title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Association between -799C/T single nucleotide polymorphism of the MMP‑8 promoter region and thoracic aortic dissection. | Thoracic aortic dissection (TAD) is a life-threatening vascular condition, in which matrix metalloproteinases (MMPs) are involved. Since the key determinants underlying MMP action remain elusive, the present study investigated the correlation between single nucleotide polymorphisms (SNPs) in the promoter region of the MMP‑8 gene and a predisposition to TAD, by comparing genotypes of TAD patients and healthy controls. From 154 TAD patients and 148 healthy individuals, DNA samples were obtained from venous blood, and genotyping was performed by a combination of polymerase chain reaction and automatic sequencing to detect SNPs in the MMP‑8 promoter. Data were analyzed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. P<0.05 was considered to indicate a statistically significant result. Two SNPs, -799C/T and -767A/T, were identified in the MMP‑8 promoter. Distribution of the -767A/T genotype was not significantly different between the patients and healthy controls. The -799C/C genotype was utilized as a match control, and significant differences in the genotypic distribution were observed between the patients with TAD and the controls. Furthermore, it was identified that the distribution of the ‑799C/T+T/T and -799C/C genotypes between the TAD and control populations was significantly different. The frequency of T allele distribution was higher in the TAD group (27%) than in the control group (13.5%). The genotype distribution followed the Hardy-Weinberg equilibrium. In the present study, it was concluded that the ‑799C/T polymorphism in the promoter region of MMP‑8 may be associated with the development of TAD and that the T allele may increase patient predisposition to the disease. | 25,109,362 | [
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Limitations of split-night polysomnography for the diagnosis of nocturnal hypoventilation and titration of non-invasive positive pressure ventilation in amyotrophic lateral sclerosis. | Split-night polysomnography is performed at our centre in all patients with ALS who require assessment for nocturnal hypoventilation and their response to non-invasive ventilation. The purpose of this study was to determine how successful this practice has been, reflected by whether a complete assessment was achieved by a single split-night polysomnogram. We undertook a systematic, retrospective review of all consecutive split-night polysomnograms in ALS patients between 2005 and 2012. A total of 47 cases were reviewed. Forty-three percent of patients had an incomplete test, resulting in a recommendation to repeat the polysomnogram. Poor sleep efficiency and absence of REM sleep in the diagnostic portion of the study were strongly associated with incomplete studies. Clinical variables that reflect severity of ALS (FVC, PaCO2, ALSFRS-R) and use of REM-suppressing antidepressants or sedative-hypnotics were not associated with incomplete split-night polysomnogram. In conclusion, a single, split-night polysomnogram is frequently inconclusive for the assessment of nocturnal hypoventilation and complete titration of non-invasive positive pressure ventilation in patients with ALS. Poor sleep efficiency and absence of REM sleep are the main limitations of split-night polysomnography in this patient population. | 25,109,404 | [
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Pterostilbene suppresses oral cancer cell invasion by inhibiting MMP-2 expression. | Polyphenol compounds, present in a wide variety of natural plants, exhibit antioxidant and free radical scavenging ability and induce apoptosis in various cancer cells. However, the effect of pterostilbene on oral cancer cell metastasis has not been clarified. The present study aimed to examine the anti-metastatic properties of pterostilbene in human oral squamous cell carcinoma (SCC)-9 cells. In this study, pterostilbene treatment significantly inhibited migration/invasion capacities of SCC-9 cells in vitro. The results of zymography and western blotting revealed that the activities and protein levels of the MMP-2 and urokinase-type plasminogen activator (u-PA) was inhibited by pterostilbene. Western blot analysis also showed that pterostilbene inhibits the phosphorylation of Akt, extracellular signal-regulated kinase 1/2 and p38. Determinations of the mRNA levels, real-time polymerase chain reaction and promoter assays were conducted to evaluate the inhibitory effects of pterostilbene on MMP-2 and u-PA expression in SCC-9 cells. Such inhibitory effects were associated with the upregulation of tissue inhibitor of metalloproteinase-2, plasminogen activator inhibitor-1 and the downregulation of the transcription factors of NF-κB, SP-1 and CREB signaling pathways. Pterostilbene may have potential use as a chemopreventive agent against oral cancer metastasis. | 25,109,417 | [
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One-stage surgical correction of congenital tracheal stenosis complicated with congenital heart disease in infants and young children. | Although the outcome of surgical treatment of congenital tracheal stenosis (CTS) has improved, surgical intervention for these patients, especially for those with associated congenital heart disease (CHD) remains challenging. In this report, we summarized our experience with these defects. Clinical data were collected for children undergoing tracheoplasty and CHD surgery from January 2001 to March 2013. Bivariate and multiple regression analyses were used to determine the correlation between the variables. Forty-three patients underwent simultaneous repair of CTS and CHD. Their ages ranged from two months to nine years (mean 23.16 months) and weights from 3.5 to 46.1 kg (mean 10.71 kg). Associated CHD included pulmonary artery sling (n = 31), tetralogy of Fallot (n = 5), ventricular septal defect (n = 4), atrial septal defect (n = 4), double aortic arch (n = 2), and pulmonary atresia with ventricular septal defect (n = 1). Five patients underwent simple tracheal resection, eight patients underwent tracheal autograft, and 30 patients received slide tracheoplasty. There were seven deaths, five early and two late; the most common cause was the growth of granulation tissue. In bivariate analysis, the length of tracheal stenosis (p < 0.01), age (p < 0.01), and complications (p < 0.01) were associated with mortality. Shorter duration of postoperative mechanical ventilation (p < 0.05) and less serious complications (p < 0.05) were associated with slide tracheoplasty. The percentage of slide tracheoplasty was higher in long-segmental and diffuse tracheal stenosis (p < 0.01). Slide tracheoplasty is the best option for surgical treatment of long-segmental and diffuse tracheal stenosis. Simultaneous repair of associated CHD did not increase the complication rate and is the procedure of choice for patients with combined CTS and CHD. | 25,109,422 | [
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Physiological and cognitive consequences of suppressing and expressing emotion in dyadic interactions. | Engaging in emotional suppression typically has negative consequences. However, relatively little is known about response-focused emotion regulation processes in dyadic interactions. We hypothesized that interacting with suppressive partners would be more threatening than interacting with expressive partners. To test predictions, two participants independently watched a negatively-valenced video and then discussed their emotional responses. One participant (the regulator) was assigned to express/suppress affective signals during the interaction. Their partner was given no special instructions prior to the interaction. Engaging in suppression versus expression elicited physiological responses consistent with threat-sympathetic arousal and increased vasoconstriction-in anticipation of and during dyadic interactions. Partners of emotional suppressors also exhibited more threat responses during the interaction, but not before, compared to partners of emotional expressors. Partner and interaction appraisals mirrored physiological findings. Emotional suppressors found the task more uncomfortable and intense while their partners reported them as being poor communicators. This work broadens our understanding of connections between emotion regulation, physiological responses, and cognitive processes in dyads. | 25,109,434 | [
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Affinity assisted selection of antibodies for Point of Care TSH immunoassay with limited wash. | Molecular binding characteristics of several thyroid stimulating hormone (TSH) antibodies were determined for the TSH antigen, along with its closely related endogenous interfering hormones, follicle stimulating hormone (FSH), luteinizing hormone (LH) and chorionic gonadotropin (CG). This data was compared to the same antibodies used in the low wash sandwich ELISA immunoassay system, the Point of Care i-STAT® immunoassay. From this information we developed binding criteria useful in the low wash i-STAT® immunoassay to permit good signal generation from TSH and low cross-reactivity from its interfering hormones. For the TSH Assay we have developed characteristics that enable antibody selection in the i-STAT® immunoassay cartridge. Our antibody screening approach used a dot blot approach as a first screen to select for the most useful antibodies. We then compared a FRET (Förster Resonance Energy Transfer) and electrochemical cartridge approach to determine the appropriate antibody combinations. Both methods generated similar data, but the FRET method was not capable of differentiating the antibody with the best characteristics as a capture antibody or a detection conjugate in a sandwich ELISA assay. Finally, we performed binding characterizations of the antibodies using each of the above mentioned glycoproteins. We found that we need sub-picomolar detection of TSH, and at least 100 fold or higher values for the cross-reacting species. | 25,109,443 | [
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Micro- and nano-hydroxyapatite as active reinforcement for soft biocomposites. | Pectin-based biocomposite hydrogels were produced by internal gelation, using different hydroxyapatite (HA) powders from commercial source or synthesized by the wet chemical method. HA possesses the double functionality of cross-linking agent and inorganic reinforcement. The mineralogical composition, grain size, specific surface area and microstructure of the hydroxyapatite powders are shown to strongly influence the properties of the biocomposites. Specifically, the grain size and specific surface area of the HA powders are strictly correlated to the gelling time and rheological properties of the hydrogels at room temperature. Pectin pH is also significant for the formation of ionic cross-links and therefore for the hydrogels stability at higher temperatures. The obtained results point out that micrometric-size hydroxyapatite can be proposed for applications which require rapid gelling kinetics and improved mechanical properties; conversely the nanometric hydroxyapatite synthesized in the present work seems the best choice to obtain homogeneous hydrogels with more easily controlled gelling kinetics. | 25,109,458 | [
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Genome-wide association study of sleep duration in the Finnish population. | Sleep duration is genetically regulated, but the genetic variants are largely unknown. We aimed to identify such genes using a genome-wide association study (GWAS) combined with RNA expression at the population level, and with experimental verification. A GWAS was performed in a Finnish sample (n = 1941), and variants with suggestive association (P < 5 × 10(-5) ) were tested in a follow-up sample from the same population with sleep duration (n = 6834) and time in bed (n = 1720). Variants with pointwise association of P < 0.05 in the follow-up sample were analysed further. First, we correlated genotypes with transcript expression levels with sleep duration (n = 207). The expression levels of significant transcripts were further studied in experimental sleep restriction. Of the 31 variants with P < 5 × 10(-5) in the discovery sample, three variants showed nominal allelic association (P < 0.05) in the follow-up sample: rs10914351, near PTPRU (P = 0.049), rs1037079 in PCDH7-CENTD1 (P = 0.011) and rs2031573 near KLF6 (P = 0.044). The risk alleles for shorter sleep (rs2031573 and rs1037079) were also associated with higher KLF6 and PCDH7 expression levels (P < 0.05). Experimental sleep restriction increased the expression of KLF6 (P < 0.01). These data suggest that rs2031573 near KLF6 or related loci and rs1037079 between PCDH7-CENTD1 or related loci may contribute to the regulation of sleep duration via gene expression. These results illustrate the utility of combining different analytical approaches to identify genetic determinants for traits related to sleep physiology. However, additional studies are needed in order to understand the roles of KLF6 and PCDH7 in sleep regulation. | 25,109,461 | [
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Cellular and proteomics analysis of the endomembrane system from the unicellular Entamoeba histolytica. | Entamoeba histolytica is the protozoan parasite agent of amoebiasis, an infectious disease of the human intestine and liver. Specific active pathogenic factors are secreted toward the external milieu upon interaction of the parasite with human tissue. Trafficking dynamics and secretion of these factors is not known and characterization of the dynamics interplay of subcellular compartments such as the ER or Golgi apparatus is still pending. In this work, we took advantage of cell fractionation and a wide proteomic analysis to search for principal components of the endomembrane system in E. histolytica. Over 1500 proteins were identified and the two top categories contained components of trafficking machinery and GTPases. Trafficking related proteins account for over 100 markers from the ER, Golgi, MVB, and retromers. The lack of important components supporting Golgi polarization was also highlighted. The data further describe principal components of the endosomal traffic highlighting Alix in isolated vesicles and during parasite division. This work represents the first in-depth proteomics analysis of subcellular compartments in E. histolytica and allows a detailed map of vesicle traffic components in an ancient single-cell organism that lacks a stereotypical ER and Golgi apparatus to be established. | 25,109,464 | [
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Dopamine transporter imaging using 99mTc-TRODAT-1 SPECT in Parkinson's disease. | Although the decrease in striatal dopamine transporter (DAT) density has been described in North American, European, and Asian Parkinson's disease (PD) patients, studies on this issue are required in the rest of the world. This study examined the diagnostic utility of DAT imaging in Brazilian PD patients. Twenty PD patients (13 males, 7 females, median age: 62 years, median age at disease onset: 56 years, median disease duration: 5 years, and median UPDRS-III score: 29) and 9 age- and sex-matched healthy subjects underwent single-photon emission computerized tomography (SPECT) using 99mTc-TRODAT-1. PD patients showed a significant decrease in the striatum, caudate nucleus, and putamen DAT densities compared with data from healthy subjects. Striatal 99mTc-TRODAT-1 bindings had the highest diagnostic accuracy compared to those estimates from caudate nucleus and putamen. For the diagnosis of PD, a striatal 99mTc-TRODAT-1 binding cut-off value of 0.90 was associated with a sensitivity of 100% and a specificity of 89%. There was no significant difference between striatal 99mTc-TRODAT-1 binding values provided by different readers, contrary to 99mTc-TRODAT-1 binding estimates in the caudate nucleus. Striatal DAT imaging using 99mTc-TRODAT-1 can be considered a marker for differentiating PD patients from healthy individuals, with a good interobserver reproducibility. | 25,109,468 | [
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Organometallic nanoprobe to enhance optical response on the polycyclic aromatic hydrocarbon benzo[a]pyrene immunoassay using SERS technology. | We demonstrated the use of a new organometallic nanoprobe for competitive surface-enhanced Raman scattering (SERS) immunoassay devoted to the detection of polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene (BaP) in seawater. The nanoprobes are gold nanoparticles (GNPs) labeled by a Raman reporter, the 5,5'-dithiobis(succinimidyl-2-nitrobenzoate) (DSNB) and functionalized with monoclonal antibodies anti-BaP. The antibodies are bound with a high specificity to the analyte while the GNPs enhanced the Raman scattering of the DSNB. This type of immunoassay involved the grafting of BaP onto a sensing surface. Thus, NH<sub2</sub-terminated self-assembled monolayer is formed on the surface of gold substrate using cysteamine. Amines finally reacted with 6-formylbenzo[a]pyrene. So, this SERS detection involves four steps: (i) the nanoprobes are incubated with the sample; (ii) a drop of the mixture is then put onto the substrate; (iii) the surface is rinsed; and (iv) the surface is analyzed by Raman spectroscopy. To synthesize the nanoprobes, firstly, we prepared GNPs according to Frens' method. Then, GNPs were spontaneously labeled by the DSNB Raman reporter, thanks to a strong gold-sulfur interaction. Thereafter, BaP antibodies were cross-linked to the DSNB labeled GNPs by reaction of proteins primary amino groups with N-hydroxyl succinimide (NHS). Before use in SERS detection, their activity was controlled by surface plasmon resonance technique. The present method allows us to detect BaP at trace concentration (2 nmol/L). The results demonstrate that the proposed method has a great potential for application in the monitoring of seawater. | 25,109,469 | [
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Beneficial effects of inhaled NO on apoptotic pneumocytes in pulmonary thromboembolism model. | Lung ischemia-reperfusion injury (LIRI) may occur in the region of the affected lung after reperfusion therapy. Inhaled NO may be useful in treating acute and chronic pulmonary thromboembolism (PTE) due to the biological effect property of NO. A PTE canine model was established through selectively embolizing blood clots to an intended right lower lobar pulmonary artery. PaO2/FiO2, the mPAP and PVR were investigated at the time points of 2, 4, 6 hours after inhaled NO. Masson's trichrome stain, apoptotic pneumocytes and lung sample ultrastructure were also investigated among different groups. The PaO2/FiO2 in the Inhaled NO group increased significantly when compared with the Reperfusion group at time points of 4 and 6 hours after reperfusion, mPAP decreased significantly at point of 2 hours and the PVR decreased significantly at point of 6 hours after reperfusion. The amounts of apoptotic type II pneumocytes in the lower lobar lung have negative correlation trend with the arterial blood PaO2/FiO2 in Reperfusion group and Inhaled NO group. Inhaled nitric oxide given at 20 ppm for 6 hours can significantly alleviate the LIRI in the model. Dramatic physiological improvements are seen during the therapeutic use of inhaled NO in pulmonary thromboembolism canine model. Inhaled NO may be useful in treating LIRI in acute or chronic PTE by alleviating apoptotic type II pneumocytes. This potential application warrants further investigation. | 25,109,474 | [
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Nasal lavage VEGF and TNF-α levels during a natural cold predict asthma exacerbations. | Asthma exacerbations contribute to significant morbidity, mortality and healthcare utilization. Furthermore, viral infections are associated with asthma exacerbations by mechanisms that are not fully understood. The aim of this analysis was to determine whether cytokine patterns in patients with colds could identify risks for subsequent asthma exacerbations. We analysed cytokine levels in nasal lavage fluid (NLF) in 59 subjects (46 with asthma) with acute upper respiratory symptoms and after symptomatic resolution. Analyte choice was based on potential relevance to asthma exacerbations: antiviral (IFN-α, IFN-β, IFN-γ, IFN-λ1, IP-10, TRAIL), cell recruiting (G-CSF, IL-1β, IL-8, MCP-1, MCP-3, TNF-α), polarizing (CXCL13, IL-10, IL-13, IL-17, TSLP), and injury remodelling (fibronectin, IL-33, MMP-9, VEGF). The overall cytokine response induced during viral infections was not different between asthmatic and non-asthmatic individuals for a wide array of cytokines. However, mean levels of VEGF, TNF-α and IL-1β were 1.7-, 5.1- and 4.7-fold higher in samples from asthma subjects who exacerbated in the first 3 weeks of the cold compared with those who did not exacerbate (P = 0.006, 0.01, 0.048, respectively). Using receiver operating characteristic curve-defined thresholds, high VEGF and TNF-α levels predicted a shorter time-to-exacerbation after NLF sampling (25% exacerbation rate: 3 vs. 45 days, and 3 vs. 26 days; P = 0.03, 0.04, respectively). Although they produce similar cytokine responses to viral infection as non-asthmatics, asthmatics with higher levels of VEGF and TNF-α in NLF obtained during acute cold phases predicted subsequent asthma exacerbations in this cohort of patients with mild-to-moderate disease. In the future, stratifying the risk of an asthma exacerbation by cytokine profile may aid the targeting of personalized treatment and intervention strategies. | 25,109,477 | [
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Cardiopulmonary reserve as determined by cardiopulmonary exercise testing correlates with length of stay and predicts complications after radical cystectomy. | To investigate whether poor preoperative cardiopulmonary reserve and comorbid state dictate high-risk status and can predict complications in patients undergoing radical cystectomy (RC). In all, 105 consecutive patients with transitional cell carcinoma (TCC; stage T1-T3) undergoing robot-assisted (38 patients) or open (67) RC in a single UK centre underwent preoperative cardiopulmonary exercise testing (CPET). Prospective primary outcome variables were all-cause complications and postoperative length of stay (LOS). Binary logistic regression analysis identified potential predictive factor(s) and the predictive accuracy of CPET for all-cause complications was examined using receiver operator characteristic (ROC) curve analysis. Correlations analysis employed Spearman's rank correlation and group comparison, the Mann-Whitney U-test and Fisher's exact test. Any relationships were confirmed using the Mantel-Haenszel common odds ratio estimate, Kaplan-Meier analysis and the chi-squared test. The anaerobic threshold (AT) was negatively (r = -206, P = 0.035), and the ventilatory equivalent for carbon dioxide (VE/VCO₂) positively (r = 0.324, P = 0.001) correlated with complications and LOS. Logistic regression analysis identified low AT (<11 mL/kg/min), high VE/VC0₂ (≥33) and hypertension as significant factors, such that, in their presence patients were 5.55-times more likely to have complications at 90 days postoperatively [P = 0.001, 95% confidence interval (CI) 2.2-13.9]. ROC analysis showed a high significance (area under the curve 0.78, 95% CI 0.69-0.87; P < 0.001). In addition, based on CPET criteria >50% of patients presenting for RC had significant heart failure, whereas preoperatively only very few (2%) had this diagnosis. Analysis using the Mann-Whitney test showed that a VE/VCO₂ ≥33 was the most significant determinant of LOS (P = 0.004). Kaplan-Meier analysis showed that patients in this group had an additional median LOS of 4 days (P = 0.008). Finally, patients with an American Society of Anesthesiologists grade of 3 (ASA 3) and those on long-term β-blocker therapy were found to be at particular risk of myocardial infarction (MI) and death after RC with odds ratios of 4.0 (95% CI 1.05-15.2; P = 0.042) and 6.3 (95% CI 1.60-24.8; P = 0.008). Patients with poor cardiopulmonary reserve and hypertension are at higher risk of postoperative complications and have increased LOS after RC. Heart failure is known to be a significant determinant of perioperative death and is significantly under diagnosed in this patient group. | 25,109,512 | [
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Fine-grained stimulus representations in body selective areas of human occipito-temporal cortex. | Neurophysiological and functional imaging studies have investigated the representation of animate and inanimate stimulus classes in monkey inferior temporal (IT) and human occipito-temporal cortex (OTC). These studies proposed a distributed representation of stimulus categories across IT and OTC and at the same time highlighted category specific modules for the processing of bodies, faces and objects. Here, we investigated whether the stimulus representation within the extrastriate (EBA) and the fusiform (FBA) body areas differed from the representation across OTC. To address this question, we performed an event-related fMRI experiment, evaluating the pattern of activation elicited by 200 individual stimuli that had already been extensively tested in our earlier monkey imaging and single cell studies (Popivanov et al., 2012, 2014). The set contained achromatic images of headless monkey and human bodies, two sets of man-made objects, monkey and human faces, four-legged mammals, birds, fruits, and sculptures. The fMRI response patterns within EBA and FBA primarily distinguished bodies from non-body stimuli, with subtle differences between the areas. However, despite responding on average stronger to bodies than to other categories, classification performance for preferred and non-preferred categories was comparable. OTC primarily distinguished animate from inanimate stimuli. However, cluster analysis revealed a much more fine-grained representation with several homogeneous clusters consisting entirely of stimuli of individual categories. Overall, our data suggest that category representation varies with location within OTC. Nevertheless, body modules contain information to discriminate also non-preferred stimuli and show an increasing specificity in a posterior to anterior gradient. | 25,109,529 | [
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The influence of spontaneous brain oscillations on apparent motion perception. | A good example of inferential processes in perception is long-range apparent motion (AM), the illusory percept of visual motion that occurs when two spatially distinct stationary visual objects are presented in alternating sequence. The AM illusion is strongest at presentation frequencies around 3 Hz. At lower presentation frequencies, the percept varies from trial to trial between AM and sequential alternation, while at higher frequencies perception varies between AM and two simultaneously flickering objects. Previous studies have demonstrated that prestimulus alpha oscillations explain trial-to-trial variability in detection performance for visual stimuli presented at threshold. In the present study, we investigated whether fluctuations of prestimulus alpha oscillations can also account for variations in AM perception. Prestimulus alpha power was stronger when observers reported AM perception in subsequent trials with low presentation frequencies, while at high presentation frequencies there were no significant differences in alpha power preceding AM and veridical flicker perception. Moreover, when observers perceived AM the prestimulus functional connectivity between frontal and occipital channels was increased in the alpha band, as revealed by the imaginary part of coherency, which is insensitive to artefacts from volume conduction. Dynamic causal modelling of steady-state responses revealed that the most likely direction of this fronto-occipital connectivity was from frontal to occipital sources. These results point to a role of ongoing alpha oscillations in the inferential process that gives rise to the perception of AM and suggest that fronto-occipital interactions bias perception towards internally generated predictions. | 25,109,531 | [
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[Otoacoustic emissions as cochlear function analyser in children with language disorders]. | Speech perception that takes place in the cochlea is involved in the process of language. The objective was to describe the findings in transient otoacoustic emissions in children with language problems before and after 6 months of speech therapy. There were 17 children with language problems between 3 and 6 years of age diagnosed with anarthric language delay (expressive and mixed language disorder). They underwent medical history, otoscopy, intelligence level testing, initial language test, tympanometry of 226Hz, audiometry and transient otoacoustic emission test. We evaluated the 17 patients again after 6 months of attending speech therapy. The percentage of overall reproducibility of transient otoacoustic emissions in both ears was adequate to perform frequency analysis. We found a statistically significant difference (P≤0.01) in the frequency of 1kHz reproducibility when comparing results before and after therapy in the right ear. There was a significant difference (P≤0.05) when comparing the results of audiometry at frequencies of 0.5, 1.5, 2, 4 and 8kHz in the right ear and a highly significant difference (P=0.001) in the frequency of 3kHz in the left ear. The analysis of sound through the cochlea is involved in the process of language acquisition. A poor processing of speech sounds in the peripheral system could result in poor processing at the central level. Consequently, it is important to consider our results when making a diagnosis and carrying out rehabilitation treatment in children with language disorders. | 25,109,541 | [
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Proton conductivity of hexagonal and cubic BaTi1-xScxO3-δ (0.1 ≤x≤ 0.8). | BaTi1-xScxO3-δ (x = 0.1-0.8) was prepared via solid state reaction. High resolution X-ray powder diffraction was used to characterise the synthesised materials. It was found that low substitution (x = 0.1 and 0.2) of Ti(4+) for Sc(3+) gives a hexagonal perovskite structure, whereas high substitution (x = 0.5-0.7) results in a cubic perovskite structure. Thermogravimetric analysis revealed significant levels of protons in both as-prepared and hydrated samples. Electrical conductivity was measured by AC impedance methods under oxygen, argon and under dry and humid, both H2O and D2O, conditions for BaTi1-xScxO3-δ (x = 0.2, 0.6 and 0.7). In the temperature range of 150-600 °C, under humid conditions, the conductivity is significantly higher than that under the dry conditions. The increase in conductivity is especially prominent for the cubic phases, indicating that protons are the dominant charge carriers. The proton conductivity of hexagonal BaTi0.8Sc0.2O3-δ is approx. two orders of magnitude lower than that of the more heavily substituted cubic phases. Conductivity is also found to be higher in dry O2 than in Ar in the whole temperature range of 150-1000 °C, characteristic of a significant contribution from p-type charge carriers under oxidising atmospheres. Greater Sc(3+) substitution leads to a higher proton concentration and the highest proton conductivity (σ∼ 2 × 10(-3) S cm(-1) at 600 °C) is found for the BaTi0.3Sc0.7O3-δ composition. | 25,109,548 | [
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Sleep electroencephalographic characteristics of the Cynomolgus monkey measured by telemetry. | Cynomolgus monkeys are widely used as models of diseases and in pre-clinical studies to assess the impact of new pharmacotherapies on brain function and behaviour. However, the time course of electroencephalographic delta activity during sleep, which represents the main marker of sleep intensity associated with recovery during sleep, has never been described in this non-human primate. In this study, telemetry implants were used to record one spontaneous 24-h sleep-wake cycle in four freely-moving Cynomolgus monkeys, and to quantify the time course of electroencephalographic activity during sleep using spectral analysis. Animals presented a diurnal activity pattern interrupted by short naps. During the dark period, most of the time was spent in sleep with non-rapid eye movement sleep/rapid eye movement sleep alternations and sleep consolidation profiles intermediate between rodents and humans. Deep non-rapid eye movement sleep showed a typical predominance at the beginning of the night with decreased propensity in the course of the night, which was accompanied by a progressive increase in rapid eye movement sleep duration. Spectral profiles showed characteristic changes between vigilance states as reported in other mammalian species. Importantly, delta activity also followed the expected time course of variation, showing a build-up with wakefulness duration and dissipation across the night. Thus, Cynomolgus monkeys present typical characteristics of sleep architecture and spectral structure as those observed in other mammalian species including humans, validating the use of telemetry in this non-human primate model for translational sleep studies. | 25,109,588 | [
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Copper-catalyzed one-pot synthesis of unsymmetrical arylurea derivatives via tandem reaction of diaryliodonium salts with N-arylcyanamide. | An efficient "one-pot" approach to multiple substituted ureas from N-arylcyanamide and diaryliodonium salts has been presented. The two-step procedure involved the weak base-promoted chemoselective arylation of secondary amines with diaryliodonium and Cu-catalyzed nucleophilic addition of N-arylcyanamide with second diaryliodonium. The diverse unsymmetrical arylureas were obtained in up to 91% yield for 29 examples. | 25,109,616 | [
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Optical characterization of the antigen-antibody thin layer using the whispering gallery mode. | We immobilized an antibody (anti-β-Galactosidase) on a polystyrene microsphere by using a covalent bond, and observed the resonance peaks in the scattered light intensity spectra related to the whispering gallery mode (WGM) excitation of the microsphere. The amount and the optical parameters, i.e., thickness and refractive index, of anti-β-Galactosidase on the sphere surface were evaluated based on an absorbance measurement and a resonance peak shift measurement, respectively. Moreover, we measured the variation of the WGM spectra depending on the concentration of the enzyme solution (β-Galactosidase), which allowed us to optically evaluate the thickness and the refractive index of the antigen-antibody layer from the shift of the WGM spectra peak. | 25,109,641 | [
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A label-free fluorescence assay for trypsin based on the electron transfer between oligonucleotide-stabilized Ag nanoclusters and cytochrome c. | A label-free fluorescent assay for the detection of trypsin by using oligonucleotide-templated silver nanoclusters (Ag NCs) and cytochrome c (Cyt c) has been demonstrated. When negatively charged Ag NCs and positively charged Cyt c are mixed, they tend to form a hybrid complex, and then lead the fluorescence of Ag NCs to be quenched significantly due to electron transfer between Ag NCs and the heme cofactor of Cyt c. In the presence of trypsin, it catalyzes the hydrolytic cleavage of Cyt c to small peptide fragments, and releases the heme moiety from the Ag NCs/Cyt c complex; the quenched fluorescence restores therewith. By virtue of this specific response, the fluorescent biosensor has a linear range of from 0.7 to 4 μg mL(-1) and from 9 to 120 μg mL(-1) with a detection limit of 58.7 ng mL(-1). Aside from the easy manufacture aspect, our method also possesses a high signal-to-background ratio (~11), excellent selectivity and good biocompatibility, which makes it a promising bioanalysis for a trypsin activity assay. | 25,109,643 | [
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A simple tool to identify elderly patients with a surgically important acute subdural haematoma. | ASDH in the elderly is a common and increasing problem, and differs in its pathophysiology from ASDH in younger people. Admitting doctors may have difficulty identifying those elderly patients whose lesions may benefit from surgery. The objective of this study was to determine whether simple neuroradiological measurements could identify those patients, who need urgent neurosurgical referral for consideration for surgery. A retrospective cohort study. All patients aged 65 years or greater referred to Salford Royal Foundation Trust with the diagnosis of ASDH between 01/01/2008 and 31/12/2011. The initial presenting CT brain scans were reviewed. The linear dimensions, degree of midline shift and haematoma volume (using ABC/2 method) of all scans were measured and recorded. All presenting radiology was also assessed by a consultant neurosurgeon blind to clinical and CT scan measurement data and patients were categorised as having "surgical" lesions or not. Receiver operating characteristic (ROC) curves were generated and cut point value for 100% sensitivity and specificity were tabled to assess which combination of scan parameters best predicted a "surgical" ASDH. 212/483 patients were considered to have a 'surgical' lesion. All 'surgical' lesions had a volume of >35ml (range 35-435), maximum thickness of ≥10mm (range 10-49) and 99% had midline shift ≥1mm (range 0-32). The best predictor of a 'surgical' lesion was a combination of maximum haematoma thickness and midline shift which offered 100% (95% CI 98.3-100) sensitivity with 83% (95% CI 77.6-87) specificity. Surgically relevant cases of ASDH in the elderly can be reliably and objectively identified by two easily performed scan measurements, haematoma thickness and midline shift. If used in routine practice, these measurements could clarify those patients who may need urgent neurosurgical referral and might avoid unnecessary transfer to neurosurgical units in this cohort. | 25,109,659 | [
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Vision loss with bending over. | A 66-year-old African American man presented with episodic transient visual loss triggered by bending forward. The initial examination did not suggest intraocular pathology and the patient was nearly sent for vascular evaluation given his cardiovascular risk factors. Fundus photographs taken during an episode of visual loss suggested an intraocular process, however. Gonioscopy revealed a microhyphema causing a "snow globe" effect in the anterior chamber, most likely related to recent bleb manipulation in the affected eye. | 25,109,655 | [
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Assignment of the oxidation states of Zr and Co in a highly reactive heterobimetallic Zr/Co complex using X-ray absorption spectroscopy (XANES). | The reduced heterobimetallic complex (THF)Zr(MesNP(i)Pr2)3CoN2 (1) has been examined along with a series of structurally similar reference compounds using X-ray absorption near edge structure (XANES) spectroscopy. Complex 1 has been shown to be highly reactive, often via one-electron pathways that might be expected for a d(1) Zr(III) complex. However, the presence of two strongly interacting metals in complex 1 renders the assignment of oxidation states ambiguous. Both Zr and Co K-edge XANES spectra reveal that the most accurate description of complex 1 is that of a Zr(IV)/Co(-I) zwitterion. Electronic structure calculations support this assignment. | 25,109,663 | [
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The Greek version of the 9-item European Heart Failure Self-care Behaviour Scale: a multidimensional or a uni-dimensional scale? | To evaluate the dimensionality of the Greek version of the European Heart Failure Self-care Behaviour Scale (Gr9-EHFScBS) in a Greek-Cypriot population. EHFScBS is a valid and reliable scale which is widely used for assessing heart failure (HF) patients' self-care behaviors. EHFScBS was translated into Greek and was administered to 128 Greek-Cypriot HF patients. The internal consistency, construct validity and discriminant validity of the scale were assessed. Confirmatory factor analysis failed to capture the proposed theoretical structure. Further exploratory factor analysis provided a three-factor solution accounting for 53.35% of the variance, though the scale is better used as a whole. Cronbach's alpha was moderate 0.66, but deletion of any item decreased the alpha coefficient. Discriminant validity was supported by the poor correlation between EHFScBS and Minnesota Living with Heart Failure Questionnaire scores. Even though results do not conform to the multidimensionality of the scale, assessment of the tool provided acceptable validity and reliability measures to support its usage among Greek speaking populations. | 25,109,661 | [
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Metal binding properties of the zinc finger metallome--insights into variations in stability. | Zinc is one of the most widespread metal ions found in biological systems. Of the expected 3000 zinc proteins in the human proteome, most contain zinc in structural sites. Among these structures, the most important are zinc fingers, which are well suited to facilitate interactions with DNA, RNA, proteins and lipid molecules. Knowledge regarding their stability is a critical issue in understanding the function of zinc fingers and their reactivity under fluxing cellular Zn(II) availability and different redox states. Zinc stability constants that have been determined using a variety of methods demonstrate wide diversity. Recent studies on the stability of consensus zinc fingers have demonstrated that the known metal-ion affinities for zinc fingers may have been underestimated by as much as three or more orders of magnitude. Here, using four natural ββα zinc fingers, we compare in detail several different methods that have been used for the determination of zinc finger stability constants, such as common reverse-titration, potentiometry, competition with metal chelators, and a new approach based on a three-step spectrophotometric titration. We discuss why the stabilities of zinc fingers that are determined spectrophotometrically are frequently underestimated due to the lack of effective equilibrium competition, which leads to large errors during the processing of the titration data. The literature stability constants of many natural zinc fingers have been underestimated, and they are significantly lower when compared with the consensus peptides. Our data show that in the cell, some naturally occurring zinc fingers may potentially be unoccupied and are instead loaded transiently with Zn(II). Large variations in stability within the same class of zinc fingers have demonstrated that the thermodynamic effects hidden in the sequence and structure are the key elements responsible for the differentiation of the stability of the zinc finger metallome. | 25,109,667 | [
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Transcriptome instability as a molecular pan-cancer characteristic of carcinomas. | We have previously proposed transcriptome instability as a genome-wide, pre-mRNA splicing-related characteristic of colorectal cancer. Here, we explore the hypothesis of transcriptome instability being a general characteristic of cancer. Exon-level microarray expression data from ten cancer datasets were analyzed, including breast cancer, cervical cancer, colorectal cancer, gastric cancer, lung cancer, neuroblastoma, and prostate cancer (555 samples), as well as paired normal tissue samples from the colon, lung, prostate, and stomach (93 samples). Based on alternative splicing scores across the genomes, we calculated sample-wise relative amounts of aberrant exon skipping and inclusion. Strong and non-random (P < 0.001) correlations between these estimates and the expression levels of splicing factor genes (n = 280) were found in most cancer types analyzed (breast-, cervical-, colorectal-, lung- and prostate cancer). This suggests a biological explanation for the splicing variation. Surprisingly, these associations prevailed in pan-cancer analyses. This is in contrast to the tissue and cancer specific patterns observed in comparisons across healthy tissue samples from the colon, lung, prostate, and stomach, and between paired cancer-normal samples from the same four tissue types. Based on exon-level expression profiling and computational analyses of alternative splicing, we propose transcriptome instability as a molecular pan-cancer characteristic. The affected cancers show strong and non-random associations between low expression levels of splicing factor genes, and high amounts of aberrant exon skipping and inclusion, and vice versa, on a genome-wide scale. | 25,109,687 | [
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Colonisation and competition dynamics can explain incomplete sterilisation parasitism in ant-plant symbioses. | Sterilisation of parasites prevents host reproduction, thereby diverting host resources to their own benefit. Previous theory predicts that parasites should evolve maximum virulence, yet hosts are often incompletely sterilised. Whereas prior attempts to resolve this paradox have sought evolutionary explanations, we present theory and experiments showing that incomplete sterilisation can arise from ecologically driven fluctuations in parasite load. The African ant-plant Acacia drepanolobium reproduced more when occupied by small colonies of the sterilising symbiont Crematogaster nigriceps. In nature, small colonies result from interference competition between ant colonies; these territorial conflicts thus provide intermittent windows of opportunity for host reproduction. Our mean-field model shows that numerical insufficiency of parasites can produce partial sterilisation of host populations, creating the appearance of reduced virulence even if ants have evolved to sterilise completely. This general framework helps explain both the apparent ubiquity of partial sterilisation parasitism and the ability of these symbiotic associations to persist. | 25,109,706 | [
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Characterization and activity of an immobilized antimicrobial peptide containing bactericidal PEG-hydrogel. | A single step immobilization-polymerization strategy of a highly active antimicrobial peptide into a soft hydrogel network on a poly(ethylene terephthalate) surface using thiol-ene chemistry is described. The bactericidal hydrogel was molecularly characterized via Coomassie and Lowry assay protein staining agents as well as by X-ray photoelectron spectroscopy. The bactericidal activity was established against Staphylococcus aureus and Staphylococcus epidermidis, two bacterial strains commonly associated with biomaterial infections. To gain further insight into the biological stability, the hydrogels were incubated with human serum prior to activity testing without loss of activity. These studies revealed a promising bactericidal hydrogel with good stability under physiological conditions. | 25,109,707 | [
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Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia. | Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs. In this case-control study, 160 Malaysian subjects were recruited, including both with CRC and controls. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. Genotyping was carried out using Illumina's BeadArray platform. Information on blood group, occupation, medical history, family history of cancer, intake of red meat and vegetables, exposure to radiation, smoking and drinking habits, etc was collected. Odds ratio (OR), 95% confidence interval (CI) were calculated. A panel of 23 SNPs significantly associated with colorectal cancer risk was identified (P<0.01). Of these, 12 SNPs increased the risk of CRC and 11 reduced the risk. Among the environmental risk factors investigated, high intake of red meat (more than 50% daily proportion) was found to be significantly associated with increased risk of CRC (OR=6.52, 95% CI :1.93-2.04, P=0.003). Two SNPs including rs2069521 and rs10046 in genes of cytochrome P450 (CYP) superfamily were found significantly associated with CRC risk. For gene-environment analysis, the A allele of rs2069521 showed a significant association with CRC risk when stratified by red meat intake. In this preliminary study, a panel of SNPs found to be significantly associated with CRC in Malaysian population, was identified. Also, red meat consumption and lack of physical exercise were risk factors for CRC, while consumption of fruits and vegetables served as protective factor. | 25,109,722 | [
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0.00453639... |
Chironomid midges as allergens: evidence from two species from West Bengal, Kolkata, India. | Arthropods of different taxonomic identity including chironomid midges are known to induce allergic response in humans. The present study was done to access two common chironomid species Chironomus circumdatus and Polypedilum nubifer for their sensitizing potential as an allergen in atopic patients and controls. Following preparation of allergenic extracts of the two chironomid species separately, 198 atopic patients attending an allergy clinic and 50 age matched controls were tested along with a routine panel of allergens to assess sensitization. The skin prick test (SPT) results revealed that 189 of the 198 patients (95.4%) demonstrated sensitization to both the chironomid species. Higher levels of total IgE was observed in atopic subjects than in the control group. The results suggest that the chironomid midges Chironomus circumdatus and Polypedilum nubifer can elicit sensitization in humans. A potential risk for allergic reactions by susceptible individuals exists due to these chironomid species, owing to their abundance and chances of contact with human beings. Further studies may be initiated to characterize the nature of the allergens and to assess their clinical relevance. | 25,109,727 | [
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Histopathological changes due to the effect of selenium in experimental cockerels. | Selenium usually acts as an antioxidant at optimal levels in the body and increased levels are toxic. In this study an attempt was made to evaluate the effect of an optimum dose (0.14 mg) of selenium on histopathological changes in experimental hypercholesterolemia in cockerels. The effect of selenium (0.14 mg) was investigated on histopathological changes in four tissues namely liver, kidney, heart, and descending aorta in cockerel animal model. Animals were either fed with stock diet (group C), stock diet with cholesterol (group CH), stock diet with selenium (group Se), stock diet, selenium and cholesterol (group CH+Se) for six months. Animals were sacrified and the tissues were isolated and subjected to histopathological study. Xanthochromatic collections in liver were observed in group CH; hydropic degeneration in group Se and lobular disarray, hydropic degeneration and kuppfer cell hyperplasia in group CH+Se were observed. In kidney, mild mononuclear infiltration was observed in interstitium in groups CH, Se and CH+Se. myocyte disruption, and mononuclear infiltration in group CH and c0 H+Se, and disruption of muscle bundles with vascular congestion in group Se were observed. Smooth muscle proliferation in the media of blood vessel was observed in groups CH, Se and CH+Se. The results of the present study suggested that the optimum dose of (140 μg/day) feeding induced atherogenesis by inflammation and smooth muscle proliferation in cockerels with experimentally induced hypercholesterolaemia. | 25,109,728 | [
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The long-term impact of diabetes on graft patency after coronary artery bypass grafting surgery: a substudy of the multicenter Radial Artery Patency Study. | The study objective was to determine the impact of diabetes on radial artery and saphenous vein graft occlusion and clinical outcomes more than 5 years after coronary artery bypass surgery in the multicenter Radial Artery Patency Study (NCT00187356). A total of 529 patients aged less than 80 years with triple-vessel disease undergoing coronary bypass surgery participated in this study. Angiographic follow-up occurred more than 5 years after surgery with annual clinical follow-up. The primary objective was to compare the proportion of complete graft occlusion between radial artery and saphenous vein grafts among diabetic and nondiabetic persons. Additional objectives included determining predictors of complete graft occlusion and comparison of major adverse cardiac events defined by cardiac death, late myocardial infarction, and reintervention. There were 148 of 529 patients (27.8%) with diabetes; 269 patients (83/269 [30.9%] diabetic) underwent late angiography at mean of 7.7±1.5 years after surgery. In diabetic patients, the proportion of complete graft occlusion was significantly lower in the radial grafts (4/83 [4.8%]) than in the saphenous grafts (21/83 [25.3%]) (P=.0004), and this was similar in nondiabetic patients (P=.19). Multivariate modeling showed that the use of the radial artery and high-grade target vessel stenosis were protective against late graft occlusion, whereas female gender, smoking history, and elevated creatinine were associated with an increased risk; interaction between diabetic status and conduit type also was significant (P=.02). Major adverse cardiac events were higher in diabetic patients (23/148 [15.5%] vs 35/381 [9.2%], P=.04). The use of the radial artery should be strongly considered in diabetic patients undergoing coronary bypass surgery, especially with high-grade target vessel stenosis. | 25,109,754 | [
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Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome. | Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately one half of HLHS survivors will exhibit neurobehavioral symptoms believed to be associated with this injury, although the exact timing of the injury is unknown. Neonates with HLHS were recruited for pre- and postoperative monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using 2 noninvasive optical-based techniques: diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomic magnetic resonance imaging was performed before and approximately 1 week after surgery to quantify the extent and timing of the acquired white matter injury. The risk factors for developing new or worsened white matter injury were assessed using uni- and multivariate logistic regression. A total of 37 neonates with HLHS were studied. On univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time to surgery (P=.0003). In a multivariate model, a longer time between birth and surgery, delayed sternal closure, and greater preoperative cerebral blood flow were predictors of postoperative white matter injury. Additionally, a longer time to surgery and greater preoperative cerebral blood flow on the morning of surgery correlated with lower cerebral oxygen saturation (P=.03 and P=.05, respectively) and greater oxygen extraction fraction (P=.05 for both). A longer time to surgery was associated with new postoperative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation might decrease the likelihood of acquiring postoperative white matter injury. | 25,109,755 | [
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Acute parvovirus B19 infection in adults: a retrospective study of 49 cases. | Our aim was to describe the epidemiologic, clinical, and laboratory characteristics of acute parvovirus B19 infection in adults. This study describes all cases of acute parvovirus B19 infection in patients older than 18 years of age who were treated at Hospital Universitario La Paz in Madrid, Spain, in 2012. Forty-nine adults were treated for acute parvovirus B19 infection. Most were young women who were infected in the spring or early summer. In over half the cases skin lesions were key diagnostic signs.We saw the full range of types of rash of purplish exanthems that were fairly generalized; vasculitis was relatively common (in >18%). Mild or moderate abnormalities in blood counts and indicators of liver dysfunction resolved spontaneously in all but 2 immunocompromised patients, who developed chronic anemia. This is the largest case series of acute parvovirus B19 infection published to date. This infection should be suspected on observing signs of purplish skin rashes, no matter the location or pattern of distribution, or vasculitis, especially if accompanied by fever and joint pain in young women in the spring. Measures to avoid infection should be recommended to individuals at risk. | 25,109,767 | [
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MicroRNA-302a inhibits adipogenesis by suppressing peroxisome proliferator-activated receptor γ expression. | The present study explored the involvement of miR-302a in adipocyte differentiation via interaction with 3'-untranslated region of peroxisome proliferator-activated receptor gamma (PPARγ) mRNA. In differentiating 3T3-L1 adipocytes, expression of miR-302a was negatively correlated with that of the adipogenic gene aP2 and PPARγ. Overexpression of miR-302a inhibited adipogenic differentiation with lipid accumulation, and inversely anti-miR-302a increased the differentiation. In silico analysis revealed a complementary region of miR-302a seed sequence in 3'-UTR of PPARγ mRNA. Luciferase assay showed the direct interaction of miR-302a with PPARγ at the cellular level. The miR-302a inhibition of adipocyte differentiation was reversed by PPARγ overexpression. These findings suggest that miR-302a might be a negative regulator of adipocyte differentiation and that the dysregulation of miR-302a should lead to metabolic disorders. | 25,109,777 | [
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The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. | The gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) acutely suppress appetite. The short chain fatty acid (SCFA) receptor, free fatty acid receptor 2 (FFA2) is present on colonic enteroendocrine L cells, and a role has been suggested for SCFAs in appetite regulation. Here, we characterise the in vitro and in vivo effects of colonic propionate on PYY and GLP-1 release in rodents, and investigate the role of FFA2 in mediating these effects using FFA2 knockout mice. We used Wistar rats, C57BL6 mice and free fatty acid receptor 2 knockout (FFA(-/-)) mice on a C57BL6 background to explore the impact of the SCFA propionate on PYY and GLP-1 release. Isolated colonic crypt cultures were used to assess the effects of propionate on gut hormone release in vitro. We subsequently developed an in vivo technique to assess gut hormone release into the portal vein following colonic infusion of propionate. Propionate stimulated the secretion of both PYY and GLP-1 from wild-type primary murine colonic crypt cultures. This effect was significantly attenuated in cultures from FFA2(-/-) mice. Intra-colonic infusion of propionate elevated PYY and GLP-1 levels in jugular vein plasma in rats and in portal vein plasma in both rats and mice. However, propionate did not significantly stimulate gut hormone release in FFA2(-/-) mice. Intra-colonic administration of propionate stimulates the concurrent release of both GLP-1 and PYY in rats and mice. These data demonstrate that FFA2 deficiency impairs SCFA-induced gut hormone secretion both in vitro and in vivo. | 25,109,781 | [
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Ectopic cardiovascular fat in middle-aged men: effects of race/ethnicity, overall and central adiposity. The ERA JUMP study. | Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear. Body mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans). Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values<0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value<0.05). Racial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF. | 25,109,783 | [
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Retinal vessel diameter in normal-tension glaucoma patients with asymmetric progression. | To investigate the longitudinal changes in the central retinal vessel diameter in asymmetric progressive normal-tension glaucoma (NTG) patients. This study included 27 patients with bilateral NTG without any systemic vascular disease who showed glaucomatous progression in one eye at the mean follow-up of 24.3 months (range, 18-29 months). Progression was determined by the development of new retinal nerve fiber layer (RNFL) defects or widening of pre-existing defects on red-free RNFL photographs. The central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE) were measured at baseline and at the mean follow-up of 24.3 months. We classified the eyes of each patient as either progressed or stable eyes, and compared the differences and changes in the CRAE and CRVE. No significant inter-eye difference was observed at baseline in the mean CRAE (167.5 ± 22.2 μm vs. 168.2 ± 15.5 μm, p = 0.809) and in the mean CRVE (276.3 ± 18.2 μm vs. 281.6 ± 21.9 μm, p = 0.267) between the progressed and stable eyes. There were significant changes in CRAE in the progressed eyes between baseline and 2 years after baseline (from 167.5 ± 22.2 μm to 146.9 ± 18.0 μm, p < 0.0001), but there were no significant changes in the stable eyes (from 168.2 ± 15.5 μm to 167.5 ± 14.8 μm, p = 0.084). In our series of NTG patients with asymmetric progression, central retinal artery diameter decreased over time in the progressed eyes, whereas no significant decrease in the central retinal artery diameter was seen in the stable eyes. | 25,109,787 | [
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Nanoparticulate drug delivery platforms for advancing bone infection therapies. | The ongoing surge of resistance of bacterial pathogens to antibiotic therapies and the consistently aging median member of the human race signal an impending increase in the incidence of chronic bone infection. Nanotechnological platforms for local and sustained delivery of therapeutics hold the greatest potential for providing minimally invasive and maximally regenerative therapies for this rare but persistent condition. Shortcomings of the clinically available treatment options, including poly(methyl methacrylate) beads and calcium sulfate cements, are discussed and their transcending using calcium-phosphate/polymeric nanoparticulate composites is foreseen. Bone is a composite wherein the weakness of each component alone is compensated for by the strength of its complement and an ideal bone substitute should be fundamentally the same. Discrepancy between in vitro and in vivo bioactivity assessments is highlighted, alongside the inherent imperfectness of the former. Challenges entailing the cross-disciplinary nature of engineering a new generation of drug delivery vehicles are delineated and it is concluded that the future for the nanoparticulate therapeutic carriers belongs to multifunctional, synergistic and theranostic composites capable of simultaneously targeting, monitoring and treating internal organismic disturbances in a smart, feedback fashion and in direct response to the demands of the local environment. | 25,109,804 | [
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Economic impact of multiple sclerosis in Italy: focus on rehabilitation costs. | The study estimates the cost of multiple sclerosis (MS) in Italy quantifying the impact of the rehabilitation on cost of illness. Patients with MS were enrolled at MS clinical centres, in rehabilitation units and among members with MS of the Italian MS Society across the Italy. The MS costs were captured with a questionnaire and were estimated taking into account both healthcare and non-healthcare costs as well as the productivity losses. Mean total annual costs per patients were €37,948, increasing for different disease severity: from €22,750 at an EDSS score of 0-3 to €63,047 at an EDSS score equal to or more than 7. €3,418 was due to rehabilitation (about 26.7% of direct healthcare costs) and of these 44% was attributable to admission to rehabilitation. The multivariate analysis showed a consistent trend toward increased total cost with progressive severity of MS, with presence of relapses, while the total cost decreases with a better quality of life. The burden increases as the MS becomes more severe and with relapse occurrence, moreover we observed high costs due to admission to rehabilitation suggesting that different rehabilitation setting might be considered to reduce the financial burden and increase the quality of life for person with MS. | 25,109,816 | [
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Spy'ing on differentiation in neuroblastoma. | Comment on: Lubanska D and Porter LA. The atypical cell cycle regulator Spy1 suppresses differentiation of the neuroblastoma stem cell population. Oncoscience. 2014; 1: 336-348. | 25,109,839 | [
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Developmental pathways activated in melanocytes and melanoma. | Cutaneous malignant melanomas originate primarily within epidermal melanocytic cells. Melanoma cells share many characteristics with melanocyte precursors, suggesting that melanoma cells utilize the developmental programs of their normal counterpart for their own progression. The pigmentation system provides an advantageous model to assess survival pathway interactions in the melanocytic lineage, as genetic alterations controlling melanocyte development can be easily detectable by coat color phenotype that do not affect the viability of an animal. By integrating combinatorial gene knockout approaches, cell-based assays and immunohistochemical observations, recent studies have illustrated several genes and pathways that play important roles both in melanocyte specification and maintenance and in melanoma formation and progression. We are reviewing those genes and pathways to understand the connection between normal and cancerous development and to reveal therapeutic potential of targeting developmental pathways for melanoma therapy. | 25,109,840 | [
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Phenotyping: targeting genotype's rich cousin for diagnosis. | There are many current and evolving tools to assist clinicians in their daily work of phenotyping. In medicine, the term 'phenotype' is usually taken to mean some deviation from normal morphology, physiology and behaviour. It is ascertained via history, examination and investigations, and a primary aim is diagnosis. Therefore, doctors are, by necessity, expert 'phenotypers'. There is an inherent and partially realised power in phenotypic information that when harnessed can improve patient care. Furthermore, phenotyping developments are increasingly important in an era of rapid advances in genomic technology. Fortunately, there is an expanding network of phenotyping tools that are poised for clinical translation. These tools will preferentially be implemented to mirror clinical workflows and to integrate with advances in genomic and information-sharing technologies. This will synergise with and augment the clinical acumen of medical practitioners. We outline key enablers of the ascertainment, integration and interrogation of clinical phenotype by using genetic diseases, particularly rare ones, as a theme. Successes from the test bed or rare diseases will support approaches to common disease. | 25,109,851 | [
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Instrumental intelligent test of food sensory quality as mimic of human panel test combining multiple cross-perception sensors and data fusion. | Instrumental test of food quality using perception sensors instead of human panel test is attracting massive attention recently. A novel cross-perception multi-sensors data fusion imitating multiple mammal perception was proposed for the instrumental test in this work. First, three mimic sensors of electronic eye, electronic nose and electronic tongue were used in sequence for data acquisition of rice wine samples. Then all data from the three different sensors were preprocessed and merged. Next, three cross-perception variables i.e., color, aroma and taste, were constructed using principal components analysis (PCA) and multiple linear regression (MLR) which were used as the input of models. MLR, back-propagation artificial neural network (BPANN) and support vector machine (SVM) were comparatively used for modeling, and the instrumental test was achieved for the comprehensive quality of samples. Results showed the proposed cross-perception multi-sensors data fusion presented obvious superiority to the traditional data fusion methodologies, also achieved a high correlation coefficient (>90%) with the human panel test results. This work demonstrated that the instrumental test based on the cross-perception multi-sensors data fusion can actually mimic the human test behavior, therefore is of great significance to ensure the quality of products and decrease the loss of the manufacturers. | 25,109,863 | [
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One-pot synthesis of magnetic colloidal nanocrystal clusters coated with chitosan for selective enrichment of glycopeptides. | Selective enrichment of glycopeptides prior to the mass spectrometry (MS) analysis is essential due to ion suppression effect during ionization caused by the co-presence of non-glycosylated peptides. Among the enrichment approaches, hydrophilic interaction liquid chromatography (HILIC) based on magnetic separation has become a popular method in recent years. As the conventional synthesis procedures of these materials are tedious and time-consuming with at least four steps. Herein, magnetic colloidal nanocrystal clusters coated with chitosan (Fe3O4@CS MCNCs) have been successfully prepared by a simple one-pot method. The resulting Fe3O4@CS MCNCs demonstrated an excellent ability for glycopeptide enrichment with high selectivity, low detection limit and high binding capacity. Furthermore, in the analysis of real complicated biological sample, 283 unique N-glycosylation sites corresponding to 175 glycosylated proteins were identified in three replicate analyses of 45μg protein sample extracted from HeLa cells, indicating the great potential in detection and identification of low abundant glycopeptides in glycoproteome analysis. | 25,109,867 | [
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The genetic variability of glycoproteins among respiratory syncytial virus subtype A in China between 2009 and 2013. | Human respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants and children under 5years of age. The novel genotype ON1 has a 72-nucleotide duplication, which is the largest duplicated genome portion of RSV. Whether the ON1 genotype will follow the pattern of the BA genotype, which has a 60-nucleotide duplication, and become the predominant RSV-A strain is a global concern. To obtain information regarding the prevalence of the ON1 genotype in Chongqing in Southwestern China, we examined the circulation pattern of RSV-A identified over four consecutive years (June 2009 to August 2013). In this study, 312 (12%) RSV-A strains were isolated from 2601 nasopharyngeal aspirates, and partial G gene was sequenced successfully in 250 isolates. Of the sequenced Chongqing RSV-A isolates, 237 (94.8%) strains were the NA1 genotype, 4 (1.6%) strains were the NA3 genotype, 4 (1.6%) strains were the NA4 genotype, 1 (0.4%) strain was the GA1 genotype, and 4 (1.6%) strains were identified as the ON1 genotype. Analysis of the distribution, phylogeny, and evolution of the ON1 strains that were collected globally until December 2013 revealed that the ON1 genotype has rapidly disseminated across the world under positive selection pressures. Future studies will determine whether this new genotype will continue to spread and become the dominant strain of RSV-A worldwide. These findings may contribute to the understanding of RSV evolution and to the potential development of a vaccine against RSV. | 25,109,878 | [
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Home-based resistance training for older adults: a systematic review. | Home-based resistance exercise is commonly used for individuals who might not have access or the ability to use traditional resistance exercise. However, the extent to which home-based resistance exercise can improve both strength and functional ability has not been investigated in healthy older individuals using a systematic analysis. The current article systematically reviewed the effectiveness of home-based resistance exercise on strength and functional ability. Search engines included Academic Search Premier, CINAHL, PubMed, PsycINFO, MEDLINE, SPORTDiscus and Web of Science. A total of 649 articles were found using the key words "home-based" and "strength" and "older" or "elderly", with eight articles meeting the final criteria. The average age of the participants was 76 years, with the average duration of exercise training ranging from 8 weeks to 120 weeks. Of the eight studies, a significant increase in knee extension strength was found in five studies. Functional ability significantly improved in seven of the eight studies, with the average decrease in Timed Up & Go test being -0.8 ± 0.5 s. Three studies included greater amounts of supervised visits compared with the other five studies (∼51% vs ∼7%). The more supervised studies had significant increases in strength and functional ability. Overall, home-based resistance exercise can improve both strength and functional ability, but the improvements are generally small. The intensity of the exercises might not progress sufficiently enough to produce large improvements in strength as a result of less supervision or a lack of motivation to increase the intensity further. | 25,109,883 | [
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CCAAT/enhancer-binding protein β regulates interleukin-6-induced transmembrane and ubiquitin-like domain containing 1 gene expression in hepatocytes. | Transmembrane and ubiquitin-like domain containing 1 (Tmub1) protein has a negative effect on liver regeneration; however, the mechanisms of Tmub1 expression regulation are currently unknown. CCAAT/enhancer-binding protein β (C/EBPβ) is a key transcription factor associated with interleukin-6 (IL-6) in liver regeneration. The present study aimed to investigate the involvement of C/EBPβ in the IL-6‑induced upregulation of Tmub1. A series of Tmub1 luciferase reporter vectors were constructed to detect the effects of IL‑6 on the transcriptional activity of Tmub1. Small interfering RNA and overexpression vectors were employed to either inhibit or enhance the expression of C/EBPβ, respectively, to determine the effect of C/EBPβ on Tmub1 expression in liver cells. Additionally, chromatin immunoprecipitation experiments were performed to determine whether C/EBPβ bound to the Tmub1 gene, and the sequences associated with the regulation of Tmub1 expression by C/EBPβ were subsequently determined. Several potential binding sites of C/EBPβ were identified in the 5'‑upstream region of the Tmub1 gene. C/EBPβ expression was positively correlated with Tmub1 gene expression in rat liver cells. Furthermore, it was demonstrated that C/EBPβ bound to 5'‑upstream sequences of the Tmub1 gene to enhance the promoter activity. The present study demonstrated that C/EBPβ is a key transcription factor, which can positively regulate the expression of Tmub1 during liver cell proliferation through a possible association with IL-6. | 25,109,894 | [
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Selenium treatment significantly inhibits tumor necrosis factor-α-induced cell death and tau hyperphosphorylation in neuroblastoma cells. | The hyperphosphorylation of the protein tau disrupts its normal function on regulating axonal transport and leads to the accumulation of neurofibrillary tangles (NFT), which are involved in the pathogenesis of Alzheimer's disease (AD). This study was performed to investigate whether sodium selenite may inhibit the hyperphosphorylation of tau induced by treatment with tumor necrosis factor‑α (TNF‑α). For this purpose, we studied the changes in cell viability, tau phosphorylation and activity of tau kinases in TNF‑α+selenite-treated neuroblastoma cells. Cell viability was significantly recovered in the group cotreated with TNF‑α and 5 µM selenite for 24 h, but not in the groups treated with TNF‑α and lower concentrations of selenite. Tau phosphorylation was significantly higher in the group treated with TNF‑α+vehicle (instead of selenite) compared to the non‑treated group. However, in the TNF‑α+selenite‑treated group, the total phosphorylation level of tau protein at the Ser404 site was significantly reduced compared to the TNF‑α+vehicle group, although western blot analysis revealed one band of increased intensity in the p‑tau sample, corresponding to a phosphorylated tau isoform of 65‑70 kDa. In addition, sodium selenite treatment led to a significant recovery in the immunofluorescence intensity of the p‑tau protein in the cytoplasm and nucleus and in the apoptotic rate of neuroblastoma cells stained with the p‑tau antibody and 4',6‑diamidino‑2‑phenylindole (DAPI). The phosphorylation of two protein kinases responsible for phosphorylation of tau, glycogen synthase kinase 3β (GSK‑3β) and Akt, also known as protein kinase B, was markedly decreased in the TNF‑α+selenite‑treated group relative to the TNF‑α+vehicle‑treated group. Overall, these results provide strong evidence that sodium selenite (selenium) can inhibit cell death and tau phosphorylation induced by TNF‑α in neuroblastoma cells, through the inhibition GSK‑3β and Akt phosphorylation. | 25,109,896 | [
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Lipopolysaccharide induces amyloid formation of antimicrobial peptide HAL-2. | Lipopolysaccharide (LPS), the important component of the outer membrane of Gram-negative bacteria, contributes to the integrity of the outer membrane and protects the cell against bactericidal agents, including antimicrobial peptides. However, the mechanisms of interaction between antimicrobial peptides and LPS are not clearly understood. Halictines-2 (HAL-2), one of the novel antimicrobial peptides, was isolated from the venom of the eusocial bee Halictus sexcinctus. HAL-2 has exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria and even against cancer cells. Here, we studied the interactions between HAL-2 and LPS to elucidate the antibacterial mechanism of HAL-2 in vitro. Our results show that HAL-2 adopts a significant degree of β-strand structure in the presence of LPS. LPS is capable of inducing HAL-2 amyloid formation, which may play a vital role in its antimicrobial activity. | 25,109,934 | [
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Assessing adaptation of the cancer kinome in response to targeted therapies. | Cancer cells are dependent on protein kinase signalling networks to drive proliferation and to promote survival, and, accordingly, kinases continue to represent a major target class for development of anti-cancer therapeutics. Kinase inhibitors nevertheless have yielded only limited success with many different malignancies due to the inability of single agents to sustain a durable clinical response. Cancer cell kinomes are highly resilient and able to bypass targeted kinase inhibition, leading to tumour resistance. A novel platform has been developed to analyse the activity of the expressed kinome using MIBs (multiplexed inhibitor beads), which consist of Sepharose beads with covalently immobilized inhibitors that preferentially bind activated kinases. Coupling MIB capture with MS (MIB-MS) allows simultaneous determination of the activity of over 75% of the expressed kinome, facilitating high-throughput assessment of adaptive kinase responses resulting from deregulated feedback and feedforward regulatory mechanisms. The adaptive response frequently involves transcriptional up-regulation of specific kinases that allow bypass of the targeted kinase. Understanding how the kinome reprogrammes to targeted kinase inhibition will allow novel therapeutic strategies to be developed for durable clinical responses. | 25,109,955 | [
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About the dangers, costs and benefits of living an aerobic lifestyle. | The era in which ROS (reactive oxygen species) were simply the 'bad boys of biology' is clearly over. High levels of ROS are still rightfully considered to be toxic to many cellular processes and, as such, contribute to disease conditions and cell death. However, the high toxicity of ROS is also extremely beneficial, particularly as it is used to kill invading micro-organisms during mammalian host defence. Moreover, a transient, often more localized, increase in ROS levels appears to play a major role in signal transduction processes and positively affects cell growth, development and differentiation. At the heart of all these processes are redox-regulated proteins, which use oxidation-sensitive cysteine residues to control their function and by extension the function of the pathways that they are part of. Our work has contributed to changing the view about ROS through: (i) our characterization of Hsp33 (heat-shock protein 33), one of the first redox-regulated proteins identified, whose function is specifically activated by ROS, (ii) the development of quantitative tools that reveal extensive redox-sensitive processes in bacteria and eukaryotes, and (iii) the discovery of a link between early exposure to oxidants and aging. Our future research programme aims to generate an integrated and system-wide view of the beneficial and deleterious effects of ROS with the central goal to develop more effective antioxidant strategies and more powerful antimicrobial agents. | 25,109,979 | [
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Ultra-endurance exercise: unanswered questions in redox biology and immunology. | Ultra-endurance races are extreme exercise events that can take place over large parts of a day, several consecutive days or over weeks and months interspersed by periods of rest and recovery. Since the first ultra-endurance races in the late 1970s, around 1000 races are now held worldwide each year, and more than 100000 people take part. Although these athletes appear to be fit and healthy, there have been occasional reports of severe complications following ultra-endurance exercise. Thus there is concern that repeated extreme exercise events could have deleterious effects on health, which might be brought about by the high levels of ROS (reactive oxygen species) produced during exercise. Studies that have examined biomarkers of oxidative damage following ultra-endurance exercise have found measurements to be elevated for several days, which has usually been interpreted to reflect increased ROS production. Levels of the antioxidant molecule GSH (reduced glutathione) are depleted for 1 month or longer following ultra-endurance exercise, suggesting an impaired capacity to cope with ROS. The present paper summarizes studies that have examined the oxidative footprint of ultra-endurance exercise in light of current thinking in redox biology and the possible health implications of such extreme exercise. | 25,109,991 | [
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The role of oxidative stress in the cardiovascular actions of particulate air pollution. | Air pollution has been estimated to be responsible for several millions of deaths worldwide per year, the majority of which have been attributed to cardiovascular causes. The particulate matter in air pollution has been shown impair vascular function, increase blood pressure, promote thrombosis and impair fibrinolysis, accelerate the development of atherosclerosis, increase the extent of myocardial ischaemia, and increase susceptibility to myocardial infarction. The pathways underlying these effects are complex and poorly understood; however, particulate-induced oxidative stress repeatedly emerges as a potential mechanism in all of these detrimental cardiovascular actions. The present mini-review will use diesel exhaust as an example of a pollutant rich in combustion-derived nanoparticles, to describe the potential by which oxidative stress could drive the cardiovascular effects of air pollution. | 25,109,994 | [
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The fate of arsenic in a river acidified by volcanic activity and an acid thermal water and sedimentation mechanism. | The Shozu-gawa river, located in the Aomori Prefecture, northern Japan, is affected by volcanic activities and acid thermal waters. The river is unique because both solid arsenic (As; as orpiment, As2S3) and dissolved As are supplied to the river from the uppermost caldera lake (Usori-ko Lake) and thermal ponds. The watershed is an excellent site for investigating the fate of different As species in a fluvial system. Upstream sediments near the caldera lake and geothermal ponds are highly contaminated by orpiment. This solid phase is transported as far as the mouth of the river. On the other hand, dissolved As is removed from the river system by hydrous ferric oxides (HFOs); however, HFO formation and removal of dissolved As do not occur in the uppermost area of the watershed, resulting in further downstream transport of dissolved As. Consequently, upstream river sediments are enriched in orpiment, whereas As(v), which is associated with HFOs in river sediments, increases downstream. Furthermore, orpiment particles are larger, and possibly heavier, than those of HFO with sorbed As. Fractionation between different chemical states of As during transport in the Shozu-gawa river is facilitated not only by chemical processes (i.e., sorption of dissolved As by HFOs), but also by physical factors (i.e., gravity). In contrast to acid mine drainage (AMD), in some areas of the Shozu-gawa river, both solid forms of As (as sulfide minerals) and dissolved As are introduced into the aquatic system. Considering that the stabilities of sulfide minerals are rather different from those of oxides and hydroxides, river sediments contacted with thermal waters possibly act as sources of As under both aerobic and anaerobic conditions. | 25,110,041 | [
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Role of neuropeptide Y in myocardial contractility of rats during early postnatal ontogeny. | We studied the effect of neuropeptide Y in concentrations of 10(-10)-10(-6) M on myocardial contractility of rats at the age of 7, 21, and 100 days. Studying the isometric contraction of myocardial strips showed that neuropeptide Y decreases the force of myocardial contraction in 7-day-old rat pups. Exogenous neuropeptide Y produced a biphasic effect in 21-day-old rats, which was manifested in the increase and subsequent decrease in myocardial contractility. Neuropeptide Y had little effect on myocardial contractility of 100-day-old animals. | 25,110,075 | [
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Myocardial serotonin during ischemia under conditions of ischemic preconditioning. | We studied the dynamics of interstitial serotonin during local myocardial ischemia under conditions of ischemic preconditioning in Wistar rats. Ischemic preconditioning increased serotonin content in the dialysate (p=0.003). During 30-min ischemia, ischemic preconditioning delayed serotonin increase just before the 20th min of ischemia. Ischemic preconditioning promoted short-term increase in the serotonin level in the myocardial interstitium but followed by prolonged ischemia, it delayed the accumulation of serotonin in the myocardial interstitium. | 25,110,083 | [
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Rare species occupy uncommon niches. | The fact that temperate grasslands often contain upwards of 30 vascular plant species per m(2) yet these species seem to have relatively similar life histories and resource requirements has made explaining species coexistence in these communities a major focus of research. While the reduction of competition by disturbance has been a popular explanation for species coexistence, in tallgrass prairies any level of disturbance either has no effect, or decreases diversity, since it favors the dominant plants. Although there has long been speculation that grassland species could coexist by niche partitioning the concept received renewed interest when it was shown that soil hydrology could explain species coexistence. One aspect of community structure that has not been explained by niche partitioning is the rareness and commonness of species within communities. There are three classes of explanations for rareness: narrow habitat requirements, low competitive ability combined with frequency dependent fitness and, dispersal ability. However, evidence for these explanations tend to be anecdotal, focusing on particular species. Here I show that in tallgrass prairies common and rare species consistently occupy different parts of niche space, with rare species being restricted by the cover of common species and occupying the rare available niches. | 25,110,113 | [
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Soluble a‑proliferation‑inducing ligand (sAPRIL), a novel serum biomarker predicting the recurrence and metastasis of pancreatic adenocarcinoma after surgery. | Pancreatic adenocarcinoma (PA) is a leading cause of adult cancer mortality, and surgery is still the best available treatment strategy. However, PA can recur at any time and has limited prognosis. It is therefore necessary to explore novel serum biomarkers of PA to allow the early diagnosis of PA. Soluble a-proliferation-inducing ligand (sAPRIL), a promising inducer of the epithelial-mesenchymal transition (EMT), is often found overexpressed in a variety of autoimmune diseases. To determine whether serum sAPRIL can constitute a PA biomarker, the protein level of sAPRIL was examined by immunohistochemistry and western blot, and the mRNA level was quantified by RT-qPCR. The PA cell line PanC-1 was transfected with vectors bearing the sAPRIL gene and sAPRIL short hairpin RNA (shRNA) oligos. Increased expression of serum sAPRIL was observed in patients with PA recurrence or metastasis after five-year surgery compared to subjects without PA recurrence or metastasis. The growth rate of PanC-1 cells transfected with the sAPRIL expression vector was increased by 23% (P<0.01, vs. control group), and was reduced by 17% (P<0.01, vs. control group) in the sAPRIL shRNA-silenced cell line. Thus, sAPRIL is highly expressed in PA, and serum levels of sAPRIL can serve as a useful indicator for the recurrence or metastasis of PA after surgery. Additional validation studies on the use of serum sAPRIL as a diagnostic marker in PA are however needed. | 25,110,120 | [
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Artemisinin prevents electric remodeling following myocardial infarction possibly by upregulating the expression of connexin 43. | Artemisinin has been demonstrated to exert beneficial effects on ventricular remodeling. The present study investigated whether artemisinin was able to decrease the ventricular fibrillation threshold (VFT) in rats following myocardial infarction (MI) and aimed to determine the possible underlying mechanisms. The rats were subjected to surgery to induce MI by ligation of the left anterior descending artery and were randomly allocated to receive vehicle or artemisinin (75 mg/kg/day) treatment for four weeks. Programmed electrical stimulation demonstrated a significantly increased VFT in the artemisinin-treated group compared with the vehicle-treated group. The electrophysiological improvement of the VFT was accompanied by increased immunofluorescence-stained connexin 43 (Cx43), myocardial Cx43 protein and mRNA levels in artemisinin-treated rats. The present study also demonstrated that artemisinin significantly decreased tissue tumor necrosis factor (TNF)-α levels at the infarcted border zone. Thus, artemisinin demonstrated a protective effect on ventricular arrhythmias following MI. Although the precise mechanism by which artemisinin modulates the dephosphorylation of Cx43 is unknown, it is likely that artemisinin increased the expression of Cx43 via the inhibition of TNF-α. | 25,110,145 | [
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Test-retest reliability for assessment of postural stability using center of pressure spatial patterns of three-dimensional statokinesigrams in young health participants. | This study investigated the test-retest reliability for assessment of postural stability using a quantitative method for identification of center of pressure (CoP) spatial patterns of three-dimensional statokinesigrams (3D-SKG). Twenty-one healthy participants (11 women, age 26.8 ± 7.2 years, body mass index 25.6 ± 5.3 kg/m²) were submitted to four consecutive 60-s trials while performing undisturbed upright stance with feet together, with or without visual input each. CoP data was used to calculate parameters from the 3D-SKG (quantity of high-density regions, nHDR). Stabilogram (standard deviation, range, maximum velocity) and statokinesigram (elliptical area, average velocity) were also calculated. Intraclass correlation coefficients (ICC2,1 and ICC2,4) and repeated-measures analysis-of-variance were used for statistical analysis. Significant differences in nHDR among trials were not noticed in both protocols, as well as for any parameter of the stabilogram or statokinesigram (all P > 0.05). Reliability for identification of nHDR with or without visual input was either excellent (ICC2,4 = 0.844 and 0.792, respectively) or fair to good (ICC2,1 = 0.575 and 0.488, respectively). Reliability of parameters from stabilogram and statokinesigram varied from excellent to poor for either postural task with (ICC2,4 range: 0.961-0.491; ICC2,1 range: 0.859-0.194) or without visual input (ICC2,4 range: 0.990-0.444; ICC2,1 range: 0.960-0.166). Test-retest reliability for identification of CoP spatial patterns is excellent or fair to good using averaged or single measurements of nHDR, respectively. No learning effect on repeated trials for identification of CoP spatial patterns was detected but deserves further research. | 25,110,166 | [
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Frank Beach Award Winner: Steroids as neuromodulators of brain circuits and behavior. | Neurons communicate primarily via action potentials that transmit information on the timescale of milliseconds. Neurons also integrate information via alterations in gene transcription and protein translation that are sustained for hours to days after initiation. Positioned between these two signaling timescales are the minute-by-minute actions of neuromodulators. Over the course of minutes, the classical neuromodulators (such as serotonin, dopamine, octopamine, and norepinephrine) can alter and/or stabilize neural circuit patterning as well as behavioral states. Neuromodulators allow many flexible outputs from neural circuits and can encode information content into the firing state of neural networks. The idea that steroid molecules can operate as genuine behavioral neuromodulators - synthesized by and acting within brain circuits on a minute-by-minute timescale - has gained traction in recent years. Evidence for brain steroid synthesis at synaptic terminals has converged with evidence for the rapid actions of brain-derived steroids on neural circuits and behavior. The general principle emerging from this work is that the production of steroid hormones within brain circuits can alter their functional connectivity and shift sensory representations by enhancing their information coding. Steroids produced in the brain can therefore change the information content of neuronal networks to rapidly modulate sensory experience and sensorimotor functions. | 25,110,187 | [
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Molecular mechanisms of antiproliferative effects induced by Schisandra-derived dibenzocyclooctadiene lignans (+)-deoxyschisandrin and (-)-gomisin N in human tumour cell lines. | A different behavior of the two dibenzocyclooctadiene lignans (+)-deoxyschisandrin (1) and (-)-gomisin N (2), from Schisandra chinensis fruits, was observed against two human tumour cell lines, (2008 and LoVo). These lignans inhibited cell growth in a dose-dependent manner on both cell lines, but inducing different types of cell death. In particular, (+)-deoxyschisandrin (1) caused apoptosis in colon adenocarcinoma cells (LoVo) but not in ovarian adenocarcinoma cells (2008), while (-)-gomisin N (2) induced apoptosis on both the cell lines used. Mitochondrial-mediated pathway was not involved in apoptotic stimuli. Both compounds caused G2/M phase cell growth arrest correlated with tubulin polymerization. | 25,110,194 | [
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Antibacterial tetraoxygenated xanthones from the immature fruits of Garcinia cowa. | A phytochemical investigation of the acetone extract from the immature fruits of Garcinia cowa led to the isolation of two novel tetraoxygenated xanthones, garcicowanones A (1) and B (2), together with eight known tetraoxygeanted xanthones. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their antibacterial activity against Bacillus cereus TISTR 688, Bacillus subtilis TISTR 008, Micrococcus luteus TISTR 884, Staphylococcus aureus TISTR 1466, Escherichia coli TISTR 780, Pseudomonas aeruginosa TISTR 781, Salmonella typhimurium TISTR 292 and Staphylococcus epidermidis ATCC 12228. α-Mangostin showed potent activity (MIC 0.25-1 μg/mL) against three Gram-positive strains and garcicowanone A and β-mangostin exhibited strong antibacterial activity against B. cereus with the same MIC values of 0.25 μg/mL. | 25,110,196 | [
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Co-immunization with virus-like particle and DNA vaccines induces protection against respiratory syncytial virus infection and bronchiolitis. | This study demonstrates that immunization with non-replicating virus-like particle (FFG VLP) containing RSV F and G glycoproteins together with RSV F DNA induced T helper type 1 antibody responses to RSV F similar to live RSV infection. Upon RSV challenge 21weeks after immunization, FFG VLP vaccination induced protection against RSV infection as shown by clearance of lung viral loads, and the absence of eosinophil infiltrates, and did not cause lung pathology. In contrast, formalin-inactivated RSV (FI-RSV) vaccination showed significant pulmonary eosinophilia, severe mucus production, and extensive histopathology resulting in a hallmark of pulmonary pathology. Substantial lung pathology was also observed in mice with RSV re-infections. High levels of systemic and local inflammatory cytokine-secreting cells were induced in mice with FI-RSV but not with FFG VLP immunization after RSV challenge. Therefore, the results provide evidence that recombinant RSV FFG VLP vaccine can confer long-term protection against RSV without causing lung pathology. | 25,110,201 | [
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5'-coding sequence of the nasA gene of Azotobacter vinelandii is required for efficient expression. | The operon nasACBH in Azotobacter vinelandii encodes nitrate and nitrite reductases that sequentially reduce nitrate to nitrite and to ammonium for nitrogen assimilation into organic molecules. Our previous analyses showed that nasACBH expression is subject to antitermination regulation that occurs upstream of the nasA gene in response to the availability of nitrate and nitrite. In this study, we continued expression analyses of the nasA gene and observed that the nasA 5'-coding sequence plays an important role in gene expression, as demonstrated by the fact that deletions caused over sixfold reduction in the expression of the lacZ reporter gene. Further analysis suggests that the nasA 5'-coding sequence promotes gene expression in a way that is not associated with weakened transcript folding around the translational initiation region or codon usage bias. The findings from this study imply that there exists potential to improve gene expression in A. vinelandii by optimizing 5'-coding sequences. | 25,110,215 | [
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Vernix caseosa peritonitis: report of two cases. | Vernix caseosa peritonitis is a rare complication caused by inflammatory response to amniotic fluid spilled into the maternal peritoneal cavity. Most cases occur after cesarean section. We discuss herein two patients, aged 33 and 29 years, who presented with vernix caseosa peritonitis seven to nine days after a cesarean delivery. Laparotomy was performed and it revealed neither uterine rupture nor other surgical emergencies, but cheesy exudates on the serosal surface of all viscera. Appendicectomy was performed. Histopathologic study revealed acute fibrinous serositis and a mixed cellular infiltrate, rich in neutrophils, around fetal desquamated anucleate squamous cells. Patients´ recovery was complete. Clinical diagnosis of vernix caseosa peritonitis should be suspected in patients presenting post-cesarean section with an acute abdomen. Distinctive histopathologic findings allow making the correct diagnosis. Vigilant monitoring after diagnosis is essential as delayed morbidities may appear. | 25,110,245 | [
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Who should receive biologic therapy for IBD?: The rationale for the application of a personalized approach. | The therapeutic approach in inflammatory bowel disease has evolved to target end-organ inflammation to heal intestinal mucosa and avoid structural damage. Objective therapeutic monitoring is required to achieve this goal. Earlier intervention with biologic therapy has been shown, indirectly, to be associated with higher clinical response and remission rates. A personalized approach to risk stratification with consideration of key clinical factors and inflammatory biomarker concentrations is recommended when deciding whether or not to start a patient on biologic therapy. | 25,110,251 | [
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Anti-tumor necrosis factor-α monotherapy versus combination therapy with an immunomodulator in IBD. | Inflammatory bowel disease (IBD) treatment has progressed significantly over the past decade with the advent of biologics. Anti-tumor necrosis factor (anti-TNF) agents are the most widely available biologics, but the optimal approach when using them remains unclear. In this review, we highlight the currently available evidence regarding the use of anti-TNF monotherapy versus combination therapy with an immunomodulator. We focus on those patients at greatest risk for adverse events and outline the clinical approach when considering the use of combination therapy. We review the available tools through which providers may efficiently communicate these data to patients in the clinical setting. | 25,110,252 | [
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The effect of sleep restriction on neurobehavioural functioning in normally developing children and adolescents: insights from the Attention, Behaviour and Sleep Laboratory. | In the current paper, we first introduce the research themes of the attention, behaviour and sleep (ABS) laboratory, namely, sleep and ADHD, sleep and obesity, and sleep and academic performance. We then focus in on the topic to be reviewed in the current paper - the association between sleep restriction and neurobehavioral functioning (NBF) in typically developing children. We review the research thus far conducted by the ABS lab specific to this topic and posit the unique methodological contributions of the ABS lab (e.g. home-based assessment of sleep architecture and patterns, extensive phenotyping, etc.) in terms of advancing this research area. In the second section of the paper, we review 13 studies investigating the causal association between experimental sleep restriction and NBF in normally developing pediatric populations. Eight of the 13 studies found that sleep restriction causes impairments in neurobehavioural functioning. However, given the inconsistency in outcome measures, experimental protocols and statistical power, the studies reviewed herein are difficult to interpret. Strategies used by the ABS including implementing home assessments of sleep, restricting sleep relative to the participants' typical sleep schedules, blinding raters who assess NBF, and using valid and reliable NBF assessments are an attempt to address the gaps in this research area and clarify the causal relationship between sleep restriction and NBF in typically developing children and adolescents. | 25,110,282 | [
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[The Glivec® case: the first example of a global debate on the drug patent system]. | To describe the sequence of events involving the Glivec® case in India and to analyze the opinions generated in distinct settings. We performed a systematic search for articles concerning the imatinib (Glivec®) patent in India. We selected those sources that described the events, decisions of the authorities involved, and press and scientific opinions. Dates and arguments presented by the involved parties were clearly identified. Of 886 documents initially obtained, we selected 40 documents published between 2003 and 2013. Most of them were press news and commentaries. The process lasted 7 years, starting in 2006 when the Indian Patent Office rejected the patent application filed by Novartis. It ended in 2013 when the Indian Supreme Court upheld this decision. It was argued that the Indian Patent Law would facilitate access to medicines in the Third World and the final decision has received support by the general population. Although the court's final decision has been supported by several institutions, an objective analysis should also take into account the arguments of the pharmaceutical companies and other entities. The Glivec® case gave rise to an intense debate on the appropriateness of international standards on patents, their applicability and how they should be adopted in each country. This case, as well as other cases, should serve to stimulate reflection on the international patent system and to achieve scenarios in which the health of the poorest populations is protected but also balanced against intellectual property protection and innovation. | 25,110,309 | [
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Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin. | The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. From January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. The outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin. | 25,110,329 | [
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Impact of obesity on surgical and oncologic outcomes in ovarian cancer. | The aim of this study is to determine the impact of obesity on surgical and oncologic outcomes after primary debulking surgery (PDS) in advanced epithelial ovarian cancer (EOC). Women with stage IIIC/IV EOC who underwent PDS with curative intent between 1/2/2003 and 12/30/2011 were included. Patient characteristics, intraoperative and postoperative outcomes, recurrence and status were abstracted. Complications were graded according to the 4-point Accordion classification. For analyses, patients were divided into three groups according to body mass index (BMI): group 1-BMI <25.0 kg/m(2); group 2-BMI 25.0-39.9 kg/m(2); and group 3-BMI ≥40.0 kg/m(2). Of the 620 patients included in the study, 36.6%, 56.9%, and 6.5% were in weight groups 1, 2, and 3, respectively. Weight group 3 was an independent predictor of severe complications after adjusting for confounders (adjusted odds ratio (95% CI): 2.93 (1.38, 6.20) for group 3 vs. group 2). Weight group was not associated with differences in residual disease (p=0.80). The 90-day mortality rates were 11.9%, 6.7%, and 15.7%, respectively, in weight group 1, 2, and 3 (p=0.049 unadjusted, p=0.01 adjusted). There was no difference in OS (p=0.52) or PFS (p=0.23) between weight groups. BMI ≥40.0 kg/m(2) is an independent predictor of severe 30-day postoperative morbidity and 90-day mortality after PDS for EOC-information useful in preoperative counseling. BMI does not appear to impact long-term oncologic outcomes including residual disease at PDS, although we had limited power at the extremes of BMI. BMI may be an important factor to consider in risk-adjustment models and reimbursement strategies. | 25,110,330 | [
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mRNA transport meets membrane traffic. | Active transport and local translation of mRNAs ensure the appropriate spatial organization of proteins within cells. Recent work has shown that this process is intricately connected to membrane trafficking. Here, we focus on new findings obtained in fungal model systems. Important highlights are that RNA-binding proteins recognize cargo mRNA synergistically and that mRNAs are co-transported with membranous compartments such as the endoplasmic reticulum (ER) and endosomes. We further discuss a novel concept of endosome-coupled translation that loads shuttling endosomes with septin cargo, a process important for correct septin filamentation. Interestingly, evidence is accumulating that RNA and membrane trafficking are also tightly interwoven in higher eukaryotes, suggesting that this phenomenon is a common theme and not an exception restricted to fungi. | 25,110,341 | [
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Focal chromosomal copy number aberrations in cancer-Needles in a genome haystack. | The extent of focal chromosomal copy number aberrations (CNAs) in cancer has been uncovered through technical innovations, and this discovery has been critical for the identification of new cancer driver genes in genomics projects such as TCGA and ICGC. Unlike constitutive copy number variations (CNVs), focal CNAs are the result of many selection events during the evolution of cancer genomes. Therefore, it is possible that a single gene in a focal CNA gives the tumor a selective growth advantage. This concept has been instrumental in the discovery of new cancer driver genes. However, focal CNAs lack a consensus definition; therefore, we propose one based on pragmatic considerations. We also describe different strategies to identify focal CNAs and procedures to distinguish them from large CNAs and CNVs. | 25,110,350 | [
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The importance of an extensive elemental analysis of single-walled carbon nanotube soot. | Few manufacturers provide elemental analysis information on the certificates of analysis of their single-walled carbon nanotube (SWCNT) soot products, and those who do primarily perform surface sensitive analyses that may not accurately represent the bulk properties of heterogeneous soot samples. Since the accurate elemental analysis of SWCNT soot is a requisite for exacting assessments of product quality and environmental health and safety (EH&S) risk, the purpose of this work was to develop a routine laboratory procedure for an extensive elemental analysis of SWCNT soot using bulk methods of analyses. Herein, a combination of carbon, hydrogen, nitrogen, sulfur, and oxygen (CHNS/O) combustion analyses, oxygen flask combustion/anion chromatography (OFC/AC), graphite furnace-atomic absorption spectroscopy (GF-AAS), and inductively coupled plasma-mass spectroscopy (ICP-MS) were used to generate a 77-element analysis of two as-received CoMoCAT<sup®</sup SWCNT soot products. Fourteen elements were detected in one product, nineteen in the other, and each data set was compared to its respective certificate of analysis. The addition of the OFC/AC results improved the accuracy of elements detected by GF-AAS and ICP-MS, and an assessment was performed on the results that concluded that the trace elemental impurities should not pose an EH&S concern if these soot products became airborne. | 25,110,357 | [
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Design and Synthesis of an Inositol Phosphate Analog Based on Computational Docking Studies. | A virtual library of 54 inositol analog mimics of In(1,4,5)P<sub3</sub has been docked, scored, and ranked within the binding site of human inositol 1,4,5-trisphosphate 3-kinase A (IP<sub3</sub-3KA). Chemical synthesis of the best scoring structure that also met distance criteria for 3'-OH to -P in Phosphate has been attempted along with the synthesis of (1<iS</i,2<iR</i,3<iS</i,4<iS</i)-3-fluoro-2,4-dihydroxycyclohexanecarboxylic acid as an inositol analog, useful for non-invasive visualization and quantitation of IP<sub3</sub-3KA enzymatic activity. | 25,110,363 | [
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Markov Transition Model to Dementia with Death as a Competing Event. | This study evaluates the effect of death as a competing event to the development of dementia in a longitudinal study of the cognitive status of elderly subjects. A multi-state Markov model with three transient states: intact cognition, mild cognitive impairment (M.C.I.) and global impairment (G.I.) and one absorbing state: dementia is used to model the cognitive panel data; transitions among states depend on four covariates age, education, prior state (intact cognition, or M.C.I., or G.I.) and the presence/absence of an apolipoprotein E-4 allele (APOE4). A Weibull model and a Cox proportional hazards (Cox PH) model are used to fit the survival from death based on age at entry and the APOE4 status. A shared random effect correlates this survival time with the transition model. Simulation studies determine the sensitivity of the maximum likelihood estimates to the violations of the Weibull and Cox PH model assumptions. Results are illustrated with an application to the Nun Study, a longitudinal cohort of 672 participants 75+ years of age at baseline and followed longitudinally with up to ten cognitive assessments per nun. | 25,110,380 | [
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Guidelines for Adapting Manualized Interventions for New Target Populations: A Step-Wise Approach Using Anger Management as a Model. | The use of manual-based interventions tends to improve client outcomes and promote replicability. With an increasingly strong link between funding and the use of empirically supported prevention and intervention programs, manual development and adaptation have become research priorities. As a result, researchers and scholars have generated guidelines for developing manuals from scratch, but there are no extant guidelines for adapting empirically supported, manualized prevention and intervention programs for use with new populations. Thus, this article proposes step-by-step guidelines for the manual adaptation process. It also describes two adaptations of an extensively researched anger management intervention to exemplify how an empirically supported program was systematically and efficiently adapted to achieve similar outcomes with vastly different populations in unique settings. | 25,110,403 | [
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Preventing infective complications in inflammatory bowel disease. | Over the past decade there has been a dramatic change in the treatment of patients with Crohn's disease and ulcerative colitis, which comprise the inflammatory bowel diseases (IBD). This is due to the increasing use of immunosuppressives and in particular the biological agents, which are being used earlier in the course of disease, and for longer durations, as these therapies result in better clinical outcomes for patients. This, however, has the potential to increase the risk of opportunistic and serious infections in these patients, most of which are preventable. Much like the risk for potential malignancy resulting from the use of these therapies long-term, a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection. This outcome is achieved by the physician's tailored use of justified therapies, and the patients' education and actions to minimize infection risk. The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections. | 25,110,408 | [
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Specific metabolic biomarkers as risk and prognostic factors in colorectal cancer. | Advances in genomics, molecular pathology and metabolism have generated many candidate biomarkers of colorectal cancer with potential clinical value. Epidemiological and biological studies suggest a role for adiposity, dyslipidaemia, hyperinsulinemia, altered glucose homeostasis, and elevated expression of insulin-like growth factor (IGF) axis members in the risk and prognosis of cancer. This review discusses some recent past and current approaches being taken by researches in obesity and metabolic disorders. The authors describe three main systems as the most studied metabolic candidates of carcinogenesis: dyslipidemias, adipokines and insulin/IGF axis. However, each of these components is unsuccessful in defining the diseases risk and progression, while their co-occurrence increases cancer incidence and mortality in both men and women. | 25,110,413 | [
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Controversies in the pathological assessment of colorectal cancer. | Pathologic assessment of colorectal cancer specimens plays an essential role in patient management, informing prognosis and contributing to therapeutic decision making. The tumor-node-metastasis (TNM) staging system is a key component of the colorectal cancer pathology report and provides important prognostic information. However there is significant variation in outcome of patients within the same tumor stage. Many other histological features such as tumor budding, vascular invasion, perineural invasion, tumor grade and rectal tumor regression grade that may be of prognostic value are not part of TNM staging. Assessment of extramural tumor deposits and peritoneal involvement contributes to TNM staging but there are some difficulties with the definition of both of these features. Controversies in colorectal cancer pathology reporting include the subjective nature of some of the elements assessed, poor reporting rates and reproducibility and the need for standardized examination protocols and reporting. Molecular pathology is becoming increasingly important in prognostication and prediction of response to targeted therapies but accurate morphology still has a key role to play in colorectal cancer pathology reporting. | 25,110,416 | [
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CacyBP/SIP nuclear translocation induced by gastrin promotes gastric cancer cell proliferation. | To investigate the role of nuclear translocation of calcyclin binding protein, also called Siah-1 interacting protein (CacyBP/SIP), in gastric carcinogenesis. The expression of CacyBP/SIP protein in gastric cancer cell lines was detected by Western blot. Immunofluorescence experiments were performed on gastric cancer cell lines that had been either unstimulated or stimulated with gastrin. To confirm the immunofluorescence findings, the relative abundance of CacyBP/SIP in nuclear and cytoplasmic compartments was assessed by Western blot. The effect of nuclear translocation of CacyBP/SIP on cell proliferation was examined using MTT assay. The colony formation assay was used to measure clonogenic cell survival. The effect of CacyBP/SIP nuclear translocation on cell cycle progression was investigated. Two CacyBP/SIP-specific siRNA vectors were designed and constructed to inhibit CacyBP/SIP expression in order to reduce the nuclear translocation of CacyBP/SIP, and the expression of CacyBP/SIP in stably transfected cells was determined by Western blot. The effect of inhibiting CacyBP/SIP nuclear translocation on cell proliferation was then assessed. CacyBP/SIP protein was present in most of gastric cancer cell lines. In unstimulated cells, CacyBP/SIP was distributed throughout the cytoplasm; while in stimulated cells, CacyBP/SIP was found mainly in the perinuclear region. CacyBP/SIP nuclear translocation generated a growth-stimulatory effect on cells. The number of colonies in the CacyBP/SIP nuclear translocation group was significantly higher than that in the control group. The percentage of stimulated cells in G1 phase was significantly lower than that of control cells (69.70% ± 0.46% and 65.80% ± 0.60%, control cells and gastrin-treated SGC7901 cells, P = 0.008; 72.99% ± 0.46% and 69.36% ± 0.51%, control cells and gastrin-treated MKN45 cells, P = 0.022). CacyBP/SIPsi1 effectively down-regulated the expression of CacyBP/SIP, and cells stably transfected by CacyBP/SIPsi1 were then chosen for further cellular assays. In CacyBP/SIPsi1 stably transfected cells, CacyBP/SIP was shown to be distributed throughout the cytoplasm, irregardless of whether they were stimulated or not. After CacyBP/SIP nuclear translocation was reduced, there had no major effect on cell proliferation, as shown by MTT assay. There had no enhanced anchorage-dependent growth upon stimulation, as indicated by colony formation in flat plates. No changes appeared in the percentage of cells in G0-G1 phase in either cell line (71.09% ± 0.16% and 70.86% ± 0.25%, control cells and gastrin-treated SGC7901-CacyBP/SIPsi1 cells, P = 0.101; 74.17% ± 1.04% and 73.07% ± 1.00%, control cells and gastrin-treated MKN45-CacyBP/SIPsi1 cells, P = 0.225). CacyBP/SIP nuclear translocation promotes the proliferation and cell cycle progression of gastric cancer cells. | 25,110,433 | [
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KISS1 methylation and expression as predictors of disease progression in colorectal cancer patients. | To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer (CRC) and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target. KISS1 promoter methylation, mRNA expression and protein expression were detected by methylation-specific polymerase chain reaction (PCR), real-time quantitative PCR and Western blotting, respectively, in 126 CRC tissues and 142 normal colorectal tissues. Human CRC cells with KISS1 promoter hypermethylation and poor KISS1 expression were treated in vitro with 5-aza-2'-deoxycytidine (5-Aza-CdR). After treatment, KISS1 promoter methylation, KISS1 mRNA and protein expression and cell migration and invasion were evaluated. Hypermethylation of KISS1 occurred frequently in CRC samples (83.1%, 105/126), but was infrequent in normal colorectal tissues (6.34%, 9/142). Moreover, KISS1 methylation was associated with tumor differentiation, the depth of invasion, lymph node metastasis and distant metastasis (P < 0.001). KISS1 methylation was also associated with low KISS1 expression (P < 0.001). Furthermore, we observed re-expression of the KISS1 gene and decreased cell migration after 5-Aza-CdR treatment in a CRC cell line. These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC. | 25,110,434 | [
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Imaging findings of primary gastric plasmacytoma: a case report. | Primary gastric plasmacytoma (GP) is a rare extramedullary plasmacytoma with clinical and imaging features that are common among other gastric tumors, such as gastric adenocarcinomas, gastric stromal tumors, and lymphomas. Here, we present a histologically confirmed case of primary GP examined with biphasic computed tomography (CT), magnetic resonance imaging (MRI), and endosonography. A well-circumscribed extraluminal mass appearing as homogeneous attenuation/intensity with gradual enhancement was identified on biphasic enhancement CT and MRI. This mass was hyperintense on diffusion-weighted imaging and hypointense on the apparent diffusion coefficient map, implying that water diffusion in the mass was restricted. In addition, endosonography indicated a low echogenic mass in the gastric wall. These imaging findings increase the available knowledge about imaging of this disease and provide valuable information for differentiating primary GP from common gastric tumors. | 25,110,449 | [
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Veno-venous ECMO: a synopsis of nine key potential challenges, considerations, and controversies. | Following the 2009 H1N1 Influenza pandemic, extracorporeal membrane oxygenation (ECMO) emerged as a viable alternative in selected, severe cases of ARDS. Acute Respiratory Distress Syndrome (ARDS) is a major public health problem. Average medical costs for ARDS survivors on an annual basis are multiple times those dedicated to a healthy individual. Advances in medical and ventilatory management of severe lung injury and ARDS have improved outcomes in some patients, but these advances fail to consistently "rescue" a significant proportion of those affected. Here we present a synopsis of the challenges, considerations, and potential controversies regarding veno-venous ECMO that will be of benefit to anesthesiologists, surgeons, and intensivists, especially those newly confronted with care of the ECMO patient. We outline a number of points related to ECMO, particularly regarding cannulation, pump/oxygenator design, anticoagulation, and intravascular fluid management of patients. We then address these challenges/considerations/controversies in the context of their potential future implications on clinical approaches to ECMO patients, focusing on the development and advancement of standardized ECMO clinical practices. Since the 2009 H1N1 pandemic ECMO has gained a wider acceptance. There are challenges that still must be overcome. Further investigations of the benefits and effects of ECMO need to be undertaken in order to facilitate the implementation of this technology on a larger scale. | 25,110,462 | [
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Nasal high-flow oxygen therapy in patients with hypoxic respiratory failure: effect on functional and subjective respiratory parameters compared to conventional oxygen therapy and non-invasive ventilation (NIV). | Aim of the study was to compare the short-term effects of oxygen therapy via a high-flow nasal cannula (HFNC) on functional and subjective respiratory parameters in patients with acute hypoxic respiratory failure in comparison to non-invasive ventilation (NIV) and standard treatment via a Venturi mask. Fourteen patients with acute hypoxic respiratory failure were treated with HFNC (FiO2 0.6, gas flow 55 l/min), NIV (FiO2 0.6, PEEP 5 cm H2O Hg, tidal volume 6-8 ml/kg ideal body weight,) and Venturi mask (FiO2 0.6, oxygen flow 15 l/min,) in a randomized order for 30 min each. Data collection included objective respiratory and circulatory parameters as well as a subjective rating of dyspnea and discomfort by the patients on a 10-point scale. In a final interview, all three methods were comparatively evaluated by each patient using a scale from 1 (=very good) to 6 (=failed) and the patients were asked to choose one method for further treatment. PaO2 was highest under NIV (129 ± 38 mmHg) compared to HFNC (101 ± 34 mmHg, p <0.01 vs. NIV) and VM (85 ± 21 mmHg, p <0.001 vs. NIV, p <0.01 vs. HFNC, ANOVA). All other functional parameters showed no relevant differences. In contrast, dyspnea was significantly better using a HFNC (2.9 ± 2.1, 10-point Borg scale) compared to NIV (5.0 ± 3.3, p <0.05), whereas dyspnea rating under HFNC and VM (3.3 ± 2.3) was not significantly different. A similar pattern was found when patients rated their overall discomfort on the 10 point scale: HFNC 2.7 ± 1.8, VM 3.1 ± 2.8 (ns vs. HFNC), NIV 5.4 ± 3.1 (p <0.05 vs. HFNC). In the final evaluation patients gave the best ratings to HFNC 2.3 ± 1.4, followed by VM 3.2 ± 1.7 (ns vs. HFNC) and NIV 4.5 ± 1.7 (p <0.01 vs. HFNC and p <0.05 vs. VM). For further treatment 10 patients chose HFNC, three VM and one NIV. In hypoxic respiratory failure HFNC offers a good balance between oxygenation and comfort compared to NIV and Venturi mask and seems to be well tolerated by patients. GERMAN CLINICAL TRIALS REGISTER: DRKS00005132. | 25,110,463 | [
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Clinical Outcomes of Posterior C2-C3 Fixation for Unstable Hangman's Fracture Compared with Posterior C1-C3 Fusion. | To verify the clinical outcomes of posterior C2-C3 fixation for unstable Hangman's fracture compared with posterior C1-C3 fixation. Twenty four patients for unstable Hangman's fracture were enrolled between July 2007 and June 2010 in this study. Thirteen patients underwent posterior C2-C3 fusion and 11 patients underwent posterior C1-C3 fusion. Clinical outcomes were evaluated using Neck Disability Index (NDI) scores and Visual Analogue Scale (VAS) scores during preoperative and postoperative follow up period. Plain radiographs were obtained on postoperative 1 day, 1 week, and then at 1, 2, 6, and 12 months. CT was done at postoperative 12 months in all patients for evaluation of bone fusion. The mean period of clinical follow-up was 15 months. The mean ages were 43.3 years in C2-C3 group and 50.0 years in C1-C3 group. Mean follow-up period was 17.2 months in C2-C3 group and 16.3 months in C1-C3 group. VAS scores and NDI scores in C2-C3 group were much less than those in C1-C3 group at each follow-up period. The differences of VAS score and NDI scores between C2-C3 and C1-C3 groups at each follow-up period were statistically significant (p<0.001) by paired T-test. Solid Bone fusion was confirmed in all cases at the final follow-up. C2-C3 group showed better clinical and biomechanical results than C1-C3 group in terms of axial pain and disability of neck. | 25,110,480 | [
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Unusual clinical presentations of cervical or lumbar dorsal ramus syndrome. | Patients with cervical (CDRS) or lumbar dorsal ramus syndrome (LDRS) are characterized by neck or low back pain with referred pain to upper or lower extremities. However, we experienced some CDRS or LDRS patients with unusual motor or bladder symptoms. We analyzed and reviewed literatures on the unusual symptoms identified in patients with CDRS or LDRS. This study included patients with unusual symptoms and no disorders of spine and central nervous system, a total of 206 CDRS/LDRS patients over the past 3 years. We diagnosed by using double diagnostic blocks for medial branches of dorsal rami of cervical or lumbar spine with 1% lidocaine or 0.5% bupivacaine for each block with an interval of more than 1 week between the blocks. Greater than 80% reduction of the symptoms, including unusual symptoms, was considered as a positive response. The patients with a positive response were treated with radiofrequencyneurotomy. The number of patients diagnosed with CDRS and LDRS was 86 and 120, respectively. Nine patients (10.5%) in the CDRS group had unusual symptoms, including 4 patients with motor weakness of the arm, 3 patients with tremors, and rotatory torticollis in 2 patients. Ten patients (8.3%) in the LDRS group showed unusual symptoms, including 7 patients with motor weakness of leg, 2 patients with leg tremor, and urinary incontinence in 1 patient. All the unusual symptoms combined with CDRS or LDRS were resolved after treatment. It seems that the clinical presentationssuch as motor weakness, tremor, urinary incontinence without any other etiologic origin need to be checked for unusual symptoms of CDRS or LDRS. | 25,110,484 | [
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Intramedullary spinal cysticercosis: a case report and review of literature. | To report a case of spinal intramedullary cysticercosis in thoracic spine. A 47-year old man living in Korea referred to our hospital with both feet tingling sensation for about a year. Laboratory evaluations, including serologic tests were not helpful. Magnetic resonance imaging revealed a 1.7 cm intramedullary mass at T10-11 level, which believed to be a tumor instead, rather than a cysticercosis preoperatively. Successful operation was done with a histopathological result confirmed it as cysticercosis. Even though the prevalence of intramedullary spinal cysticercosis is extremely rare, and radiologic exams mimic other common tumors like ependymoma or astrocytoma, the disease should be considered as differential diagnosis. | 25,110,489 | [
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Pure spinal epidural cavernous hemangioma with intralesional hemorrhage: a rare cause of thoracic myelopathy. | Although cavernous hemangiomas occur frequently in the intracranial structures, they are rare in the spine. Most of spinal hemangiomas are vertebral origin and "pure" epidural hemangiomas not originating from the vertebral bone are very rare. Our spinal hemangioma case is extremely rare because of its "pure" epidural involvement and intralesional hemorrhage. A 64-year-old man presented with progressive paraparesis from two months ago. His motor weakness was rated as grade 4/5 in bilateral lower extremities. He also complained of decreased sensation below the T4 sensory dermatome, which continuously progressed to the higher dermatome level. Magnetic resonance imaging demonstrated thoracic spinal tumor at T3-T4 level. The tumor was located epidural space compressing thoracic spinal cord ventrally. The tumor was not involved with the thoracic vertebral bone. We performed T3-5 laminectomy and removed the tumor completely. The tumor was not infiltrating into intradural space or vertebral bone. The histopathologic study confirmed the epidural tumor as cavernous hemangioma. Postoperatively, his weakness improved gradually. Four months later, his paraparesis recovered completely. Here, we present a case of pure spinal epidural cavernous hemangioma, which has intralesional hemorrhage. We believe cavernous hemangioma should be included in the differential diagnosis of the spinal epidural tumors. | 25,110,490 | [
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Ant Colony Optimization Based Feature Selection Method for QEEG Data Classification. | Many applications such as biomedical signals require selecting a subset of the input features in order to represent the whole set of features. A feature selection algorithm has recently been proposed as a new approach for feature subset selection. Feature selection process using ant colony optimization (ACO) for 6 channel pre-treatment electroencephalogram (EEG) data from theta and delta frequency bands is combined with back propagation neural network (BPNN) classification method for 147 major depressive disorder (MDD) subjects. BPNN classified R subjects with 91.83% overall accuracy and 95.55% subjects detection sensitivity. Area under ROC curve (AUC) value after feature selection increased from 0.8531 to 0.911. The features selected by the optimization algorithm were Fp1, Fp2, F7, F8, F3 for theta frequency band and eliminated 7 features from 12 to 5 feature subset. ACO feature selection algorithm improves the classification accuracy of BPNN. Using other feature selection algorithms or classifiers to compare the performance for each approach is important to underline the validity and versatility of the designed combination. | 25,110,496 | [
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The validities and efficiencies of korean ADHD rating scale and korean child behavior checklist for screening children with ADHD in the community. | The purpose of this study is to examine the validity of primary screening tools for attention deficit hyperactivity disorder (ADHD) in a community-based sample of children using the Korean version of the Child Behavior Checklist (K-CBCL) and the Korean version of the ADHD Rating Scale (K-ARS). A large-scale community-based study for ADHD screening was conducted in the Jeollabuk province in the Republic of Korea. In 2010-2011, we surveyed a total of 49,088 first- and fourth-grade elementary school students. All of the participants in this study were assessed by the K-ARS-Parent version (K-ARS-P) and the K-ARS-Teacher version (K-ARS-T) as the primary screening instruments. The Diagnostic Interview Schedule for Children Version IV (DISC-IV) was used for confirming the diagnosis of ADHD. DISC-IV was administered to subjects who received top 10% scores in the K-ARS-P or K-ARS-T tests. Of the 3,085 subjects who completed the DISC-IV, 1,215 were diagnosed as having ADHD. A reasonable level of sensitivity, specificity, and negative predictive value were obtained when the total K-ARS-P scores were ≥90th percentile. The positive predictive value and specificity increased significantly when the total K-ARS-P scores were ≥90th percentile, T scores were ≥60 in the attention problems of K-CBCL, and T scores were ≥63 in the total problems of K-CBCL. These results suggested that the K-ARS-P could effectively serve as a primary screening tool to identify elementary school children with ADHD in the community. Also, there might be some increment in the effectiveness of K-ARS-P when combined with K-CBCL-A and K-CBCL-T as a secondary screening tool. | 25,110,498 | [
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Surgical management of colorectal cancer metastases to the liver: multimodality approach and a single institutional experience. | Over the past 30 years, the treatment of metastatic colorectal cancer to the liver has undergone major changes. Once considered terminal and incurable, the prognosis of patients with colorectal hepatic metastases has seen dramatic improvements using modern multimodality therapy and now long-term survival and even cure are possible in some patients. Despite the advances seen in systemic therapy, hepatic resection offers the longest survival potential and remains the only curative option. Based on long-term outcomes and the improved safety of hepatic resection using modern operative techniques and critical care support, an aggressive locoregional approach to colorectal hepatic metastasis has become the standard of care. This article focuses on the management of colorectal hepatic metastases and highlights the importance of multimodality therapy. We also report our 18-year experience treating patients with hepatic resection for colorectal metastases. | 25,110,522 | [
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Late, not early mismatch responses to changes in frequency are reduced or deviant in children with dyslexia: an event-related potential study. | Developmental disorders of oral and written language have been linked to deficits in the processing of auditory information. However, findings have been inconsistent, both for behavioural and electrophysiological measures. In this study, we examined event-related potentials (ERPs) in 20 6- to 14-year-old children with developmental dyslexia and 20 age-matched controls, divided into younger (6-11 years, n = 10) and older (11-14 years, n = 10) age bands. We focused on early (mismatch negativity; MMN) and late (late discriminative negativity; LDN) conventional mismatch responses and associated measures derived from time-frequency analysis (inter-trial coherence and event-related spectral perturbation). Responses were elicited using an auditory oddball task, whereby a stream of 1000-Hz standards was interspersed with rare large (1,200 Hz) and small (1,030 Hz) frequency deviants. Conventional analyses revealed no significant differences between groups in the size of the MMN to either large or small frequency deviants. However, the younger age band of children with dyslexia showed an enhanced inter-trial coherence in the theta frequency band over the time window corresponding to the MMN to small deviants. By contrast, these same children showed a reduced-amplitude LDN for the small deviants relative to their age-matched controls, whilst the older children with dyslexia showed a shorter and less intense period of event-related desynchronization over this time window. Initial detection and discrimination of auditory frequency change appears normal or even enhanced in children with dyslexia. Rather, deficits in late-stage auditory processing appear to be a feature of this population. | 25,110,526 | [
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... |
Influences on modern multifactorial falls prevention interventions and fear of falling in non-frail older adults: a literature review. | This review explores underlying features that may influence fear of falling and the effectiveness of multifactorial falls prevention programs in community dwelling non-frail adults aged 65 and older. It also examines the interrelationship between fear of falling and multifactorial falls prevention interventions. A literature search of medical databases was conducted to identify articles that address the fear of falling and multifactorial programs as either a primary or secondary component of their findings. Multifactorial interventions were assessed in terms of their program content, design, demographics, implementation techniques, and cost-effectiveness. Falls are a common, but preventable, cause of morbidity and injury in older adults 65 and over. In addition to physiological variables, fear of falling and self-efficacy are psychosocial factors that impact the incidence of falls in this population. Addressing fear of falling in addition to physiological parameters may influence the success of multifactorial falls prevention programs for adults 65 and over. | 25,110,534 | [
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Accuracy of unstimulated Basal serum thyroglobulin levels in assessing the completeness of thyroidectomy. | Complete excision is important for proper surgical treatment of thyroid disorders. Functional thyroid tissue can be identified based on the level of serum thyroglobulin (Tg), which is produced only by the thyroid follicular cells, and nuclear scan. Serum thyroid stimulating hormone (TSH), free thyroxin (FT4), basal (unstimulated) Tg and anti-Tg antibody (anti-Tg ab) were measured at the sixth postoperative month in 100 patients with benign thyroid disorders treated by total thyroidectomy. Thyroid nuclear scan was obtained to identify functional remnant of the thyroid gland. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the Tg levels in assessing thyroid remnant were calculated. Positive scan showed thyroid remnant in 23 patients, among whom 16 were Tg positive (true positive) and seven were Tg negative (< 0.5 ng/mL) (false negative). In these patients, the nuclear scan revealed pyramidal lobe remnants. In 77 patients with negative scan, the Tg levels were also negative (true negative), and the PPV, NPV, sensitivity, specificity and accuracy of the Tg levels were 100%, 92%, 70%, 100% and 93%, respectively. The positive basal Tg (> 0.5 ng/mL) level accurately indicated the functional thyroid remnant after total thyroidectomy. The negative Tg (< 0.5 ng/mL) level supported complete excision of the thyroid gland. The surgical completeness of total thyroidectomy was accurately evaluated based on the serum Tg levels. Therefore, serum Tg levels should be measured in postoperative follow-up to determine the completeness of total thyroidectomy. | 25,110,541 | [
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0.2950484,
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Chronic subdural hematoma in patients over 90 years old in a super-aged society. | Chronic subdural hematoma (CSDH) is one of the most common diseases in neurosurgical practice, particularly among aged patients. With the continuing increase in the aged population, further increases in incidence are expected. However, few studies have focused on CSDH in super-aged patients over 90 years old. We retrospectively reviewed medical records for 20 consecutive patients over 90 years old with CSDH treated in our department between 2007 and 2013. The diagnosis of CSDH was confirmed by computed tomography (CT). Patients were divided into a surgery group and a conservative group. Surgical procedures included burr-hole surgery followed by insertion of a subdural drain under local anesthesia. Clinical data were compared and analyzed. Neurological status was evaluated according to the modified Rankin Scale at three time points: before suffering from CSDH; at the time of referral or admission to our department; and at discharge or 1 month after the first referral. Statistical tests were used to analyze data and values of P < 0.05 were considered significant. Mean age for the 20 cases was 92.6 years (range, 90 - 96 years). The leading symptoms in this population were hemiparesis and gait disturbance, followed by disturbance of consciousness and speech disturbance. Twelve patients underwent burr-hole surgery. Mean maximum thickness of subdural hematoma as measured on CT was significantly higher in the surgery group (28.2 ± 5.4 mm) than in the conservative group (17.0 ± 3.8 mm; P < 0.01). Postoperatively, mean neurological status was significantly improved in the surgery group (P < 0.01). After surgery, 66.7% of patients could return home directly from hospital. No significant perioperative complications directly related to surgery were encountered in the surgery group, except for transient postoperative restlessness and bruising of extremities due to falls. Surgery for CSDH is safe and positively recommended even in super-aged patients over 90 years old if the patient's physical status is fair. Pre-illness status is the most important factor for considering operative indications and represents a limiting factor for postoperative outcomes in this age population. | 25,110,543 | [
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0.1049247,
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0.327178,
0.1788139... |
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