title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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The case of diagnostics of invasive pulmonary aspergillosis by in vivo probe-based confocal laser endomicroscopy of central and distal airways. | We present a case of 41-year-old patient with invasive pulmonary aspergillosis (IPA) in which probe-based confocal laser endomicroscopy (pCLE) imaging of central and distal airways was first performed in vivo. pCLE imaging showed the signs of complete or partial destruction of elastin network of alveolar wall with fibrillar branching fluorescent structures in the zone with typical IPA changes on HRCT. | 25,180,153 | [
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Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages. | Macrophages come across active prostaglandin (PG) metabolism during inflammation, shunting early production of pro-inflammatory towards anti-inflammatory mediators terminating the process. This work for the first time provides evidence that a phytochemical may modulate the arachidonate (AA) metabolism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, promoting the ultimate formation of anti-inflammatory cyclopentenone 15deoxy-PGJ2. Added 1 h before LPS, indicaxanthin from Opuntia Ficus Indica prevented activation of nuclear factor-κB (NF-κB) and over-expression of PGE2 synthase-1 (mPGES-1), but up-regulated cyclo-oxygenase-2 (COX-2) and PGD2 synthase (H-PGDS), with final production of the anti-inflammatory cyclopentenone. The effects were positively related with concentration between 50 and 100 µM. Indicaxanthin did not have any effect in the absence of LPS. A kinetic study investigating the redox status of LPS-stimulated macrophages between 0.5 and 12 h, either in the absence or in the presence of 50-100 µM indicaxanthin, revealed a differential control of ROS production, with early (0.5-3 h) modest inhibition, followed by a progressive (3-12 h) concentration-dependent enhancement over the level induced by LPS alone. In addition, indicaxanthin caused early (0.5-3 h) concentration-dependent elevation of conjugated diene lipid hydroperoxides, and production of hydroxynonenal-protein adducts, over the amount induced by LPS. In LPS-stimulated macrophages indicaxanthin did not affect PG metabolism when co-incubated with either an inhibitor of NADPH oxidase or vitamin E. It is concluded that LPS-induced pro-oxidant activity of indicaxanthin at the membrane level allows formation of signaling intermediates whose accumulation modulates PG biosynthetic pathway in inflamed macrophages. | 25,180,166 | [
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Effect of hypoxia on the calcium and magnesium content, lipid peroxidation level, and Ca²⁺-ATPase activity of syncytiotrophoblast plasma membranes from placental explants. | In the current study the possible relationship between the Ca(2+)/Mg(2+) ratio of human syncytiotrophoblast plasma membranes and their lipid peroxidation and Ca(2+)-ATPase activity was determined. Syncytiotrophoblast plasma membranes of placental explants cultured under hypoxia increased their lipid peroxidation and Ca(2+) content, diminished their Ca(2+)-ATPase activity, and kept their Mg(2+) content unchanged. Membranes preincubated with different concentrations of Ca(2+) increased their Ca(2+) content without changes in their Mg(2+) content. There is a direct relationship between Ca(2+) content and lipid peroxidation of the membranes, as well as an inverse relationship between their Ca(2+) content and Ca(2+)-ATPase activity. On the contrary, preincubation of membranes with different concentrations of Mg(2+) showed a higher Mg(2+) content without changing their lipid peroxidation and Ca(2+)-ATPase activity. Explants cultured under hypoxia in the presence of 4 mM MgSO4 showed similar values of lipid peroxidation and Ca(2+)-ATPase activity of their membranes compared to those of explants cultured under normoxia. Increased Ca(2+) content of the membranes by interacting with negatively charged phospholipids could result in destabilizing effects of the membrane structure, exposing hydrocarbon chains of fatty acids to the action of free radicals. Mg(2+) might exert a stabilizing effect of the membranes, avoiding their exposure to free radicals. | 25,180,187 | [
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A novel mutation in the transglutaminase-1 gene in an autosomal recessive congenital ichthyosis patient. | Structure-function implication on a novel homozygous Trp250/Gly mutation of transglutaminase-1 (TGM1) observed in a patient of autosomal recessive congenital ichthyosis is invoked from a bioinformatics analysis. Structural consequences of this mutation are hypothesized in comparison to homologous enzyme human factor XIIIA accepted as valid in similar structural analysis and are projected as guidelines for future studies at an experimental level on TGM1 thus mutated. | 25,180,191 | [
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Invasive potential of melanoma cells correlates with the expression of MT1-MMP and regulated by modulating its association with motility receptors via N-glycosylation on the receptors. | Matrix remodeling and invasion of basement membrane are the major determinants of malignant progression. Matrix degrading enzymes play a pivotal role in this process and have been shown to be regulated at multiple levels. Using high metastatic B16F10 and its invasive variant B16BL6 cells, we previously demonstrated that the expression of β1,6 branched N-oligosaccharides promotes cellular adhesion on different matrix components which in turn induces secretion of MMP9. The present investigations report that although the two cell lines do not differ in the expression of uPAR, expression of MT1-MMP is significantly higher on B16BL6 cells. Analysis of the transcripts of tissue inhibitors of matrix metalloproteinases (TIMPs) showed that expression of both TIMP1 and TIMP2 correlates negatively with the invasive potential of cells. CD44 and β1 integrin, the two important receptors involved in motility, were identified to carry β1,6 branched N-oligosaccharides in an invasive potential dependent manner. However, their glycosylation status did not appear to influence their surface expression. Although glycosylation on CD44 had no effect, that on β1 integrin significantly affected association of β1 integrin with MT1-MMP. The results thus demonstrate that the cancer cells use multiple mechanisms for degradation of matrix in a controlled manner to couple it with movement for effective invasion. | 25,180,193 | [
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Reconsideration at field scale of the relationship between hydraulic conductivity and porosity: the case of a sandy aquifer in South Italy. | To describe flow or transport phenomena in porous media, relations between aquifer hydraulic conductivity and effective porosity can prove useful, avoiding the need to perform expensive and time consuming measurements. The practical applications generally require the determination of this parameter at field scale, while most of the empirical and semiempirical formulas, based on grain size analysis and allowing determination of the hydraulic conductivity from the porosity, are related to the laboratory scale and thus are not representative of the aquifer volumes to which one refers. Therefore, following the grain size distribution methodology, a new experimental relation between hydraulic conductivity and effective porosity, representative of aquifer volumes at field scale, is given for a confined aquifer. The experimental values used to determine this law were obtained for both parameters using only field measurements methods. The experimental results found, also if in the strict sense valid only for the investigated aquifer, can give useful suggestions for other alluvial aquifers with analogous characteristics of grain-size distribution. Limited to the investigated range, a useful comparison with the best known empirical formulas based on grain size analysis was carried out. The experimental data allowed also investigation of the existence of a scaling behaviour for both parameters considered. | 25,180,202 | [
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A novel algorithm for imbalance data classification based on neighborhood hypergraph. | The classification problem for imbalance data is paid more attention to. So far, many significant methods are proposed and applied to many fields. But more efficient methods are needed still. Hypergraph may not be powerful enough to deal with the data in boundary region, although it is an efficient tool to knowledge discovery. In this paper, the neighborhood hypergraph is presented, combining rough set theory and hypergraph. After that, a novel classification algorithm for imbalance data based on neighborhood hypergraph is developed, which is composed of three steps: initialization of hyperedge, classification of training data set, and substitution of hyperedge. After conducting an experiment of 10-fold cross validation on 18 data sets, the proposed algorithm has higher average accuracy than others. | 25,180,211 | [
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Using SEM-EDX and ICP-OES to investigate the elemental composition of green macroalga Vaucheria sessilis. | The biomass of Vaucheria sessilis forms algal mats in many freshwaters. There is a need to find the method of algal biomass utilization. Vaucheria sessilis is a rich source of micro- and macronutrients and can be used as a soil amendment. In the paper, the elemental composition of enriched, via bioaccumulation process, macroalga was investigated. For this purpose, two independent techniques were used: scanning electron microscopy with an energy dispersive X-ray analytical system (SEMEDX) and inductively coupled plasma optical emission spectroscopy (ICP-OES). The biomass was exposed to two microelemental solutions, with Cu(II) and Zn(II) ions. After two weeks of the experiment, macroalga accumulated 98.5 mg of Zn(II) ions in 1 g of dry biomass and 68.9 mg g(-1) of Cu(II) ions. Micrographs performed by SEM proved that bioaccumulation occurred. Metal ions were bound on the surface and in the interior of cells. Mappings of all cations showed that in the case of the surface of biomass (biosorption), the elements constituted aggregations and in the case of the cross section (bioaccumulation) they were evenly distributed. The algal biomass with permanently bound microelements can find an application in many branches of the industry (feed, natural fertilizers, etc.). | 25,180,212 | [
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Avian influenza in Poland. | Poland has experienced four episodes of avian influenza (AI) outbreaks over the past two decades. The first epidemic was caused by a low pathogenicity (LPAIV) H7N7 subtype and occurred in fattening and breeder turkeys in 1995. Two waves of H5N1 high pathogenicity avian influenza (HPAI) took place in 2006 and 2007. In spring 2006, 64 cases of the H5N1 virus were detected, mostly in mute swans. In December 2007, ten outbreaks of H5N1 HPAI were detected in commercial poultry (n = 9) and wild birds kept in captivity (n = 1). The outbreaks in 2006 and 2007 were caused by genetically similar but clearly distinguishable viruses of the 2.2 clade. In 2013, an H9N2 avian influenza virus was detected in 4 fattening turkey holdings. The virus was low pathogenic and a phylogenetic study has shown a close relatedness to the Eurasian lineage of AIV of the wild bird origin. Neither preventive nor prophylactic vaccinations have ever been used in poultry or other birds. Emergency vaccinations using autogenous vaccine were introduced only to control the H7N7 LPAI outbreaks in 1995. The baseline surveillance for AI in live migratory birds and poultry provides a valuable insight into the ecology of AIV at the wild and domestic bird interface. Passive surveillance is in place of early detection of HPAIV infection in dead or moribund birds. | 25,180,221 | [
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Introduction to molecular biology of influenza a viruses. | This minireview presents an overview of current knowledge on virion structure, genome organization and basic events in the development of influenza A virus. The processes of entry, transcription/replication and viral release are described. In this context, the roles of viral proteins (including recently discovered minor polypeptides) in the subsequent stages of viral development are also discussed. | 25,180,226 | [
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Modification of fulleropyrazolines modulates their cleavage by light. | The extraordinary electrochemistry and the tunability of their energy levels allows the use of fulleropyrazolines in photovoltaics and charge-transfer systems. Here we show that substitution in position 1 tunes photolytic stability; electron-donating groups facilitate 1,3-dipolar cycloreversion to fullerene. This discovery has implications not only for photovoltaic stability but also highlights a potential strategy for photo-controlled fullerene release systems ('photo-caged'/'photo-activated' fullerene). | 25,180,246 | [
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Decoding calcium signaling across the nucleus. | Calcium (Ca(2+)) is an important multifaceted second messenger that regulates a wide range of cellular events. A Ca(2+)-signaling toolkit has been shown to exist in the nucleus and to be capable of generating and modulating nucleoplasmic Ca(2+) transients. Within the nucleus, Ca(2+) controls cellular events that are different from those modulated by cytosolic Ca(2+). This review focuses on nuclear Ca(2+) signals and their role in regulating physiological and pathological processes. | 25,180,265 | [
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Graph analysis of functional brain networks: practical issues in translational neuroscience. | The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective, communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires the know-how of all the methodological steps of the pipeline that manipulate the input brain signals and extract the functional network properties. On the other hand, knowledge of the neural phenomenon under study is required to perform physiologically relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes. | 25,180,301 | [
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Perspective: network-guided pattern formation of neural dynamics. | The understanding of neural activity patterns is fundamentally linked to an understanding of how the brain's network architecture shapes dynamical processes. Established approaches rely mostly on deviations of a given network from certain classes of random graphs. Hypotheses about the supposed role of prominent topological features (for instance, the roles of modularity, network motifs or hierarchical network organization) are derived from these deviations. An alternative strategy could be to study deviations of network architectures from regular graphs (rings and lattices) and consider the implications of such deviations for self-organized dynamic patterns on the network. Following this strategy, we draw on the theory of spatio-temporal pattern formation and propose a novel perspective for analysing dynamics on networks, by evaluating how the self-organized dynamics are confined by network architecture to a small set of permissible collective states. In particular, we discuss the role of prominent topological features of brain connectivity, such as hubs, modules and hierarchy, in shaping activity patterns. We illustrate the notion of network-guided pattern formation with numerical simulations and outline how it can facilitate the understanding of neural dynamics. | 25,180,302 | [
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From Caenorhabditis elegans to the human connectome: a specific modular organization increases metabolic, functional and developmental efficiency. | The connectome, or the entire connectivity of a neural system represented by a network, ranges across various scales from synaptic connections between individual neurons to fibre tract connections between brain regions. Although the modularity they commonly show has been extensively studied, it is unclear whether the connection specificity of such networks can already be fully explained by the modularity alone. To answer this question, we study two networks, the neuronal network of Caenorhabditis elegans and the fibre tract network of human brains obtained through diffusion spectrum imaging. We compare them to their respective benchmark networks with varying modularities, which are generated by link swapping to have desired modularity values. We find several network properties that are specific to the neural networks and cannot be fully explained by the modularity alone. First, the clustering coefficient and the characteristic path length of both C. elegans and human connectomes are higher than those of the benchmark networks with similar modularity. High clustering coefficient indicates efficient local information distribution, and high characteristic path length suggests reduced global integration. Second, the total wiring length is smaller than for the alternative configurations with similar modularity. This is due to lower dispersion of connections, which means each neuron in the C. elegans connectome or each region of interest in the human connectome reaches fewer ganglia or cortical areas, respectively. Third, both neural networks show lower algorithmic entropy compared with the alternative arrangements. This implies that fewer genes are needed to encode for the organization of neural systems. While the first two findings show that the neural topologies are efficient in information processing, this suggests that they are also efficient from a developmental point of view. Together, these results show that neural systems are organized in such a way as to yield efficient features beyond those given by their modularity alone. | 25,180,307 | [
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Epigenetic engineering and the art of epigenetic manipulation. | A report on the Epigenetic Engineering Meeting hosted by the Barts Institute of Cancer, held in London, UK, May 7, 2014. | 25,180,340 | [
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Non-cavitated carious lesions detection methods: a systematic review. | The aim of this study was to critically appraise the performance of detection methods for non-cavitated carious lesions (NCCLs). A detailed search of Medline (via OVID), the Cochrane Collaboration, Scielo and EMBASE identified 2054 publications. After title and abstract review by three investigators (JG, MT, AI), 124 publications were selected for further review. The final publications evaluated the following methods: Visual (V), Caries Lesion Activity Assessment (CLAA), Laser Fluorescence (LF), Radiographic (R), Fibre-optic Transillumination (FOTI), Electrical Conductance (EC) and Quantitative Light-induced Fluorescence (QLF). All included studies used histological assessment as a gold standard for in vitro studies or clinical/visual validation for the in vivo designs. They reported outcomes measures such as sensitivity (SE), specificity (SP), area under the receiver operating characteristic curve (AUROC) and reliability. Data were extracted from the selected studies independently by two reviewers and checked for errors. The quality of the studies was evaluated as described by Bader et al. (2002). Of the 124 articles, 42 were included that described 85 clinical assessments. Overall, the quality of evidence on detection methods was rated ‘poor’, except for EC that was rated ‘fair’. The SE rates were as follows: V (0.17–0.96), LF or DIAGNOdent (DD) (0.16–0.96), R (0.12–0.84), FOTI (0.21–0.96), EC (0.61–0.92) and QLF (0.82). The SP rates were as follows: V (0.46–1.0), LF (0.25–1.00), R (0.55–0.99), FOTI (0.74-0.88), EC (0.73–1.0) and QLF (0.92). There is a large variation in SE and SP values for methods and a lack of consistency in definition of disease and analytical methods. EC and QLF seem to be promising for detection of early lesions. For both cost and practicality considerations, visual methods should remain the standard for clinical assessment in dental practice. | 25,180,412 | [
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Precision high-throughput proton NMR spectroscopy of human urine, serum, and plasma for large-scale metabolic phenotyping. | Proton nuclear magnetic resonance (NMR)-based metabolic phenotyping of urine and blood plasma/serum samples provides important prognostic and diagnostic information and permits monitoring of disease progression in an objective manner. Much effort has been made in recent years to develop NMR instrumentation and technology to allow the acquisition of data in an effective, reproducible, and high-throughput approach that allows the study of general population samples from epidemiological collections for biomarkers of disease risk. The challenge remains to develop highly reproducible methods and standardized protocols that minimize technical or experimental bias, allowing realistic interlaboratory comparisons of subtle biomarker information. Here we present a detailed set of updated protocols that carefully consider major experimental conditions, including sample preparation, spectrometer parameters, NMR pulse sequences, throughput, reproducibility, quality control, and resolution. These results provide an experimental platform that facilitates NMR spectroscopy usage across different large cohorts of biofluid samples, enabling integration of global metabolic profiling that is a prerequisite for personalized healthcare. | 25,180,432 | [
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The value of specialty pharmaceuticals - a systematic review. | Novel specialty biopharmaceuticals hold promise for patients living with complex and chronic conditions. However, high research and development costs, special handling, and other necessary enhancements to patient support programs all contribute to frequently higher prices for these products. This study sought to assess the value of specialty pharmaceuticals through an examination of the clinical, functional, and economic benefits of these treatments for the top 3 disease areas by pharmaceutical spend: rheumatoid arthritis (RA), multiple sclerosis (MS), and breast cancer (BC). Systematic literature review. A systematic review of market research and cost-effectiveness articles was conducted for each disease area to assess clinical, functional, and economic outcomes associated with specialty medicine treatments versus the previous standard of care. All RA clinical (American College of Rheumatology) and functional (Health Assessment Questionnaire) outcome articles were classified as positive. The median cost-effectiveness ratio was $38,900 per quality-adjusted life year (QALY). All MS clinical outcome (relapse rate) articles were positive. The MS functional outcome (Expanded Disability Status Scale) findings were less conclusive. The median cost-effectiveness ratio was $248,000 per QALY. The majority of BC articles yielded statistically inconclusive results for survival. All functional outcome (Quality of Life Questionnaire- Core 30) articles were positive. The median cost-effectiveness ratio was $51,900 per QALY. Novel specialty therapies hold promise for arresting disease progression and improving quality of life for the 3 conditions associated with the highest specialty pharmaceutical spend. These findings demonstrate a strong value proposition for specialty pharmaceuticals, and suggest even greater potential individual patient benefit with consideration of patient heterogeneity. | 25,180,434 | [
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Patient-centered medical home and quality measurement in small practices. | To assess performance on quality measures among small primary care practices that recently adopted an electronic health record (EHR), and how performance differs between practices that have achieved patient-centered medical home (PCMH) recognition and those that have not. Retrospective cohort study. Comparison of practice characteristics and performance on quality measures across 150 independent practices from 2009 to 2011 by recognition status for Physician Practice Connections-PCMH. PCMH-recognized practices performed significantly better than nonrecognized practices on 5 out of 7 clinical quality measures at baseline, and the differences were maintained over the 2-year study period. Both groups improved on all clinical quality measures. Though the magnitude of differences was small, PCMHrecognized practices had a higher number of patients diagnosed with hypertension and proportionally more black patients. A significant difference in PCMH-recognized practices is that they received, on average, 4 additional quality improvement visits compared with nonrecognized practices. Among small practices that have adopted EHRs, practices with PCMH recognition consistently outperformed practices without recognition on most clinical quality measures. With adequate assistance, small, resource-strapped practices can continue to have higher performance on clinical quality measures. | 25,180,435 | [
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Health insurance and breast-conserving surgery with radiation treatment. | To examine the impact of health insurance type on treatment of early-stage breast cancer using breast-conserving surgery (BCS) with radiation therapy (RT) among women in Florida and identify factors that contribute to the variations in receiving the treatment in women with the same health insurance type. Breast cancer cases diagnosed during 1997 to 2002 were obtained from the Florida Cancer Data System. Women 40 years and older diagnosed with localized breast cancer were included. Demographic, insurance, and treatment information were extracted and linked with 2000 census data. χ² and multilevel logistic regression analyses were used. A total of 33,706 women were diagnosed with localized breast cancer in Florida during 1997 to 2002. The average age of the women was 66 years, 58.62% had BCS while 38.61% had mastectomy, and only 2.77% had no surgical treatment. Type of health insurance plays a significant role in receiving BCS with RT. Furthermore, we found significant variations in the use of BCS with RT among women who have the same type health insurance by marital status, age, tumor size, year of diagnosis, level of education, and poverty level. Although clinical practice guidelines recommend BCS with RT to treat women with localized breast cancer, significant differences in receiving the recommended treatment is found between and within types of health insurance. Identifying cultural barriers and educating the public about available treatment options are the major policy implications of this study. These observed differences require further study. | 25,180,437 | [
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Association of inflammatory response and oxidative injury in the pathogenesis of liver steatosis and insulin resistance following subchronic exposure to malathion in rats. | Insulin resistance and risk of type 2 diabetes are the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of liver on metabolic pathways regulation, in particular blood glucose homeostasis, we focused on liver inflammation and oxidative damages in a subchronic model of toxicity by malathion. Adult male Wistar rats of body weight 200-250g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation for 28 days. Glycemic and insulin resistance indices, markers of liver injury, markers of inflammation and oxidative stress were assessed. Malathion-treated rats showed increased glycemia, insulinemia and glycated hemoglobin level, HOMA-IR and HOMA-β indices, plasma activities of hepatocellular enzymes, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) and pro-inflammatory cytokines when decreased antioxidant status in liver was noted. Most of our study indicates that malathion promotes insulin resistance, inflammation and Hepatosteatosis in subchronic model of exposure. On the basis of biochemical and molecular findings, it is concluded that insulin resistance induced by malathion occurs through oxidative stress and related pro-inflammatory markers in a way to result in a reduced function of insulin in liver cells. | 25,180,440 | [
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Rapid and efficient multiple healing of flexible conductive films by near-infrared light irradiation. | Healable, electrically conductive films are essential for the fabrication of reliable electronic devices to reduce their replacement and maintenance costs. Here we report the fabrication of near-infrared (NIR) light-enabled healable, highly electrically conductive films by depositing silver nanowires (AgNWs) on polycaprolactone (PCL)/poly(vinyl alcohol) (PVA) composite films. The bilayer film has sheet resistance as low as 0.25 Ω·sq(-1) and shows good flexibility to repeated bending/unbending treatments. Multiple healing of electrical conductivity lose caused by cuts of several tens of micrometers wide on the bilayer film can be conveniently achieved by irradiating the film with mild NIR light. The AgNW layer functions not only as an electrical conductor but also as a NIR light-induced heater to initiate the healing of PCL/PVA film, which then imparts its healability to the conductive AgNW layer. | 25,180,454 | [
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Long-term sexual functioning in women after surgical treatment of cervical cancer stages IA to IB: a prospective controlled study. | Women with cervical cancer (CC) may be faced with changes in sexual functioning resulting from the cancer itself and/or its surgical treatment. The aims of this study were to prospectively investigate sexual adjustment of CC patients during a follow-up period of 2 years after radical hysterectomy without adjuvant treatment and to compare the results with women who underwent a hysterectomy for a benign gynecological condition and with healthy control women. In this prospective controlled study, participants completed the Short Sexual Functioning Scale, Specific Sexual Problems Questionnaire, Beck Depression Inventory Scale, World Health Organization-5 Well-Being Scale, and Dyadic Adjustment Scale to assess various aspects of sexual and psychosocial functioning at certain time intervals, namely, before surgery and 6 months, 1 year, and 2 years after surgical treatment. Thirty-one women with CC, 93 women with a benign gynecological condition, and 93 healthy controls completed the survey. In CC survivors, no differences were found in sexual functioning during prospective analyses and in comparison with women with a benign gynecological condition. However, compared with healthy women, preoperatively and postoperatively, significantly more CC patients reported sexual dysfunctions, including sexual arousal dysfunction, entry dyspareunia, deep dyspareunia, abdominal pain during intercourse, and reduced intensity of the orgasm. Furthermore, compared with healthy controls, CC patients reported worse psychological functioning before surgery and at 6 months after surgery. Finally, before surgery, quality of partner relationship was rated significantly better by CC patients compared with healthy controls; however, quality of the partner relationship declined during the first year of follow-up compared with the situation before surgery. In CC patients, no differences were found in sexual functioning when prospectively comparing the situation before and after surgery. However, when compared with healthy controls, CC patients are at high risk for sexual dysfunctions, both before and after surgical treatment. | 25,180,463 | [
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Plasticity of human dental pulp stromal cells with bioengineering platforms: a versatile tool for regenerative medicine. | In recent years, human dental pulp stromal cells (DPSCs) have received growing attention due to their characteristics in common with other mesenchymal stem cells, in addition to the ease with which they can be harvested. In this study, we demonstrated that the isolation of DPSCs from third molar teeth of healthy individuals allowed the recovery of dental mesenchymal stem cells that showed self-renewal and multipotent differentiation capability. DPSCs resulted positive for CD73, CD90, CD105, STRO-1, negative for CD34, CD45, CD14 and were able to differentiate into osteogenic and chondrogenic cells. We also assayed the angiogenic potential of DPSCs, their capillary tube-like formation was assessed using an in vitro angiogenesis assay and the uptake of acetylated low-density lipoprotein was measured as a marker of endothelial function. Based on these results, DPSCs were capable of differentiating into cells with phenotypic and functional features of endothelial cells. Furthermore, this study investigated the growth and differentiation of human DPSCs under a variety of bioengineering platforms, such as low frequency ultrasounds, tissue engineering and nanomaterials. DPSCs showed an enhanced chondrogenic differentiation under ultrasound application. Moreover, DPSCs were tested on different scaffolds, poly(vinyl alcohol)/gelatin (PVA/G) sponges and human plasma clots. We showed that both PVA/G and human plasma clot are suitable scaffolds for adhesion, growth and differentiation of DPSCs toward osteoblastic lineages. Finally, we evaluated the interactions of DPSCs with a novel class of nanomaterials, namely boron nitride nanotubes (BNNTs). From our investigation, DPSCs have appeared as a highly versatile cellular tool to be employed in regenerative medicine. | 25,180,486 | [
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Developing the evidence base for families living with parental psychiatric disabilities: crossing the bridge while we're building it. | For this special issue, the latest research findings on the topic of families living with parental psychiatric disabilities were solicited and compiled, to inform policymakers and practitioners with the best research available, while informing researchers about new developments in the field. The creative efforts of practitioners on the ground who strategically cobble together service responses for parents and families, as well as the extraordinary efforts of parents, adult children, young carers, and advocates who continue to bring attention to family issues in psychiatric rehabilitation, are applauded. These things are happening as we build the evidence base. That is, we are "crossing the bridge" to evidence-based practice while we are "building it." This is not without its challenges, in policy, practice, or research. (PsycINFO Database Record (c) 2014 APA, all rights reserved). | 25,180,526 | [
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Hearing-related, health-related quality of life in patients who have undergone otosclerosis surgery: a long-term follow-up study. | The aims of the study were to assess health-related quality of life and hearing-related disability in subjects with otosclerosis 30 years after surgery. An observational study was performed. Medical records were reviewed, a clinical examination as well as audiometric assessments were performed. Generic health-related quality of life was assessed by the SF-36v2 and hearing disability by a shortened version of SSQ (speech spatial and qualities of hearing scale). Sixty-five individuals, who had undergone stapedectomy in 1977-79 at a tertiary referral center. Generic health-related quality of life according to SF-36 subscale scores was comparable to that of an age- and sex-matched reference population. The SF-36 mental component summary score (MCS) was, however, significantly better than that of the reference population. The mental and physical summary component scores correlated significantly to hearing disability measured by the SSQ but not to hearing impairment. Hearing disability was displayed in all SSQ sub-scores, especially in more complex listening situations and in the localization of sounds. This study shows that individuals with otosclerosis, 30 years after surgery, have a good generic health-related quality of life, despite moderate to severe hearing loss and significant hearing disabilities. | 25,180,536 | [
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Clark T. Sawin historical vignette: what do criminology, Harry Houdini, and King George V have in common with postpartum thyroid dysfunction? | The history of postpartum thyroid dysfunction (PPTD) dates back almost two millennia, when Soranus of Ephesus, who practiced obstetrics and neonatology, observed swelling in the necks (presumably goiters) of women after pregnancy. The next reference to PPTD appeared in artwork more than 1000 years later, with many portraits illustrating women with goiter while holding infants. In the early to mid-19th century, Caleb Hillier Parry and Armand Trousseau described postpartum hyperthyroidism, while in the late 1800s, Sir Horatio Bryan Donkin reported the first patient with postpartum hypothyroidism. The modern era of PPTD began with the description in the late 1940s by H.E.W. Roberton of women after delivery reporting hypothyroid symptoms and responding to thyroid extract. The immunologic influence on PPTD was recognized initially by Parker and Beierwaltes in the early 1960s, and the clinical variability and natural history were carefully documented by numerous investigators in the 1970s-1980s. The past two decades have seen further refinements in understanding the prevalence, etiology, and treatment of PPTD. Yet to be determined is the role of screening as a cost-effective measure. | 25,180,618 | [
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ACR appropriateness Criteria® early-stage non-small-cell lung cancer. | Early-stage non-small-cell lung cancer (NSCLC) is diagnosed in about 15% to 20% of lung cancer patients at presentation. In order to provide clinicians with guidance in decision making for early-stage NSCLC patients, the American College of Radiology Appropriateness Criteria Lung Cancer Panel was recently charged with a review of the current published literature to generate up-to-date management recommendations for this clinical scenario. For patients with localized, mediastinal lymph node-negative NSCLC, optimal management should be determined by an expert multidisciplinary team. For medically operable patients, surgical resection is the standard of care, with generally no role for adjuvant therapies thereafter. For patients with medical comorbidities making them at high risk for surgery, there is emerging evidence demonstrating the availability of low toxicity curative therapies, such as stereotactic body radiotherapy, for their care. As a general statement, the American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. | 25,180,631 | [
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An interactive, all-payer, multidomain primary care performance dashboard. | Engaging physicians and practice leaders through regular performance reporting is a key goal of patient-centered medical home improvement efforts. We developed and implemented an interactive, Web-based performance dashboard for primary care practices with input from provider focus groups. Adapting a business software application, individual physician and practice-level reports included information on visit-based and panel productivity, patient panel demographics, and outcome measures (quality of care, patient experience of care, and resource utilization). User training occurred prior to dissemination. Over 2 rounds of reporting, 69% to 77% of users viewed their report within 30 days and 79% of users found the report informative. | 25,180,649 | [
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Androgen receptor polymorphisms and testicular cancer risk. | Testicular cancer (TC) is currently the most common malignant solid tumour in Caucasian males aged 15-39 years. Epidemiological evidence suggests that its onset may be due to an imbalance in the action of steroidal sex hormones and their receptors. A faulty androgen receptor signalling pathway can, in fact, cause various male reproductive disorders. The androgen receptor (AR) gene has two polymorphic segments consisting of CAG and GGC repeats. The length of CAG repeats has been shown to affect the regulation of AR activity. In our study, we used fragment analysis to evaluate the AR gene repeats of 302 TC patients and 322 controls, to establish if there is any association between repeat number and TC. This study of the largest Italian caseload investigated to date highlighted three particularly significant aspects. First, a CAG repeat number of ≥25 may be considered a risk factor for the onset of TC, given its greater frequency in patients in comparison with controls. This difference became significant for the non-seminoma group. Second, men with CAG repeats below 21 or above 24 were found to have a, respectively, 50 and 76% higher risk of TC than those with CAG 21-24, suggesting that these too can be considered a risk factor for TC. Finally, stage II patients were more likely to have a CAG repeat number <21 or >24 than stage I patients. | 25,180,665 | [
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Aligned nanostructured polymers by magnetic-field-directed self-assembly of a polymerizable lyotropic mesophase. | Magnetic-field-directed assembly of lyotropic surfactant mesophases provides a scalable approach for the fabrication of aligned nanoporous polymers by templated polymerization. We develop and characterize a lyotropic liquid crystalline system containing hexagonally packed cylindrical micelles of a polymerizable surfactant in a polymerizable solvent. The system exhibits negative magnetic anisotropy, resulting in the degenerate alignment of cylindrical micelles perpendicular to the magnetic field. Sample rotation during field alignment is used to effectively break this degeneracy and enable the production of uniformly well-aligned mesophases. High-fidelity retentions of the hexagonal structure and alignment were successfully achieved in polymer films produced upon UV exposure of the reactive system. The success of this effort provides a route for the fabrication of aligned nanoporous membranes suitable for highly selective separations, sensing, and templated nanomaterial synthesis. | 25,180,677 | [
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Immune responses to ectoparasites of horses, with a focus on insect bite hypersensitivity. | Horses are affected by a wide variety of arthropod ectoparasites, ranging from lice which spend their entire life on the host, through ticks which feed over a period of days, to numerous biting insects that only transiently visit the host to feed. The presence of ectoparasites elicits a number of host responses including innate inflammatory responses, adaptive immune reactions and altered behaviour; all of which can reduce the severity of the parasite burden. All of these different responses are linked through immune mechanisms mediated by mast cells and IgE antibodies which have an important role in host resistance to ectoparasites, yet immune responses also cause severe pathological reactions. One of the best described examples of such pathological sequelae is insect bite hypersensitivity (IBH) of horses; an IgE-mediated type 1 hypersensitivity to the salivary proteins of Culicoides spp. associated with T-helper-2 production of IL4 and IL13. Importantly, all horses exposed to Culicoides have an expanded population of Culicoides antigen-specific T cells with this pattern of cytokine production, but in those which remain healthy, the inflammatory reaction is tempered by the presence of FoxP3+ CD4+ regulatory T cells that express IL10 and TGF-beta, which suppresses the IL4 production by Culicoides antigen-activated T cells. | 25,180,696 | [
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Evaluation of a continuing education course for occupational therapy practitioners on the use of applied behavior analysis. | A three hour continuing education course combining occupational therapy practice and behavior analysis strategies related to children with autism spectrum disorders was developed and delivered to 24 occupational therapy practitioners. Participants completed evaluations pre-course, post-course, and one month follow up on their self-efficacy, knowledge, and skills in managing challenging behaviors of children with autism spectrum disorders. Overall, ratings scores showed an increase in participants' self-efficacy and knowledge and skill at post-course and one-month follow-up. Despite this increase, participants continued to implement sensory strategies to decrease challenging behaviors due to increased self-efficacy in using sensory strategies and the lack of support in implementing behavior techniques outside their session time. | 25,180,710 | [
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The mRNAs associated to a zinc finger protein from Trypanosoma cruzi shift during stress conditions. | Trypanosome gene expression is regulated almost exclusively at the posttranscriptional level, through mRNA stability, storage and degradation. Here, we characterize the ribonucleoprotein complex (mRNPs) corresponding to the zinc finger protein TcZC3H39 from T. cruzi comparing cells growing in normal conditions and under nutritional stress. The nutritional stress is a key step during T. cruzi differentiation from epimastigote form to human infective metacyclic trypomastigote form. The mechanisms by which the stress, altogether with other stimuli, triggers differentiation is not well understood. This work aims to characterize the TcZC3H39 protein during stress response. Using cells cultured in normal and stress conditions, we observed a dynamic change in TcZC3H39 granule distribution, which appeared broader in stressed epimastigotes. The protein core of the TcZC3H39-mRNP is composed of ribosomes, translation factors and RBPs. The TcZC3H39-mRNP could act sequestering highly expressed mRNAs and their associated ribosomes, potentially slowing translation in stress conditions. A shift were observed in the mRNAs associated with TcZC3H39: the number of targets in unstressed epimastigotes was smaller than that in stressed parasites, with no clear functional clustering in normal conditions. By contrast, in stressed parasites, the targets of TcZC3H39 were mRNAs encoding ribosomal proteins and a remarkable enrichment in mRNAs for the cytochrome c complex (COX), highly expressed mRNAs in the replicative form. This identification of a new component of RNA granules in T. cruzi, the TcZC3H39 protein, provides new insight into the mechanisms involved in parasite stress responses and the regulation of gene expression during T. cruzi differentiation. | 25,180,711 | [
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Developing genetically engineered encapsulin protein cage nanoparticles as a targeted delivery nanoplatform. | Protein cage nanoparticles are excellent candidates for use as multifunctional delivery nanoplatforms because they are built from biomaterials and have a well-defined structure. A novel protein cage nanoparticle, encapsulin, isolated from thermophilic bacteria Thermotoga maritima, is prepared and developed as a versatile template for targeted delivery nanoplatforms through both chemical and genetic engineering. It is pivotal for multifunctional delivery nanoplatforms to have functional plasticity and versatility to acquire targeting ligands, diagnostic probes, and drugs simultaneously. Encapsulin is genetically engineered to have unusual heat stability and to acquire multiple functionalities in a precisely controlled manner. Hepatocellular carcinoma (HCC) cell binding peptide (SP94-peptide, SFSIIHTPILPL) is chosen as a targeting ligand and displayed on the surface of engineered encapsulin (Encap_loophis42C123) through either chemical conjugation or genetic insertion. The effective and selective targeted delivery of SP94-peptide displaying encapsulin (SP94-Encap_loophis42C123) to HepG2 cells is confirmed by fluorescent microscopy imaging. Aldoxorubicin (AlDox), an anticancer prodrug, is chemically loaded to SP94-Encap_loophis42C123 via thiol-maleimide Michael-type addition, and the efficacy of the delivered drugs is evaluated with a cell viability assay. SP94-Encap_loophis42C123-AlDox shows comparable killing efficacy with that of free drugs without the platform's own cytotoxicity. Functional plasticity and versatility of the engineered encapsulin allow us to introduce targeting ligands, diagnostic probes, and therapeutic reagents simultaneously, providing opportunities to develop multifunctional delivery nanoplatforms. | 25,180,761 | [
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Secondary confessions: the influence (or lack thereof) of incentive size and scientific expert testimony on jurors' perceptions of informant testimony. | The goal of this research was to determine whether the size of the incentive (none, small, medium, or large, in terms of sentence reduction) a jailhouse informant receives for testifying, as well as scientific expert testimony regarding the fundamental attribution error, would influence mock juror decision-making in a criminal trial involving a secondary confession. Participants read a murder trial transcript involving informant testimony in which incentive size and expert testimony were manipulated and then provided verdict judgments, made attributions for the informant's decision to testify, and rated the informant and expert on a number of dimensions. Neither expert testimony nor size of incentive had a direct influence on verdicts. However, contrary to previous research on the influence of incentives on jurors' perceptions of secondary confessions, the presence of an incentive did influence verdict decisions, informant ratings, and attributional responses. Results imply that jury-eligible community members may be becoming aware of the issues with informant testimony as a function of incentive but that they are insensitive to the size of the incentive, and expert testimony may not sensitize them to the limitations of such testimony. | 25,180,762 | [
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Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland. | In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established. We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012. By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women. To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake. | 25,180,766 | [
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Thinking aloud: effects on text comprehension by children with specific language impairment and their peers. | Many lines of evidence now suggest that inferencing plays a substantial role in text comprehension. However, inferencing appears to be difficult for children with language impairments, many of whom are also struggling readers. To assess the effects of a 'think-aloud' procedure on inference generation and narrative text comprehension by children with expressive-receptive specific language impairment (SLI) and age-matched peers with typical language development (TLD). An SLI group (n = 12; mean age = 10;5) and an age-matched TLD group (n = 12) participated in the study. Narrative passages were read silently by participants and simultaneously read aloud by the examiner in two conditions: (1) uninterrupted reading and (2) a think-aloud, in which children verbalized their understanding as the text was read. Following the passages in both conditions, children responded to comprehension questions requiring either literal or inferential information (specifically, 'informational' and 'causal' inferences). The children's comprehension scores were analysed by group, condition and question type. The statements children generated during the think-aloud were also compared by group and examined in relation to children's comprehension scores. The SLI group scored lower than the TLD group on all questions (literal, informational and causal), in both conditions. For both groups, however, comprehension scores on all three types of questions increased when the think-aloud procedure was implemented. During the think-aloud, the SLI group generated a comparable number of literal statements compared with the TLD group, but fewer informational and causal statements. The number of causal statements children made correlated with their scores on the inferential comprehension questions. Children with expressive-receptive SLI showed poorer comprehension of narrative texts than children with TLD, as expected. However, both groups' comprehension improved when participating in the think-aloud condition. While further investigation is warranted, the think-aloud procedure shows promise as a strategy to enhance narrative text comprehension in school-age children with, and without, language impairments. | 25,180,778 | [
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Nonrigid registration improves MRI T2 quantification in heart transplant patient follow-up. | To evaluate the use of a nonrigid registration technique for detecting acute heart transplant rejection by MRI T2 quantification. Myocardial T2 quantification was achieved in 279 consecutive examinations from 78 different patients. The protocol consisted of 10 successive black-blood fast spin echo sequences with varying echo times, and a postprocessing based on image registration and exponential fitting. An automatic nonrigid registration method was applied to correct for myocardium misalignment. Finally T2 values were compared with those obtained with a conventional rigid registration followed by manual correction. Nonrigid registration was feasible in 98% of the datasets and was judged of higher quality compared with conventional processing (P < 0.001). No significant difference was found in the clinical outcome (average septal T2 ) between nonrigid and conventional registration (P = 0.66). Interobserver variability was improved with 95% limits of agreement of 2.7 ms (against 3.7 ms with conventional registration). The quality of T2 fitting, as assessed by the coefficient of determination R(2) , was significantly improved (P < 0.001). Nonrigid registration improves T2 quantification in heart-transplant patient follow-up. | 25,180,788 | [
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Salvage lymph node dissection for nodal recurrence of prostate cancer after radical prostatectomy. | We analyzed the impact of salvage lymph node dissection on the prognosis in patients with biochemical recurrence and positive lymph nodes on positron emission tomography/computerized tomography after radical prostatectomy. We retrospectively analyzed the records of 58 patients who underwent pelvic and/or retroperitoneal salvage lymph node dissection from June 2005 to February 2012. Biochemical response was defined as prostate specific antigen less than 0.2 ng/ml 40 days after salvage treatment. Biochemical recurrence in those with a biochemical response was defined as prostate specific antigen greater than 0.2 ng/ml and increasing. Kaplan-Meier curves were used to assess time to biochemical recurrence, clinical recurrence and cancer specific survival. Cox and binary logistic regressions were used to determine factors influencing clinical recurrence and biochemical response. Median followup after salvage lymph node dissection was 39 months. A total of 13 patients (22.4%) achieved a biochemical response. Only 1 patient remained free of biochemical recurrence during followup. Clinical recurrence developed in 25 patients (48.1%) after salvage treatment. Six patients (10.3%) died of disease, including 4 with indeterminate extralymphatic findings on positron emission tomography/computerized tomography before salvage therapy. The 5-year cancer specific survival rate was 71.1%. Patients with a complete biochemical response showed a trend toward a longer time to clinical recurrence (p = 0.20). Biochemical response did not influence cancer specific survival. Salvage lymph node dissection in patients with biochemical recurrence and positive lymph nodes on positron emission tomography/computerized tomography led to a biochemical response in a certain proportion. Most patients progressed to biochemical recurrence after salvage treatment but almost half showed no further clinical recurrence. Cancer specific mortality occurred predominantly in patients with prior suspicion of extralymphatic lesions. Salvage lymph node dissection may delay androgen deprivation therapy and clinical recurrence in select patients. | 25,180,792 | [
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Continuous variation rather than specialization in the egg phenotypes of cuckoos (Cuculus canorus) parasitizing two sympatric reed warbler species. | The evolution of brood parasitism has long attracted considerable attention among behavioural ecologists, especially in the common cuckoo system. Common cuckoos (Cuculus canorus) are obligatory brood parasites, laying eggs in nests of passerines and specializing on specific host species. Specialized races of cuckoos are genetically distinct. Often in a given area, cuckoos encounter multiple hosts showing substantial variation in egg morphology. Exploiting different hosts should lead to egg-phenotype specialization in cuckoos to match egg phenotypes of the hosts. Here we test this assumption using a wild population of two sympatrically occurring host species: the great reed warbler (Acrocephalus arundinaceus) and reed warbler (A. scirpaceus). Using colour spectrophotometry, egg shell dynamometry and egg size measurements, we studied egg morphologies of cuckoos parasitizing these two hosts. In spite of observing clear differences between host egg phenotypes, we found no clear differences in cuckoo egg morphologies. Interestingly, although chromatically cuckoo eggs were more similar to reed warbler eggs, after taking into account achromatic differences, cuckoo eggs seemed to be equally similar to both host species. We hypothesize that such pattern may represent an initial stage of an averaging strategy of cuckoos, that--instead of specializing for specific hosts or exploiting only one host--adapt to multiple hosts. | 25,180,796 | [
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Elusiveness of menstrual cycle effects on mate preferences: comment on Gildersleeve, Haselton, and Fales (2014). | This comment uses meta-analytic techniques to reconcile the apparent conflict between Gildersleeve, Haselton, and Fales's (2014) conclusion of "robust" effects of menstrual cycles on women's preferences for men of purported genetic quality and Wood, Kressel, Joshi, and Louie's (2014) assessment that the few, limited effects in this literature appear to be research artifacts. Despite these divergent conclusions, the literature in both reviews shows a broad distribution of effects, with fully one third of findings countering evolutionary psychology predictions. We demonstrate that Gildersleeve et al.'s conclusions were influenced by a small minority of supportive studies. Furthermore, we show that in both reviews, these supportive studies used imprecise estimates of women's cycle phase by failing to validate cycle day (e.g., with hormonal tests) or by including a large number of days in the fertile phase. More recently, as published studies have used more precise methods to estimate menstrual phase, the effect has declined to zero. Additionally, publication status proved important in both reviews, with published but not unpublished studies showing the predicted effects. In general, the limited evidence for evolutionary psychology predictions calls for more sophisticated models of hormonal processes in human mating. | 25,180,804 | [
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Paraoxonase responses to exercise and niacin therapy in men with metabolic syndrome. | Our purpose was to characterize changes in paraoxonase 1 (PON1) activity and concentration after single aerobic exercise sessions conducted before and after 6 weeks of niacin therapy in men with metabolic syndrome (MetS). Twelve men with MetS expended 500 kcal by walking at 65% of VO2max before and after a 6-week regimen of niacin. Niacin doses were titrated by 500 mg/week from 500 to 1500 mg/day and maintained at 1500 mg/day for the last 4 weeks. Fasting blood samples were collected before and 24 hours after each exercise session and analyzed for PON1 activity, PON1 concentration, myeloperoxidase (MPO), apolipoprotein A1, oxidized low-density lipoprotein (oLDL), lipoprotein particle sizes and concentrations. PON1 activity, PON1 concentration, MPO, and oLDL were unaltered following the independent effects of exercise and niacin (P > 0.05 for all). High-density lipoprotein particle size decreased by 3% (P = 0.040) and concentrations of small very low-density lipoprotein increased (P = 0.016) following exercise. PON1 activity increased 6.1% (P = 0.037) and PON1 concentrations increased 11.3% (P = 0.015) with the combination of exercise and niacin. Exercise and niacin works synergistically to increase PON1 activity and concentration with little or no changes in lipoproteins or markers of lipid oxidation. | 25,180,827 | [
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Genetic analyses of HIV-1 pol sequences from Zimbabwean patients. | This study analysed the sequence of HIV-1 pol gene derived from Zimbabwean infected patients. Sequence analysis, performed on 8 samples, revealed that sequences were classified as subtype C (n=5), subtype B (n=2) and CRF01_AE (n=1). Two patients, treated with a therapeutic regimen containing NRTI/NNRTI, harboured drug resistance mutations in HIV-1 DNA. Phylogenetic analysis performed on subtype C sequences showed that our strains were aggregated in different clusters depending on the country of origin. | 25,180,853 | [
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[Galectin-3 expression in peripheral blood mononuclear cells of chronic hepatitis B patients treated with pegylated interferon alpha-2a]. | To study the relationship between therapeutic efficacy of pegylated interferon alpha-2a (Peg-IFNa-2a) in patients with chronic hepatitis B (CHB) and expression of Galectin-3 in peripheral blood mononuclear cells (PBMCs). Fifty CHB patients treated with a 48-week course of Peg-IFNa-2a (180 mug/week, subcutaneous) were divided into groups according to treatment response, with 14 patients in the 24-week responder group, 21 patients in the 48-week responder group and 15 patients in the non-responder groups. Twenty healthy volunteers served as the normal control group. Gene and protein expression of Galectin-3 in PBMCs was detected by PCR and westen blotting. PBMC expression of Galectin-3 was significantly higher in the effective treatment (responders) group compared to the control group and the non-responder group. In addition, the 24-week responders had significantly higher than the 48-week responders, and the 48-week responders had significantly higher Galectin-3 expression than the non-responders at 24 weeks. Peg-IFNa-2a may inhibit HBV DNA replication by up-regulating the expression of Galectin-3 in PBMCs. | 25,180,866 | [
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Meeting international standards: a cultural approach in implementing the mini-CEX effectively in Indonesian clerkships. | Abstract Background: Medical schools all over the world try to adapt their programs to meet international standards. However, local culture might hamper innovation attempts. To describe challenges in implementing the mini-CEX in Indonesia and investigate its effect on students' clinical competence. The study was conducted in the Internal Medicine and Neurology departments of the Universitas Gadjah Mada, Indonesia. Implementing the mini-CEX into the existing curriculum, while taking the Indonesian culture into account, implied a shift from group to individual feedback. We compared students' final clinical competence before (Internal Medicine n = 122, Neurology n = 183) and after (n = 183 and 186, respectively) the implementation of the mini-CEX, using a modified Objective Structured Long Examination Record (OSLER). The Mann-Whitney test was used to analyze the data. We took power distance and individualism into account to facilitate the implementation process. After implementing the mini-CEX, the OSLER results were significant higher in Internal Medicine (p < 0.05). However, no differences were found in Neurology. By managing the innovation process carefully and taking culture and local context into account, the mini-CEX can be implemented without changing the underlying concept. The shift from group to individual feedback seems to have a positive effect on student learning. | 25,180,877 | [
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Thirty years of illness scripts: Theoretical origins and practical applications. | This study describes the introduction and spread of the concept of "illness script" in the medical education literature. First, I will concisely discuss the development of the "script" concept in the general psychological literature and the results of the studies performed to provide it with the necessary empirical basis. Next, I will sketch how "scripts" entered the medical domain via efforts to develop diagnostic systems in the field of artificial intelligence. Subsequently, I will describe how the illness script concept was elaborated and specified by medical educators and educational researchers. The illness script concept has solid underpinnings and can be used to elucidate aspects of medical expertise development. It can also be used to formulate recommendations for clinical teaching and has yielded a specific test, the Script Concordance Test. | 25,180,878 | [
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Race and ethnic differences in early childhood maltreatment in the United States. | In the United States, over 6 million children were referred to child protective services in 2012. Black children are overrepresented among children investigated for child abuse and neglect. Understanding why black children are disproportionately reported for maltreatment is critical to informing policy and practice solutions. Two competing theories attribute disproportionality to either racial bias or concentrated risk factors. Although prior work has focused on national data, this study examines the relationship between risk factors and maltreatment at the state level, focusing on outcomes for young children. We examine the relationship between early childhood poverty and maltreatment victimization across white, black, and Hispanic children (0-3 years). Using state-level data (N = 48), we determine ratios of disproportionate outcomes in child maltreatment and associations to poverty and other risk factors. Study findings for state-level data show greater disproportionality of black and Hispanic children living in poverty relative to their white counterparts. This imbalance is associated with greater disproportionality in maltreatment rates. Results also indicate that disproportionality of maltreatment rates was associated with state disproportionality in rates of unmarried and teenage mothers for blacks and Hispanics. Exposure to risks such as poverty is an important factor driving the overrepresentation of minority groups in the child welfare system. Effective strategies for reducing maltreatment must include strategies for reducing poverty and supporting young at-risk mothers. | 25,180,892 | [
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Domestic and sexual violence against patients with severe mental illness. | Domestic and sexual violence are significant public health problems but little is known about the extent to which men and women with severe mental illness (SMI) are at risk compared with the general population. We aimed to compare the prevalence and impact of violence against SMI patients and the general population. Three hundred and three randomly recruited psychiatric patients, in contact with community services for ⩾ 1 year, were interviewed using the British Crime Survey domestic/sexual violence questionnaire. Prevalence and correlates of violence in this sample were compared with those from 22 606 general population controls participating in the contemporaneous 2011/12 national crime survey. Past-year domestic violence was reported by 27% v. 9% of SMI and control women, respectively [odds ratio (OR) adjusted for socio-demographics, aOR 2.7, 95% confidence interval (CI) 1.7-4.0], and by 13% v. 5% of SMI and control men, respectively (aOR 1.6, 95% CI 1.0-2.8). Past-year sexual violence was reported by 10% v. 2.0% of SMI and control women respectively (aOR 2.9, 95% CI 1.4-5.8). Family (non-partner) violence comprised a greater proportion of overall domestic violence among SMI than control victims (63% v. 35%, p < 0.01). Adulthood serious sexual assault led to attempted suicide more often among SMI than control female victims (53% v. 3.4%, p < 0.001). Compared to the general population, patients with SMI are at substantially increased risk of domestic and sexual violence, with a relative excess of family violence and adverse health impact following victimization. Psychiatric services, and public health and criminal justice policies, need to address domestic and sexual violence in this at-risk group. | 25,180,908 | [
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Engineering specificity in a dynamic protein complex with a single conserved mutation. | It has been demonstrated that the complex of yeast cytochrome c (Cc) and cytochrome c peroxidase (CcP) exists as a delicate equilibrium of a specific, active state and the non-specific, dynamic encounter state. An ortholog of yeast Cc, horse Cc, binds CcP but forms a much more dynamic complex, as demonstrated by NMR spectroscopy. A single conservative mutation of lysine 13 to arginine reduces the dynamics and enhances the specificity. The crystal structure of the stereospecific complex resembles the yeast Cc-CcP complex. In contrast, the K13A mutation increases the dynamic nature of the complex with CcP, showing that specificity in a redox protein complex can depend on the interactions of a single side chain in the binding interface. | 25,180,929 | [
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Dissociable effects of dorsal and ventral hippocampal DHA content on spatial learning and anxiety-like behavior. | Chronic deficiency of dietary docosahexaenoic acid (DHA) during critical developmental windows results in severe deficits in spatial learning, anxiety and hippocampal neuroplasticity that parallel a variety of neuropsychiatric disorders. However, little is known regarding the influence of long-term, multigenerational exposure to dietary DHA enrichment on these same traits. To characterize the potential benefits of multigenerational DHA enrichment, mice were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 0.1% preformed DHA/kg feed weight or 1.0% preformed DHA/kg feed weight through three generations. General locomotor activity, spatial learning, and anxiety-like behavior were assessed in adult male offspring of the third generation. Following behavioral assessments, ventral and dorsal hippocampus was collected for DHA and arachidonic acid (AA) analysis. Animals consuming the 0.1% and 1.0% DHA diet did not differ from control animals for locomotor activity or on performance during acquisition learning, but made fewer errors and showed more stable across-day performance during reversal learning on the spatial task and showed less anxiety-like behavior. Consumption of the DHA-enriched diets increased DHA content in the ventral and dorsal hippocampus in a region-specific manner. DHA content in the dorsal hippocampus predicted performance on the reversal training task. DHA content in the ventral hippocampus was correlated with anxiety-like behavior, but AA content in the dorsal hippocampus was a stronger predictor of this behavior. These results suggest that long-term, multigenerational DHA administration improves performance on some aspects of complex spatial learning, decreases anxiety-like behavior, and that modulation of DHA content in sub-regions of the hippocampus predicts which behaviors are likely to be affected. | 25,180,934 | [
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Triamcinolone acetonide-Eudragit(®) RS100 nanofibers and nanobeads: Morphological and physicochemical characterization. | The aim of the present research was to fabricate triamcinolone acetonide (TA)-Eudragit(®) RS100 nanostructures using the electrospraying method. The physicochemical properties of the electrosprayed formulations as well as drug release patterns were assessed. The particle size and morphology were evaluated using scanning electron microscopy. X-ray crystallography and differential scanning calorimetry were also conducted to investigate the crystallinity and polymorphic alterations of the drug in the formulations. Probable chemical interactions between the drug and the carrier during the preparation process were analyzed using FT-IR spectroscopy. The drug release kinetic was also considered to predict the release mechanism. Increasing the concentration of injected polymer solution resulted in the formation of more fibers and fewer beads, with the particle diameter ranging from 60 nm to a few micrometers based on the drug: polymer ratio. The drug crystallinity was notably decreased during the electrospraying process; however, no interaction between drug and polymer was detected. The electrosprayed formulations with 1:10 drug: polymer ratio showed an almost similar drug release rate compared to the pure drug, while those with 1:5 ratio revealed slower release profiles. The release data were best fitted to the Weibull model, so that the corresponding shape factor values of the Weibull model were less than 0.75, indicating the diffusion controlled release mechanism. Our findings revealed that TA loaded Eudragit(®) RS100 nanofibers and nanobeads were properly prepared by the electrospraying method, which is a simple, surfactant-free and cost effective technique for producing drug: polymer nanostructures. | 25,180,944 | [
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Postabdominoplasty Wound Dehiscence in Bariatric Patients: Biliopancreatic Diversion Versus Gastric Bypass: A Preliminary Study. | Surgical procedures with an extended follow-up and therefore recognized as safe in literature are classified into 2 categories: procedures limiting the introduction of food mechanically (restrictive interventions such as adjustable gastric banding, vertical banded gastroplasty, and sleeve gastrectomy) or functionally (mini gastric bypass or gastric bypass) and procedures limiting absorption (mainly biliopancreatic diversion [BPD]). Seventy-nine patients who underwent postbariatric abdominoplasty to correct serious flaws resulting from weight loss surgery were included in this retrospective study. Dehiscence of the surgical wound was carefully investigated between the population previously submitted to BPD and gastric bypass. The data were analyzed by correlating the incidence of postoperative dehiscence by Fisher exact test, with a statistical significance level of P<0.05. Among the 42 abdominoplasties after BPD, dehiscence rate was 33% (14 patients), whereas in the group of 37 patients who underwent gastric bypass, the occurrence of dehiscence was 8% (3 patients).The Fisher exact test highlighted previously performed BPD as statistically significant for the onset of postoperative dehiscence (P=0.012). There is a great need to validate these data on large or multicentric studies. The previous bariatric surgery procedure may play a role similar to so many other widely investigated risk factors such as smoking and body mass index, and some categories of patients should require even more attention in the preoperative, intraoperative, and postoperative management. | 25,180,957 | [
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The development and test re-test reliability of a work-related asthma screening questionnaire. | Work-related asthma (WRA) is under-recognized and delays in recognition contribute to long-term morbidity. The objective of the project was to develop a WRA screening questionnaire for use by primary care providers in the assessment of individuals with asthma, and to evaluate the respondent burden, test re-test reliability and face validity of the questionnaire. A literature search was undertaken and an expert advisory committee was convened. A questionnaire was drafted and assessed for feasibility of use and content validity. The study enrolled patients with asthma attending outpatient clinics and an asthma education center. Participants were asked to respond to the questionnaire on two occasions, and comment on the content (face validity) and ease of completion (respondent burden). Ethics approval was obtained from an institutional review board. A 14-item self-administered screening questionnaire was created. Thirty-nine participants were recruited, and 26 participants completed a second administration of the questionnaire. The items on the relation of asthma symptoms to work demonstrated substantial agreement between testings. The workplace exposures items were found to have good reproducibility. The majority of participants denied that items were repetitive, not useful or difficult to understand. We have developed a WRA screening questionnaire designed to aid primary care providers in the recognition of possible WRA. The tool exhibited content and face validity, good test re-test reliability and low respondent burden. Participant feedback is being considered in revisions of the questionnaire. | 25,180,965 | [
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Atherosclerosis in intracranial, extracranial, and coronary arteries with aortic plaques in patients with ischemic stroke of undetermined etiology. | We investigated the association of cerebral and coronary artery atherosclerosis with the presence, burden and type of atherosclerotic plaques of the aorta (AP) in patients with ischemic stroke of undetermined etiology. 48 consecutive patients (32 males, mean age 68 ± 11 years) with acute ischemic stroke of unknown etiology after thorough stroke workup were investigated using ECG-gated CT-Angiography (CTA) for the detection of embolic AP. Intima media thickness (IMT), presence of carotid plaques and stenosis ≥ 50% and intracranial stenosis were assessed as parameters of cerebral atherosclerosis, the Agatston score (AS) and coronary artery stenosis ≥ 50% (CAS) in CTA as parameters of coronary atherosclerosis. Plaque burden was classified as mild or severe and plaque types were classified according to their morphology in calcified, non-calcified or mixed. APs were found in 36 patients (75%). AP presence was associated with higher IMT values (p = 0.029), intracranial stenosis (p = 0.047), CAS (p = 0.033) and AS (p = 0.026). Twenty-three of 31 (74.2%) patients with both carotid atherosclerosis and AP revealed plaque calcification (p = 0.041). Ten of 14 (71.4%) patients with AP and intracranial stenosis had calcified plaques (p = 0.030). AP in more than one aortic segment was found in patients with bilateral carotid stenosis ≥ 50% (p = 0.038), intracranial stenosis (p = 0.042), high IMT (p = 0.040) and higher AS (p = 0.019). Aortic atherosclerotic plaques are common in patients with ischemic stroke of undetermined etiology and in particular those with carotid, intracranial and coronary atherosclerosis or high IMT values. In these patients, CTA of aorta should be seriously considered. | 25,180,988 | [
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[Diagnosis and treatment of rheumatoid arthritis]. | Rheumatoid arthritis today is still not curable but satisfactory treatable. Treatment targets include clinical remission (or at least low disease activity), lack of radiological destructions and functional disability as well as acceptable life quality and unimpaired working ability. Diagnosing and adequately treating the disease as early as possible is essential for a favourable long-term outcome. Treatment to target with validation and if necessary modification at least every three months until target is achieved ensures good results. Predominantly treatment starts with a combination of methotrexate and glucocorticoids followed by a conventional DMARD combination and then addition of a biologic DMARD in case of failing target. Presence of adverse risk factors and/or high disease activity a cDMARD/bDMARD combination might be used already after starting treatment failure. Additional treatment options such as physiotherapy should be added. Altogether with current treatment possibilities burden of disease declined dramatically in recent years. | 25,180,998 | [
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Preserved modular network organization in the sedated rat brain. | Translation of resting-state functional connectivity (FC) magnetic resonance imaging (rs-fMRI) applications from human to rodents has experienced growing interest, and bears a great potential in pre-clinical imaging as it enables assessing non-invasively the topological organization of complex FC networks (FCNs) in rodent models under normal and various pathophysiological conditions. However, to date, little is known about the organizational architecture of FCNs in rodents in a mentally healthy state, although an understanding of the same is of paramount importance before investigating networks under compromised states. In this study, we characterized the properties of resting-state FCN in an extensive number of Sprague-Dawley rats (n = 40) under medetomidine sedation by evaluating its modular organization and centrality of brain regions and tested for reproducibility. Fully-connected large-scale complex networks of positively and negatively weighted connections were constructed based on Pearson partial correlation analysis between the time courses of 36 brain regions encompassing almost the entire brain. Applying recently proposed complex network analysis measures, we show that the rat FCN exhibits a modular architecture, comprising six modules with a high between subject reproducibility. In addition, we identified network hubs with strong connections to diverse brain regions. Overall our results obtained under a straight medetomidine protocol show for the first time that the community structure of the rat brain is preserved under pharmacologically induced sedation with a network modularity contrasting from the one reported for deep anesthesia but closely resembles the organization described for the rat in conscious state. | 25,181,007 | [
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Confidence interval estimation for standardized effect sizes in multilevel and latent growth modeling. | Multilevel and latent growth models are frequently used interchangeably to examine differences between groups in trajectories of outcomes from controlled clinical trials. The unstandardized coefficient for the effect from group to slope (the treatment effect) from such models can be converted to a standardized mean difference (Cohen's d) between the treatment and control groups at end of study. This article addresses the confidence interval (CI) for this effect size. Two sets of equations for estimating the CI for the treatment effect size in multilevel models were derived, and the usage of each was illustrated with data from the National Youth Study (Elliott, Huizinga, & Menard, 1989). Validity of the CIs was examined with a Monte Carlo simulation study that manipulated effect potency and sample size. The equivalence of the 2 new CI estimation methods was demonstrated, and the Monte Carlo study found that bias in the CI for the effect size was not appreciably larger than bias in the CI for the widely used unstandardized coefficient. Investigators reporting this increasingly popular effect size can estimate its CI with equations presented in this article. | 25,181,028 | [
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RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis. | Drug resistance and metastasis are lethal characteristics of tumors. We previously demonstrated that silencing of ribophorin II (RPN2), which is part of the N-oligosaccharyl transferase complex, efficiently induced apoptosis and reduced resistance to docetaxel in human breast cancer cells. Here, we report the clinical and functional correlations of RPN2 expression in osteosarcoma. Immunohistochemical evaluation of 35 osteosarcoma patient biopsies revealed that RPN2 was moderately to highly expressed in all specimens, and higher RPN2 mRNA expression was significantly correlated with poor prognosis. To investigate whether lethal phenotypes of osteosarcoma could be reduced by regulating the expression of RPN2, we conducted a study of RNAi-induced RPN2 knockdown in highly metastatic human osteosarcoma cells. The results indicated that RPN2 silencing reduced cell proliferation, sphere formation, cell invasion, and sensitized drug response in vitro. Mice bearing RPN2-silenced highly metastatic osteosarcoma xenografts showed reduced tumor growth and lung metastasis, and survived longer than mice bearing control tumor xenografts. Taken together, our data suggest that RPN2 silencing contributes to regulation of lethal osteosarcoma phenotypes and could be a novel target for RNAi-based therapeutics against osteosarcoma. | 25,181,275 | [
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Investigating the intrinsic aggregation potential of evolutionarily conserved segments in p53. | Protein aggregation and amyloid formation are known to play a role both in diseases and in biological functions. Transcription factor p53 plays a major role in tumor suppression by maintaining genomic stability. Recent studies have suggested that amyloid formation of p53 could lead to its loss of physiological function as a tumor suppressor. Here, we investigated the intrinsic amyloidogenic nature of wild-type p53 using sequence analysis. We used bioinformatics and aggregation prediction algorithms to establish the evolutionarily conserved nature of aggregation-prone sequences in wild-type p53. Further, we analyzed the amyloid forming capacity of conserved and aggregation-prone p53-derived peptides PILTIITL and YFTLQI in vitro using various biophysical techniques, including all atom molecular dynamics simulation. Finally, we probed the seeding ability of the PILTIITL peptide on p53 aggregation in vitro and in cells. Our data demonstrate the intrinsic amyloid forming ability of a sequence stretch of the p53 DNA binding domain (DBD) and its aggregation templating behavior on full-length and p53 core domain. Therefore, p53 aggregation, instigated through an amyloidogenic segment in its DBD, could be a putative driving force for p53 aggregation in vivo. | 25,181,279 | [
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Best practices for mapping replication origins in eukaryotic chromosomes. | Understanding the regulatory principles ensuring complete DNA replication in each cell division is critical for deciphering the mechanisms that maintain genomic stability. Recent advances in genome sequencing technology facilitated complete mapping of DNA replication sites and helped move the field from observing replication patterns at a handful of single loci to analyzing replication patterns genome-wide. These advances address issues, such as the relationship between replication initiation events, transcription, and chromatin modifications, and identify potential replication origin consensus sequences. This unit summarizes the technological and fundamental aspects of replication profiling and briefly discusses novel insights emerging from mining large datasets, published in the last 3 years, and also describes DNA replication dynamics on a whole-genome scale. | 25,181,303 | [
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Transient hypermutagenesis accelerates the evolution of legume endosymbionts following horizontal gene transfer. | Horizontal gene transfer (HGT) is an important mode of adaptation and diversification of prokaryotes and eukaryotes and a major event underlying the emergence of bacterial pathogens and mutualists. Yet it remains unclear how complex phenotypic traits such as the ability to fix nitrogen with legumes have successfully spread over large phylogenetic distances. Here we show, using experimental evolution coupled with whole genome sequencing, that co-transfer of imuABC error-prone DNA polymerase genes with key symbiotic genes accelerates the evolution of a soil bacterium into a legume symbiont. Following introduction of the symbiotic plasmid of Cupriavidus taiwanensis, the Mimosa symbiont, into pathogenic Ralstonia solanacearum we challenged transconjugants to become Mimosa symbionts through serial plant-bacteria co-cultures. We demonstrate that a mutagenesis imuABC cassette encoded on the C. taiwanensis symbiotic plasmid triggered a transient hypermutability stage in R. solanacearum transconjugants that occurred before the cells entered the plant. The generated burst in genetic diversity accelerated symbiotic adaptation of the recipient genome under plant selection pressure, presumably by improving the exploration of the fitness landscape. Finally, we show that plasmid imuABC cassettes are over-represented in rhizobial lineages harboring symbiotic plasmids. Our findings shed light on a mechanism that may have facilitated the dissemination of symbiotic competency among α- and β-proteobacteria in natura and provide evidence for the positive role of environment-induced mutagenesis in the acquisition of a complex lifestyle trait. We speculate that co-transfer of complex phenotypic traits with mutagenesis determinants might frequently enhance the ecological success of HGT. | 25,181,317 | [
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Fast adsorption of Cd²⁺ and Pb²⁺ by EGTA dianhydride (EGTAD) modified ramie fiber. | In this study, the removal of Cd(2+) and Pb(2+) from aqueous solutions was investigated using a novel chelating material. The first part described the synthesis of ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid dianhydride (EGTAD), mercerization treatment of ramie fiber (MRF), and the MRF was then reacted with EGTAD to prepare the new material (ERF). The obtained material was characterized by weight gain, SEM, FTIR, and elemental analysis. The results of FTIR and elemental analysis confirmed that ester bond, carboxyl and amine groups were introduced onto ERF. The adsorption capacity of metals on ERF was evaluated at different contact times, pH values, initial metal concentrations, and temperatures in the second part. The adsorption equilibrium was reached within 5 min for Cd(2+) and Pb(2+). Adsorption isotherm could be well fitted by the Langmuir model, and the maximum adsorption capacities were 159.11 and 273.78 mg g(-1) for Cd(2+) and Pb(2+) at 298 K, respectively. Thermodynamic analysis showed that the adsorption process was spontaneous and endothermic. The molar ratio of adsorbed cation to grafted EGTA is close to 1.8:1, which confirmed that the adsorption was chemical process involving both surface chelation reaction and ion exchange. In addition, the absorbent was successfully regenerated using HCl and ultrasonic treatment. | 25,181,330 | [
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Total inhibition of (1)O2-induced oxidative damage to guanine bases of DNA/RNA by turmeric extracts. | The guanine base of nucleic acids is known to be very reactive towards degradation by (1)O2-induced oxidative stress. Oxidative reactions of DNA are linked to many human diseases including cancer. Among the various forms of reactive O2 species (OH, (1)O2 or O2(-)), the oxidative stress caused by (1)O2 is of particular physiologic importance because of its selectively long life in aqueous medium and its ability to diffuse through a cell membrane. In this study we investigated the degradation of a model compound guanosine (Guo) by (1)O2, which was generated by riboflavin-induced photosensitization and by molybdate ion catalyzed disproportionation of H2O2. We observed the remarkable ability of an aqueous and alcoholic extracts of Turmeric (Curcuma longa) as an extraordinary scavenger of (1)O2 to completely inhibit the degradation of Guo. The alcoholic extracts were more effective in their antioxidant activity than the corresponding water extract. This naturally occurring antioxidant offers a most economical supplement to protect biologically significant molecules from the oxidative stress induced by (1)O2. | 25,181,345 | [
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Who reports it best? A comparison between parent-report, self-report, and the real life social behaviors of adults with Williams syndrome. | Given the reliance on self-report in studies of adults with intellectual disabilities, this study examined individual vs. parental reports concerning the social approach behaviors of adults with Williams syndrome (WS) across a hypothetical and a live behavioral setting. Individuals with WS (N = 30) were asked whether they would approach strangers in two hypothetical, laboratory tasks (yes/no questionnaire vs. judging facial stimuli of individuals with different emotional expressions). Similarly, their parents also responded to a rating scale of their child's social approach behavior toward strangers displaying various emotions. Then, in a community setting, behavioral coders recorded actual social approaches of individuals with WS toward strangers. Although self-report ratings were consistent across measures, these measures did not correspond to the individuals' actual behaviors during the community observations. Conversely, parental reports did not correspond to their child's self-report measures, but parents did more accurately predict their child's real-life social approach behaviors. Implications are discussed for both research and practice. | 25,181,359 | [
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Stratification of patients with liver fibrosis using dual-energy CT. | Assessing the severity of liver fibrosis has direct clinical implications for patient diagnosis and treatment. Liver biopsy, typically considered the gold standard, has limited clinical utility due to its invasiveness. Therefore, several imaging-based techniques for staging liver fibrosis have emerged, such as magnetic resonance elastography (MRE) and ultrasound elastography (USE), but they face challenges that include limited availability, high cost, poor patient compliance, low repeatability, and inaccuracy. Computed tomography (CT) can address many of these limitations, but is still hampered by inaccuracy in the presence of confounding factors, such as liver fat. Dual-energy CT (DECT), with its ability to discriminate between different tissue types, may offer a viable alternative to these methods. By combining the "multi-material decomposition" (MMD) algorithm with a biologically driven hypothesis we developed a method for assessing liver fibrosis from DECT images. On a twelve-patient cohort the method produced quantitative maps showing the spatial distribution of liver fibrosis, as well as a fibrosis score for each patient with statistically significant correlation with the severity of fibrosis across a wide range of disease severities. A preliminary comparison of the proposed algorithm against MRE showed good agreement between the two methods. Finally, the application of the algorithm to longitudinal DECT scans of the cohort produced highly repeatable results. We conclude that our algorithm can successfully stratify patients with liver fibrosis and can serve to supplement and augment current clinical practice and the role of DECT imaging in staging liver fibrosis. | 25,181,365 | [
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The shape of the scene background determines the perceived path of a moving object. | Studies of the perception of motion in three-dimensional scenes have provided extensive information about the effects of changes in the size, speed, and disparity of an object's image on the perception of the object's trajectory. The present study demonstrates that this perception is not determined primarily by the object's motion but by the shape of the background against which this motion is displayed. The effect of a scene background on judgments of the trajectory of a moving object was examined in 2 experiments with 33 observers. In the first experiment, observers judged whether the trajectory was concave or convex. In the second experiment, observers judged which of 2 displays, differing in curvature of the motion path and curvature of the background, depicted the more curved motion path. Judgments of sign of curvature and judgments of relative magnitude of curvature were determined almost entirely by the background curvature. | 25,181,369 | [
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Committee opinion: onabotulinumtoxinA and the bladder. | In January 2013, the US Food and Drug Administration approved the use of onabotulinumtoxinA (also known as Botox A) for the treatment of overactive bladder, thus providing another treatment option for women. Symptoms of overactive bladder have been shown to significantly improve after onabotulinumtoxinA injections compared with no intervention, placebo, pharmacological treatments, and bladder instillation technique. Before considering medical or surgical treatment, all patients in whom overactive bladder is diagnosed should receive instruction in behavioral techniques (eg, bladder retraining drills and timed voids), fluid management, or pelvic muscle exercises with or without physical therapy. Intradetrusor onabotulinumtoxinA may be a second-line treatment option for overactive bladder in appropriate patients, and consideration of its use requires shared decision making between the patient and health care provider. Patients who are candidates for onabotulinumtoxinA injections into the bladder should be counseled about its risks and possible postprocedure adverse events, including the risk of postprocedure urinary retention, urinary tract infections, hematuria, pain, and transient body weakness. Health care providers who perform onabotulinumtoxinA injections must have appropriate training and experience in treating women with pelvic floor disorders, operative cystoscopy privileges, and the ability to diagnose and manage any adverse outcomes after onabotulinumtoxinA injections into the bladder. | 25,181,372 | [
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Validation of genetically matched wild-type strain and lysyl oxidase-like 1 knockout mouse model of pelvic organ prolapse. | Lysyl oxidase-like 1 knockout (Loxl1) mice demonstrate deficient elastin homeostasis associated with pelvic organ prolapse (POP). To further investigate the pathophysiology of POP in these animals, a genetically matched homozygous positive (Loxl1) or wild-type strain is needed. This study sought to create and validate genetically matched Loxl1 and Loxl1 strains. Female Loxl1 mice were backcrossed with male wild-type mice. The resultant heterozygous mice were bred to produce Loxl1 and Loxl1 mice, whose genotype was confirmed by polymerase chain reaction (PCR). Multiparous female Loxl1 (n = 7) and Loxl1 (n = 9) mice were assessed for POP weekly for 12 weeks after their first vaginal delivery. Pelvic organ prolapse was compared between groups using a Kaplan-Meier survival curve with P of less than 0.05 indicating a significant difference. Vaginal connective tissue histologic finding was assessed qualitatively and quantitatively. There were no significant differences between the groups in age or parity. Of the 7 Loxl1 mice, 4 developed prolapse by 8 weeks and 6 by 12 weeks postpartum. No Loxl1 mouse prolapsed. Loxl1 mice had significantly larger vaginas as determined by area within the lumen and total cross-sectional tissue area. Striated muscle fibers of the urethra in Loxl1 mice were less organized, shorter, and thinner than in Loxl1 mice. Genetically matched Loxl1 and Loxl1 strains can be reliably created by a backcross method and differentiate in their prolapse phenotype. Loxl1 mice demonstrate pathology primarily characterized by enlargement of the vagina. Further studies are needed to elucidate the cause of this finding. | 25,181,380 | [
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The neuropsychological assessment battery categories test as a measure of executive dysfunction in patients with Parkinson's disease and essential tremor: an exploratory study. | Patients with Parkinson's disease (PD) and essential tremor (ET) can experience deficits in executive functioning (EF) secondary to abnormalities in fronto-striatal and cerebellar-frontal pathways respectively. The assessment of EF can be confounded in these patients due to motor difficulties and slowed processing speed. Thus, instruments which do not require speeded motor responses are potentially attractive in this population. The Neuropsychological Assessment Battery-Categories Test (NABCAT) is one such instrument. This study evaluated the convergent and divergent validity of this measure as well as its diagnostic accuracy in comparison to other commonly administered tests. Records for 28 patients with PD and/or ET who presented for evaluation pre-deep brain stimulation surgery were analyzed. The NABCAT had modest correlations with other measures of EF, as well as memory. However, it demonstrated relatively poor sensitivity and modest specificity to executive dysfunction. The NABCAT did not demonstrate adequate psychometric properties to replace traditional measures of EF in this population; however, it may have utility as a screening instrument for more significant dysfunction. | 25,181,389 | [
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Weakening of the stratospheric polar vortex by Arctic sea-ice loss. | Successive cold winters of severely low temperatures in recent years have had critical social and economic impacts on the mid-latitude continents in the Northern Hemisphere. Although these cold winters are thought to be partly driven by dramatic losses of Arctic sea-ice, the mechanism that links sea-ice loss to cold winters remains a subject of debate. Here, by conducting observational analyses and model experiments, we show how Arctic sea-ice loss and cold winters in extra-polar regions are dynamically connected through the polar stratosphere. We find that decreased sea-ice cover during early winter months (November-December), especially over the Barents-Kara seas, enhances the upward propagation of planetary-scale waves with wavenumbers of 1 and 2, subsequently weakening the stratospheric polar vortex in mid-winter (January-February). The weakened polar vortex preferentially induces a negative phase of Arctic Oscillation at the surface, resulting in low temperatures in mid-latitudes. | 25,181,390 | [
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Developing content for a mHealth intervention to promote postpartum retention in prevention of mother-to-child HIV transmission programs and early infant diagnosis of HIV: a qualitative study. | Maternal attendance at postnatal clinic visits and timely diagnosis of infant HIV infection are important steps for prevention of mother-to-child transmission (PMTCT) of HIV. We aimed to use theory-informed methods to develop text messages targeted at facilitating these steps. We conducted five focus group discussions with health workers and women attending antenatal, postnatal, and PMTCT clinics to explore aspects of women's engagement in postnatal HIV care and infant testing. Discussion topics were informed by constructs of the Health Belief Model (HBM) and prior empirical research. Qualitative data were coded and analyzed according to the construct of the HBM to which they related. Themes were extracted and used to draft intervention messages. We carried out two stages of further messaging development: messages were presented in a follow-up focus group in order to develop optimal phrasing in local languages. We then further refined the messages, pretested them in individual cognitive interviews with selected health workers, and finalized the messages for the intervention. Findings indicated that brief, personalized, caring, polite, encouraging, and educational text messages would facilitate women bringing their children to clinic after delivery, suggesting that text messages may serve as an important "cue to action." Participants emphasized that messages should not mention HIV due to fear of HIV testing and disclosure. Participants also noted that text messages could capitalize on women's motivation to attend clinic for childhood immunizations. Applying a multi-stage content development approach to crafting text messages--informed by behavioral theory--resulted in message content that was consistent across different focus groups. This approach could help answer "why" and "how" text messaging may be a useful tool to support maternal and child health. We are evaluating the effect of these messages on improving postpartum PMTCT retention and infant HIV testing in a randomized trial. | 25,181,408 | [
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Osteoprotegerin, fibroblast growth factor 23, and vitamin D3 levels in male patients with hypogonadism. | Cardiometabolic disorders and osteoporosis are prevalent in patients with hypogonadism. Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF-23), are co-secreted from bones and vascular endothelium, regulating bone mineral metabolism and vascular functions. Vitamin D is another hormone with dual effects on bone and vascular metabolism. The aim of this study was to search for any difference between the serum levels of OPG, FGF-23, and vitamin D in patients with hypogonadism and the healthy controls. We also aimed to search for any relationship between these parameters and endothelial dysfunction or insulin resistance. Forty-nine male patients with congenital hypogonadotropic hypogonadism (CHH) (mean age 20.71 ± 1.75 years) and 43 BMI matched healthy male subjects (mean age 21.37 ± 1.04 years) were enrolled. OPG, FGF-23, vitamin D, and asymmetric dimethylarginine (ADMA) levels were measured from the fasting serum samples. The insulin sensitivity was estimated by homeostatic model assessment-insulin resistance (HOMA-IR) formula. Triglycerides, insulin, HOMA-IR, and ADMA levels in the patient group were significantly higher than the values of the control group (p = 0.014, p = 0.002, p = 0.003, p < 0.001, respectively). The OPG, FGF-23, and vitamin D levels of the patients were not significantly different from the healthy controls. In addition, these markers were not correlated to ADMA or HOMA-IR levels. The results show that young and treatment naive subjects with CHH have endothelial dysfunction and insulin resistance when compared to their healthy counterparts. However, the OPG, FGF-23, and vitamin D levels were similar in the 2 groups. In addition, these parameters are not significantly related to the endothelial functions or insulin resistance in these subjects. | 25,181,418 | [
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Molecular analysis for screening human bacterial pathogens in municipal wastewater treatment and reuse. | Effective and sensitive monitoring of human pathogenic bacteria in municipal wastewater treatment is important not only for managing public health risk related to treated wastewater reuse, but also for ensuring proper functioning of the treatment plant. In this study, three different 16S rRNA gene molecular analysis methodologies were employed to screen bacterial pathogens in samples collected at three different stages of an activated sludge plant. Overall bacterial diversity was analyzed using next generation sequencing (NGS) on the Illumina MiSeq platform, as well as PCR-DGGE followed by band sequencing. In addition, a microdiversity analysis was conducted using PCR-DGGE, targeting Escherichia coli. Bioinformatics analysis was performed using QIIME protocol by clustering sequences against the Human Pathogenic Bacteria Database. NGS data were also clustered against the Greengenes database for a genera-level diversity analysis. NGS proved to be the most effective approach screening the sequences of 21 potential human bacterial pathogens, while the E. coli microdiversity analysis yielded one (O157:H7 str. EDL933) out of the two E. coli strains picked up by NGS. Overall diversity using PCR-DGGE did not yield any pathogenic sequence matches even though a number of sequences matched the NGS results. Overall, sequences of Gram-negative pathogens decreased in relative abundance along the treatment train while those of Gram-positive pathogens increased. | 25,181,426 | [
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Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice. | Epidemiological studies have indicated that postmenopausal women have a higher incidence of intracranial aneurysms than men in the same age group. To investigate whether estrogen or estrogen receptors (ERs) mediate protective effects against the formation of intracranial aneurysms. Intracranial aneurysms were induced in mice by combining a single injection of elastase into the cerebrospinal fluid with deoxycorticosterone acetate salt hypertension. The mice were treated with estrogen (17β-estradiol), an ERα agonist (propyl pyrazole triol), and an ERβ agonist (diarylpropionitrile) with and without a nitric oxide synthase inhibitor. The ovariectomized female mice had a significantly higher incidence of aneurysms than the male mice, which was consistent with findings in previous epidemiological studies. In ovariectomized female mice, an ERβ agonist, but not an ERα agonist or 17β-estradiol, significantly reduced the incidence of aneurysms. The protective effect of the ERβ agonist was absent in the ovariectomized ERβ knockout mice. The protective effect of the ERβ agonist was negated by treatment with a nitric oxide synthase inhibitor. The effects of sex, menopause, and estrogen treatment observed in this animal study were consistent with previous epidemiological findings. Stimulation of estrogen receptor-β was protective against the formation of intracranial aneurysms in ovariectomized female mice. | 25,181,430 | [
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Persistent differences in mortality patterns across industrialized countries. | The epidemiological transition has provided the theoretical background for the expectation of convergence in mortality patterns. We formally test and reject the convergence hypothesis for a sample of industrialized countries in the period from 1960 to 2008. After a period of convergence in the decade of 1960 there followed a sustained process of divergence with a pronounced increase at the end of the 1980's, explained by trends within former Socialist countries (Eastern countries). While Eastern countries experienced abrupt divergence after the dissolution of the Soviet Union, differences within Western countries remained broadly constant for the whole period. Western countries transitioned from a strong correlation between life expectancy and variance in 1960 to no association between both moments in 2008 while Eastern countries experienced the opposite evolution. Taken together, our results suggest that convergence can be better understood when accounting for shared structural similarities amongst groups of countries rather than through global convergence. | 25,181,447 | [
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The effect of social support on the health of Indigenous Australians in a metropolitan community. | The factors driving the disparity in health outcomes between Indigenous and non-Indigenous Australians continue to be poorly understood. Despite this, studies confirm that social connections are a very important part of Indigenous life, and it is likely these connections play an important role in influencing health outcomes among this population. Examining the support provided by social connections in relation to health behaviour may assist our understanding of health outcomes among Indigenous Australians. The current study is focused on exploring Indigenous participants' impressions of their social network and social support using Participatory Action Research methodology and qualitative methods. The objective was to identify the influence of social support on the health outcomes of Indigenous people within a Western Australian metropolitan community. Seventeen members of the community were interviewed during the study. The participants had extensive social networks that mainly comprised members of their kinship group. The consequences of this social network included: (1) the positive effects of social support from bonded relationships; (2) the negative effects of social support produced by over-obligation and unidirectional support involving bonded relationships; (3) limited or inadequate social support caused by withdrawal from bonded relationships; (4) lack of social support from bridging relationships; and (5) a strong desire for connection and a sense of belonging. | 25,181,473 | [
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mGluR1-mediated excitation of cerebellar GABAergic interneurons requires both G protein-dependent and Src-ERK1/2-dependent signaling pathways. | Stimulation of type I metabotropic glutamate receptors (mGluR1/5) in several neuronal types induces slow excitatory responses through activation of transient receptor potential canonical (TRPC) channels. GABAergic cerebellar molecular layer interneurons (MLIs) modulate firing patterns of Purkinje cells (PCs), which play a key role in cerebellar information processing. MLIs express mGluR1, and activation of mGluR1 induces an inward current, but its precise intracellular signaling pathways are unknown. We found that mGluR1 activation facilitated spontaneous firing of mouse cerebellar MLIs through an inward current mediated by TRPC1 channels. This mGluR1-mediated inward current depends on both G protein-dependent and -independent pathways. The nonselective protein tyrosine kinase inhibitors genistein and AG490 as well as the selective extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors PD98059 and SL327 suppressed the mGluR1-mediated current responses. Following G protein blockade, the residual mGluR1-mediated inward current was significantly reduced by the selective Src tyrosine kinase inhibitor PP2. In contrast to cerebellar PCs, GABAB receptor activation in MLIs did not alter the mGluR1-mediated inward current, suggesting that there is no cross-talk between mGluR1 and GABAB receptors in MLIs. Thus, activation of mGluR1 facilitates firing of MLIs through the TRPC1-mediated inward current, which depends on not only G protein-dependent but also Src-ERK1/2-dependent signaling pathways, and consequently depresses the excitability of cerebellar PCs. | 25,181,481 | [
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Regular breakfast consumption and type 2 diabetes risk markers in 9- to 10-year-old children in the child heart and health study in England (CHASE): a cross-sectional analysis. | Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children. We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%-37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%-37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%-2.0%), glucose (percent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers. Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk. Please see later in the article for the Editors' Summary. | 25,181,492 | [
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Divided attention can enhance early-phase memory encoding: the attentional boost effect and study trial duration. | Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better for stimuli co-occurring with targets. The present experiments indicate that the ABE arises during an early phase of memory encoding that involves initial stimulus perception and comprehension rather than at a later phase entailing controlled, elaborative rehearsal. Experiment 1 demonstrated that the ABE was robust at a short study duration (700 ms) and did not increase with increasing study trial durations (1,500 ms and 4,000 ms). Furthermore, the target condition is boosted to the level of memory performance in a full-attention condition for the short duration but not the long duration. Both results followed from the early-phase account. This account also predicts that for very short study times (limiting the influence of late-phase controlled encoding and thus minimizing the usual negative effect of divided attention), the target condition will produce better memory than will the full-attention condition. Experiment 2 used a study time of 400 ms and found that words presented with targets lead to greater recognition accuracy than do either words presented with distractors or words in the full-attention condition. Consistent with the early-phase account, a divided attention condition actually produced superior memory than did the full-attention condition, a very unusual but theoretically predicted result. | 25,181,494 | [
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Comparison of Segmental Colon Transit Time With Total Energy Expenditure in Psychiatry Unit Patients. | Physical activity is associated with a reduced risk of colorectal cancer. We examined the colon transit time (CTT) according to the total energy expenditure (TEE) in psychiatry unit patients. The study participants included 67 adults, with a mean age of 49.8 years. The participants used an accelerometer for 7 days to measure their 1-week TEE. They took a capsule containing 20 radio-opaque markers for 3 days. On the 4th day and 7th day, a supine abdominal radiography was performed. According to the TEE of all study participants, the upper 30%, middle 30%, and lower 40% were classified into groups according to high (H), moderate (M), and low (L) physical activity. The mean total CTT was 52.0 hours. The segmental CTT for the right, left, and recto-sigmoid colon were 15.3 hours, 19.2 hours, and 17.4 hours. Total CTT in the H group was significantly shorter than that in the L group (p = .010). A comparison of the segmental CTT between the L, M, and H groups showed that the right CTT (p = .010) of the H group was significantly shorter than that of the M group. The left CTT of the M group (p = .028) and H group (p = .004) was significantly shorter than that of the L group. The recto-sigmoid CTT (p = .016) of the M group was significantly shorter than that of the L group. The study showed that moderate and high TEE was assisted with reduced CTT. | 25,181,498 | [
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Synthesis of non-linear protein dimers through a genetically encoded Thiol-ene reaction. | Site-specific incorporation of bioorthogonal unnatural amino acids into proteins provides a useful tool for the installation of specific functionalities that will allow for the labeling of proteins with virtually any probe. We demonstrate the genetic encoding of a set of alkene lysines using the orthogonal PylRS/PylTCUA pair in Escherichia coli. The installed double bond functionality was then applied in a photoinitiated thiol-ene reaction of the protein with a fluorescent thiol-bearing probe, as well as a cysteine residue of a second protein, showing the applicability of this approach in the formation of heterogeneous non-linear fused proteins. | 25,181,502 | [
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... |
Adverse outcomes of anticoagulant use among hospitalized patients with chronic kidney disease: a comparison of the rates of major bleeding events between unfractionated heparin and enoxaparin. | Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding. To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH) and enoxaparin users. One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10-59 ml/min/1.73 m(2)) who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes. Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05-10.35]). Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113] × 10(3)/µL vs 205.56 [123] × 10(3)/µL; P<0.001), and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85-12.36]). Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03-6.25]); longer length of hospitalization (HR, 1.04 [95% CI, 1.01-1.06]); and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10-2.91]). Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted. | 25,181,525 | [
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Recombinant antibody color resulting from advanced glycation end product modifications. | Recombinant antibodies produced in Chinese hamster ovary (CHO) cells often exhibit a slight yellow-brown color, but the molecular basis for this color has remained elusive. We predicted that the color results from post-translational modifications on the antibody, because colored species were found to coelute with antibody products during size exclusion chromatography. Previously, modification by oxidation and advanced glycation end products (AGEs) had been shown to give rise to colored and fluorescent species whose spectral properties are in agreement with the spectral properties of CHO-derived recombinant antibodies. To test whether these modifications give rise to the color exhibited in our CHO-derived antibodies, we searched for 8 different oxidation and 28 different glycation and AGE modifications by mass spectrometry in a variety of samples exhibiting varying color intensities. Oxidation and glycation modifications correlated weakly with color in a subset of samples, but several AGEs exhibited a strong correlation with product color in all samples tested. This strong correlation with sample color was verified for a specific AGE, carboxymethyllysine, by ELISA, thus validating the mass spectrometry data. These data indicate that AGEs are at least partially responsible for the color seen in CHO-derived recombinant antibodies. | 25,181,536 | [
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Two-compartmental population balance modeling of a pulsed spray fluidized bed granulation based on computational fluid dynamics (CFD) analysis. | In this work a two-compartmental population balance model (TCPBM) was proposed to model a pulsed top-spray fluidized bed granulation. The proposed TCPBM considered the spatially heterogeneous granulation mechanisms of the granule growth by dividing the granulator into two perfectly mixed zones of the wetting compartment and drying compartment, in which the aggregation mechanism was assumed in the wetting compartment and the breakage mechanism was considered in the drying compartment. The sizes of the wetting and drying compartments were constant in the TCPBM, in which 30% of the bed was the wetting compartment and 70% of the bed was the drying compartment. The exchange rate of particles between the wetting and drying compartments was determined by the details of the flow properties and distribution of particles predicted by the computational fluid dynamics (CFD) simulation. The experimental validation has shown that the proposed TCPBM can predict evolution of the granule size and distribution within the granulator under different binder spray operating conditions accurately. | 25,181,553 | [
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Polyaromatic hydrocarbons do not disturb liquid-liquid phase coexistence, but increase the fluidity of model membranes. | Polyaromatic hydrocarbons (PAHs) is a group of compounds, many of which are toxic, formed by incomplete combustion or thermal processing of organic material. They are highly lipophilic and thus present in some seed oils used for human consumption as well as being increasingly common in aquaculture diets due to inclusion of vegetable oils. Cytotoxic effects of PAHs have been thought to be partly due to a membrane perturbing effect of these compounds. A series of studies were here performed to examine the effects of three different PAHs (naphthalene, phenanthrene and benzo[a]pyrene) with different molecular sizes (two, three and five rings, respectively) and fat solubility (Kow 3.29, 4.53 and 6.04, respectively) on membrane models. The effects of PAHs on liquid-liquid phase coexistence in solid-supported lipid bilayers (dioleoylphosphocholine:dipalmitoylphosphatidylcholine:cholesterol) were assessed using fluorescence microscopy. Benzo[a]pyrene had a slight affinity for the liquid-ordered phase, but there were no effects of adding any of the other PAHs on the number or size of the liquid domains (liquid-ordered and liquid-disordered). Benzo[a]pyrene and phenanthrene, but not naphthalene, lowered the transition temperature (Tm) and the enthalpy (ΔH) characterising the transition from the solid to the liquid-crystalline phase in DPPC vesicles. The membrane effects of the PAH molecules are likely related to size, with bigger and more fat-soluble molecules having a fluidising effect when embedded in the membrane, possibly causing some of the observed toxic effects in fish exposed to these contaminants. | 25,181,555 | [
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The reliability of a VISION COACH task as a measure of psychomotor skills. | The VISION COACH™ interactive light board is designed to test and enhance participants' psychomotor skills. The primary goal of this study was to examine the test-retest reliability of the Full Field 120 VISION COACH task. One hundred eleven male and 131 female adult participants completed six trials where they responded to 120 randomly distributed lights displayed on the VISION COACH interactive light board. The mean time required for a participant to complete a trial was 101 seconds. Intraclass correlation coefficients, ranging from 0.962 to 0.987 suggest the VISION COACH Full Field 120 task was a reliable task. Cohen's d's of adjacent pairs of trials suggest learning effects did not negatively affect reliability after the third trial. | 25,181,563 | [
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Efficient synthesis of ABAB functionalized phthalocyanines. | ABAB-type Zn(II) phthalocyanines, crosswise-functionalized with two and four iodine atoms, respectively, have been efficiently prepared using statistical condensation procedures. Key to the selective preparation of the opposite ABAB isomers versus the adjacent AABB ones is the use of bulky 3,6-(3',5'-bis(trifluoromethyl)phenyl)phthalonitrile with hampered self-condensation capabilities. | 25,181,582 | [
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Sensorimotor trigeminal unbalance modulates pupil size. | We studied whether patients affected by Temporo-Mandibular Disorder (TMD), showing asymmetric electromyographic (EMG) activity of masticatory muscles also display asymmetries in pupil size. In 30 pain free TMD patients a highly significant, positive correlation was found between left-right differences in EMG and pupil size. The asymmetry in pupil size was induced by the asymmetric sensorimotor signals arising from the orofacial region, since pupils became of about the same size following orthotic correction, which greatly reduced the EMG asymmetry. Moreover, bite wearing bilaterally increased the mydriasis induced by performing haptic tasks. Finally, unbalancing the occlusion by a precontact increased the diameter of the ipsilateral pupil and abolished the mydriasis induced by haptic tasks. In conclusion, trigeminal sensorimotor signals may exert a tonic control on autonomic structures regulating pupil size at rest and during sensorimotor tasks. Since task-associated mydriasis is correlated with task performance and is strictly proportional to the phasic release of noradrenaline at cerebral cortical level, the present findings may suggest an impact of unbalanced trigeminal activity on brain processing not directly related to the orofacial region. | 25,181,592 | [
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Optimization of ethanol production from microfluidized wheat straw by response surface methodology. | In this study, wheat straw was pretreated with a microfluidizer to improve its enzymatic hydrolysis and ethanol yields. The pretreatment was performed at various pressures (500, 1000, and 1500 bar) and solid loadings (1, 2, and 3%). The microfluidized biomass was then subjected to hydrolysis and simultaneous saccharification and co-fermentation (SSCF) experiments at different enzyme loadings (5, 10, and 15 FPU/g dry wheat straw) using a mutant yeast. The results indicated that the microfluidization method alters the structure of biomass and leads to a reduction in lignin content. The samples pretreated at 1% solid loading contained the minimum lignin concentration and provided the maximum sugar and ethanol yields. These results signified that the microfluidization method is more effective on biomass at low solid loadings. The process conditions were optimized for higher ethanol and sugar yields using response surface methodology (RSM). The optimum pressure and solid and enzyme loadings were found as 1500 bar, 1%, and 15 FPU/g dry wheat straw, respectively. The yields obtained at this condition were 82%, 94%, and 65% for glucose, xylose, and ethanol, respectively. High sugar yields implied that microfluidization is an effective pretreatment method for cellulosic ethanol production. On the other hand, low ethanol yield may indicate that the microorganism was sensitive to inhibitory compounds present in the fermentation medium. | 25,181,638 | [
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Transoral robotic surgery and oropharyngeal cancer: a literature review. | The incidence of head and neck squamous cell carcinoma has risen steadily over the past decade due to the increase in cancers associated with the human papillomavirus (HPV). The prognosis for the treatment of this type of cancer with radiotherapy and chemoradiotherapy is good. However, because these treatments can have detrimental effects on organ function and quality of life, researchers are looking into transoral robotic surgery (TORS) as a possible alternate therapy. TORS might have a positive effect on postoperative function and quality of life for cancer survivors. The aim of this review is to report on the current situation regarding the treatment of oropharyngeal cancer with TORS, with a focus on the long-term oncologic and functional outcomes of this strategy. The articles cited in this review were selected from the PubMed and MEDLINE database. They contain study results pertaining to TORS implementation, complications, oncologic and functional outcomes, and the implications of HPV-associated cancer. We found that while TORS has some clear advantages and strengths and almost certainly a permanent place in future treatment, further research is necessary to correctly evaluate the role it will play in the complete management of oropharyngeal cancer. | 25,181,669 | [
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Primary diffuse large B-cell lymphoma of the ethmoid sinus: a case report. | B-cell lymphoma of the paranasal sinuses is rare. We present the case of a 42-year-old woman who presented with proptosis, diplopia, and vision disturbances in the right eye. She was diagnosed with diffuse large B-cell lymphoma of the ethmoid sinus. We describe the general clinical presentation, diagnosis, and differential diagnosis of this entity, and we review the pathology of diffuse large B-cell lymphoma. | 25,181,675 | [
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β-Aryl-α-nitro-α,β-enals as heterodienes and dienophiles. | As demonstrated with the β-(2-furyl)-substituted analogue 1b, β-aryl-α-nitro-α,β-enals (1) behave as heterodienes against enamines and enol ethers using their enal unit (e.g., 1b → 12). α-Nitro-α,β-enals can act as well as highly reactive dienophiles to render adducts endowed with nitrogenated quaternary centers (e.g., 1b → 15a). A hetero-Diels-Alder (HDA)/Diels-Alder (DA) sequence from 1b also proved feasible on serial treatment with ethyl vinyl ether and Danishefsky's diene (1b → 14). | 25,181,678 | [
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Addressing health disparities: Brown University School of Public Health. | Health disparities are a public health concern in Rhode Island and around the world. Faculty members and students in the Brown University School of Public Health are working to understand, address, and ultimately eliminate disparities in health and health care affecting diverse populations. Our educational offerings and research efforts are directed toward understanding and addressing the social, cultural, and environmental factors that contribute to these health disparities. Research methods to carry out this work include implementing interdisciplinary, community-based, quantitative and qualitative research with the goal of preventing, reducing, and eliminating health disparities. This article focuses on some of the School's work with vulnerable communities confronting issues around the following: HIV/AIDS, obesity, nutrition, physical activity and delivery of health services. | 25,181,746 | [
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Transport of graphene oxide nanoparticles in saturated sandy soil. | We examined the transport properties of graphene oxide nanoparticles (GONPs) in saturated sandy soil, under different solution chemistry conditions and flow velocities. GONPs exhibited high mobility in soil, even at 50 mM NaCl. While at relatively high ionic strength GONPs were less mobile in soil than in quartz sand, the differences were not significant. At a concentration of 0.5 mM, Ca(2+) significantly inhibited the transport of GONPs in soil, but only slightly inhibited the transport in quartz sand. This was because by complexing with the surface O-functionalities of both GONPs and soil components, Ca(2+) could enhance the aggregation of GONPs and bridge GONPs and soil grains. Increasing pH from 4 to 9 only slightly enhanced the transport of GONPs in soil, probably because the mobility of GONPs was already high at low pH. The presence of 10 mg L(-1) Suwannee River humic acid significantly enhanced the transport of GONPs in quartz sand at 35 mM, but only had a small effect for the transport in soil. This was possibly linked to the much smaller grain sizes and much more heterogeneous nature of the soil. Flow velocity had marked effects on the transport in soil, but essentially no effects on the transport in quartz sand. A two-site transport model incorporating both the blocking-affected attachment process and straining effects can effectively model the transport of GONPs. The high mobility of GONPs may have important implications for their environmental fate and effects. | 25,181,756 | [
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Conducted electrical weapons within healthcare: a comprehensive use of force model. | Healthcare settings are experiencing increased amounts of violent activity that are challenging to the health care security profession. There is difficulty in addressing this issue completely. Some of this difficulty is because of factors that include inexperienced and untrained clinicians and administrators that are often the decision-makers in the health care setting. As part of an effective solution, we propose that a security plan, including a comprehensive use of force program incorporating conducted electrical weapons, is a necessary and best-practice goal. This paper outlines the background of the problem and discusses the challenges we encountered in reaching this goal as well as the benefits we have discovered along the way. This paper will be beneficial to any healthcare security professional that is interested in enhancing or improving their current health care security use of force model to further counter the increasing violent activity in their respective healthcare setting. | 25,181,791 | [
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How the millennial generation is transforming employee benefits. | According to a number of recent studies, the millennial generation, today's incoming young-adult employees, shows far more interest than older generations in a broad spectrum of employee bene its to protect them from various life risks. They are more cautious than boomers or Gen Xers in choosing their financial portfolios and more focused on planning for their long-term future. Millennials even value health insurance almost as much as older adults--despite the fact they're much less likely to use it. These findings are in broad alignment with broader millennial generational traits that LifeCourse Associates has been studying fo many years. | 25,181,813 | [
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Requiring work during FMLA. Vess v. Scott Medical Corp., 2013 WL 1100068 (N.D.Ohio 2013). | Calls regarding job responsibilities were permissible; allegedly requiring supervisor to complete educational competencies before returning to work, complete evaluations of respiratory therapists and enter blood gas data was not. | 25,181,819 | [
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Melanoma risk prediction models. | The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. This case-control study included 697 participants (341 patients and 356 controls) that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR) and alternating decision trees (ADT) prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS) based on the outcome of the LR model was presented. The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724-9.366 for those that sometimes used sunbeds), solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage), hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair), the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931), the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119), Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were only present in melanoma patients and thus were strongly associated with melanoma. The percentage of correctly classified subjects in the LR model was 74.9%, sensitivity 71%, specificity 78.7% and AUC 0.805. For the ADT percentage of correctly classified instances was 71.9%, sensitivity 71.9%, specificity 79.4% and AUC 0.808. Application of different models for risk assessment and prediction of melanoma should provide efficient and standardized tool in the hands of clinicians. The presented models offer effective discrimination of individuals at high risk, transparent decision making and real-time implementation suitable for clinical practice. A continuous melanoma database growth would provide for further adjustments and enhancements in model accuracy as well as offering a possibility for successful application of more advanced data mining algorithms. | 25,181,836 | [
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