title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Analysis of fMRI data using improved self-organizing mapping and spatio-temporal metric hierarchical clustering. | The self-organizing mapping (SOM) and hierarchical clustering (HC) methods are integrated to detect brain functional activation; functional magnetic resonance imaging (fMRI) data are first processed by SOM to obtain a primary merged neural nodes image, and then by HC to obtain further brain activation patterns. The conventional Euclidean distance metric was replaced by the correlation distance metric in SOM to improve clustering and merging of neural nodes. To improve the use of spatial and temporal information in fMRI data, a new spatial distance (node coordinates in the 2-D lattice) and temporal correlation (correlation degree of each time course in the exemplar matrix) are introduced in HC to merge the primary SOM results. Two simulation studies and two in vivo fMRI data that both contained block-design and event-related experiments revealed that brain functional activation can be effectively detected and that different response patterns can be distinguished using these methods. Our results demonstrate that the improved SOM and HC methods are clearly superior to the statistical parametric mapping (SPM), independent component analysis (ICA), and conventional SOM methods in the block-design, especially in the event-related experiment, as revealed by their performance measured by receiver operating characteristic (ROC) analysis. Our results also suggest that the proposed new integrated approach could be useful in detecting block-design and event-related fMRI data. | 18,815,099 |
Efficient segmentation by sparse pixel classification. | Segmentation methods based on pixel classification are powerful but often slow. We introduce two general algorithms, based on sparse classification, for optimizing the computation while still obtaining accurate segmentations. The computational costs of the algorithms are derived, and they are demonstrated on real 3-D magnetic resonance imaging and 2-D radiograph data. We show that each algorithm is optimal for specific tasks, and that both algorithms allow a speedup of one or more orders of magnitude on typical segmentation tasks. | 18,815,104 |
Toward realistic and practical ideal observer (IO) estimation for the optimization of medical imaging systems. | The ideal observer (IO) employs complete knowledge of the available data statistics and sets an upper limit on observer performance on a binary classification task. However, the IO test statistic cannot be calculated analytically, except for cases where object statistics are extremely simple. Kupinski have developed a Markov chain Monte Carlo (MCMC) based technique to compute the IO test statistic for, in principle, arbitrarily complex objects and imaging systems. In this work, we applied MCMC to estimate the IO test statistic in the context of myocardial perfusion SPECT (MPS). We modeled the imaging system using an analytic SPECT projector with attenuation, distant-dependent detector-response modeling and Poisson noise statistics. The object is a family of parameterized torso phantoms with variable geometric and organ uptake parameters. To accelerate the imaging simulation process and thus enable the MCMC IO estimation, we used discretized anatomic parameters and continuous uptake parameters in defining the objects. The imaging process simulation was modeled by precomputing projections for each organ for a finite number of discretely-parameterized anatomic parameters and taking linear combinations of the organ projections based on continuous sampling of the organ uptake parameters. The proposed method greatly reduces the computational burden and allows MCMC IO estimation for a realistic MPS imaging simulation. We validated the proposed IO estimation technique by estimating IO test statistics for a large number of input objects. The properties of the first- and second-order statistics of the IO test statistics estimated using the MCMC IO estimation technique agreed well with theoretical predictions. Further, as expected, the IO had better performance, as measured by the receiver operating characteristic (ROC) curve, than the Hotelling observer. This method is developed for SPECT imaging. However, it can be adapted to any linear imaging system. | 18,815,105 |
Genetic variation revealed in the chloroplast-encoded RNA polymerase beta' subunit of downy mildew-resistant genotype of opium poppy. | Two accessions of opium poppy, Pps-1 (dark green leaves, highly resistant to downy mildew [DM]) and H-9 (yellowish green leaves, susceptible to DM), which originated from common progenitor SPS49 were selected, and their F(1) and F(2) progenies showed that leaf color trait was governed by single recessive nuclear gene, whereas DM resistance appeared to be the interaction between cytoplasmic and nuclear genes. Chloroplast DNA (cpDNA) analysis of these 2 accessions through arbitrarily-primed polymerase chain reaction generated a unique fragment in Pps-1. Subsequent sequence analysis upon cloning of this cpDNA fragment revealed its similarity with the plastid-encoded RNA polymerase beta' subunit (rpoCI). Full-length rpoCI DNA was therefore isolated from both the genotypes that was 2707 bp long with a 658-bp intron (436-1093) and a 2049-bp open reading frame encoding 682 amino acid long polypeptide. Comparative sequence analysis of the rpoC1 gene from both the genotypes, revealed 4 single-nucleotide substitutions at 4 positions that caused 3 amino acid changes in the protein sequence--1) A to C transversion at position 825 (Glu275Asp), 2) A to G transition at position 1203 (Ile401Met), and 3) T to C transition at position 1422 and G to A transition at position 1423 both in same codon of the reading frame (Ala475Thr). This investigation is the first report indicating base substitution changes in the plastid-encoded rpoCI gene in DM-resistant genotypes of opium poppy. This finding may lead to implication of possible role of RNA polymerase beta' subunit in resistance to DM caused by Peronospora arborescens. | 18,815,118 |
Modulation of genotoxicity and cytotoxicity by radish grown in metal-contaminated soils. | Members of the Brassicaceae family are known for their anticarcinogenic and genetic material protective effects. However, many of the species of this family accumulate high amounts of metals, which is an undesirable feature. Radish (Raphanus sativus L.) has shown to accumulate metals in roots to a higher extent than others members of Brassicaceae. The main objectives of this work are (i) to study the distribution of the accumulated As, Pb and Cd in radish plants and (ii) to establish the genotoxic, antigenotoxic and cytotoxic activities of the root and shoot of this vegetable. Results indicate that (i) the shoots of radish accumulate higher concentrations of metal(oid)s than roots; (ii) the shoots were genotoxic at the different concentrations studied, with the root showing such genotoxic effect only at the highest concentration assayed; (iii) the antigenotoxic potential of radish is reduced in plants with high metal content and (iv) the tumouricide activities of the radish plants were negatively correlated to their metal(oid) contents. An interaction between metal(oid)s and the isotyocianates (hydrolysis products of the glucosinolates) contained in the radish is suggested as the main modulator agents of the genotoxic activity of the plants grown in contaminated soils with metal(oid)s. | 18,815,122 |
Temporal perturbation of tyrosine phosphoproteome dynamics reveals the system-wide regulatory networks. | Signal transduction systems are known to widely regulate complex biological events such as cell proliferation and differentiation. Because phosphotyrosine-dependent networks play a key role in transmitting signals, a comprehensive and fine description of their dynamic behavior can lead us to systematically analyze the regulatory mechanisms that result in each biological effect. Here we established a mass spectrometry-based framework for analyzing tyrosine phosphoproteome dynamics through temporal network perturbation. A highly time-resolved description of the epidermal growth factor-dependent signaling pathways in human A431 cells revealed a global view of their multiphase network activation, comprising a spike signal transmission within 1 min of ligand stimulation followed by the prolonged activation of multiple Src-related molecules. Temporal perturbation of Src family kinases with the corresponding inhibitor PP2 in the prolonged activation phase led to the down-regulation of the molecules related to cell adhesion and receptor degradation, whereas the canonical cascades as well as the epidermal growth factor receptor relatively maintained their activities. Our methodology provides a system-wide view of the regulatory network clusters involved in signal transduction that is essential to refine the literature-based network structures for a systems biology analysis. | 18,815,124 |
Regulation dynamics of WGD genes during yeast metabolic oscillation. | Saccharomyces cerevisiae and its close relatives are characterized by their propensity to ferment even in the presence of oxygen. It was hypothesized that whole-genome duplication (WGD) led to the development of this efficient fermentative lifestyle (WGD-fermentation hypothesis, Piskur 2001. In this study, we found that a significantly higher proportion of WGD genes than non-WGD genes are dynamically regulated during metabolic oscillation in response to oxygen change. The same data set also shows that the WGD genes, as compared with the smaller scale duplicate genes, are enriched with pairs where both copies have cyclic expression during the metabolic oscillation (either with the same or different phases). These results provide new evidences for the WGD-fermentation hypothesis and new insights into the relationship between the genome duplication and the evolution of new lifestyles in eukaryotic organisms. | 18,815,125 |
Role of the HIV gp120 conserved domain 1 in processing and viral entry. | The importance of the N-terminal region of HIV gp120 conserved domain 1 (gp120-C1) to envelope function has been examined by alanine-scanning mutagenesis and subsequent characterization of the mutagenic effects on viral entry; envelope expression, processing, and incorporation; and gp120 association with gp41. With respect to the wild-type gp120, mutational effects on viral entry fall into two classes: functional, as defined by >20% entry with respect to wild type, and impaired, as defined by <20% entry with respect to wild type. Based on Western blot analyses of cell lysates and virions, the entry impairment of W35A, V38A, Y39A, Y40A, G41A, V42A, and I52A is due primarily to disruption of envelope processing. The entry impairment of P43A and W45A is apparently due to a combination of effects on processing and incorporation into virions. In contrast, the entry impairment of V44A and F53A is primarily due to disruption of the gp120-gp41 interaction, which results in dissociation of gp120 from the virion. We present a model for gp120-C1 interactions with gp120-C5 and the gp41 disulfide loop in unprocessed gp160 and processed gp120/gp41. | 18,815,131 |
Acute exercise protects against doxorubicin cardiotoxicity. | Numerous methods have been used to minimize the cardiotoxic effects of the chemotherapeutic agent doxorubicin (DOX), and most have had limited success. Chronic endurance exercise has been shown to protect against DOX cardiotoxicity, but little is known regarding the effects of acute exercise on DOX-induced cardiac dysfunction. The purpose of this study was to determine the effects of a single bout of acute endurance exercise on the cardiac dysfunction associated with DOX treatment. Male Sprague-Dawley rats either performed an acute exercise bout on a motorized treadmill for 60 minutes at a maximal speed of 25 m/min with a 5% grade (EX) or remained sedentary (SED) 24 hours before receiving either a 15-mg/kg DOX bolus dose or saline (SAL). Cardiac function was then analyzed 5 days post injection using a Langendorff isolated perfused heart model. In addition, myocardial lipid peroxidation was analyzed as an indicator of oxidative stress. Doxorubicin treatment alone (SED+DOX) promoted a significant decline in end-systolic pressure (-35%), left ventricular developed pressure (-59%), and the maximal rate of left ventricular pressure development (-43%) as well as a 45% increase in lipid peroxidation products when compared with SED+SAL (P<.05). Acute exercise 24 hours before DOX treatment, however, had a cardioprotective effect, as end-systolic pressure, left ventricular developed pressure, and the maximal rate of left ventricular pressure development were significantly higher in EX+DOX compared with SED+DOX (P<.05) and EX+DOX had similar levels of lipid peroxidation products as SED+SAL CONCLUSIONS: An acute exercise bout performed 24 hours before DOX treatment protected against cardiac dysfunction, and this exercise-induced cardioprotection may partly be explained by a reduction in the generation of reactive oxygen species. | 18,815,146 |
Is prompt exploratory laparotomy the best attitude for mesenteric ischemia after cardiac surgery? | Mesenteric ischemia following cardiac surgery is a life-threatening complication. Early identification of patients may help optimizing management and improving outcome. Between January 2000 and July 2007, surgical exploration was realized when mesenteric ischemia was suspected after coronary-artery bypass grafts (CABG). Patients were divided in two groups according to diagnosis confirmation upon laparotomy. Peri-operative predictors of complication and death were analyzed. Of 1634 consecutive patients, 13 (0.8%) developed acute abdomen with suspicion of mesenteric ischemia. Seven (0.4%) underwent resection for ischemic lesions (group 1), of whom two were during a second look laparotomy. The other six patients had normal bowel (group 2). Both groups were comparable according to preoperative status, clinical signs, biological and radiological findings. Delays to laparotomy were 13.7+/-19.0 and 51.4+/-29.0 h in group 1 and 2, respectively (P=0.02). Mortality rates were 46.1% (6/13) overall, 42.8% for group 1 and 50% for group 2. All deaths occurred within the first nine postoperative days. Mesenteric ischemia following CABG is a fatal complication in almost half the cases. Diagnostic tools and timely laparotomy still need to be optimized. Low threshold-based strategy for prompt surgical intervention is efficient for both diagnosis and treatment. | 18,815,161 |
Aggressive organ donor management protocol. | As of August 2007, 96 900 people are awaiting organ transplantation in the United States, while only 28 930 transplants were performed in 2006. With such a large gap between organ need and organ availability, it is inevitable that many will die while awaiting transplantation. This organ shortage has become a national public health crisis, and as a response, the United States Department of Health and Human Services launched the Organ Donation Breakthrough Collaborative, an ambitious campaign to dramatically increase the number of transplantable organs. One of the suggested strategies involves maximizing the number of organs obtained from the available cadaveric "brain dead'' donor pool by using donor management protocols that optimize and treat the profound physiological disturbances that are associated with brain death. The use of these standardized and aggressive donor management protocols has been shown to increase the number of transplanted organs and prevent the number of donors lost due to medical failures. A protocol-driven approach by a dedicated organ donor management team should be considered a key component of any program designed to bridge the gap between organ supply and demand. | 18,815,202 |
Inhibitors of GlyT1 affect glycine transport via discrete binding sites. | In the forebrain, synaptic glycine concentrations are regulated through the glycine transporter GlyT1. Because glycine is a coagonist of the N-methyl-D-aspartate (NMDA) receptor (NMDAR), which has been implicated in schizophrenia, inhibition of GlyT1 is thought to provide an option for the treatment of schizophrenia. In support of this hypothesis, GlyT1 inhibitors facilitate in vivo NMDAR function and demonstrate antipsychotic-like effects in animal models. Among the specific GlyT1 inhibitors, substituted N-methyl-glycine (sarcosine) derivatives (e.g., (R)-N[3-(4'fluorophenyl)-3-(4'phenyl-phenoxy)propyl]-sarcosine [NFPS], (R)-N[3-phenyl-3-(4'-(4-toluoyl)phenoxy)-propyl]sarcosine [(R)-NPTS], and (R,S)-(+/-)N-methyl-N-[(4-trifluoromethyl)phenoxy]-3-phenyl-propylglycine [Org24589]), and non-sarcosine-containing inhibitors, such as 2-chloro-N-[(S)-phenyl[(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide, monohydrochloride (SSR504734), have been described. In the present study, we analyzed the mode of interaction of these compounds with GlyT1 by using electrophysiological measurements in Xenopus laevis oocytes, and with two binding assays, using [(3)H](R)-NPTS or 2-chloro-N-[(S)-phenyl[(2S)-N-methylpiperidin-2-yl]-methyl]-3-trifluoromethyl benzamide monohydrochloride ([(3)H]N-methyl-SSR504734) as radioligands. Inhibition of electrogenic glycine transport by sarcosine-based compounds was apparently irreversible and independent of glycine concentration. The latter indicates a noncompetitive mode of action. In contrast, both SSR504734 and N-methyl-SSR504734 exhibited reversible and competitive inhibition of glycine transport. In GlyT1-expressing membranes, the binding of the novel radioligand [(3)H]N-methyl-SSR504734 to a single site on GlyT1 was competitively displaced by glycine and SSR504734 but noncompetitively by sarcosine-based compounds. Inversely, [(3)H](R)-NPTS binding was competitively inhibited by sarcosine-based compounds, whereas glycine, SSR504734, and N-methyl-SSR504734 noncompetitively decreased maximal binding. Our data indicate that besides exerting an apparently irreversible or reversible inhibition, GlyT1 inhibitors differ by exhibiting either a noncompetitive or competitive mode of inhibition. The divergent modes of inhibition may significantly affect the efficacy and tolerability of these drugs. | 18,815,213 |
The monomeric G proteins AGS1 and Rhes selectively influence Galphai-dependent signaling to modulate N-type (CaV2.2) calcium channels. | Activator of G protein Signaling 1 (AGS1) and Ras homologue enriched in striatum (Rhes) define a new group of Ras-like monomeric G proteins whose signaling properties and physiological roles are just beginning to be understood. Previous results suggest that AGS1 and Rhes exhibit distinct preferences for heterotrimeric G proteins, with AGS1 selectively influencing Galphai and Rhes selectively influencing Galphas. Here, we demonstrate that AGS1 and Rhes trigger nearly identical modulation of N-type Ca(2+) channels (Ca(V)2.2) by selectively altering Galphai-dependent signaling. Whole-cell currents were recorded from HEK293 cells expressing Ca(V)2.2 and Galphai- or Galphas-coupled receptors. AGS1 and Rhes reduced basal current densities and triggered tonic voltage-dependent (VD) inhibition of Ca(V)2.2. Additionally, each protein attenuated agonist-initiated channel inhibition through Galphai-coupled receptors without reducing channel inhibition through a Galphas-coupled receptor. The above effects of AGS1 and Rhes were blocked by pertussis toxin (PTX) or by expression of a Gbetagamma-sequestering peptide (masGRK3ct). Transfection with HRas, KRas2, Rap1A-G12V, Rap2B, Rheb2, or Gem failed to duplicate the effects of AGS1 and Rhes on Ca(V)2.2. Our data provide the first demonstration that AGS1 and Rhes exhibit similar if not identical signaling properties since both trigger tonic Gbetagamma signaling and both attenuate receptor-initiated signaling by the Gbetagamma subunits of PTX-sensitive G proteins. These results are consistent with the possibility that AGS1 and Rhes modulate Ca(2+) influx through Ca(V)2.2 channels under more physiological conditions and thereby influence Ca(2+)-dependent events such as neurosecretion. | 18,815,223 |
Potentially exposed but uninfected individuals produce cytotoxic and polyfunctional human immunodeficiency virus type 1-specific CD8(+) T-cell responses which can be defined to the epitope level. | We measured CD8(+) T-cell responses in 12 potentially exposed but uninfected men who have sex with men by using cytokine flow cytometry. Four of the individuals screened exhibited polyfunctional immune responses to human immunodeficiency virus type 1 Gag or Vif. The minimum cytotoxic T lymphocyte epitope was mapped in one Gag responder. | 18,815,234 |
Effects of medial meniscus posterior horn avulsion and repair on tibiofemoral contact area and peak contact pressure with clinical implications. | Avulsion of the posterior horn attachment of the medial meniscus can compromise load-bearing ability, produce meniscus extrusion, and result in tibiofemoral joint-space narrowing, articular cartilage damage, and osteoarthritis. Avulsion of the posterior horn of the medial meniscus will increase peak contact pressure and decrease contact area in the medial compartment of the knee, and posterior horn repair will restore contact area and peak contact pressures to values of the control knee. Controlled laboratory study. Eight fresh-frozen human cadaveric knees had tibiofemoral peak contact pressures and contact area measured in the control state. The posterior horn of the medial meniscus was avulsed from its insertion and knees were retested. The meniscal avulsion was repaired by suture through a transosseous tunnel and the knees were tested a third time. Avulsion of the posterior horn attachment of the medial meniscus resulted in a significant increase in medial joint peak contact pressure (from 3841 kPa to 5084 kPa) and a significant decrease in contact area (from 594 mm(2) to 474 mm(2)). Repair of the avulsion resulted in restoration of the loading profiles to values equal to the control knee, with values of 3551 kPa for peak pressure and 592 mm(2) for contact area. Posterior horn medial meniscal root avulsion leads to deleterious alteration of the loading profiles of the medial joint compartment and results in loss of hoop stress resistance, meniscus extrusion, abnormal loading of the joint, and early knee medial-compartment degenerative changes. The repair technique described restores the ability of the medial meniscus to absorb hoop stress and eliminate joint-space narrowing, possibly decreasing the risk of degenerative disease. | 18,815,238 |
Mitochondria modulate Ca2+-dependent glutamate release from rat cortical astrocytes. | Vesicular glutamate release from astrocytes depends on mobilization of free Ca(2+) from the endoplasmic reticulum (ER), and extracellular space to elevate cytosolic Ca(2+) (Ca(2+)(cyt)). Although mitochondria in neurons, and other secretory cells, have been shown to sequester free Ca(2+) and have been implicated in the modulation of Ca(2+)-dependent transmitter release, the role of mitochondria in Ca(2+)-dependent glutamate release from astrocytes is not known. A pharmacological approach was taken to manipulate Ca(2+) accumulation in mitochondria and thereby affect Ca(2+)(cyt) of solitary astrocytes in response to mechanical stimuli. Ca(2+)(cyt) responses and levels of glutamate release were measured optically in parallel experiments using a fluorescent Ca(2+) indicator and an enzyme-linked assay, respectively. It was observed that inhibiting mitochondrial Ca(2+) accumulation is correlated to increased Ca(2+)(cyt) and glutamate release, whereas enhancing mitochondrial Ca(2+) accumulation is correlated to decreased Ca(2+)(cyt) and glutamate release. These observations suggest that, in addition to the activity of ER and plasma membrane ion channels, mitochondria modulate Ca(2+)(cyt) dynamics in astrocytes and play a role in Ca(2+)-dependent glutamate release from astrocytes. | 18,815,254 |
Increased vesicular monoamine transporter binding during early abstinence in human methamphetamine users: Is VMAT2 a stable dopamine neuron biomarker? | Animal data indicate that methamphetamine can damage striatal dopamine terminals. Efforts to document dopamine neuron damage in living brain of methamphetamine users have focused on the binding of [(11)C]dihydrotetrabenazine (DTBZ), a vesicular monoamine transporter (VMAT2) positron emission tomography (PET) radioligand, as a stable dopamine neuron biomarker. Previous PET data report a slight decrease in striatal [(11)C]DTBZ binding in human methamphetamine users after prolonged (mean, 3 years) abstinence, suggesting that the reduction would likely be substantial in early abstinence. We measured striatal VMAT2 binding in 16 recently withdrawn (mean, 19 d; range, 1-90 d) methamphetamine users and in 14 healthy matched-control subjects during a PET scan with (+)[(11)C]DTBZ. Unexpectedly, striatal (+)[(11)C]DTBZ binding was increased in methamphetamine users relative to controls (+22%, caudate; +12%, putamen; +11%, ventral striatum). Increased (+)[(11)C]DTBZ binding in caudate was most marked in methamphetamine users abstinent for 1-3 d (+41%), relative to the 7-21 d (+15%) and >21 d (+9%) groups. Above-normal VMAT2 binding in some drug users suggests that any toxic effect of methamphetamine on dopamine neurons might be masked by an increased (+)[(11)C]DTBZ binding and that VMAT2 radioligand binding might not be, as is generally assumed, a "stable" index of dopamine neuron integrity in vivo. One potential explanation for increased (+)[(11)C]DTBZ binding is that VMAT2 binding is sensitive to changes in vesicular dopamine storage levels, presumably low in drug users. If correct, (+)[(11)C]DTBZ might be a useful imaging probe to correlate changes in brain dopamine stores and behavior in users of methamphetamine. | 18,815,269 |
Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo. | Expression of latent membrane protein 2 (LMP2A) during B-cell development leads to global alterations in gene transcription similar to those seen in Hodgkin Reed-Sternberg cells of Hodgkin lymphoma (HL). Along with the consistent detection of LMP2A in Epstein-Barr virus-associated HL, this implicates a role for LMP2A in the pathogenesis of HL. We have shown that LMP2A constitutively activates the Notch1 pathway to autoregulate the LMP2A promoter. To determine whether constitutive activation of the Notch pathway is important for LMP2A-mediated alterations in B-cell development in vivo, TgE-LMP2A-transgenic mice were intercrossed with mice expressing loxP-flanked Notch1 genes and Cre recombinase. B cells from TgE Notch1(lox/lox)-CD19(+/Cre) mice have an increase in immunoglobulin M and CD43 and a decrease in CD5 expression in the bone marrow compared with TgE Notch1(lox/lox) mice, indicating the LMP2A signal for developmental aberrations is impaired in the absence of Notch1. Real-time reverse-transcribed polymerase chain reaction analysis reveals that LMP2A requires the Notch1 pathway to alter levels of B cell-specific transcription factors, E2A and EBF. Interestingly, Notch1 appears to be important for LMP2A-mediated survival in low interleukin-7. We propose that LMP2A and the Notch1 pathway may cooperate to induce the alterations in B-cell identity seen in Hodgkin Reed-Sternberg cells. | 18,815,281 |
Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor-CD3 expression in enteropathy-associated T-cell lymphoma. | Enteropathy-associated T-cell lymphoma, an often fatal complication of celiac disease, can result from expansion of aberrant intraepithelial lymphocytes in refractory celiac disease type II (RCD II). Aberrant intraepithelial lymphocytes and lymphoma cells are intracellularly CD3epsilon(+) but lack expression of the T-cell receptor (TCR)-CD3 complex on the cell surface. It is unknown what causes the loss of TCR-CD3 expression. We report the isolation of a cell line from an RCD II patient with the characteristic phenotype of enteropathy-associated T-cell lymphoma. We demonstrate that in this cell line the TCR-alpha and -beta chains as well as the CD3gamma, CD3delta, CD3epsilon, and zeta-chains are present intracellularly and that assembly of the CD3gammaepsilon, CD3deltaepsilon, and zetazeta-dimers is normal. However, dimerization of the TCR chains and proper assembly of the TCR-CD3 complex are defective. On introduction of exogenous TCR-beta chains, but not of TCR-alpha chains, assembly and functional cell surface expression of the TCR-CD3 complex were restored. Defective synthesis of both TCR chains was found to underlie loss of TCR expression in similar cell lines isolated from 2 additional patients. (Pre)malignant transformation in RCD II thus correlates with defective synthesis or defective association of the TCR chains, resulting in loss of surface TCR-CD3 expression. | 18,815,285 |
Mutational analysis of cis-acting RNA signals in segment 7 of influenza A virus. | The genomic viral RNA (vRNA) segments of influenza A virus contain specific packaging signals at their termini that overlap the coding regions. To further characterize cis-acting signals in segment 7, we introduced synonymous mutations into the terminal coding regions. Mutation of codons that are normally highly conserved reduced virus growth in embryonated eggs and MDCK cells between 10- and 1,000-fold compared to that of the wild-type virus, whereas similar alterations to nonconserved codons had little effect. In all cases, the growth-impaired viruses showed defects in virion assembly and genome packaging. In eggs, nearly normal numbers of virus particles that in aggregate contained apparently equimolar quantities of the eight segments were formed, but with about fourfold less overall vRNA content than wild-type virions, suggesting that, on average, fewer than eight segments per particle were packaged. Concomitantly, the particle/PFU and segment/PFU ratios of the mutant viruses showed relative increases of up to 300-fold, with the behavior of the most defective viruses approaching that predicted for random segment packaging. Fluorescent staining of infected cells for the nucleoprotein and specific vRNAs confirmed that most mutant virus particles did not contain a full genome complement. The specific infectivity of the mutant viruses produced by MDCK cells was also reduced, but in this system, the mutations also dramatically reduced virion production. Overall, we conclude that segment 7 plays a key role in the influenza A virus genome packaging process, since mutation of as few as 4 nucleotides can dramatically inhibit infectious virus production through disruption of vRNA packaging. | 18,815,307 |
Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis. | Intratumoral innate immunity can play a significant role in blocking the effective therapeutic spread of a number of oncolytic viruses (OVs). Histone deacetylase inhibitors (HDIs) are known to influence epigenetic modifications of chromatin and can blunt the cellular antiviral response. We reasoned that pretreatment of tumors with HDIs could enhance the replication and spread of OVs within malignancies. Here, we show that HDIs markedly enhance the spread of vesicular stomatitis virus (VSV) in a variety of cancer cells in vitro, in primary tumor tissue explants and in multiple animal models. This increased oncolytic activity correlated with a dampening of cellular IFN responses and augmentation of virus-induced apoptosis. These results illustrate the general utility of HDIs as chemical switches to regulate cellular innate antiviral responses and to provide controlled growth of therapeutic viruses within malignancies. HDIs could have a profoundly positive impact on the clinical implementation of OV therapeutics. | 18,815,361 |
cAMP/PKA signaling and RIM1alpha mediate presynaptic LTP in the lateral amygdala. | NMDA receptor-dependent long-term potentiation (LTP) of glutamatergic synaptic transmission in sensory pathways from auditory thalamus or cortex to the lateral amygdala (LA) underlies the acquisition of auditory fear conditioning. Whereas the mechanisms of postsynaptic LTP at thalamo-LA synapses are well understood, much less is known about the sequence of events mediating presynaptic NMDA receptor-dependent LTP at cortico-LA synapses. Here, we show that presynaptic cortico-LA LTP can be entirely accounted for by a persistent increase in the vesicular release probability. At the molecular level, we found that signaling via the cAMP/PKA pathway is necessary and sufficient for LTP induction. Moreover, by using mice lacking the active-zone protein and PKA target RIM1alpha (RIM1alpha(-/-)), we demonstrate that RIM1alpha is required for both chemically and synaptically induced presynaptic LTP. Further analysis of cortico-LA synaptic transmission in RIM1alpha(-/-) mice revealed a deficit in Ca(2+)-release coupling leading to a lower baseline release probability. Our results reveal the molecular mechanisms underlying the induction of presynaptic LTP at cortico-LA synapses and indicate that RIM1alpha-dependent LTP may involve changes in Ca(2+)-release coupling. | 18,815,362 |
Analysis and synthesis of high-amplitude Cis-elements in the mammalian circadian clock. | Mammalian circadian clocks consist of regulatory loops mediated by Clock/Bmal1-binding elements, DBP/E4BP4 binding elements, and RevErbA/ROR binding elements. As a step toward system-level understanding of the dynamic transcriptional regulation of the oscillator, we constructed and used a mammalian promoter/enhancer database (http://promoter.cdb.riken.jp/) with computational models of the Clock/Bmal1-binding elements, DBP/E4BP4 binding elements, and RevErbA/ROR binding elements to predict new targets of the clock and subsequently validated these targets at the level of the cell and organism. We further demonstrated the predictive nature of these models by generating and testing synthetic regulatory elements that do not occur in nature and showed that these elements produced high-amplitude circadian gene regulation. Biochemical experiments to characterize these synthetic elements revealed the importance of the affinity balance between transactivators and transrepressors in generating high-amplitude circadian transcriptional output. These results highlight the power of comparative genomics approaches for system-level identification and knowledge-based design of dynamic regulatory circuits. | 18,815,372 |
Opposing functions of IKKbeta during acute and chronic intestinal inflammation. | NF-kappaB is a key transcriptional regulator of inflammatory responses, but also controls expression of prosurvival genes, whose products protect tissues from damage and may thus act indirectly in an antiinflammatory fashion. The variable importance of these two distinct NF-kappaB-controlled responses impacts the potential utility of NF-kappaB inhibition as a treatment strategy for intractable inflammatory conditions, such as inflammatory bowel disease. Here, we show in murine models that inhibition of IKKbeta-dependent NF-kappaB activation exacerbates acute inflammation, but attenuates chronic inflammatory disease in the intestinal tract. Acute ulcerating inflammation is aggravated because of diminished NF-kappaB-mediated protection against epithelial cell apoptosis and delayed mucosal regeneration secondary to reduced NF-kappaB-dependent recruitment of inflammatory cells that secrete cytoprotective factors. In contrast, in IL-10-deficient mice, which serve as a model of chronic T cell-dependent colitis, ablation of IKKbeta in the intestinal epithelium has no impact, yet IKKbeta deficiency in myeloid cells attenuates inflammation and prolongs survival. These results highlight the striking context and tissue dependence of the proinflammatory and antiapoptotic functions of NF-kappaB. Our findings caution against the therapeutic use of IKKbeta/NF-kappaB inhibitors in acute inflammatory settings dominated by cell loss and ulceration. | 18,815,378 |
Cicatrising conjunctivitis with anti-basement membrane autoantibodies in ectodermal dysplasia. | To report circulating and mucosa-deposited anti-basement membrane zone autoantibodies in a series of six ectodermal dysplasia patients with severe bilateral cicatrising conjunctivitis and blindness due to both corneal disease and intractable surface inflammation. We also report clinical improvement with steroid-sparing systemic immunosuppression combined with clearance of bacterial colonisation. Conjunctival and buccal immunohistopathology, and serological analysis using a panel of epithelial basement membrane zone proteins including the bullous pemphigoid antigen 180 (BP180) were carried out as part of an ocular pemphigoid work-up in each patient. The degree of photophobia, conjunctival inflammation and visual acuity were monitored to evaluate the response to immunosuppression. The mean duration of follow-up was 31 (SD 6) months. Four of the six patients showed positive immunopathology: direct immunofluorescence testing of the conjunctiva in one patient demonstrated linear IgA deposition along the basement membrane zone, and IgG and IgM in the buccal mucosa of another patient. Circulating autoantibodies to BP180 were detected in two other patients. Treatment with systemic immunosuppression, combined with clearance of bacterial colonisation, reduced the severity of photophobia and degree of conjunctival inflammation in 5/6 (83%) patients. Systemic immunosuppression, used as steroid-sparing therapy, combined with clearance of bacterial colonisation can control inflammation and disabling photophobia, and allow improvement in vision, in a subgroup of ectodermal dysplasia patients who have severe cicatrising conjunctivitis which shares clinical and immunopathological features with ocular mucous membrane pemphigoid. | 18,815,422 |
The elasticity and rigidity of the outer coats of the eye. | The aim of this study was to measure the elastic moduli of the cornea and sclera and the rigidity of the eyeball. Elastic moduli of the cornea and sclera were measured on 22 fresh intact porcine eyes using the relationship between elasticity and changes in pressure and volume applicable to pressure vessel models. Rigidity was determined from the relationship between changes in volume and intraocular pressure (IOP). Induced volume changes were up to 300 mul and within the physiological range of IOP (12-25 mm Hg). IOP readings taken with a transducer were used in calculations. Tonometric values were taken for comparison. For cornea and sclera, the relationship between circumferential stress and volumetric strain (which defines the elastic modulus) was closely approximated to linear (R(2) = 0.96), but better fitted with a second order polynomial (R(2) = 1.00). Elastic moduli ranged from 0.05 to 0.24 MPa and 0.15 to 0.83 MPa for the cornea and sclera, respectively. The mean value of ocular rigidity was found to be 0.0024. The effect of increasing IOP on the average corneal radius of curvature was not statistically significant, but it altered the scleral radius of curvature by 0.07 mm/mmHg. The elasticity of the porcine cornea and sclera could be approximated to constant over the physiological range, but showed a tendency to non-linearity. The modulus of elasticity for the sclera is 3 to 3.5 times that of the cornea. The cornea is more resistant than the sclera to IOP changes within the physiological range. | 18,815,423 |
Novel splice donor site mutation in MERTK gene associated with retinitis pigmentosa. | Mutations in MERTK, a member of the MER/AXL/TYRO3 receptor kinase family, have been associated with disruption of the Retinal Pigment Epithelium (RPE) phagocytosis pathway and settling of autosomal recessive RP (arRP) in humans. This study reports a novel MERTK mutation (IVS16+1G>T) in a Spanish consanguineous family presenting arRP. 21 genes were screened by high-throughput SNP multiplexing assay. Subsequent direct sequencing was performed in exons and intronic boundaries of the cosegregating gene. The effect of the mutation in mRNA splicing was confirmed by cDNA analysis. Haplotypic data revealed MERTK cosegregation with RP in affected individuals. MERTK sequencing showed a G-to-T substitution at the first nucleotide of intron 16. Finally, cDNA analysis confirmed the lack of exon 16 in the mRNA splicing process. IVS16+1G>T disrupts the splice donor site causing exon 16 skipping. Absence of exon 16 causes a frameshift and, subsequently, the introduction of a premature termination codon into exon 17 creating an altered mRNA transcript with a seriously affected tyrosine kinase domain. | 18,815,424 |
Do attention deficits influence IQ assessment in children and adolescents with ADHD? | To characterize the relationship between IQ and attention deficits in children with ADHD and to estimate the inattention-related mean influence on IQ when children are tested before stimulant drug treatment has been initiated. Studies of various methodologies are reviewed. Correlation studies show mostly weak associations between IQ scores and attention deficits. Meta-analyses report the average short-term stimulant treatment effect on IQ in children with ADHD to be 2 to 7 IQ points. The associations between IQ and attention deficits in ADHD are generally modest, with the mean influence on IQ probably amounting to 2 to 5 IQ points. This may serve as a benchmark when clinicians interpret the validity of IQ in this clinical population. | 18,815,437 |
"I'm a different kind of nurse": advice from nurses in rural and remote Canada. | The sustainability of the rural and remote nursing workforce in Canada is increasingly at issue as the country becomes more urbanized and the nursing workforce ages. In order to support the retention of nurses in rural and remote communities and the recruitment of nurses to these communities, we require a better understanding of what is important to rural and remote nurses themselves. As part of the in-depth interviews conducted within The Nature of Nursing Practice in Rural and Remote Canada, a national research project, registered nurses (RNs) were asked what advice they would have for new nurses, educators, administrators and policy makers. This is the first of two papers describing that advice. It focuses on RNs in acute care, long-term care, home care, community health/public health and primary care roles in rural and remote communities across the country. The RNs were generous with their advice and gave many rich examples. While they were enthusiastic about their nursing practice and encouraging of other nurses to work in rural settings, they were intent that improvements be made in several key areas: education available to new practitioners and themselves, working conditions for rural and remote nurses, leadership, organizational supports and policies that better support rural and remote practice and communities. | 18,815,470 |
Sleep in the intensive care unit setting. | Sleep is essential to human life. Sleep patterns are significantly disrupted in patients who are hospitalized, particularly those in the intensive care unit. Sleep deprivation is pervasive in this patient population and impacts health and recovery from illness. Immune system dysfunction, impaired wound healing, and changes in behavior are all observed in patients who are sleep deprived. Various factors including anxiety, fear, and pain are responsible for the sleep deprivation. Noise, light exposure, and frequent awakenings from caregivers also add to these effects. Underlying medical illnesses and medications can also dramatically affect a patient's ability to sleep efficiently. Therapy with attempts to minimize sleep disruption should be integrated among all of the caregivers. Minimization of analgesics and other medications known to adversely affect sleep should also be ensured. Although further research in the area of sleep deprivation in the intensive care unit setting needs to be conducted, effective protocols can be developed to minimize sleep deprivation in these settings. | 18,815,477 |
Muscle fascicle and tendon behavior during human locomotion revisited. | High-speed ultrasonography has revealed that, in human locomotion, the nature of fascicle and tendon length changes varies depending on the task, contraction intensity, and the muscles involved. The findings emphasize that the active fascicles of the gastrocnemius muscle are suddenly stretched, although they are shortening. This short-lasting stretch triggers the stretch reflex, timing of which is dependent on running speed. | 18,815,488 |
Hispanics and health insurance coverage: the rising disparity. | Many reports have focused attention on the rising percentage of adults in the United States without health insurance. This hides the fact that the uninsured rate for non-Hispanic nonelderly adults has held fairly steady since 1983, while the rate for Hispanics has increased. To document the trends in the coverage rate by source of coverage for different population groups between 1983 and 2003 and suggest how changes in the composition of these groups have contributed to these trends. We stack panels of the Survey of Income and Program Participation to create a nationally representative 20-year pooled cross-section of nonelderly adults. We calculate actual trends in insurance coverage as well as 2 hypothetical time series that disentangle the effect of the decreasing coverage rate for Hispanics from the growth of the Hispanic adult population. Although the increase in uninsured rate is largest for Hispanic noncitizens, US-born Hispanics also have a significant upward trend, primarily driven by a decrease in private coverage, with little change in public coverage. Although the increase in the Hispanic population contributed to the increase in the number of uninsured adults, the widening coverage disparity was more important. Hispanic nonelderly adults, both US-born and immigrants, have fallen behind non-Hispanic nonelderly adults in insurance coverage. Although combinations of economic growth and private and public insurance policy changes have maintained, and in some cases improved, overall coverage rates for non-Hispanics, these changes have not helped Hispanic adults, leading to increased disparities in coverage. | 18,815,531 |
Pdx-1-driven overexpression of aurora a kinase induces mild ductal dysplasia of pancreatic ducts near islets in transgenic mice. | To further explore the oncogenic activity of Aurora A kinase while attempting to develop a useful mouse model for pancreatic cancer, Aurora A kinase was targeted to pancreatic duodenal homeobox gene-1 (Pdx-1)-positive cells. Aurora A kinase overexpression was targeted to mouse pancreas tissues using the Pdx-1 promoter in a transgenic model. The pancreas tissues of 7- to 11-month-old transgenic animals were evaluated for metastatic adenocarcinomas, preinvasive ductal neoplasia, or other histological anomalies. Examination of pancreatic tissue from Pdx-1-Aurora A transgenic mice revealed abnormalities, such as mild islet cell hyperplasia, lymphocytic infiltration, and general dysplasia between ductal/islet cell interfaces. However, most tissues from these transgenic mice were normal. The overexpression of Aurora A can potentially initiate the development of mild abnormalities in pancreatic tissue; however, neither preinvasive ductal neoplasia nor fully metastatic adenocarcinomas were observed. Combining the Pdx-1-Aurora A transgenic model with other genetic alterations may provide additional insight. | 18,815,537 |
Prophylactic octreotide administration does not prevent post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. | There is no consensus whether octreotide can prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We performed a meta-analysis comparing octreotide with placebo in randomized controlled trials. : Electronic databases, including MEDLINE, EMBASE, Cochrane controlled trials register, the Cochrane Library, and the Science Citation Index updated to January 2007, were searched to retrieve relevant randomized controlled trials. Outcome measures were post-ERCP pancreatitis. : Fifteen trials were identified, and statistical homogeneity was present among these selected trials. After all the trials were pooled, post-ERCP pancreatitis occurred in 7.0% of controls (92 of 1320) versus 5.5% of treated patients (72 of 1301), without statistical significance (odds ratio, 0.78; 95% confidence interval, 0.57-1.08). Subsequent sensitivity analyses and subgroup analyses also produced no significant effect. Only in large-scale trials (>200 cases) that octreotide could statistically, significantly prevent pancreatitis (odds ratio, 0.50; 95% confidence interval, 0.32-0.79). : On the basis of current best evidence, octreotide cannot prevent post-ERCP pancreatitis. | 18,815,543 |
Islet auto transplantation following total pancreatectomy: a long-term assessment of graft function. | Total pancreatectomy is considered the final resort in the treatment of chronic pancreatitis; however, here we show that simultaneous islet autotransplantation can abrogate the onset of diabetes. : In Leicester, 46 patients have now undergone total pancreatectomy with immediate islet auto transplant, and they have received a median of 2246 islet equivalent (IEQ)/kg body weight (range, 405-20,385 IEQ/kg body weight). : Twelve patients have shown periods of insulin independence, for a median of 16.5 months (range, 2-63 months), and 5 remain insulin independent. Over the 10 years of follow-up, there has been a notable increase in insulin requirement per kilogram per day, and percentage of glycosylated hemoglobin levels have increased significantly (r = 0.66, P = 0.01). However, 100% of patients tested were C-peptide positive at their most recent assessment, and high fasting and stimulated C-peptide values recorded at 10 years after transplantation, 1.44 (range, 1.09-1.8 ng/mL) and 2.86 ng/mL (range, 1.19-4.53 ng/mL), respectively, suggest significant graft function in the long term. In addition, median serum creatinine has increased very little after the operation (71 nmol/L [range, 49-125 nmol/L] atpreoperation vs 76.5 nmol/L [range 72-81 nmol/L] at year 10), suggesting no diabetic nephropathy. : Although there is a notable decline in islet function after islet auto transplant, there is still evidence of significant long-term insulin secretion and possible protection against diabetic complications. | 18,815,550 |
Involvement of phosphatidylinositol-3 kinase/AKT/PKCzeta/lambda pathway in the effect of palmitate on glucose-induced insulin secretion. | In the present study, a novel pathway by which palmitate potentiates glucose-induced insulin secretion by pancreatic beta cells was investigated. Groups of freshly isolated islets were incubated in 10 mM glucose with palmitate, LY294002, wortmannin, and fumonisin B1 for measurement of insulin secretion by radioimmunoassay (RIA). Also, phosphorylation and content of AKT and PKC proteins were evaluated by immunoblotting. Glucose plus palmitate and glucose plus LY294002 or wortmannin (PI3K inhibitors) increased glucose-induced insulin secretion by isolated pancreatic islets. Glucose at 10 mM induced AKT and PKCzeta/lambda phosphorylation. Palmitate (0.1 mM) abolished glucose stimulation of AKT and PKCzeta/lambda phosphorylation possibly through PI3K inhibition because both LY294002 (50 microM) and wortmannin (100 nM) caused the same effect. The inhibitory effect of palmitate on glucose-induced AKT and PKCzeta/lambda phosphorylation and the stimulatory effect of palmitate on glucose-induced insulin secretion were not observed in the presence of fumonisin B1, an inhibitor of ceramide synthesis. These findings support the proposition that palmitate increases insulin release in the presence of 10 mM glucose by inhibiting PI3K activity through a mechanism that involves ceramide synthesis. | 18,815,554 |
Are acute effects of maximal dynamic contractions on upper-body ballistic performance load specific? | This study investigated the acute effects of upper-body maximal dynamic contractions on maximal throwing speed with 0.55- and 4-kg medicine balls. It was hypothesized that heavy preloading would transiently improve throwing performance only when overcoming the heavier of the two loads. Twenty-three male volunteers were randomly allocated into experimental (n = 11) and control (n = 12) groups. Both groups performed initial and final seated medicine ball throws from the chest, and the maximal medicine ball speed was measured by means of a radar gun. Between the two measurements, the control group rested passively for 15 minutes, and the experimental group performed three sets of three-repetition maximum bench presses. For the 0.55-kg load, a 2 x 2 repeated-measures analysis of variance revealed no significant effect of time x group interaction (p = 0.22), as well as no significant time (p = 0.22) or group (p = 0.72) effects. In contrast, for the 4-kg load, a significant time x group interaction (p = 0.004) and a significant time (p = 0.035) but not group (p = 0.77) effect were observed. Analysis of simple main effects revealed that the experimental group significantly (8.3%; p < 0.01) improved maximal throwing speed with the 4-kg load. These results support our research hypothesis and suggest that the acute effects of heavy preloading on upper-body ballistic performance might be load specific. In a practical sense, our findings suggest that the use of upper-body heavy resistance exercise before ballistic throwing movements against moderate external loads might be an efficient training strategy for improving an athlete's upper-body explosive performance. | 18,815,568 |
Promoter-driven splicing regulation in fission yeast. | The meiotic cell cycle is modified from the mitotic cell cycle by having a pre-meiotic S phase that leads to high levels of recombination, two rounds of nuclear division with no intervening DNA synthesis and a reductional pattern of chromosome segregation. Rem1 is a cyclin that is only expressed during meiosis in the fission yeast Schizosaccharomyces pombe. Cells in which rem1 has been deleted show decreased intragenic meiotic recombination and a delay at the onset of meiosis I (ref. 1). When ectopically expressed in mitotically growing cells, Rem1 induces a G1 arrest followed by severe mitotic catastrophes. Here we show that rem1 expression is regulated at the level of both transcription and splicing, encoding two proteins with different functions depending on the intron retention. We have determined that the regulation of rem1 splicing is not dependent on any transcribed region of the gene. Furthermore, when the rem1 promoter is fused to other intron-containing genes, the chimaeras show a meiotic-specific regulation of splicing, exactly the same as endogenous rem1. This regulation is dependent on two transcription factors of the forkhead family, Mei4 (ref. 2) and Fkh2 (ref. 3). Whereas Mei4 induces both transcription and splicing of rem1, Fkh2 is responsible for the intron retention of the transcript during vegetative growth and the pre-meiotic S phase. | 18,815,595 |
ROS3 is an RNA-binding protein required for DNA demethylation in Arabidopsis. | DNA methylation is an important epigenetic mark for transcriptional gene silencing (TGS) in diverse organisms. Recent studies suggest that the methylation status of a number of genes is dynamically regulated by methylation and demethylation. In Arabidopsis, active DNA demethylation is mediated by the ROS1 (repressor of silencing 1) subfamily of 5-methylcytosine DNA glycosylases through a base excision repair pathway. These demethylases have critical roles in erasing DNA methylation and preventing TGS of target genes. However, it is not known how the demethylases are targeted to specific sequences. Here we report the identification of ROS3, an essential regulator of DNA demethylation that contains an RNA recognition motif. Analysis of ros3 mutants and ros1 ros3 double mutants suggests that ROS3 acts in the same genetic pathway as ROS1 to prevent DNA hypermethylation and TGS. Gel mobility shift assays and analysis of ROS3 immunoprecipitate from plant extracts shows that ROS3 binds to small RNAs in vitro and in vivo. Immunostaining shows that ROS3 and ROS1 proteins co-localize in discrete foci dispersed throughout the nucleus. These results demonstrate a critical role for ROS3 in preventing DNA hypermethylation and suggest that DNA demethylation by ROS1 may be guided by RNAs bound to ROS3. | 18,815,596 |
Future practice of graduates of the New Zealand Diploma of Obstetrics and Gynaecology or Certificate in Women's Health. | To determine: why Diploma of Obstetrics (DipObs), Diploma of Obstetrics and Medical Gynaecology (DipOMG), or Certificate in Women's Health graduates enrolled; course usefulness; and subsequent practice. 588 University of Otago DipObs, DipOMG, and Certificate in Women's Health graduates (1992-2006) plus Auckland University graduates (1996-2006) were identified. All were doctors. Questionnaires were sent to the 477 with New Zealand medical registration and responses analysed. 334 of the 477 graduates returned completed questionnaires--70% response rate. 73% had worked as GPs, 10% at family planning clinics, 6% at sexual health clinics; and 13% specialised in OandG. 80% enrolled to further knowledge in women's health, 20% in children's health, and 43% to practise GP obstetrics. Most respondents who enrolled in the 1990s intended to practise GP obstetrics but by 2000 most did not. Of 137 New Zealand-based GP respondents who enrolled to practise GP obstetrics, only 5 (3.6%) currently practise intrapartum obstetric care. Twenty-three GPs still practise shared maternity care. Of 220 primary care practitioners, 90% provide early antenatal care. 93% described the course as useful-extremely useful. The DipObs, Dip OMG and Certificate in Women's Health have continued to provide useful postgraduate training in women's health during a changing time in New Zealand pregnancy care. While many graduates of the 1990s enrolled to practise GP obstetrics, most recent graduates did not, and few GPs still practise intrapartum obstetrics. | 18,815,601 |
What can the history tell us? An argument for observed history-taking in the trainee intern long case assessment. | History-taking is one of the most important clinical skills for the medical student to learn and remains the core component of a doctor's diagnostic 'toolkit'. Yet, it is one of the most difficult clinical skills to assess. Clinical assessment at a trainee intern level has typically focussed on examination skills, and case presentation, which are more easily measured. History-taking is assumed to be of an adequate standard on the basis of the case presentation rather than by direct observation. In this paper we discuss the importance of assessing the patient-doctor encounter directly through observation, in the context of the trainee intern long case examination. Despite changing assessment trends in medical education, these authors argue for the retention of the long case as an assessment tool for final year medical students on the basis of its high face validity and close resemblance to "real life" patient encounters. However, we believe addition of an observing examiner during the history-taking and physical examination augments the inherent value of the longcase and is recommended in order to increase the reliability of the assessment. Observation allows for direct assessment of the student-patient interaction and the hypothetico-deductive approach taken by the student to diagnosis. It provides opportunity to reconcile the multiple interactions occurring between the context and the construct (skills and knowledge) measured in an assessment. Importantly, at a trainee intern level it provides students with a final opportunity to receive feedback on their history taking and diagnostic skills, an integral part of all medical practice, prior to their graduation as junior doctors. | 18,815,604 |
Genetic analysis of the role of protein kinase Ctheta in platelet function and thrombus formation. | PKCtheta is a novel protein kinase C isozyme, predominately expressed in T cells and platelets. PKCtheta(-/-) T cells exhibit reduced activation and PKCtheta(-/-) mice are resistant to autoimmune disease, making PKCtheta an attractive therapeutic target for immune modulation. Collagen is a major agonist for platelets, operating through an immunoreceptor-like signalling pathway from its receptor GPVI. Although it has recently been shown that PKCtheta positively regulates outside-in signalling through integrin alpha(IIb)beta(3) in platelets, the role of PKCtheta in GPVI-dependent signalling and functional activation of platelets has not been assessed. In the present study we assessed static adhesion, cell spreading, granule secretion, integrin alpha(IIb)beta(3) activation and platelet aggregation in washed mouse platelets lacking PKCtheta. Thrombus formation on a collagen-coated surface was assessed in vitro under flow. PKCtheta(-/-) platelets exhibited reduced static adhesion and filopodia generation on fibrinogen, suggesting that PKCtheta positively regulates outside-in signalling, in agreement with a previous report. In contrast, PKCtheta(-/-) platelets also exhibited markedly enhanced GPVI-dependent alpha-granule secretion, although dense granule secretion was unaffected, suggesting that PKCtheta differentially regulates these two granules. Inside-out regulation of alpha(IIb)beta(3) activation was also enhanced downstream of GPVI stimulation. Although this did not result in increased aggregation, importantly thrombus formation on collagen under high shear (1000 s(-1)) was enhanced. These data suggest that PKCtheta is an important negative regulator of thrombus formation on collagen, potentially mediated by alpha-granule secretion and alpha(IIb)beta(3) activation. PKCtheta therefore may act to restrict thrombus growth, a finding that has important implications for the development and safe clinical use of PKCtheta inhibitors. | 18,815,612 |
In situ observation of modulated light emission of fiber fuse synchronized with void train over hetero-core splice point. | Fiber fuse is a process of optical fiber destruction under the action of laser radiation, found 20 years ago. Once initiated, opical discharge runs along the fiber core region to the light source and leaves periodic voids whose shape looks like a bullet pointing the direction of laser beam. The relation between damage pattern and propagation mode of optical discharge is still unclear even after the first in situ observation three years ago. Fiber fuse propagation over hetero-core splice point (Corning SMF-28e and HI 1060) was observed in situ. Sequential photographs obtained at intervals of 2.78 micros recorded a periodic emission at the tail of an optical discharge pumped by 1070 nm and 9 W light. The signal stopped when the discharge ran over the splice point. The corresponding damage pattern left in the fiber core region included a segment free of periodicity. The spatial modulation pattern of the light emission agreed with the void train formed over the hetero-core splice point. Some segments included a bullet-shaped void pointing in the opposite direction to the laser beam propagation although the sequential photographs did not reveal any directional change in the optical discharge propagation. | 18,815,621 |
The sensitivity to key data imputations of recent estimates of income poverty and inequality in South Africa. | Existing literature using South African censuses reports an increase in both poverty and inequality over the 1996 to 2001 period. This paper assesses the robustness of these results to a number of weaknesses in the personal income variable. We use a sequential regression multiple imputation approach to impute missing values and to explicitly assess the influence of implausible income values and different rules used to convert income that is measured in bands into point incomes. Overall our results for 1996 and 2001 confirm the major findings from the existing literature while generating more reliable confidence intervals for the key parameters of interest than are available elsewhere. | 18,815,626 |
Ten-year follow-up of a province-wide cohort of surgical lung cancer patients in Nova Scotia. | After a diagnosis of lung carcinoma, survival is poor for all patients. We sought to assess 10-year survival and predictors of outcome after surgery for lung cancer in Nova Scotia. We identified all patients n = 130) undergoing resection for lung cancer in Nova Scotia in 1994 from the Nova Scotia Cancer Registry and hospital charts and followed them prospectively for 10 years. We used Cox proportional hazards modelling to identify predictors of survival. The patients' mean age at operation was 67.7 (standard deviation [SD] 8.2) years, and 70% of the patients were men. Most of the operations n = 80, 61.5%) were performed in Halifax, and adenocarcinoma n = 55, 42.3%) was the most common histologic type. At the time of surgery, 66.9% of the cases were stage 1, 20.0% were stage 2 and 13.1% were stage 3. Survival at 5 and 10 years was 34% and 13%, respectively. Age of 70 years or older (hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.20-2.68), large cell carcinoma (HR 2.27, 95% CI 1.31-3.94) and stage 3 cancer (HR 2.21, 95% CI 1.25-3.90) were significant independent predictors of survival. Hospital site was not associated with any difference in survival (p = 0.66), although there was a trend toward differential rates of lymph node sampling across sites (p = 0.06). The presence of node sampling was associated with improved survival in a separate multivariate model (HR 0.51, 95% CI 0.29-0.89). Actuarial survival after resection of lung carcinoma in Nova Scotia in 1994 was 34% at 5 years and 13% after 10 years. Age, stage and histology are independent predictors of survival; lymph node sampling was associated with greater survival. | 18,815,647 |
Endoscopic plantar fasciotomy in the treatment of chronic heel pain. | To evaluate endoscopic plantar fasciotomy for the treatment of recalcitrant heel pain. We undertook a retrospective study of the use of endoscopic plantar fasciotomy in the treatment of chronic heel pain that was unresponsive to conservative treatment. Over a 10-year period, we reviewed the charts of 55 patients with a minimum 12-month history of heel pain that failed to respond to standard nonoperative methods and had undergone the procedure described. All patients were clinically reviewed and completed a questionnaire based on the American Orthopaedic Foot and Ankle Society (AOFAS) score for ankle and hindfoot. The mean follow-up was 18 months. The mean preoperative AOFAS score was 66.5; the mean postoperative AOFAS score was 88.2. The mean preoperative pain score was 18.6; the mean postoperative pain score was 31.1. Complications were minimal (2 superficial wound infections). Overall, results were favourable in over 80% of patients. We conclude that endoscopic plantar fasciotomy is a reasonable option in the treatment of chronic heel pain that fails to respond to a trial of conservative treatment. | 18,815,651 |
Bis(benzimidazole)pyridine derivative as a new class of G-quadruplex inducing and stabilizing ligand. | Two new bis(benzimidazole)aryl derivatives have been prepared and one of them has been shown to induce and stabilize formation of a G-quadruplex. | 18,815,684 |
Apoferritin protein cages: a novel drug nanocarrier for photodynamic therapy. | A methylene blue-encapsulated apoferritin complex shows cytotoxic effects on MCF-7 human breast adenocarcinoma cells when irradiated at the appropriate wavelength. | 18,815,689 |
Direct observation of time and temperature dependent transition from spherical micelles to vesicles. | An interesting transition from spherical micelles to vesicles, which was time and temperature dependent, was observed for the first time; it is tentatively attributed to the thermal hysteresis of temperature-responsive poly(N-isopropylacrylamide). | 18,815,696 |
Sulfate anion-templated assembly of a [2]catenane. | The sulfate anion's templating role in catenane formation is demonstrated for the first time; a novel bis-pyridinium nicotinamide [2]catenane is prepared in a remarkable high yield and is shown to exhibit selectivity for sulfate, the templating anion. | 18,815,700 |
Impact of retirement on risky driving behavior and attitudes towards road safety among a large cohort of French drivers (the GAZEL cohort). | This study investigated changes in driving behavior and attitudes towards road safety, following retirement, in a large cohort of road users. In 2001, 14 226 participants of the GAZEL cohort in France reported their attitudes towards road safety and driving behavior using a self-administered driving behavior and road safety questionnaire. In 2004, 82% of the group (N=11 706) responded to the same questionnaire. Two complementary logistic regression analyses were performed to assess the association of (i) retirement with change in safe driving behavior and attitudes towards road safety between 2001 and 2004 and (ii) time since retirement with risky driving behavior and negative attitudes towards road safety in 2001. Among the participants who were active in 2001 (N=3927), those retiring between 2001 and 2004 (66%) were more likely to have discontinued sleepy driving [adjusted odds ratio (aOR) 2.12, P<0.001] and phone use while driving (aOR 1.74, P=0.006) than those who remained professionally active. The second analysis showed that the likelihood of sleepy driving and phone use while driving decreased soon after retirement, whereas that of speedy driving decreased over a longer interval. Retirement had no influence on driving while intoxicated or attitudes towards road safety. The results suggest that any professional activity may account for some risky road behavior. As work-related road traffic accidents are responsible for one out of every four road casualties in France, the monitoring and prevention of sleepy driving and phoning while driving among workers should be further considered. | 18,815,717 |
Meteorological conditions and the diagnosis of occupationally related contact sensitizations. | An accurate diagnosis of (occupational) contact sensitization by patch testing is a prerequisite for efficient preventive management. However, previously observed seasonal fluctuations in patch-test reactions indicate some influence of meteorological conditions. The present analysis aims at quantifying the possible impact of temperature and humidity on patch-test reactions to occupationally related allergens. Clinical data from 61 780 patients tested with standard series allergens potentially related to occupational exposure from 1993 through 2001 were collected by a contact sensitization surveillance network.The association between the patch-test results and meteorological data (air temperature and humidity) collected at the time and the approximate location of the testing was analyzed in a multinomial logistic regression analysis. For three allergens (a dye and two biocides), the odds of irritant or doubtful allergic reactions increased during cold and arid conditions. Two of them (pphenylenediamine and formaldehyde) also showed an association between weak positive allergic reactions and such weather. In contrast, reactions to various adhesive, plastic, and rubber-related allergens were not associated with weather conditions. An overall increase in skin irritation, brought on by cold and dry conditions, may instigate an increase in positive reactions by leading doubtful allergic reactions to be (falsely) categorized as allergic for at least two of the considered allergens. For the most part, however, weather conditions were not associated with reactions to occupational allergens. Thus the validity of patch testing does not largely seem to be compromised by ambient meteorological conditions. | 18,815,718 |
Body composition obtained from the body mass index: an Italian study. | Since obesity and related diseases are now considered epidemic, new and more accurate formulas for epidemiological studies are of interest to the scientific community. Several equations have been proposed to estimate the body composition simply from anthropometric measurements. However, with time, the body composition of the populations studied changes in relation to their food habits and lifestyle, and, therefore, the equations must be regularly updated and corrected. The aim of the study was to develop new equations to determine the body composition among the Italian population using the body mass index and independently by variables such as age and body structure. Bioelectrical impedance and anthropometric analysis of 764 Italian Caucasian subjects (342 females and 422 males), 11 to 80 years of age, were analysed. Females and males were analysed separately. Multiple regression analyses were performed in order to estimate the body composition of the subjects. The estimated masses were then compared with the measured masses using Bland and Altman plots. We also calculated the differences between the estimated and measured masses, reported as % of the body weight, for the 95, 85 and 75 degrees percentile of the female and male groups. Finally we compared our formulas with the Watson equations, which are used to estimate the total body water. All body masses estimated were positively correlated to the measured values. Moreover, at any percentile analysed, our formulas resulted more precise than the Watson formula. Equations: Females: FM = 1.9337 BMI - 26.422; FFM = BW - FM; BCM = 0.3655 FFM + 4.865; TBW = 0.5863 FFM + 7.1732; Males: FM = 1.407 BMI - 21.389; FFM = BW - FM; BCM = 0.4485 FFM + 3.3534; TBW = 0.6997 + 1.4567. Although an inevitable inaccuracy must be expected in epidemiological studies, our equations are adequate to analyze the body composition state and changes occurring among the Italian population by simply considering weight and height. | 18,815,722 |
Rhodamine-loaded poly(lactic-co-glycolic acid) nanoparticles for investigation of in vitro interactions with breast cancer cells. | Nanoparticle-based drug delivery systems are considered promising for the delivery of imaging agents and drugs for the detection and treatment of illnesses, including cancer. Investigation of nanoparticle interactions with the diseased cells can lead to better designs. In this work, poly(lactic-co-glycolic acid) nanoparticles loaded with rhodamine 6G were prepared by nanoprecipitation with high encapsulation efficiency. In vitro release studies demonstrated that rhodamine escaped from the nanoparticles at a very slow rate at physiological pH, thus making it ideal for imaging studies. At acidic pH this agent was released quickly, suggesting charge interactions between the polymer and rhodamine. Microscopy and flow cytometry studies show higher uptake in MDA-MB-231 breast cancer cells when exposed to rhodamine-loaded nanoparticles than to rhodamine in solution. | 18,815,729 |
Phytoestrogens and breast cancer: a complex story. | Genistein is an isoflavone with oestrogenic activity that is present in a variety of soy products as a constituent of complex mixtures of bioactive compounds, whose matrix profiles play an important role in determining the overall oestrogenic bioactivity of genistein. We review data on how the profile of soy bioactive compounds can modulate genistein-stimulated oestrogen-dependent tumour growth. Our research has focused on the effects of dietary genistein on the growth of oestrogen (E)-dependent mammary tumours both in vitro and in vivo. Genistein enhances the proliferation of E-dependent human breast cancer tumour growth. In a similar manner, dietary genistein stimulates tumour growth in the chemically-induced (NMU) mammary cancer rodent model. Genistin, the glycoside of genistein, simulates growth similar to that of genistein and withdrawal of either genistein or genistin results in tumour regression. The extent of soy processing modulates the effects of dietary genistein in vivo as soy protein isolate, a highly purified and widely used source of protein that is processed to contain low, medium, and high amounts of isoflavones, stimulate the growth of the E-dependent mammary tumours in a dose dependent manner. In contrast to the more purified diets, studies with soy flour of equivalent genistein levels did not stimulate the growth of E-dependent breast cancer tumours in vivo. However, the size of these tumours also did not regress as is observed in control groups in which oestrogen and genistein have been withdrawn. The expression of the oestrogen-target genes of pS2, progesterone receptor, and cyclin D1 correlates with the growth of E-dependent tumours and has been consistently observed to be induced in response to treatment with dietary genistein. To evaluate whether dietary genistein interacts with current anti-oestrogen breast cancer therapies such as tamoxifen (TAM), we implanted E-dependent tumours into ovariectomized athymic mice and administered oestradiol, oestradiol plus TAM, or oestradiol, TAM, and dietary genistein. In these studies dietary genistein was able to negate the inhibitory effect of TAM on E-stimulated tumour growth. In summary, genistein can act as an oestrogen agonist resulting in proliferation of E-dependent human breast cancer tumours in vivo and its activity can be modulated by the presence of other bioactive components in complex soy foods. Additionally, dietary genistein can negate the inhibitory effects of TAM on E-stimulated growth of MCF-7 cell tumours implanted into ovariectomized athymic mice. | 18,815,740 |
Tracheal compliance and limit flow rate changes in a murine model of asthma. | Trachea is the unique passage for air to flow in and out. Its tone is of importance for the respiration system. However, investigation on how tracheal tone changes due to asthma is limited. Aiming at studying how the mechanical property changes due to asthma as well as the compliance and flow limitation, the following methods are adopted. Static and passive pressure-volume tests of rats' trachea of the asthmatic and control groups are carried out and a new type of tube law is formulated to fit the experimental data, based on which changes of compliance and limit flow rate are investigated. In order to give explanation to such changes, histological examinations with tracheal soft tissues are made. The results show that compliance, limit flow rate and material constants included in the tube law largely depend on the longitudinal stretching ratio. Compared with the control group, the tracheal compliance of asthmatic animals decreases significantly, which results in an increased limit flow rate. Histological studies indicate that asthma can lead to hyperplasia/hypertrophy of smooth muscle cells, and increase elastin and collagen fibres in the muscular membrane. Though decreasing compliance increases stability, during the onset of asthma, limit flow rate is much smaller due to the lower transmural pressure. Asthma leads to a stiffer trachea and the obtained results reveal some aspects relevant to asthma-induced tracheal remodelling. | 18,815,756 |
Antibacterial, antifungal and cytotoxic activity of terrestrial cyanobacterial strains from Serbia. | Cyanobacteria are known to be a rich source of biologically active compounds some of which can have pharmaceutical importance. In this work we present the screening results of cyanobacterial strains for their antibacterial, antifungal, and cytotoxic activity. Cyanobacterial strains were isolated from various soil types in province of Vojvodina and Central Serbia, Republic of Serbia. The screening included 9 strains of Anabaena and 9 strains of Nostoc. Both, extracellular products (from the culture liquid) and cellular crude lipophilic extracts were tested against 13 bacterial strains and 8 fungal strains. Cytotoxic activity was tested against three human cell lines. Methanol extracts were prepared according to Østensvik. Antibacterial and antifungal activities were determined measuring inhibition zone, 48 h after inoculation. The cytotoxic activity was determined by sulforhodamine B (SRB) colorimetric assay. Of all cyanobacterial strains tested, 52% showed some antifungal and 41% antibacterial activity. Two out of six tested strains possessed cytotoxic activity. The cytotoxic activity of Anabaena strain S12 was found both in culture liquid and crude cell extract. It occurred specifically between the 21st and 42nd day of cultivation against HeLa and MCF7 cells, but had no activity against cell line derived from a healthy tissue. A high percentage of the active strains among the tested strains justify the effort of screening cyanobacteria that are isolated from terrestrial environments. The most promising strains for the further study are Anabaena strain S12 which showed strong cytotoxic and antibacterial activity and Anabaena strain S20 which produces a potent antifungal compound. The future work, besides further screening and chemical identification of the active compounds, should also include the development of culture techniques that would lead to more efficient production of biologically active compounds. | 18,815,758 |
Positive effects of nicotine on cognition: the deployment of attention for prospective memory. | Human and animal studies over the last two decades report that nicotine can improve cognitive performance. Prospective memory (PM), the retrieval and implementation of a previously encoded intention, is also improved by pre-administration of nicotine. As with other nicotine effects, however, predicting precisely how and when nicotine improves the processes engaged by PM has proved less straightforward. We present two studies that explore the source of nicotine's enhancement of PM. Experiment 1 tests for effects of nicotine on preparatory attention (PA) for PM target detection. Experiment 2 asks whether nicotine enhances processing of the perceptual attributes of the PM targets. Young adult non-smokers matched on baseline performance measures received either 1 mg nicotine or matched placebo via nasal spray. Volunteers completed novel PM tasks at 15 min post-administration. Experiment 1 confirmed that pre-administration of nicotine to non-smokers improved detection rate for prospective memory targets presented during an attention-demanding ongoing task. There was no relationship between PM performance and measures of preparatory attention. In experiment 2, salient targets were more likely to be detected than non-salient targets, but nicotine did not confer any additional advantage to salient targets. The present study suggests that nicotinic stimulation does not work to enhance perceptual salience of target stimuli (experiment 2), nor does it work through better deployment of preparatory working attention (experiment 1). An alternative explanation that nicotine promotes PM detection by facilitating disengagement from the ongoing task is suggested as a future line of investigation. | 18,815,772 |
Tumour and tumour-like lesions of the patella--a multicentre experience. | Fifty-nine cases of lesions presenting in the patella were identified after review of the databases of four European bone tumour registries. Of the 59 cases, 46% were non neoplastic, 39% were benign and 15% were malignant. The commonest benign neoplasm was giant cell tumour (GCT) (11 cases). Younger patients were more likely to have a benign neoplasm. Lesions in patients less than 40 years of age included giant cell tumour, chondroblastoma, aneurysmal bone cyst (ABC), osteomyelitis, osteoid osteoma and solitary bone cyst. In patients older than 40 years, the following were common lesions: intra-osseous gout, metastasis and intra-osseous ganglion. Expansion of the patella with thinning of cortex was seen more commonly in GCT and brown tumour in hyperparathyroidism. There was associated soft tissue extension in gout and malignant lesions. | 18,815,789 |
Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis. | Src family kinases (SFKs) are signaling enzymes that have long been recognized to regulate critical cellular processes such as proliferation, survival, migration, and metastasis. Recently, considerable work has elucidated mechanisms by which SFKs regulate normal and pathologic processes in vascular biology, including endothelial cell proliferation and permeability. Further, when inappropriately activated, SFKs promote pathologic inflammatory processes and tumor metastasis, in part through their effects on the regulation of endothelial monolayer permeability. In this review, we discuss the roles of aberrantly activated SFKs in mediating endothelial permeability in the context of inflammatory states and tumor cell metastasis. We further summarize recent efforts to translate Src-specific inhibitors into therapy for systemic inflammatory conditions and numerous solid organ cancers. | 18,815,812 |
Enhanced removal of dimethyl sulfide from a synthetic waste gas stream using a bioreactor inoculated with Microbacterium sp. NTUT26 and Pseudomonas putida. | The removal of dimethyl sulfide (DMS) from industrial gas streams has received a high priority due to its very low odorous threshold value and relatively low biodegradability compared to other reduced sulfur compounds. A variety of bacteria that utilize DMS as a carbon/energy source have been studied and the degradation pathway elucidated. However, to date, there have been few reports on the industrial application of such bacteria inoculated into a bioreactor for DMS treatment. An additional problem of such systems is the accumulation of intermediate metabolites that strongly impact on DMS removal by the microbe. The results reported here were obtained using a bioreactor inoculated with the H(2)S-degrader Pseudomonas putida and the DMS-degrader Microbacterium sp. NTUT26 to facilitate removal of metabolic intermediates and DMS. This bioreactor performed well (1.71 g-S/day/kg-dry packing material) in terms of DMS gas removal, based on an evaluation of the apparent kinetics and maximal removal capacity of the system. Under varying conditions (changes in start-up, inlet loading, shutdown, and re-start), the bioreactor inoculated with Microbacterium sp. NTUT26 and P. putida enhanced removal of high concentrations of DMS. Our results suggest that this type of bioreactor system has significant potential applications in treating (industrial) DMS gas streams. | 18,815,822 |
Biodegradation of chlorpyrifos in soil by enriched cultures. | Three aerobic bacterial consortia, AC, BC, and DC, developed from pesticide-contaminated soils of Punjab were able to degrade chlorpyrifos after 21 days of incubation in basal medium by 54, 46, and 61% and chlorpyrifos (50 mg/L) in soil after 30 days by 50, 56, and 64%. Pseudomonas aeruginosa, Bacillus cereus, Klebsiella sp., and Serratia marscecens obtained from these consortia showed 84, 84, 81, and 80% degradation of chlorpyrifos (50 mg/L) in liquid medium after 20 days and 92, 60, 56, and 37% degradation of chlorpyrifos (50 mg/L) in soil after 30 days. Populations of Bacillus cereus, Klebsiella sp., and Serratia marscecens remained steady in soil experiments except for P. aeruginosa, where the population showed a substantial increase. Formation of 3,5,6-trichloro-2-pyridinol, the major metabolite of chlorpyrifos degradation, was observed during the degradation of chlorpyrifos by P. aeruginosa, which disappeared to negligible amounts. | 18,815,830 |
Ergonomic risk associated with assisting in minimally invasive surgery. | Given the physical risks associated with performing laparoscopic surgery, ergonomics to date has focused on the primary minimally invasive surgeon. Similar studies have not extended to other operating room staff. Simulation of the assistant's role as camera holder and retractor during a Nissen fundoplication allowed investigation of the ergonomic risks involved in these tasks. Seven subjects performed camera navigation and retraction tasks using a box trainer on an operating room table that simulated an adult patient in low lithotomy position. Each subject stood on force plates at the simulated patient's left side. A laparoscope was introduced through a port into the training box with four 2-cm circles as rear-panel targets located in relation to the assistant as distal superior, proximal superior, distal inferior, and proximal inferior target effects. The subjects held the camera with their left hand, pointing it at a target. The task was to match the target to a circle overlaid on the monitor. Simultaneously, a grasper in the right hand grasped and pulled a panel-attached band. A minute signal moved the subject to the next target. Each trial had three four-target repetitions (phase effect). The subjects performed two separate trials: one while holding the camera from the top and one while holding it from the bottom (grip effect). A 4 x 3 x 2 (target x phase x grip) repeated-measures design provided statistics. Dividing the left force-plate vertical ground reaction forces (VGRF) by the total VGRF from both plates provided a weight-loading ratio (WLR). The WLR significantly increased (p < 0.005) with proximal targets (2 by 80% and 4 by 79%). The WLR decreased 75%, 74%, and 71% over time. No difference existed between the grip strategies (grip effect, p > 0.5). A high-risk ergonomic situation is created by the assistant's left or caudal leg disproportionately bearing 70-80% of body weight over time. A distance increase between the camera head location and the camera holder increases ergonomic risk. The phase effect was interpreted as a compensatory rebalancing to reduce ergonomic risk. Ergonomic solutions minimizing ergonomic risks associated with laparoscopic assistance should be considered. | 18,815,838 |
Exudation of alcohol and aldehyde sugars from roots of defoliated Lolium perenne L. grown under sterile conditions. | Root exudates were collected over a 27 day period from defoliated and non-defoliated Lolium perenne L. plants grown under sterile conditions in microlysimeters. Eleven individual sugars, including both aldehyde and alcohol sugars, were identified and quantified with a gas chromatograph-mass spectrometer (GC-MS). There was no change in the number of sugars present between 7 and 27 days, but the exudation of alcohol sugars decreased rapidly at about day 12. Xylose and glucose were present in the largest amounts. Defoliation initially increased the total amount of sugars in the exudates, but continuous defoliation reduced total sugar exudation by 16% and induced changes in the exudation patterns of individual sugars. Defoliation enhanced exudation of erythritol, threitol, and xylitol, reduced exudation of glucose and arabitol, but had little effect on the amounts of other sugars exuded. The more complex 6 C, 5 OH aldehyde sugars, especially glucose, showed changes earlier and to a greater extent (17 days), than the 5 C, 4 OH (xylose and ribose) and 6 C 4 OH (fucose) aldehyde groups. These findings confirm the general finding that repeated defoliation reduces the quantity of total sugars exuded, but the pattern of release of individual sugars is complex and variable. | 18,815,840 |
Lymphovascular invasion and lobular histology are associated with increased incidence of isolated tumor cells in sentinel lymph nodes from early-stage breast cancer patients. | Isolated tumor cells (ITC) are more likely to be identified when serial sectioning and immunohistochemical staining are used to evaluate sentinel lymph nodes (SLN). Our goal was to identify clinicopathologic features associated with ITC in patients undergoing sentinel lymph node dissection (SLND). We reviewed clinicopathologic data for 3557 patients with no clinical evidence of lymph node metastases undergoing SLND between November 1993 and March 2007. Patients were staged according to the 6th edition of the American Joint Committee on Cancer staging system, with metastasis <or=.2 mm classified as ITC. A SLN was identified in 3475 patients (97.7%), including 2518 (72.4%) with negative nodes and 169 (4.9%) with ITC. A statistically significant association existed between lobular histology and the identification of ITC; 13.6% of patients with ITC had lobular histology versus 7.3% of patients with a negative SLN (P = .003). The presence of lymphovascular invasion (LVI) was also associated with ITC; 18.3% of patients with ITC had LVI in the primary tumor versus 8.5% of patients with a negative SLN (P < .001). No difference existed between patients with and without ITC with respect to T stage, grade, estrogen receptor, progesterone receptor, HER2/neu status, or biopsy method. The association between ITC and LVI, a known predictor of poor outcome, suggests ITC may have clinical relevance. The relationship between lobular histology and ITC is consistent with the known pattern of lobular metastases, which frequently present as small foci requiring immunohistochemistry for detection. Longer follow-up is needed to determine whether ITC have prognostic significance. | 18,815,841 |
Rapid genotyping of tumor necrosis factor alpha with fluorogenic hybridization probes on the LightCycler. | Genotyping of tumor necrosis factor alpha (TNF-alpha) has become an important procedure in the selection of high-risk population of septic shock and prevention from death due to septic shock. We present a single-tube method for TNF-alpha genotyping that performed on the LightCycler by melting curve analysis with allele-specific fluorescent probe. A fragment covering the polymorphic site is amplified in the presence of two fluorescently labeled hybridization probes. During amplification, probe hybridization is observed as fluorescence increases every cycle as the product accumulates during amplification. A single base mismatch resulted in a melting temperature (Tm) shift of 7-8 degrees C, allowing for the easy distinction of a common type allele from the polymorphic allele. Using this method, genotyping of 104 samples was completed within 1 h without the need for any post-PCR sample manipulation, thereby eliminating the risks of end-product contamination and sample tracking errors. The genotypes determined with the LightCycler were identical when compared with a conventional sequencing. The simplicity, speed, and accuracy of real-time PCR analysis using FRET probes make it the method of choice in the clinical laboratory for genotyping of a variety of human DNA polymorphisms and mutations. | 18,815,866 |
Successful cryoablation in the noncoronary aortic cusp for a left anteroseptal accessory pathway. | Catheter ablation of anteroseptal accessory pathways may be difficult because of the neighboring conduction tissue that may be damaged with ablation. We report a case of an accessory pathway localized to the anteroseptal region. A pathway potential found in the noncoronary cusp of the aortic valve was successfully targeted for ablation with cryo energy. Observations during tachycardia and pacing maneuvers suggest that the supravalvar aortic musculature may be an integral component of left anteroseptal pathways that can be safely targeted for cryoablation without injury of the atrioventricular conduction system. | 18,815,874 |
Perceived control and psychological distress in women with breast cancer: a longitudinal study. | The relationship between perceived control and psychological distress in cancer patients has been widely studied, but longitudinal designs are scarce. The aim of this study was to examine whether perceived control could predict changes in the evolution of psychological distress in breast cancer patients at stages I or II. One hundred and one women were assessed on five occasions: one week after surgery, and again 1, 3, 6 and 12 months later, using the Mental Adjustment to Cancer (MAC) Scale, a Self-Efficacy Scale, the Personal Competence Scale, the Hospital Anxiety and Depression Scale (HADS), the Profile of Mood Sates (POMS), and the EORTC questionnaire of quality of life. Latent growth curve (LGC) model analysis was used to test the relationship between perceived control and psychological distress in a longitudinal, 1-year study. The results showed that perceived control increases linearly and that distress also decreases linearly. Moreover, the evolution of distress can be predicted from the initial value and the rate of change of perceived control. This close relationship between perceived control and psychological distress was found to be independent of the evolution of the physical state. These findings suggest that perceived control could be used as an early predictor of psychological adjustment to illness. | 18,815,877 |
Application of a numerical simulation to improve the separation efficiency of a sperm sorter. | This paper describes a study in which numerical simulations were applied to improve the separation efficiency of a microfluidic-based sperm sorter. Initially, the motion of 31 sperm were modeled as a sinusoidal wave. The modeled sperm were expected to move while vibrating in the fluid within the microchannel. In this analysis, the number of sperm extracted at the outlet channel and the rate of movement of the highly motile sperm were obtained for a wide range of flow velocities within the microchannel. By varying the channel height, and the width and the position of the sperm-inlet channel, we confirmed that the separation efficiency was highly dependent on the fluid velocity within the channel. These results will be valuable for improving the device configuration, and might help to realize further improvements in efficiency in the future. | 18,815,887 |
Genetic epidemiology of bladder cancer: scaling up in the identification of low-penetrance genetic markers of bladder cancer risk and progression. | Bladder cancer is an increasingly important international public health problem. As a multifactorial disease, both environmental and genetic factors are involved in its development and progression. This neoplasm is a paradigm for the participation of low-penetrance genetic variants (GSTM1-null and NAT2-slow) and provides the best established gene-environment interaction in cancer (NAT2-slow * tobacco). Genetic variants in nucleotide excision and double strand break DNA repair pathways have provided promising results, ERCC2-XPD rs238406 being the most consistent variant associated with an increased of bladder cancer risk, by itself and by interacting with tobacco. Variants in other pathways such as cell-cycle control, 1-C metabolism and inflammation have been studied, although the results are inconsistent. Three very large whole genome association studies are being undertaken using the same genotyping platform. Their results will be available soon. Genetic variants have seldom been considered as markers of prognosis or response to therapy in this tumour. The results of these studies are inconclusive. Other issues that need to be addressed are the role of genetic variants in different population subgroups--defined by ethnicity, gender and age, among others--and the association with bladder cancer subphenotypes according to clinical, pathological and molecular characteristics of the tumour. This endeavour can only be achieved by integrating multidisciplinary tools and information. Can this information be applied better to identify high-risk populations? Can the information be used to better assess prognosis or predict response to therapy? These questions require large, well-designed, multicentre studies to be conducted. Funding agencies should be aware of these needs. | 18,815,927 |
Avoidance motivation in psychological problems and psychotherapy. | Avoidance of aversive experiences is common to all human beings. However, when avoidance is too strong, it might be associated with impaired psychological functioning and psychopathology. This article examines the role of avoidance motivation in psychological problems and psychotherapy from conceptual, assessment, and empirical perspectives. The concept of avoidance motivation is introduced, and measures of the intensity and satisfaction of avoidance motivation that the author developed are presented. Empirical findings generated using these measures are also reported. The findings address the role of avoidance motivation in relation to well-being, psychological problems, and psychotherapy outcome. The theoretical and practical implications of these findings are discussed and avenues for further research explored. | 18,815,972 |
Patients' experiences of self-disclosure in psychotherapy: the effects of gender and gender role identification. | This study examined the effects of gender and gender role identification on 223 patients' experiences of self-disclosure in psychotherapy. Factor analysis of the Disclosure-to-Therapist Inventory-IV revealed two dimensions: a distress factor, reflecting the perceived difficulty and the anticipated impact of disclosures on the therapist, and an openness factor, reflecting the extent and perceived importance of disclosures and the interpersonal connection experienced during them. Female patients working with female therapists experienced greater distress in disclosure than male patients working with female therapists; in addition, patients with more flexible gender role identifications (i.e., androgynous) experienced greater openness than those with more traditional gender identifications. Findings suggest a need for greater discussion in therapy of the effects of gender on disclosure. | 18,815,982 |
Randomized control trial of an integrated therapy for comorbid anger and gambling. | This study evaluated an integrated treatment for comorbid problem gambling, anger, and substance use. Problem gamblers with comorbid anger problems (N=42), half of whom also had substance use disorders, were randomized to either a 14-week integrated treatment targeting anger and addictions (i.e., both gambling and substance use) or a specialized treatment-as-usual (TAU) for gambling and substance use. Participants were assessed at baseline (Tl), 14 weeks (T2), and 12 weeks follow-up (T3). Relative to the TAU, participants in the integrated anger and addictions treatment reported significantly less gambling at T2 and T3 and less trait anger and substance use at T3. Findings suggest that it is important to screen gambling clients for the presence of comorbid anger and substance use problems and that, when present, these problems need to be addressed concurrently in gambling treatment in order to optimize treatment outcomes. | 18,815,997 |
Patients' outcome expectancies and their impression of suitability as predictors of treatment outcome. | In treatment studies, the correlation of patients' outcome expectancies and their impression of treatment suitability with treatment outcome shows a contradictory pattern. It seems that a significant correlation can be shown only if outcome is measured with posttherapy scores or with retrospective success ratings but not if outcome is operationalized as any form of pre-post change scores. This study with 499 outpatients (222 with anxiety disorders, 63 with affective disorders, 136 with both anxiety and depression, and 78 with other disorders) examines whether this difference in the correlation pattern can be replicated by simultaneously using three kinds of outcome assessment. Three subscales of the Patients' Therapy Expectation and Evaluation questionnaire (Hope of Improvement, Fear of Change, and Suitability) were correlated with the treatment outcome. Results confirm the hypothesized model. Possible explanations of this pattern of results are discussed. | 18,815,999 |
Electronic structure study of thermal intraconversions of some dicyclopenta-fused polycyclic aromatic compounds. | The electronic structure of dicyclopenta[de,mn]anthracene (P1), dicyclopenta[ de,kl]anthracene (P2), and dicyclopenta[jk,mn]phenanthrene (P3) and their mutual isomerization processes are investigated using density functional theory. Two mechanisms for the thermal intraconversion of P1 to P2 were found. The first mechanism occurs via ethynylaceanthrylene (I0), and the second involves a 1,2-hydrogen shift. It is supposed that I0 is initially formed during the flash vacuum pyrolysis experiments, eventually rearranging to P2 on high temperatures. The energetics of the latter mechanism also indicate that P1 isomerizes to P2. The mechanism for a transformation of P2 to P3 is based on a ring contraction/ring conversion process and requires extremely high temperatures. Our investigation is in accord with the experimental results: unsuccessful synthesis of P1, stability of P2 at high temperature, and formation of P3 under extreme temperature regime. | 18,816,023 |
A computational study on some viable targets for gas-phase synthesis of metal complexes of the cyclic (B6C)-2 and their bonding pattern. | In this account, a detailed computational study is conducted to verify the geometric, energetic, and electronic properties of the planar cyclic (B 6C) (-2) (as the simplest carrier of hexacoordinate carbon) within some metal complexes. The [M(B 6C)] ((-)) (M = Li, Na, K) and [M(B 6C)] (M = Be, Mg, Ca) series are employed for this purpose. Relevant ab initio calculations at both DFT and post-HF levels vividly demonstrate that this dianion is stabilized considerably in the electric field generated by cations, whereas the geometrical and electronic properties of this ring remain almost intact in these complexes. The complementary topological analysis of charge densities confirms that cyclic (B 6C) (-2) within these complexes exhibits the same topological patterns as the naked dianion, thus confirming the presence of an unusual charge density distribution in this dianion. An electrostatic model is proposed that not only qualitatively but also quantitatively explains the observed computational trends in these complexes. This model successfully traces the polarization of the central carbon atom of the ring in the presence of a hard, multiply charged cation. To facilitate experimental detection, the photoelectron spectra of the [M(B 6C)] ((-)) (M = Li, Na, K) series are computed and the dominant features are extracted. Although considered species are not global minima on their potential energy hypersurfaces, their kinetic stabilities are verified and demonstrated unequivocally. | 18,816,031 |
Thiophene bioisosteres of spirocyclic sigma receptor ligands. 1. N-substituted spiro[piperidine-4,4'-thieno[3,2-c]pyrans]. | Herein, the synthesis and pharmacological evaluation of thiophene bioisosteres of the highly potent spirocyclic benzopyran 1 are detailed. The synthesis of 1-benzyl-6'-methoxy-6',7'-dihydrospiro[piperidine-4,4'-thieno[3.2- c]pyran] (2a) was performed starting with 3-bromothiophene (3). After introduction of the acetaldehyde substructure (7), halogen metal exchange, addition of 1-benzylpiperidin-4-one, and cyclization led to the spirocyclic thienopyran 2a. The removal of the benzyl group afforded the secondary amine 2f, which was substituted with various residues. With respect to sigma 1 affinity the N-benzyl derivative 2a, the N-cyclohexylmethyl derivative 2d, and the N-p-fluorobenzyl derivative 2i represent the most potent compounds of this series binding with K i values of 0.32, 0.29, and 0.62 nM, respectively. Electronic properties of the substituents have only little impact on sigma 1 affinity. The most potent sigma 1 ligands display high selectivity against sigma 2, 5-HT 1A, 5-HT 6, 5-HT 7, alpha 1A, alpha 2, and NMDA receptors. The activity of 2a in the mouse capsaicin assay seems to indicate sigma 1 antagonistic activity. | 18,816,044 |
Design and synthesis of a novel series of pyranonaphthoquinones as topoisomerase II catalytic inhibitors. | On the basis of previous pharmacophore modeling studies of naphthoquinones derivatives, we have designed and synthesized a new set of pyranonaphthoquinones. These compounds were obtained through a direct and highly efficient approach based on an intramolecular domino Knoevenagel hetero Diels-Alder reaction from lawsone (2-hydroxynaphthoquinone) and a variety of aldehydes containing an alkene. The synthesized pyranonaphthoquinones were evaluated against the alpha isoform of human topoisomerase II (hTopoIIalpha). Among the 11 derivatives studied, we found that six of them act as catalytic inhibitors of the enzyme in vitro. These six derivatives strongly preclude the enzyme from decatenating or relaxing suitable substrates. Finally, we correlate their active/inactive status with docking studies of these novel compounds into the ATPase domain of hTopoIIalpha. | 18,816,045 |
Fully automated molecular mechanics based induced fit protein-ligand docking method. | We describe a method for docking a ligand into a protein receptor while allowing flexibility of the protein binding site. The method employs a multistep procedure that begins with the generation of protein and ligand conformations. An initial placement of the ligand is then performed by computing binding site hotspots. This initial placement is followed by a protein side-chain refinement stage that models protein flexibility. The final step of the process is an energy minimization of the ligand pose in the presence of the rigid receptor. Thus the algorithm models flexibility of the protein at two stages, before and after ligand placement. We validated this method by performing docking and cross docking studies of eight protein systems for which crystal structures were available for at least two bound ligands. The resulting rmsd values of the 21 docked protein-ligand complexes showed values of 2 A or less for all but one of the systems examined. The method has two critical benefits for high throughput virtual screening studies. First, no user intervention is required in the docking once the initial binding site selection has been made in the protein. Second, the initial protein conformation generation needs to be performed only once for a given binding region. Also, the method may be customized in various ways depending on the particular scenario in which dockings are being performed. Each of the individual steps of the method is fully independent making it straightforward to explore different variants of the high level workflow to further improve accuracy and performance. | 18,816,046 |
Structural and thermodynamic characterization of T4 lysozyme mutants and the contribution of internal cavities to pressure denaturation. | Using small-angle X-ray scattering (SAXS) and tryptophan fluorescence spectroscopy, we have identified multiple compact denatured states of a series of T4 lysozyme mutants that are stabilized by high pressures. Recent studies imply that the mechanism of pressure denaturation is the penetration of water into the protein rather than the transfer of hydrophobic residues into water. To investigate water penetration and the volume change associated with pressure denaturation, we studied the solution behavior of four T4 lysozyme mutants having different cavity volumes at low and neutral pH up to a pressure of 400 MPa (0.1 MPa = 0.9869 atm). At low pH, L99A T4 lysozyme expanded from a compact folded state to a partially unfolded state with a corresponding change in radius of gyration from 17 to 32 A. The volume change upon denaturation correlated well with the total cavity volume, indicating that all of the molecule's major cavities are hydrated with pressure. As a direct comparison to high-pressure crystal structures of L99A T4 lysozyme solved at neutral pH [Collins, M. D., Hummer, G., Quillin, M. L., Matthews, B. W., and Gruner, S. M. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 16668-16671], pressure denaturation of L99A and the structurally similar L99G/E108V mutant was studied at neutral pH. The pressure-denatured state at neutral pH is even more compact than at low pH, and the small volume changes associated with denaturation suggest that the preferential filling of large cavities is responsible for the compactness of the pressure-denatured state. These results confirm that pressure denaturation is characteristically distinct from thermal or chemical denaturation. | 18,816,066 |
Cell adhesion to nanoligands: effects of ligand size and concentration in solution. | Cells interact with both tethered and motile ligands in their extracellular environment to initiate and regulate signaling, adhesion, and migration. A quantitative and fundamental understanding of these receptor-ligand interactions is necessary for drug discovery, tissue engineering, and biomaterial fabrication. In this paper, we present a mean field approach to quantify the fundamental thermodynamics of interaction between the cell surface receptors and motile ligands in solvent. Our studies show that the free energy of interaction between the receptors and the nanosized ligands depends strongly on the ligand size and the effects at lower and higher concentrations show completely opposite trends that cannot be explained by simple scaling laws. In addition, we also observe various regimes of strong and weak adhesion as a function of ligand size and concentration. Our calculations provide insights into understanding cell-matrix interactions at a fundamental level as well as to identify potential avenues for fabrication of nanoligands for therapeutic and biotechnological purposes. | 18,816,080 |
Shotgun proteomics of the haloarchaeon Haloferax volcanii. | Haloferax volcanii, an extreme halophile originally isolated from the Dead Sea, is used worldwide as a model organism for furthering our understanding of archaeal cell physiology. In this study, a combination of approaches was used to identify a total of 1296 proteins, representing 32% of the theoretical proteome of this haloarchaeon. This included separation of (phospho)proteins/peptides by 2-dimensional gel electrophoresis (2-D), immobilized metal affinity chromatography (IMAC), metal oxide affinity chromatography (MOAC), and Multidimensional Protein Identification Technology (MudPIT) including strong cation exchange (SCX) chromatography coupled with reversed phase (RP) HPLC. Proteins were identified by tandem mass spectrometry (MS/MS) using nanoelectrospray ionization hybrid quadrupole time-of-flight (QSTAR XL Hybrid LC/MS/MS System) and quadrupole ion trap (Thermo LCQ Deca). Results indicate that a SCX RP HPLC fractionation coupled with MS/MS provides the best high-throughput workflow for overall protein identification. | 18,816,081 |
Fluorescence resonance energy transfer in polydiacetylene liposomes. | Conjugated polydiacetylene (PDA) possessing stimuli-responsive properties has been intensively investigated for developing efficient sensors. We report here fluorescence resonance energy transfer (FRET) in liposomes synthesized using different molar ratios of dansyl-tagged diacetylene and diacetylene-carboxylic acid monomers. Photopolymerization of diacetylene resulted in cross-linked PDA liposomes. We used steady-state electronic absorption, emission, and fluorescence anisotropy (FA) analysis to characterize the thermal-induced FRET between dansyl fluorophores (donor) and PDA (acceptor). We found that the monomer ratio of acceptor to donor ( R ad) and length of linkers (functional part that connects dansyl fluorophores to the diacetylene group in the monomer) strongly affected FRET. For R ad = 10 000, the acceptor emission intensity was amplified by more than 18 times when the liposome solution was heated from 298 to 338 K. A decrease in R ad resulted in diminished acceptor emission amplification. This was primarily attributed to lower FRET efficiency between donors and acceptors and a higher background signal. We also found that the FRET amplification of PDA emissions after heating the solution was much higher when dansyl was linked to diacetylene through longer and flexible linkers than through shorter linkers. We attributed this to insertion of dansyl in the bilayer of the liposomes, which led to an increased dansyl quantum yield and a higher interaction of multiple acceptors with limited available donors. This was not the case for shorter and more rigid linkers where PDA amplification was much smaller. The present studies aim at enhancing our understanding of FRET between fluorophores and PDA-based conjugated liposomes. Furthermore, receptor tagged onto PDA liposomes can interact with ligands present on proteins, enzymes, and cells, which will produce emission sensing signal. Therefore, using the present approach, there exist opportunities for designing FRET-based highly sensitive and selective chemical and biochemical sensors. | 18,816,092 |
Immobilization of growth factors on collagen scaffolds mediated by polyanionic collagen mimetic peptides and its effect on endothelial cell morphogenesis. | Angiogenesis, a morphogenic event endothelial cells (ECs) undergo in response to 3-D environmental triggers, is critical to the survival and ultimate functional capacity of engineered tissue constructs. Here we present a new collagen mimetic peptide (CMP) architecture consisting of multiple anionic charges at the peptide's N-terminus designed to attract growth factors by charge-charge interactions and bind to collagen by CMP-collagen interaction. The anionic CMPs exhibited specific binding affinity to type I collagen substrates while attracting vascular endothelial growth factors (VEGFs), which led to enhanced morphological features of ECs, indicative of tubulogenesis. The results show that these new CMPs could be used to direct proliferation and differentiation of cells in collagen scaffolds by localization and sustained delivery of growth factors and other morphogens. | 18,816,098 |
Carboxymethyl chitosan as a matrix material for platinum, gold, and silver nanoparticles. | Carboxymethyl chitosan (CMC) was evaluated for its use in the synthesis and stabilization of catalytic nanoparticles for the first time. Many studies have reported on the ability of chitosan to bind with metal ions and support metal nanoparticles. CMC has a higher reported chelation capacity than chitosan, which has potential implications for improved catalyst formation and immobilization. Platinum, gold, and silver nanoparticles were synthesized in both chitosan and CMC. Particle size, morphology, and aggregation were examined using transmission electron microscopy (TEM). Complexation of nanoparticles was studied through Fourier transform infrared spectroscopy (FTIR). Similar nanoparticle size distributions were observed in the two polymers; however, CMC was observed to have higher rates of aggregation. This indicates that the carboxymethyl groups did not change nanoparticle formation; however, poor cross-linking and a limited anchoring ability of CMC led to the inability to immobilize the catalyst materials effectively. | 18,816,099 |
Organocatalytic asymmetric transferhydrogenation of beta-nitroacrylates: accessing beta2-amino acids. | We describe a highly efficient and enantioselective Hantzsch ester mediated conjugate reduction of beta-nitroacrylates that is catalyzed by a Jacobsen thiourea catalyst as a key step in a new route to optically active beta2-amino acids. | 18,816,115 |
Extraordinary circularly polarized luminescence activity exhibited by cesium tetrakis(3-heptafluoro-butylryl-(+)-camphorato) Eu(III) complexes in EtOH and CHCl3 solutions. | The largest CPL activity ever measured was observed for cesium tetrakis(3-heptafluoro-butylryl-(+)-camphorato) Eu(III) complexes in EtOH and CHCl3 solutions substantiating the stereospecific formation of chiral Delta-SAPR-(C4) configuration with the aid of Cs+...FC (fluorocarbon) interactions more clearly than the exciton CD spectra. | 18,816,117 |
High temperature metalation of functionalized aromatics and heteroaromatics using (tmp)2Zn x 2 MgCl2 x 2 LiCl and microwave irradiation. | A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF via direct zincation using (tmp)2Zn x 2 MgCl2 x 2 LiCl and microwave irradiation. Ester and cyano functions as well as ketones are compatible with the high temperatures of the zincation. The resulting bis-organo zinc species undergo a number of subsequent reactions leading to highly functionalized aromatics and heteroaromatics in good to excellent yields. | 18,816,136 |
Self-assembly of quantum dots and carbon nanotubes for ultrasensitive DNA and antigen detection. | A highly selective, ultrasensitive, fluorescence detection method for DNA and antigen based on self-assembly of multiwalled carbon nanotubes (CNTs) and CdSe quantum dots (QDs) via oligonucleotide hybridization is reported. Mercaptoalkyloligonucleotide molecules bind to the quantum dots, while amineoalkyloligonucleotides bind to CNTs with -COCl surface groups. QDs and CNTs further assemble into nanohybrids through DNA hybridization in the presence of target complementary oligonucleotides. The method is achieved with good repeatability with the detection limit of 0.2 pM DNA molecules and 0.01 nM antigen molecules. This novel detection system can also be used for multicomponent detection and antigen-antibody immunoreaction. The novel system has great potential in applications such as ultrasensitive pathogen DNA or antigen or antibody detection, molecular imaging, and photoelectrical biosensors. | 18,816,142 |
A mutual support mechanism through intercellular movement of CAPRICE and GLABRA3 can pattern the Arabidopsis root epidermis. | The patterning of the Arabidopsis root epidermis depends on a genetic regulatory network that operates both within and between cells. Genetic studies have identified a number of key components of this network, but a clear picture of the functional logic of the network is lacking. Here, we integrate existing genetic and biochemical data in a mathematical model that allows us to explore both the sufficiency of known network interactions and the extent to which additional assumptions about the model can account for wild-type and mutant data. Our model shows that an existing hypothesis concerning the autoregulation of WEREWOLF does not account fully for the expression patterns of components of the network. We confirm the lack of WEREWOLF autoregulation experimentally in transgenic plants. Rather, our modelling suggests that patterning depends on the movement of the CAPRICE and GLABRA3 transcriptional regulators between epidermal cells. Our combined modelling and experimental studies show that WEREWOLF autoregulation does not contribute to the initial patterning of epidermal cell fates in the Arabidopsis seedling root. In contrast to a patterning mechanism relying on local activation, we propose a mechanism based on lateral inhibition with feedback. The active intercellular movements of proteins that are central to our model underlie a mechanism for pattern formation in planar groups of cells that is centred on the mutual support of two cell fates rather than on local activation and lateral inhibition. | 18,816,165 |
Thyroid function and exposure to styrene. | Many natural substances and drugs have long been known to cause goiter or thyroid dysfunction. More recently, several environmental pollutants, such as pesticides and industrial compounds, have been investigated for their thyroid-disrupting activity and related adverse effects on human health. The aim of this study was to evaluate the effects of styrene on the thyroid axis in occupationally exposed workers. Thirty-eight exposed (E) and 123 nonexposed (NE) male workers (controls) were assessed. Serum concentrations of thyrotropin (TSH; basal and after thyrotropin-releasing hormone [TRH] administration.), free thyroxine (FT(4)), free triiodothyronine (FT(3)), anti-thyroglobulin, thyroid peroxidase antibody, and calcitonin were measured. Thyroid ultrasound examination was also performed. In E workers, urinary creatinine, mandelic acid (MA), and phenylglyoxylic acid (PGA) were also measured. No significant differences between E and NE workers were demonstrated, as far as thyroid volume, nodularity, serum thyroid antibodies, and calcitonin were analyzed. However, in the E group a positive correlation between duration of exposure and thyroid volume was detected. After exclusion of subjects with nodular or autoimmune thyroid diseases, serum concentrations of FT(4), FT(3), and TSH did not differ between the two groups. In E workers there was a positive correlation between the urinary concentrations of styrene metabolites (MA plus PGA) and FT(4) or FT(4)/FT(3) ratio (p < 0.05; r = 0.45 and p < 0.005; r = 0.61, respectively), while no correlation was observed between urinary concentrations of MA plus PGA and serum TSH (either basal and stimulated). Chronic exposure to styrene is not associated with an increase in nodular or autoimmune thyroid diseases. However, styrene could interfere with peripheral metabolism of thyroid hormones by inhibiting T(4) to T(3) conversion. Whether this is a direct effect on iodothyronine deiodinases or a consequence of a general distress, such as in nonthyroidal illnesses, remains to be established. Further studies in a larger population of exposed workers are needed to confirm these preliminary observations. | 18,816,178 |
Differentiating alternative splice variant patterns of human telomerase reverse transcriptase in thyroid neoplasms. | Although fine-needle aspiration (FNA) biopsy of thyroid nodules is very sensitive in detecting thyroid malignancy, it remains ambiguous in 20-30% of cases. Current biomarkers for thyroid cancer lack either the sensitivity or specificity to substantially address this clinical problem. The aim of this study was to investigate the gene expression patterns of human telomerase reverse transcriptase (hTERT) alternative splice variants in benign and malignant thyroid tumors in an attempt to find a more reliable biomarker in the differential diagnosis of thyroid nodules. One hundred and thirty-three thyroid tumors from eight histopathological tumor types were collected from patients undergoing thyroid surgery at Johns Hopkins Hospital. Gene expression patterns of hTERT alternative splice variants were investigated in the tumors by nested reverse transcriptase-PCR. Telomerase enzyme activity was evaluated in a subset of 16 samples associated with the different hTERT patterns. Association of c-myc expression and hTERT patterns was also examined. Malignant thyroid tumors exhibited a greater proportion of the active full-length hTERT transcript (0.57 +/- 0.15) than inactive splice variants, alpha(-) (0.13 +/- 0.02), or beta(-)/alpha(-)beta(-) deletion transcripts (0.30 +/- 0.11; p < 0.001). The opposite was observed in benign tumors, which exhibited greater proportions of beta(-)/alpha(-)beta(-) deletion transcripts (0.64 +/- 0.08) than either the full-length (0.19 +/- 0.06) or alpha(-) deletion transcripts (0.17 +/- 0.02; p < 0.001). Similar results were observed among a diagnostically challenging subset of 50 thyroid tumors that were suspicious for malignancy on FNA. Further, increased telomerase enzymatic activity was only associated with expression of the full-length hTERT isoform. In contrast, c-myc expression, which has been implicated in hTERT regulation, correlated with overall hTERT transcription without specificity for expression of the full-length isoform. These differences in gene expression patterns of hTERT alternative splice variants may provide a useful adjunct to FNA diagnosis of suspicious thyroid tumors. | 18,816,183 |
Preferences and perceived barriers to treatment for depression during the perinatal period. | Little is understood about why few women during the perinatal period will use depression treatment. In particular, beliefs and barriers related to depression treatment use have not been studied. In this study, African American and white pregnant women (n = 108) who screened > or =10 on the Edinburgh Postnatal Depression Scale (EPDS) were asked about recent formal and informal treatment use in prenatal care settings. Confidence in the helpfulness of treatment, providers, and settings and perceived barriers to treatment were assessed and compared between African American and white women. Pregnant women overall reported low rates of formal treatment use but frequently sought help from informal sources, such as friends, family, and printed materials. All women expressed greatest confidence in psychosocial treatments and lowest confidence in antidepressants. African American women reported less confidence in advice from family and friends and in antidepressants than did white women. Women expressed greatest confidence in treatments delivered by mental health professionals and religious leaders. African American women sought help more frequently and had significantly more confidence in religious leaders as treatment deliverers than white women. Women had greatest confidence in treatments delivered in professional and home settings, with African American women expressing greater confidence in religious settings than white women. All women reported greatest concern with structural barriers, compared with attitudinal and knowledge barriers. Understanding patterns of treatment use, beliefs, and barriers to depression treatment provides important information for tailoring and improving appropriate use of mental health treatment in women during the perinatal period. | 18,816,202 |
[Light chain deposition disease. Experience in our environment]. | The Light chain deposition disease (LCDD) is a strange entity characterised by the deposition of only one type of light chain in the renal tubular basement membranes. It can be associated to a plasma cell dyscrasia, however, it can occur in the absence of any detectable hematological disorder and it is called idiopathic LCDD. The clinical manifestation is renal insufficiency and nephrotic proteinuria, it does not have a clearly fixed treatment and has a severe prognosis. The aim of this work is to analyse the characteristics of the LCDD cases diagnosed within our environment. Six cases were identified, all of them between 1999 and 2005, from a total amount of 640 renal biopsies performed during this period, 4 women and 2 men, average age of 57. Multiple myeloma in 3 patients were detected (50%). The acute renal failure or rapidly progressive renal insufficiency was the most frequent clinical presentation (66%) together with nephrotic proteinuria (66%). All the biopsies showed tubular basement membranes thickening and kappa chains with a linear distribution within the same. The most frequent glomerular pathological finding was the nodular sclerosing glomerulopathy (83%). In one of the cases the affectation was exclusively tubular interstitial with tubular casts. 3 patients were treated, 2 with multiple myeloma. 5 patients needed dialysis: 3 with idiopathic LCDD within an average time of 7 days from the diagnosis to its reception and 2 with myeloma, who started needing dialysis in an average of 46 days. 4 patients died, 2 of them with myeloma. The monitoring time until the death was 13 weeks for the patients with myeloma and 110 weeks for the rest. The LCDD seems to be more frequent than what has been published and it is associated to the myeloma in half of the cases. It appears together with severe renal insufficiency and the patient's and renal prognosis is poor. | 18,816,213 |
Comparison of antigenemia assay and semiquantitative polymerase chain reaction test for monitoring active cytomegalovirus infection in allogeneic hematopoietic cell transplant recipients. | We sought to compare the antigenemia assay and in-house semiquantitative polymerase chain reaction to monitor human cytomegalovirus infection after transplant in hematopoietic cell transplant recipients. A pp65 antigen test for polymorphonuclear leukocytes and a semiquantitative polymerase chain reaction for whole blood were performed for 201 samples obtained from 26 hematopoietic cell transplant recipients over a 3-month surveillance period. Fourteen episodes of antigenemia positivity were detected in 7 patients in whom human cytomegalovirus DNA loads and pp65-positive cells ranged between < 102 to 2.96 x 104 copies/mL and 0-35/ 5 x 104 polymorphonuclear leukocytes, respectively. A significant correlation was detected between human cytomegalovirus DNA load and the antigenemia test. A receiver operating characteristic analysis determined 5000 copies/mL of human cytomegalovirus as the threshold value for initiation of ganciclovir therapy. Based on a comparison of the pp65 antigenemia assay, quantification of human cytomegalovirus DNA in whole blood can be used to guide clinical management of hematopoietic cell transplant recipients. This approach may have important advantages including superior sensitivity and efficient monitoring of preemptive therapy, allowing inclusion of kinetic criteria in clinical guidelines. Furthermore, a high human cytomegalovirus load among patients with grade II-IV acute graft-versus-host disease may indicate a high risk of human cytomegalovirus disease among hematopoietic cell transplant patients. Human cytomegalovirus reactivation must be monitored using more-sensitive assays such as real-time polymerase chain reaction. | 18,816,243 |
Comparative study of operative treatment [corrected] of varicose veins according to the Klapp and Smetana method versus Myers method. | Venous abnormalities in lower extremities are among the most frequent disorders that affects general population with significant morbidity and mortality. Usually, the problem consists of a mild form of varicose veins and teleangiectasis. Treatment in this stage of disease is highly recommended since progression can lead to chronic venous insufficiency and chronic disability with very few effective treatment options. The most effective and popular treatment of varicose veins is operative treatment; specifically two different operative procedures: method according to Myers and method according to Klapp and Smetana. We designed this study in order to determine which method is superior based on clinical parameters and patients satisfaction. Our evidence strongly support clinical superiority, as well as patient satisfaction, of Klapp and Smetana method. | 18,816,266 |
Rates of bluetongue virus transmission between Culicoides sonorensis and sheep. | Two experiments were undertaken to estimate the transmission rates of bluetongue virus (BTV) serotype 1 between a biting midge vector, Culicoides sonorensis (Wirth & Jones) (Ceratopogonidae), and a natural host, sheep. In an experiment to measure the transmission rate from vector to host (V-->H), six batches of one, five and 20 intrathoracically infected midges were fed on a total of 18 bluetongue (BT)-naïve sheep. The sheep were then monitored for 21 days for clinical signs of BT, viraemia and antibody response. All sheep fed on by five or 20 midges and five of six sheep fed on by just one midge showed signs of BT, were viraemic and developed antibody. The sixth sheep fed on by a single infected midge did not show signs of BT or have detectable viraemia; it did, however, develop a weak antibody response. A bite from a single infected midge is therefore able to transmit BTV to naïve sheep with 80-100% efficiency. Sheep fed upon by larger numbers of infected midges took less time to reach maximum viraemia and developed stronger antibody responses. Sheep exposed to greater amounts of BTV in feeding midges developed a higher level of viraemia and stronger antibody responses. In a second experiment to measure the transmission rate from host to vector (H-->V), batches of up to 500 uninfected female C. sonorensis fed every 1-2 days on two experimentally infected sheep during the course of infection. Of 3929 engorged midges that were individually titrated after surviving the extrinsic incubation period, only 23 (0.6%) were infected with BTV. Viraemia in the sheep extended for up to 19 days post-inoculation. No infected midges, however, were detected from 14 days post-infection. | 18,816,271 |
A wrinkle in time: asymmetric valuation of past and future events. | A series of studies shows that people value future events more than equivalent events in the equidistant past. Whether people imagined being compensated or compensating others, they required and offered more compensation for events that would take place in the future than for identical events that had taken place in the past. This temporal value asymmetry (TVA) was robust in between-persons comparisons and absent in within-persons comparisons, which suggests that participants considered the TVA irrational. Contemplating future events produced greater affect than did contemplating past events, and this difference mediated the TVA. We suggest that the TVA, the gain-loss asymmetry, and hyperbolic time discounting can be unified in a three-dimensional value function that describes how people value gains and losses of different magnitudes at different moments in time. | 18,816,287 |
Cytoprotective effect of mangiferin on benzo(a)pyrene-induced lung carcinogenesis in swiss albino mice. | Antioxidants are one of the key players in tumourigenesis, and several natural and synthetic antioxidants have been shown to have anticancer effects. In the present investigation, the efficacy of mangiferin on the antioxidant status of benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice was assessed. The animals were divided into five groups. The animals in groups I and V were normal control and mangiferin control, respectively. Groups II, III and IV were administered with benzo(a)pyrene (50 mg/kg body weight, orally) for 4 weeks (twice a week) to induced lung carcinogenesis. Starting 1 week prior to benzo(a)pyrene administration, group III animals were treated with mangiferin (100 mg/kg body weight) in the diet for 18 weeks; 12 weeks after benzo(a)pyrene administration, group III animals were treated with mangiferin that continued until the end of the experiment period (18 weeks). At the end of the experiment period, the reactive oxygen species, glutathione and the activities of antioxidant enzymes were assessed in both lung and liver tissues. The levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamin E and vitamin C were decreased in group II animals. However, in the mangiferin + benzo(a)pyrene-treated groups III and IV, the levels of GSH and the activities of antioxidant enzymes in both lung and liver were improved when compared with benzo(a)pyrene-induced group II animals. In addition, the finding that mangiferin decreased reactive oxygen species levels and enhanced antioxidant status suggests that this polyphenol might also be of value in the prevention of benzo(a)pyrene-induced lung carcinogenesis. | 18,816,296 |
Grievance: the underlying oedipal configuration. | In this paper the author describes some of the clinical features encountered in patients who seem to 'nurture' a persistent grievance. He gives clinical examples, and discusses the nature of the powerful underlying dynamics. He suggests that contained within the patient's grievance is a set of phantasies that constitute the expression of his fear and hatred of reality, particularly the reality of the oedipal situation, the child's relationship to the creative parental couple, which Money-Kyrle (1968, 1971) has characterised as an essential element of 'the facts of life'. The phantasies the patient has evolved serve to protect him from envy and jealousy, anxiety and guilt. The primitive oedipal phantasies on which the grievance rests also contribute to the excitement and gratification that are characteristic of the grievance. The analysis of the underlying state of mind helps to account for the persistent grip the grievance has on the patient, and the way this interferes with development. | 18,816,339 |
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