneumonia in foals and immunocompromised people. Evidence exists that neutrophils play a vital role in resistance to infection with R. equi; however, the means by which neutrophils exert their effects have not been clearly defined. In addition to directly killing bacteria, neutrophils also may exert a protective effect by linking innate and adaptive immune responses. In the present study we evaluated the cytokine expression profiles of adult equine neutrophils in response to stimulation with isogenic strains of virulent and avirulent R. equi in vitro. After 2 and 4h incubation with virulent or avirulent R. equi, adult equine neutrophils expressed significantly (P<0.05) greater tumor necrosis factor alpha (TNFalpha), interleukin (IL)-12p40, IL-6, IL-8 and IL-23p19 mRNA, but not interferon gamma (IFNgamma) or IL-12p35 mRNA than unstimulated neutrophils. Furthermore, virulent R. equi induced significantly greater IL-23p19 mRNA than avirulent R. equi. These results demonstrate that R. equi-stimulated neutrophils are a source of many proinflammatory cytokines. Furthermore, these results suggest that IL-23 may be preferentially expressed over IL-12 in response to exposure with R. equi, and that this response may be more strongly induced by virulent R. equi than avirulent R. equi. Collectively, the data presented herein suggest a non-phagocytic role for neutrophils that may influence the type of adaptive immune response to R. equi.
| 19,019,457
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Stridor due to a bridge-like subglottic stenosis in a 10-week-old male infant.
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We present an infant with post-intubation stridor caused by a bridge-like subglottic stenosis. At the age of 6 weeks he suffered from a RSV infection with the need for endotracheal intubation. At week 10 acute respiratory distress required a re-intubation. Flexible endoscopy was suggestive for laryngomalacia. Rigid endoscopy revealed a subglottic laterolateral mucosal bridge resulting in a doubling of the airway lumen. Histopathological examination showed a fibrinoid pseudomembrane. Follow up endoscopy showed a grade 1 posterior subglottic stenosis without respiratory compromise. This is the first case in the literature of an infant with a post-intubation bridge-like fibrinoid pseudomembranous subglottic lesion.
| 19,019,463
|
Differential regulation of zebrafish metallothionein-II (zMT-II) gene transcription in ZFL and SJD cell lines by metal ions.
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Two alleles of a zebrafish metallothionein II gene (zMT-II) promoter (zMT-IIA and zMT-IIB) containing 10 MREs in the 5'-flanking region (1514bp) were identified in zebrafish. These putative MREs were confirmed via electrophoretic mobility shift assay (EMSA) to have binding activities from the cellular and nuclear extracts of a zebrafish cell line, ZFL. Transient gene expression studies using zebrafish liver (ZFL) and caudal fin (SJD) cell lines also confirmed that the most distal cluster of MREs contributed to the maximal induction of zMT-IIA activity by Zn(2+) and that this Zn(2+) induction was dose-dependent. Further transient gene expression assay of the zMT-IIA gene promoter was carried out to study the effects of various metal ions (Zn(2+), Cd(2+), Cu(2+), Hg(+), As(3+), As(5+), Cr(3+) and Cr(6+)), and Zn(2+) and Cd(2+) were found to be the most efficient MT gene inducers of zMT-II. As(3+) was a weak inducer of zMT-II in the two cell lines, and Hg(+) caused significant induction only in the SJD cells. No significant induction was found in the other metal ion exposures. EMSA also identified transcription factor(s) of two different sizes from the cytoplasmic and nuclear extracts of the ZFL cells that were able to bind with the MREs, but no increase in MRE binding was detected in the extracts of these cells after Zn(2+) or Cd(2+) treatment, compared with untreated control cells. The mechanisms of MT gene transcription induction via metal ions are discussed herein.
| 19,019,466
|
The LINC-less granulocyte nucleus.
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The major blood granulocyte (neutrophil) is rapidly recruited to sites of bacterial and fungal infections. It is a highly malleable cell, allowing it to squeeze out of blood vessels and migrate through tight tissue spaces. The human granulocyte nucleus is lobulated and exhibits a paucity of nuclear lamins, increasing its capability for deformation. The present study examined the existence of protein connections between the nuclear envelope and cytoskeletal elements (the LINC complex) in differentiated cell states (i.e. granulocytic, monocytic and macrophage) of the human leukemic cell line HL-60, as well as in human blood leukocytes. HL-60 granulocytes exhibited a deficiency of several LINC complex proteins (i.e. nesprin 1 giant, nesprin 2 giant, SUN1, plectin and vimentin); whereas, the macrophage state revealed nesprin 1 giant, plectin and vimentin. Both states possessed SUN2 in the nuclear envelope. Parallel differences were observed with some of the LINC complex proteins in isolated human blood leukocytes, including macrophage cells derived from blood monocytes. The present study documenting the paucity of LINC complex proteins in granulocytic forms, in combination with previous data on granulocyte nuclear shape and nuclear envelope composition, suggest the hypothesis that these adaptations evolved to facilitate granulocyte cellular malleability.
| 19,019,491
|
The spreading of suicidal behavior: The contextual effect of community household poverty on adolescent suicidal behavior and the mediating role of suicide suggestion.
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Despite the longstanding interest of social researchers in the social factors that influence suicide and suicidal behavior, multilevel research on this topic has been limited. Using nested survey data on 5331 Icelandic adolescents (born in 1990 and 1991) in 83 school-communities, the current study examines the contextual effect of community household poverty on adolescent suicidal behavior (suicide ideation and suicide attempt). The findings show that the concentration of household poverty in the school-community has a significant, contextual effect on adolescent suicidal behavior. Furthermore, we test an "epidemic" explanation for this effect, examining the mediating role of suicide suggestion (contact with suicidal others). We find that suicide suggestion mediates a substantial part of the contextual effect of community household poverty on suicide attempt, while mediation is modest in the case of suicide ideation. The findings indicate that community household poverty increases the risk of adolescent suicidal behavior in part because communities in which household poverty is common entail a higher risk for adolescents of associating with suicidal others. The study demonstrates how the concentration of individual problems can have macrolevel implications, creating social mechanisms that cannot be reduced to the circumstances or characteristics of individuals.
| 19,019,522
|
Water quality in the upper Han River basin, China: the impacts of land use/land cover in riparian buffer zone.
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Vegetated riparian zones adjacent to rivers and streams, can greatly mitigate nutrients, sediment from surface through deposition, absorption and denitrification, yet, human activities primarily land use practices have dramatically reduced the capacity. In this study, 42 sampling sites were selected in the riverine network throughout the upper Han River basin (approximately 95,200 km(2)) of China. A total of 252 water samples were collected during the time period of 2005-2006 and analyzed for physico-chemical variables and major ions. Correlation analysis, principal components analysis and stepwise least squares multiple regression were used to determine the spatio-temporal variability of water quality variables and in particular their correlations with land use/land cover in the 100 m riparian zone along the stream network. The basin in general has a better water quality in the dry season than the rainy season, indicated by the primary pollutants including COD(Mn) and nitrogen. Major ion compositions display large spatial and seasonal differences and are significantly related to land use and land cover in the riparian zone, while riparian landscape could not explain most of the water quality variability in T, pH, turbidity, SPM and COD(Mn). The research could provide help develop sustainable land use practice of the riparian zone for water conservation in the basin.
| 19,019,532
|
The experimental establishment of ruminant nematodes in European hares (Lepus europaeus).
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The factors that control the demography of European hare Lepus europaeus populations are poorly understood, but it has been recognized that the decline of hares in Europe is associated with an increasing intensity of agricultural activity. Many mechanisms have been suggested. We propose another mechanism; a negative impact arising from ingestion of the infective larvae of ruminant livestock. We dosed juvenile hares from a worm-free colony with a conservative dose from a mixed culture of infective larvae of the nematode parasites of sheep and cattle. We examined the hares post-mortem for the establishment of those ruminant nematodes, differences in weight changes, and the shedding of eggs. We found that under the circumstances of our trial, Trichostrongylus colubriformis and to a lesser extent T. rugatus, T. vitrinus, and Teladorsagia circumcincta were able to establish as adults in the dosed animals. We found strongyle eggs in the faeces of the dosed hares, and were able to culture larvae from those eggs. However, the ecological significance of our findings, if any, remains to be elucidated. Because of their mobility, hares may transmit resistant strains of parasites between grazing properties.
| 19,019,544
|
"Gearing to a time table"; the evolution of earlier surgical eschar excision in massive burns by British burns surgeons at the battles of Cassino, 1944: an example of real-time audit.
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The effectiveness of burns care delivery is difficult to measure within a realistic workload and resource framework. In addition, workers must develop new tools for this purpose. We describe a historical example from World War II describing the evolution of burns excision in the context of thorough outcome assessment, during the allied advance from North Africa up the Italian peninsular, including the battles of Cassino 1942-1945. Patrick Clarkson and Rex Lawrie working as plastic surgeons in a small forward Maxillofacial Unit were able to fully assess the management and outcome of 800 burnt servicemen. 192 burns were full thickness and required grafting. Prospective data revealed that those burns which were surgically excised and grafted between 12 and 18 days recovered more quickly than those managed by conservative dressings until the eschar had sloughed off followed by grafting. Burns managed by excision and grafting in less than 5 weeks following burning (n=86) healed 8.6 days faster than those grafted later (n=106). This difference was increased for massive burns of over 1000 cm(2), with those grafted in less than 5 weeks (n=17) healing 13 days faster than the delayed group (n=27). Their transparent and simple method of prospective audit is described.
| 19,019,557
|
Variation in Fusobacterium necrophorum strains present on the hooves of footrot infected sheep, goats and cattle.
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Footrot is a disease of sheep, goats and cattle that causes losses in production and raises welfare issues world-wide. The disease is characterised by destruction of the hard keratin of the hoof leading to lameness, and both Dichelobacter nodosus (D. nodosus) and Fusobacterium necrophorum (F. necrophorum) are thought to be involved in the etiology of this disease. While a lot is known about the genetic diversity of D. nodosus, very little is known about variation in F. necrophorum, especially as regards its role in footrot. We used PCR in conjunction with SSCP and sequencing to analyse swabs collected from the hooves of sheep, goats and cattle with symptomatic footrot for the presence of a portion of the lktA gene of F. necrophorum. Out of 29 samples tested, 27 had amplifiable lktA sequences and within these we found four different variants of the lktA gene. Eight of the nine samples from cattle were positive for a variant that matched the type strain of F. necrophorum subsp. necrophorum. Of the 14 samples from sheep, 13 were positive for lktA, but none of theses matched the known type strains, and 11/13 of the lktA sequences were identical. This sequence was distinct to those of the type strains. None of the footrot infections carried multiple variants of lktA, suggesting that only one strain of F. necrophorum is present in each case. This is in contrast to D. nodosus in footrot infections, which have been demonstrated to have up to seven strains infecting a single hoof.
| 19,019,570
|
Virulence genotypes and phylogenetic background of fluoroquinolone-resistant and susceptible Escherichia coli urine isolates from dogs with urinary tract infection.
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The origins and virulence potential of fluoroquinolone-resistant (FQ-R) Escherichia coli from dogs with urinary tract infection (UTI) are undefined. Therefore, fluoroquinolone-resistant (n=38) or susceptible (n=62) E. coli urine isolates from dogs with UTI were characterized for phylogenetic group (A, B1, B2, D) and 61 virulence-associated genes by multiplex PCR, then were compared according to these characteristics. Compared with fluoroquinolone-susceptible (FQ-S) isolates, the fluoroquinolone-resistant isolates exhibited significantly lower prevalences for most virulence genes studied (albeit higher prevalences for several, including iutA: aerobactin receptor), significantly fewer virulence genes per isolate, and shifts away from virulence-associated group B2. Nonetheless, 26% of fluoroquinolone-resistant isolates qualified as extraintestinal pathogenic E. coli (ExPEC), suggesting possible human virulence potential. The findings call into question whether the fluoroquinolone-resistant E. coli encountered in dogs arise through conversion of fluoroquinolone-susceptible canine resident strains to resistance, or instead are imported from an external source. They also identify dogs as a possible reservoir of drug-resistant ExPEC for transmission to other pets and humans.
| 19,019,576
|
The relationship between smoking and age at the menopause: A systematic review.
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Increasing life expectancy has made it ever more important to study the factors that influence the age at the menopause, given that when it is reached outside of the normal range, it is associated with increased risk of osteoporosis and cardiovascular diseases, among other conditions. Among the factors studied in relation to early menopause, smoking is prominent. Destruction of the ovarian follicles is one of the mechanisms postulated for this effect. The aim of this study was to review and describe the associations between age at the menopause and the habit of smoking, its duration and its intensity. A systematic review of the literature indexed in the MEDLINE and LILACS databases was conducted, without restriction on publication date. After initially identifying 1325 articles and preselecting 161 articles for consideration of their complete texts, 96 articles reporting on the results from 109 studies were selected for analysis. A great majority of the studies reported an association between the habit of smoking and early menopause, but there was no clear evidence that the duration of smoking and quantity of cigarettes smoked had any association with age at the natural menopause. Additional studies are needed, preferably of prospective nature and with a large number of women, in order to deepen the knowledge of the effects of various aspects of smoking on age at the menopause. Experimental studies on animals may also contribute towards clarifying the physiopathological mechanisms through which smoking influences age at the menopause.
| 19,019,585
|
Serum lipids and neopterin in urine as new biomarkers of malnutrition and inflammation in the elderly.
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Levels of serum lipids are influenced by malnutrition and inflammation. The study aimed to find the relation of the lipidogram to positive and negative markers of inflammation in geriatric patients. Attention was paid to neopterin in urine as a non-protein positive bioindicator of inflammation. It was a local, monocentric, prospective clinical study in hospitalized patients older than 80 y. The study included 101 patients (54 women, 47 men). The average age of the entire group was 85.37 +/- 4.88 y. The dependence of the values of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triacylglycerols (TAGs) on C-reactive protein (CRP), neopterin in urine, and prealbumin was examined. When we compared CRP and serum lipids, we found a statistically significant negative correlation between levels of CRP and total cholesterol (P < 0.05), HDL (P < 0.01), and LDL (P < 0.05). Also the level of neopterin in urine was negatively correlated with levels of total cholesterol (P < 0.05) and HDL (P < 0.01). A statistically highly significant interaction was demonstrated between levels of prealbumin and total cholesterol (P < 0.001), HDL (P < 0.001), LDL (P < 0.001), and TAG (P < 0.05). A significant negative correlation between levels of inflammation markers (neopterin in urine, CRP) and total cholesterol and HDL was found. LDL was influenced to a lesser extent. A close relation between serum lipids and prealbumin was also demonstrated. Total cholesterol, HDL, and LDL can be considered novel biomarkers of malnutrition and inflammation in geriatric patients.
| 19,019,628
|
Refractive errors and schizophrenia.
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Refractive errors (myopia, hyperopia and amblyopia), like schizophrenia, have a strong genetic cause, and dopamine has been proposed as a potential mediator in their pathophysiology. The present study explored the association between refractive errors in adolescence and schizophrenia, and the potential familiality of this association. The Israeli Draft Board carries a mandatory standardized visual accuracy assessment. 678,674 males consecutively assessed by the Draft Board and found to be psychiatrically healthy at age 17 were followed for psychiatric hospitalization with schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry. Sib-ships were also identified within the cohort. There was a negative association between refractive errors and later hospitalization for schizophrenia. Future male schizophrenia patients were two times less likely to have refractive errors compared with never-hospitalized individuals, controlling for intelligence, years of education and socioeconomic status [adjusted Hazard Ratio=.55; 95% confidence interval .35-.85]. The non-schizophrenic male siblings of schizophrenia patients also had lower prevalence of refractive errors compared to never-hospitalized individuals. Presence of refractive errors in adolescence is related to lower risk for schizophrenia. The familiality of this association suggests that refractive errors may be associated with the genetic liability to schizophrenia.
| 19,019,632
|
Surface characterization of immunosensor conjugated with gold nanoparticles based on cyclic voltammetry and X-ray photoelectron spectroscopy.
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This investigation describes the surface characterization of rabbit immunoglobulin G (IgG) conjugated with gold nanoparticles. Goat anti-rabbit immunoglobulin G tagged with 5nm gold nanoparticles was applied to detect the IgG. Then, the autocatalyzed deposition of Au(3+) onto the surface of anti-IgGAu increased the surface area per gold nanoparticle. The immobilization chemistries and the atomic concentrations of Au(4f), P(2p), S(2p), C(1s), N(1s) and O(1s) of the resulting antibody-modified Au electrodes were determined by X-ray photoelectron spectroscopy (XPS). The sulfur that is involved in the cysteamine binding and the enlargement of the gold nanoparticles are identified using cyclic voltammetry. The results reveal that the surface area per gold particle, following the autocatalyzed deposition Au(3+) on the surface of anti-IgGAu, was approximately seven times higher than that before deposition.
| 19,019,639
|
Age-dependent relationship between bispectral index and sedation level.
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To determine the relationship between bispectral index (BIS) and sedation. Prospective, observational clinical study. Intensive care unit of a public hospital in Japan. 22 ASA physical status I, II, and III middle-aged (18-65 yrs) and elderly (>65 yrs) patients receiving postoperative sedation with midazolam. Patients were allocated to two groups: Group M was composed of middle-aged patients (<65 yrs) and Group H elderly patients (>65 yrs). Midazolam was administered at a bolus dose of 0.1 mg/kg, followed by a continuous dose of 0.04 mg/kg per hour, which was adjusted every two hours to achieve a target level of sedation at 3-6 on the Ramsay Sedation Scale (RSS); buprenorphine was administered at a constant rate (0.625 microg kg(-1) hr(-1)). BIS value, RSS, midazolam dose, body temperature (BT), heart rate, dopamine dose, and mean arterial pressure were recorded every two hours by an independent nurse. Data were analyzed using Spearman rank correlation and the Mann-Whitney U test. BIS values decreased depending on depth of sedation; a significant correlation was noted between groups in RSS and BIS. The BIS values at levels of RSS 5 and 6 were significantly lower in Group H than Group M. BIS correlated with sedation depth, with BIS scores in group H than group M at a deep sedation depth.
| 19,019,662
|
Management of hemorrhagic shock when blood is not an option.
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To describe an alternative approach to management of severe life- threatening hemorrhagic shock and the outcome when blood was not a treatment option. Case Report of the use of a Hemoglobin Based Oxygen Carrier (HBOC-201)when control of hemorrhage and intravenous crystalloids were unsuccessful in reversal of hemorrhagic shock and progressive ischemia. Trauma Center. Jehovah's Witness. Hospital discharge and 6 month follow-up uneventful.
| 19,019,664
|
Children's perceptions and behavior with respect to glass littering in developing countries: a case study in Palestine's Nablus district.
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The aims of this study were to assess the current situation regarding glass litter on the streets and children's attitudes, and behavior concerning glass litter. Out of 240 interviewed children, 41.7% admitted glass littering. This was reflected in the high incidence of injuries caused by street glass among children; 140 (58.3%) of the children interviewed had been injured by broken glass at least once while walking outdoors and 95 of the children had received professional medical care for the lacerations. As reported by the children who admitted to glass littering, the most effective elements (29.6%) in preventing them from littering the streets with glass were moral and religious convictions, and the next most effective practice (20.4%) was improved street cleanliness. Preventive measures such as encouraging moral and religious convictions among children, more effective street cleaning by local authorities, improved footwear, education, and glass recycling incentives, as well as engaging the community in street cleaning campaigns, are all needed to address this public health hazard. More recreational facilities should be provided. Public awareness initiatives led by environmentalists, social workers, primary health care providers or home healthcare providers may also help educate children to wear shoes, prevent glass injuries and increase glass litter awareness.
| 19,019,670
|
Abnormal thalamocortical dynamics may be altered by deep brain stimulation: using magnetoencephalography to study phantom limb pain.
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Deep brain stimulation (DBS) is used to alleviate chronic pain. Using magnetoencephalography (MEG) to study the mechanisms of DBS for pain is difficult because of the artefact caused by the stimulator. We were able to record activity over the occipital lobe of a patient using DBS for phantom limb pain during presentation of a visual stimulus. This demonstrates that MEG can be used to study patients undergoing DBS provided control stimuli are used to check the reliability of the data. We then asked the patient to rate his pain during and off DBS. Correlations were found between these ratings and power in theta (6-9) and beta bands (12-30). Further, there was a tendency for frequencies under 25 Hz to correlate with each other after a period off stimulation compared with immediately after DBS. The results are interpreted as reflecting abnormal thalamocortical dynamics, previously implicated in painful syndromes.
| 19,019,684
|
Production of low-background CuSn6-bronze for the CRESST dark-matter-search experiment.
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One of the most intriguing open questions in modern particle physics is the nature of the dark matter in our universe. As hypothetical weakly interacting massive particles (WIMPs) do interact with ordinary matter extremely rarely, their observation requires a very low-background detector environment regarding radioactivity as well as an advanced detector technique that allows for active discrimination of the still present radioactive contaminations. The CRESST experiment uses detectors operating at milli-Kelvin temperature. Energy deposition in the detectors is recorded via the simultaneous measurement of a phonon-mediated signal and scintillation emitted by the CaWO(4) crystal targets. The entire setup is made of carefully selected materials. In this note we report on the development of ultra-pure bronze (CuSn(6)) wire in small quantities for springs and clamps that are currently being used in the CRESST II setup.
| 19,019,691
|
Radiofrequency ablation: simultaneous application of multiple electrodes via switching creates larger, more confluent ablations than sequential application in a large animal model.
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To compare radiofrequency (RF) ablations created by using a sequential technique to those created simultaneously by using a switching algorithm in ex vivo and in vivo liver models. RF ablation was performed by using either sequential or switched application of three cooled electrodes in a 2-cm triangular array in ex vivo bovine liver (28 total ablations) and in vivo swine liver (12 total ablations) models. For sequential ablations, electrodes were powered for 12 minutes each with a 5-minute rest interval between activations to simulate electrode repositioning. Switched ablations were created by using a multiple-electrode switching system for 12 minutes. Temperatures were measured during ex vivo experiments at four points in the ablation zone. Ablation zones were measured for minimum and maximum diameter, cross-sectional area, and isoperimetric ratio. Mann-Whitney and Wilcoxon matched pairs tests were used to identify differences between groups. The switched application created larger and more circular zones of ablation than did the sequential application, with mean (+/-standard deviation) ex vivo cross-sectional areas of 25.4 cm(2) +/- 5 .3 and 18.8 cm(2) +/- 6.6 (P = .001), respectively, and mean in vivo areas of 17.1 cm(2) +/- 5.1 and 13.2 cm(2) +/- 4.2 (P < .05). Higher temperatures and more rapid heating occurred with the switched application; switched treatments were 74% faster than sequential treatments (12 vs 46 minutes). In the sequential group, subsequent ablations grew progressively larger due to local ischemia. Switched application of three electrodes creates larger, more confluent ablations in less time than sequential application. Thermal synergy and ablation-induced ischemia both substantially influence multiple-electrode ablations.
| 19,019,701
|
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