title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Pediatric eosinophilic esophagitis is associated with changes in esophageal microRNAs. | The incidence of eosinophilic esophagitis (EoE) has increased in the past several years, yet our understanding of its pathogenesis remains limited. To test the hypothesis that microRNAs (miRNAs) are altered in children with EoE, miRNAs were profiled in esophageal mucosa biopsies obtained from patients with active disease (n = 5) and healthy control subjects (n = 6). Fourteen miRNAs were significantly altered between groups; four of these miRNAs were decreased in EoE patients. A panel of five miRNAs (miR-203, miR-375, miR-21, miR-223, and miR-142-3p) were selected for validation in an independent set of samples from control (n = 22), active disease (n = 22), inactive disease (n = 22), and gastroesophageal reflux disease (n = 6) patients. Each panel miRNA was significantly altered among groups. miRNA changes in esophageal biopsies were not reflected in the circulating RNA pool, as no differences in panel miRNA levels were observed in sera collected from the four patient groups. In addition, in contrast to previous studies, no change in esophageal miRNA levels was detected following treatment that resolved esophageal eosinophilia. In an effort to identify the ramifications of reduced esophageal miR-203, miR-203 activity was inhibited in cultured epithelial cells via expression of a tough decoy miRNA inhibitor. Luciferase reporter assays demonstrated that miR-203 does not directly regulate human IL-15 through targeting of the IL-15 3'-untranslated region. From these experiments, it is concluded that miRNAs are perturbed in the esophageal mucosa, but not the serum, of pediatric EoE patients. Further investigation is required to decipher pathologically relevant consequences of miRNA perturbation in this context. | 25,147,232 | [
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Transforming growth factor-β2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine. | A balance between pro- and anti-inflammatory signals from milk and microbiota controls intestinal homeostasis just after birth, and an optimal balance is particularly important for preterm neonates that are sensitive to necrotizing enterocolitis (NEC). We suggest that the intestinal cytokine IL-8 plays an important role and hypothesize that transforming growth factor-β2 (TGF-β2) acts in synergy with bacterial lipopolysaccharide (LPS) to control IL-8 levels, thereby supporting intestinal homeostasis. Preterm pigs were fed colostrum (containing TGF-β2) or infant formula (IF) with or without antibiotics (COLOS, n = 27; ANTI, n = 11; IF, n = 40). Intestinal IL-8 levels and NEC incidence were much higher in IF than in COLOS and ANTI pigs (P < 0.001), but IL-8 levels did not correlate with NEC severity. Intestinal TGF-β2 levels were high in COLOS but low in IF and ANTI pigs. Based on these observations, the interplay among IL-8, TGF-β2, and LPS was investigated in a porcine intestinal epithelial cell line. TGF-β2 attenuated LPS-induced IL-6, IL-1β, and TNF-α release by reducing early ERK activation, whereas IL-8 secretion was synergistically induced by LPS and TGF-β2 via NF-κB. The TGF-β2/LPS-induced IL-8 levels stimulated cell proliferation and migration following epithelial injury, without continuous NF-κB activation and cyclooxygenase-2 expression. We suggest that a combined TGF-β2-LPS induction of IL-8 stimulates epithelial repair just after birth when the intestine is first exposed to colonizing bacteria and TGF-β2-containing milk. Moderate IL-8 levels may act to control intestinal inflammation, whereas excessive IL-8 production may enhance the damaging proinflammatory cascade leading to NEC. | 25,147,235 | [
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The utility of genotypic tropism testing in clinical practice. | A review of a large number of HIV-1 tropism test requests (n = 1148) performed at a London tertiary referral centre was carried out. The aim was to establish whether these were being performed in line with recommendations from published guidelines and whether this represented the most cost-effective use of these tests in informing prescribing decisions of the CCR5 antagonist drug, maraviroc. The cost of these assays within the UK was covered by commercial funding until April 2013 which has subsequently been withdrawn. Furthermore, all healthcare settings are under increasing cost constraints and hence establishing the real utility and appropriate use of these tests is of vital importance. | 25,147,237 | [
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Thermoregulatory strategy may shape immune investment in Drosophila melanogaster. | As temperatures change, insects alter the amount of melanin in their cuticle to improve thermoregulation. However, melanin is also central to insect immunity, suggesting that thermoregulatory strategy may indirectly impact immune defense by altering the abundance of melanin pathway components (a hypothesis we refer to as thermoregulatory-dependent immune investment). This may be the case in the cricket Allonemobius socius, where warm environments (both seasonal and geographical) produced crickets with lighter cuticles and increased pathogen susceptibility. Unfortunately, the potential for thermoregulatory strategy to influence insect immunity has not been widely explored. Here we address the relationships between temperature, thermoregulatory strategy and immunity in the fruit fly Drosophila melanogaster. To this end, flies from two separate Canadian populations were reared in either a summer- or autumn-like environment. Shortly after adult eclosion, flies were moved to a common environment where their cuticle color and susceptibility to a bacterial pathogen (Pseudomonas aeruginosa) were measured. As with A. socius, individuals from summer-like environments exhibited lighter cuticles and increased pathogen susceptibility, suggesting that the thermoregulatory-immunity relationship is evolutionarily conserved across the hemimetabolous and holometabolous clades. If global temperatures continue to rise as expected, then thermoregulation might play an important role in host infection and mortality rates in systems that provide critical ecosystem services (e.g. pollination), or influence the prevalence of insect-vectored disease (e.g. malaria). | 25,147,243 | [
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N-Acetylcysteine Ameliorates Experimental Autoimmune Myocarditis in Rats via Nitric Oxide. | Oxidative stress may play an important role in the development of myocarditis. We investigated the effects of N-acetylcysteine (NAC), a potent antioxidant, on experimental autoimmune myocarditis (EAM) in rats. A rat model of porcine myosin-induced EAM was used. After the immunization with myosin, NAC (20 mg/kg/d) or saline was injected intraperitoneally on days 1 to 21. Additional myosin-immunized rats treated with NAC were orally given 25 mg/kg/d of N(G)-nitro-l-arginine methylester (l-NAME), an inhibitor of nitric oxide (NO) synthase, and N(G)-nitro-d-arginine methylester (d-NAME), an inactive enantiomer. The NAC treatment improved cardiac pathology associated with reduced superoxide production. In the EAM rats treated with NAC associated with oral l-NAME, but not with oral d-NAME, the severity of myocarditis was not reduced. Expression of intercellular adhesion molecule 1 was reduced by NAC treatment. Myocardial c-kit(+) cells were demonstrated only in the NAC-treated group. Hemodynamic study showed that the increased left ventricular mass produced by myocardial inflammation tended to be reduced by NAC treatment. Treatment with NAC ameliorated myocardial injury via NO system in a rat model of myocarditis. | 25,147,347 | [
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Flaws in evaluations of social programs: illustrations from randomized controlled trials. | This article describes eight flaws that occur in impact evaluations. The eight flaws are grouped into four categories on how they affect impact estimates: statistical imprecision; biases; failure of impact estimates to measure effects of the planned treatment; and flaws that result from weakening an evaluation design. Each flaw is illustrated with examples from social experiments. Although these illustrations are from randomized controlled trials (RCTs), they can occur in any type of evaluation; we use RCTs to illustrate because people sometimes assume that RCTs might be immune to such problems. A summary table lists the flaws, indicates circumstances under which they occur, notes their potential seriousness, and suggests approaches for minimizing them. Some of the flaws result in minor hurdles, while others cause evaluations to fail-that is, the evaluation is unable to provide a valid test of the hypothesis of interest. The flaws that appear to occur most frequently are response bias resulting from attrition, failure to adequately implement the treatment as designed, and too small a sample to detect impacts. The third of these can result from insufficient marketing, too small an initial target group, disinterest on the part of the target group in participating (if the treatment is voluntary), or attrition. To a considerable degree, the flaws we discuss can be minimized. For instance, implementation failures and too small a sample can usually be avoided with sufficient planning, and response bias can often be mitigated-for example, through increased follow-up efforts in conducting surveys. | 25,147,355 | [
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PyBamView: a browser-based application for viewing short read alignments. | Current sequence alignment browsers allow visualization of large and complex next-generation sequencing datasets. However, most of these tools provide inadequate display of insertions and can be cumbersome to use on large datasets. I implemented PyBamView, a lightweight Web application for visualizing short read alignments. It provides an easy-to-use Web interface for viewing alignments across multiple samples, with a focus on accurate visualization of insertions. PyBamView is available as a standard python package. The source code is freely available under the MIT license at https://mgymrek.github.io/pybamview. | 25,147,359 | [
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Bullying in the clinical training of pharmacy students. | To determine whether bullying is a significant factor in the clinical training of pharmacy students. The literature as well as the Accreditation Council for Pharmacy Education (ACPE) Standards and American Association of Colleges of Pharmacy (AACP) surveys were reviewed for mention and/or measurement of bullying behaviors in the clinical training of pharmacy students. The authors used a Delphi process to define bullying behavior. The consensus definition was used to analyze 2,087 in-house student evaluations of preceptors for evidence of bullying behaviors. The authors mapped strings of text from in-house student comments to different, established categories of bullying behaviors. The ACPE Standards and AACP surveys contained no mention or measures of bullying. The 2013 AACP survey data reported overwhelmingly positive preceptor ratings. Of the 2,087 student evaluations of preceptors, 119 (5.7%) had at least 1 low rating. Within those 119 survey instruments, 34 comments were found describing bullying behaviors. Students' responses to the AACP survey were similar to data from the national cohort. Given the evidence that bullying behaviors occur in pharmacy education and that bullying has long-term and short-term damaging effects, more attention should be focused on this problem. Efforts should include addressing bullying in ACPE Standards and AACP survey tools developing a consensus definition for bullying and conducting more research into bullying in the clinical training of pharmacy students. | 25,147,389 | [
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Implementation of an integrated longitudinal curricular activity for graduating pharmacy students. | To evaluate whether a novel integrated longitudinal curricular activity to prepare graduating doctor of pharmacy (PharmD) students for 2 comprehensive examinations was successful, and to assess whether it engaged other pharmacy students in curricular discussion and learning. Thirty-eight of 91graduating third-year (P3) students in a PharmD program formed 11 teams to create and present pharmacotherapeutic posters to their peers. The impact of the novel activity on graduating students' performance on the North American Pharmacist Licensure Examination (NAPLEX) and a comprehensive commercial examination was assessed. All first-year (P1), second-year (P2), and P3 students reviewed and discussed the content of each poster. Participants in the integrated longitudinal curricular activity performed better than nonparticipants on the commercial examination (p=0.023) and NAPLEX (p=0.033). However, regardless of participation, commercial examination scores predicted a significant amount of variance (ie, 34%) in NAPLEX scores. The P3 participants (83%) believed the curricular activity assisted them in their NAPLEX preparation, while 75% of P1 students, 79% of P2 students, and 80% of P3 students agreed that poster review provided an effective summary of different disease states. Ninety percent of faculty poster evaluators reported that the posters were professional, and all evaluators agreed that participants effectively conveyed their message to the intended audience. The integrated longitudinal curricular activity provided a positive learning environment for all pharmacy students and may have better prepared graduating students' for the NAPLEX. | 25,147,396 | [
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Advanced screencasting with embedded assessments in pathophysiology and therapeutics course modules. | To implement and assess the effectiveness of a hybrid learning model using advanced screencasting with embedded assessments in pathophysiology and therapeutics modules. Two pathophysiology and therapeutics course modules on viral hepatitis and the clinical pharmacokinetics of aminoglycosides were chosen for study. The preclass portion of the hybrid model involved student completion of interactive e-lectures that were created with the use of advanced screencasting and included embedded assessments. Students viewed the e-lectures and completed the assessment questions prior to in-class lecture. Preimplementation and postimplementation test scores were compared and student survey data were analyzed. Test scores improved significantly and students' perceptions of the learning method were favorable. Test scores improved most significantly on higher-level Bloom's taxonomy questions. A hybrid model that used advanced screencasting with embedded assessments offered a novel method to afford students active-learning opportunities to progress to higher cognitive domains of learning. | 25,147,400 | [
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Two Decades of Stability and Change in Age at First Union Formation. | The landscape of union formation has been shifting; Americans are now marrying at the highest ages on record and the majority of young adults have cohabited. Yet little attention has been paid to the timing of cohabitation relative to marriage. Using the National Survey of Families and Households and 4 cycles of the National Survey of Family Growth, the authors examined the timing of marriage, cohabitation, and unions over 20 years. As the median age at first marriage has climbed, the age at cohabitation has remained stable for men and women. The changes in the timing of union formation have been similar according to race/ethnicity. The marked delay in marriage among women and men with low educational attainment has resulted in a near-convergence in the age at first marriage according to education. The authors conclude that the rise in cohabitation has offset changes in the levels and timing of marriage. | 25,147,410 | [
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Asymmetric oxidative dearomatizations promoted by hypervalent iodine(III) reagents: an opportunity for rational catalyst design? | The use of and λ<sup3</sup- and λ<sup5</sup-iodanes in the oxidative dearomatization of phenols is a well-established and general procedure for the construction of cyclohexadienone structures. However, their use in asymmetric dearomatization reactions is quite underdeveloped and, despite work by several research groups over the past several years, a general chiral aryl iodide catalyst has yet to emerge. This article will serve to highlight the significant progress that has been made in this area and will reveal some of deficiencies in the literature that the author believes may be hindering further progress. | 25,147,412 | [
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The surface density gradient of grafted poly (ethylene glycol): preparation, characterization and protein adsorption. | A surface density gradient of grafted poly (ethylene glycol) (PEG) chains was prepared using two-phase silanization of a flat silica surface. The first step was to create the surface density gradient of isocyanatopropyldimethylsilyl groups and to hydrolyze the isocyanato moiety into an amine. These surface amines were reacted with an excess of aldehyde-terminated PEG. The PEG-silica surface was characterized by dynamic contact angle measurements, X-ray photoelectron spectroscopy and ellipsometry. The length of the PEG gradient region was approximately 7 mm and the thickness in air ranged from zero to 1.1 nm. The maximum surface density of the PEG layer, as calculated from ellipsometric data, amounted to an average 0.4 PEG (molecular weight <iM</i<subw</sub = 2000 Da) molecule nm<sup-2</sup, while the surface density average of the amine groups was 1.4 molecules nm<sup-2</sup, indicating that only a fraction of the surface amines reacted with aldehyde-terminated PEG. The PEG segment density profile in the gradient PEG region was computed by a self-consistent mean field theory. The PEG (<iM</i<subw</sub = 2000 Da) segments profile was not parabolic, but showed a thin depletion zone next to the surface. The influence of the surface density of the grafted PEG chains on protein repellence was tested by the adsorption of fibrinogen from solution and from a ternary protein solution mixture containing fibrinogen, albumin and immunoglobulin G. Fibrinogen adsorption onto the silica end of the gradient was extremely low, both in the presence of the other two proteins and in their absence. As the surface density of the grafted PEG chains increased, so did the fibrinogen adsorption (up to 0.024 μg cm<sup-2</sup). It is not clear whether this low fibrinogen adsorption resulted from the interactions of the protein with the grafted PEG chains or with residual surface amines that were available due to some imperfections in the grafted PEG layer. | 25,147,429 | [
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The effects of amphiregulin induced MMP-13 production in human osteoarthritis synovial fibroblast. | Osteoarthritis (OA) belongs to a group of degenerative diseases. Synovial inflammation, cartilage abrasion, and subchondral sclerosis are characteristics of OA. Researchers do not fully understand the exact etiology of OA. However, matrix metalloproteinases (MMPs), which are responsible for cartilage matrix degradation, play a pivotal role in the progression of OA. Amphiregulin (AREG) binds to the EGF receptor (EGFR) and activates downstream proteins. AREG is involved in a variety of pathological processes, such as the development of tumors, inflammatory diseases, and rheumatoid arthritis. However, the relationship between AREG and MMP-13 in OA synovial fibroblasts (SFs) remains unclear. We investigated the signaling pathway involved in AREG-induced MMP-13 production in SFs. AREG caused MMP-13 production in a concentration- and time-dependent manner. The results of using pharmacological inhibitors and EGFR siRNA to block EGFR revealed that the EGFR receptor was involved in the AREG-mediated upregulation of MMP-13. AREG-mediated MMP-13 production was attenuated by PI3K and Akt inhibitors. The stimulation of cells by using AREG activated p65 phosphorylation and p65 translocation from the cytosol to the nucleus. Our results provide evidence that AREG acts through the EGFR and activates PI3K, Akt, and finally NF-kappaB on the MMP-13 promoter, thus contributing to cartilage destruction during osteoarthritis. | 25,147,440 | [
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Revision of the genus Hemisaprinus Kryzhanovskij, 1976 (Coleoptera, Histeridae, Saprininae). | The monophyletic genus Hemisaprinus Kryzhanovskij in Kryzhanovskij & Reichardt, 1976 is revised herein. All three species Hemisaprinus subvirescens (Ménétries, 1832), H. lutshniki (Reichardt, 1941) and H. cyprius (Dahlgren, 1981) are found to be correctly assigned to the genus and their monophyly is supported by the synapomorphy of the presence of prosternal foveae. The three species are re-described and supplemented with colour photographs as well as SEM micrographs outlining their differences. Male genitalia drawing of H. subvirescens and H. lutshniki are provided and a key to the species is given. Hemisaprinus subvirescens (Ménétries, 1832) is newly reported from Armenia, Azerbaijan, Kyrgyzstan, Uzbekistan, Turkmenistan, Tajikistan, Jordan, Cyprus and Mongolia. The lectotypes and paralectotypes of the following species are designated herein: Saprinus foveisternus Schmidt, 1884, Saprinus syriacus Marseul, 1855 and Saprinus viridulus Marseul, 1855. | 25,147,473 | [
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A Randomised Controlled Trial Comparing the Impact of Yoga and Physical Education on the Emotional and Behavioural Functioning of Middle School Children. | Yoga programs geared for school children have become more widespread, but research regarding its impact on children is lacking. Several studies have reported positive outcomes, though there is a need for more randomised controlled trials. To determine the effects of yoga on children's emotional and behavioural functioning when compared with physical education (PE) classes. Thirty middle school children were randomised to participate in either a school-based Ashtanga-informed yoga or PE class three times a week for 12 weeks. Emotional (i.e. affect, self-perceptions) and behavioural (i.e. internalising and externalising problems, aggression) functioning were measured pre and post-intervention. There were no significant changes between groups in self-reported positive affect, global self-worth, aggression indices or parent reports of their children's externalising and internalising problems. However, negative affect increased for those children participating in yoga when compared to the PE program. In general, findings suggest that yoga and PE classes do not differentially impact on middle school children's emotional and behavioural functioning. However, children reported experiencing increased negative emotions after receiving yoga while children in the PE group reported a decrease in these feelings. Implications of these results and potential directions for future research on children's yoga are discussed. | 25,147,479 | [
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Estimation of whole body fat from appendicular soft tissue from peripheral quantitative computed tomography in adolescent girls. | Assess the utility of peripheral quantitative computed tomography (pQCT) for estimating whole body fat in adolescent girls. Our sample included 458 girls (aged 10.7 ± 1.1y, mean BMI = 18.5 ± 3.3 kg/m<sup2</sup) who had DXA scans for whole body percent fat (DXA %Fat). Soft tissue analysis of pQCT scans provided thigh and calf subcutaneous percent fat and thigh and calf muscle density (muscle fat content surrogates). Anthropometric variables included weight, height and BMI. Indices of maturity included age and maturity offset. The total sample was split into validation (VS; n = 304) and cross-validation (CS; n = 154) samples. Linear regression was used to develop prediction equations for estimating DXA %Fat from anthropometric variables and pQCT-derived soft tissue components in VS and the best prediction equation was applied to CS. Thigh and calf SFA %Fat were positively correlated with DXA %Fat (r = 0.84 to 0.85; <ip</i <0.001) and thigh and calf muscle densities were inversely related to DXA %Fat (r = -0.30 to -0.44; <ip</i < 0.001). The best equation for estimating %Fat included thigh and calf SFA %Fat and thigh and calf muscle density (adj. R<sup2</sup = 0.90; SEE = 2.7%). Bland-Altman analysis in CS showed accurate estimates of percent fat (adj. R<sup2</sup = 0.89; SEE = 2.7%) with no bias. Peripheral QCT derived indices of adiposity can be used to accurately estimate whole body percent fat in adolescent girls. | 25,147,482 | [
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Learning Stimulus-Location Associations in 8- and 11-Month-Old Infants: Multimodal versus Unimodal Information. | Research on the influence of multimodal information on infants' learning is inconclusive. While one line of research finds that multimodal input has a negative effect on learning, another finds positive effects. The present study aims to shed some new light on this discussion by studying the influence of multimodal information and accompanying stimulus complexity on the learning process. We assessed the influence of multimodal input on the trial-by-trial learning of 8- and 11-month-old infants. Using an anticipatory eye movement paradigm, we measured how infants learn to anticipate the correct stimulus-location associations when exposed to visual-only, auditory-only (unimodal), or auditory and visual (multimodal) information. Our results show that infants in both the multimodal and visual-only conditions learned the stimulus-location associations. Although infants in the visual-only condition appeared to learn in fewer trials, infants in the multimodal condition showed better anticipating behavior: as a group, they had a higher chance of anticipating correctly on more consecutive trials than infants in the visual-only condition. These findings suggest that effects of multimodal information on infant learning operate chiefly through effects on infants' attention. | 25,147,483 | [
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Synthesis, spectral characterization, and biological evaluation of transition metal complexes of bidentate N, o donor schiff bases. | New series of three bidentate N, O donor type Schiff bases (L (1) )-(L (3) ) were prepared by using ethylene-1,2-diamine with 5-methyl furfural, 2-anisaldehyde, and 2-hydroxybenzaldehyde in an equimolar ratio. These ligands were further complexed with Co(II), Cu(II), Ni(II), and Zn(II) metals to produce their new metal complexes having an octahedral geometry. These compounds were characterized on the basis of their physical, spectral, and analytical data. Elemental analysis and spectral data of the uncomplexed ligands and their metal(II) complexes were found to be in good agreement with their structures, indicating high purity of all the compounds. All ligands and their metal complexes were screened for antimicrobial activity. The results of antimicrobial activity indicated that metal complexes have significantly higher activity than corresponding ligands. This higher activity might be due to chelation process which reduces the polarity of metal ion by coordinating with ligands. | 25,147,493 | [
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Oxytocin in the medial prefrontal cortex regulates maternal care, maternal aggression and anxiety during the postpartum period. | The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiety. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum, but not virgin, females. In addition, OTR blockade in the postpartum mPFC impaired maternal care behaviors and enhanced maternal aggression. Overall, these results suggest that OT in the mPFC modulates maternal care and aggression, as well as anxiety-like behavior, during the postpartum period. Although the relationship among these behaviors is complicated and further investigation is required to refine our understanding of OT actions in the maternal mPFC, these data nonetheless provide new insights into neural circuitry of OT-mediated postpartum behaviors. | 25,147,513 | [
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Cardiac magnetic resonance and computed tomography angiography for clinical imaging of stable coronary artery disease. Diagnostic classification and risk stratification. | Despite advances in the pharmacologic and interventional treatment of coronary artery disease (CAD), atherosclerosis remains the leading cause of death in Western societies. X-ray coronary angiography has been the modality of choice for diagnosing the presence and extent of CAD. However, this technique is invasive and provides limited information on the composition of atherosclerotic plaque. Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have emerged as promising non-invasive techniques for the clinical imaging of CAD. Hereby, CCTA allows for visualization of coronary calcification, lumen narrowing and atherosclerotic plaque composition. In this regard, data from the CONFIRM Registry recently demonstrated that both atherosclerotic plaque burden and lumen narrowing exhibit incremental value for the prediction of future cardiac events. However, due to technical limitations with CCTA, resulting in false positive or negative results in the presence of severe calcification or motion artifacts, this technique cannot entirely replace invasive angiography at the present time. CMR on the other hand, provides accurate assessment of the myocardial function due to its high spatial and temporal resolution and intrinsic blood-to-tissue contrast. Hereby, regional wall motion and perfusion abnormalities, during dobutamine or vasodilator stress, precede the development of ST-segment depression and anginal symptoms enabling the detection of functionally significant CAD. While CT generally offers better spatial resolution, the versatility of CMR can provide information on myocardial function, perfusion, and viability, all without ionizing radiation for the patients. Technical developments with these 2 non-invasive imaging tools and their current implementation in the clinical imaging of CAD will be presented and discussed herein. | 25,147,526 | [
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The development of sensorimotor influences in the audiovisual speech domain: some critical questions. | Speech researchers have long been interested in how auditory and visual speech signals are integrated, and the recent work has revived interest in the role of speech production with respect to this process. Here, we discuss these issues from a developmental perspective. Because speech perception abilities typically outstrip speech production abilities in infancy and childhood, it is unclear how speech-like movements could influence audiovisual speech perception in development. While work on this question is still in its preliminary stages, there is nevertheless increasing evidence that sensorimotor processes (defined here as any motor or proprioceptive process related to orofacial movements) affect developmental audiovisual speech processing. We suggest three areas on which to focus in future research: (i) the relation between audiovisual speech perception and sensorimotor processes at birth, (ii) the pathways through which sensorimotor processes interact with audiovisual speech processing in infancy, and (iii) developmental change in sensorimotor pathways as speech production emerges in childhood. | 25,147,528 | [
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Social values as arguments: similar is convincing. | Politicians, philosophers, and rhetors engage in co-value argumentation: appealing to one value in order to support another value (e.g., "equality leads to freedom"). Across four experiments in the United Kingdom and India, we found that the psychological relatedness of values affects the persuasiveness of the arguments that bind them. Experiment 1 found that participants were more persuaded by arguments citing values that fulfilled similar motives than by arguments citing opposing values. Experiments 2 and 3 replicated this result using a wider variety of values, while finding that the effect is stronger among people higher in need for cognition and that the effect is mediated by the greater plausibility of co-value arguments that link motivationally compatible values. Experiment 4 extended the effect to real-world arguments taken from political propaganda and replicated the mediating effect of argument plausibility. The findings highlight the importance of value relatedness in argument persuasiveness. | 25,147,529 | [
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The intimate relationship between human cytomegalovirus and the dendritic cell lineage. | Primary infection of healthy individuals with human cytomegalovirus (HCMV) is normally asymptomatic but results in the establishment of a lifelong infection of the host. One important cellular reservoir of HCMV latency is the CD34+ haematopoietic progenitor cells resident in the bone marrow. Viral gene expression is highly restricted in these cells with an absence of viral progeny production. However, cellular differentiation into mature myeloid cells is concomitant with the induction of a full lytic transcription program, DNA replication and, ultimately, the production of infectious viral progeny. Such reactivation of HCMV is a major cause of morbidity and mortality in a number of immune-suppressed patient populations. Our current understanding of HCMV carriage and reactivation is that cellular differentiation of the CD34+ progenitor cells through the myeloid lineage, resulting in terminal differentiation to either a macrophage or dendritic cell (DC) phenotype, is crucial for the reactivation event. In this mini-review, we focus on the interaction of HCMV with DCs, with a particular emphasis on their role in reactivation, and discuss how the critical regulation of viral major immediate-early gene expression appears to be delicately entwined with the activation of cellular pathways in differentiating DCs. Furthermore, we also explore the possible immune consequences associated with reactivation in a professional antigen presenting cell and potential countermeasures HCMV employs to abrogate these. | 25,147,545 | [
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Approaches to identify genetic variants that influence the risk for onset of fragile X-associated primary ovarian insufficiency (FXPOI): a preliminary study. | Fragile X-associated primary ovarian insufficiency (FXPOI) is due to an X-linked mutation that results from the expansion of a CGG repeat sequence located in the 5' untranslated region of the FMR1 gene (premutation, PM). About 20% of women who carry the PM have cessation of menses before age 40, a clinical condition known as premature ovarian failure (POF). This leads to a 20-fold increased risk over women in the general population. Thus, this single gene mutation has a major effect on reducing a woman's reproductive life span. Based on survival analysis of about 1300 women, we showed that the mean age at menopause among PM carriers is reduced compared with noncarriers, even after removing women who reported POF. This suggests that the majority of women with the PM, not just a subset, experience ovarian insufficiency earlier than noncarriers. To better understand the underlying mechanism of the PM and to identify genes that modify the variable expressivity of FXPOI, we conducted two pilot studies. The first focused on five common variants known to reduce age at menopause. We genotyped these SNPs in 72 women with a PM who experienced menopause and found a significant association with the total SNP risk burden and age at menopause. This suggests that these SNPs influence onset of FXPOI, after adjusting for the effect of the PM allele. In the second approach, we conducted whole genome sequencing on 10 PM carriers, five with onset of FXPOI prior to age 30 and five who experienced menopause after age 47 years. Although only a pilot study, we describe our preliminary approach to identify potential variants that may play a role in modifying onset of FXPOI and potentially play a role in idiopathic primary ovarian insufficiency. The overarching goal of both approaches is to identify predictor variants that may identify women predisposed to early onset FXPOI and to further identify genes involved in defining a woman's reproductive life span. | 25,147,555 | [
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Plasma Interleukin-10: A Likely Predictive Marker for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure. | The pathogenesis of HBV-related acute-on-chronic liver failure (HBV-ACLF) is mainly based on a heightened immune-inflammatory reaction; however, the intimate underlying mechanism remains unclear. The aim of the study was to explore potential key immune molecular targets that could serve as early predictive markers for HBV-ACLF. Twenty-seven patients with acute exacerbation of chronic hepatitis B (CHB) (defined by: alanine transaminase ≥ 20 ULN, total bilirubin ≥ 5 ULN, 40% < prothrombin time activity ≤ 60%) and without cirrhosis were divided into 18 cases which did not progress to HBV-ACLF (defined by: prothrombin time activity < 40% and development within four weeks of hepatic encephalopathy and/or ascites) and nine cases that developed HBV-ACLF. Nine healthy people defined the normal control group (NC). Interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-α and IFN-γ protein levels were assayed by Cytometric Bead Array (CBA) in blood plasma. The ELISA method was applied to confirm IL-10 detection using the CBA method. IL-4, IL-12p70 and IFN-γ were undetectable; IL-1β, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher than in NC. Moreover, cytokines reached the highest levels in acute exacerbation of CHB, with the exception of IL-2 and IL-8. When comparing the HBV-ACLF patients prior to and at the time of ACLF diagnosis, IL-10 was the only cytokine that exhibited a significant decrease (P = 0.008). IL-10 concentrations were positively correlated to ALT levels (r = 0.711, P < 0.001). The assessment of plasma IL-10 levels in chronic hepatitis B acute exacerbation may provide an early predictive marker for progression to HBV-ACLF. | 25,147,572 | [
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Preceptor preferences for participating in electronic preceptor development. | New guidelines require preceptors to deliver approximately 30% of the doctor of pharmacy curricula. With preceptor's increasing responsibilities, colleges are faced with the task of training preceptors as educators. Identifying preceptor's training format preferences (i.e. electronic vs. live) should contribute to the more effective and efficient creation of training materials and programs. A preceptor training video was created and made available electronically and was distributed to 400 preceptors with a brief 2-part questionnaire about preceptor training preferences, electronic training preferences after viewing the video, and available technology resources for participating in electronic training. 38.25% of the questionnaires were returned. The majority of respondents (57%) preferred electronic to live preceptor developing training and the majority (53%) had not previously attended the live annual preceptor development conference offered by the college. 51.6% participants reviewed the electronic training video created by the OU College of Pharmacy. Of the respondents who did not watch the video, 73% cited having too little time, problems accessing the video, or technical reasons for not watching the training video. The majority of responders in all age groups preferred electronic training to face-to-face training except those ages 61-65 and the majority (55.7%) would participate in on-line training again in the future. The majority of respondents have the technical resources to participate in electronic training. Preceptors have limited time to participate in preceptor development training, although they view training as an important activity. This study reveals three main findings: (1) the majority of preceptors prefer electronic preceptor development training programs regardless of age; (2) would participate in future electronic training after having participated in electronic training; and (3) have the available resources to participate in electronic training. Future preceptor development programs should have flexible formats to accommodate preferences for live and electronic programming. | 25,147,592 | [
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Identification of novel phenyl butenonyl C-glycosides with ureidyl and sulfonamidyl moieties as antimalarial agents. | A new series of C-linked phenyl butenonyl glycosides bearing ureidyl(thioureidyl) and sulfonamidyl moieties in the phenyl rings were designed, synthesized, and evaluated for their in vitro antimalarial activities against Plasmodium falciparum 3D7 (CQ sensitive) and K1 (CQ resistant) strains. Among all the compounds screened the C-linked phenyl butenonyl glycosides bearing sulfonamidyl moiety (5a) and ureidyl moiety in the phenyl ring (7d and 8c) showed promising antimalarial activities against both 3D7 and K1 strains with IC50 values in micromolar range and low cytotoxicity offering new HITS for further exploration. | 25,147,607 | [
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Fluorescent Probes for Subcellular Localization during Osteclast Formation. | Labeling of a small bioactive molecule with fluorescent probe has been becoming an essential tool in cell biology to reveal the subcellular distribution and the location of a molecular target. QOA-8a is a novel molecule with potent antiosteoporotic effect in vivo. To investigate the molecular mechanism of QOA-8a, novel fluorescence-tagged chemical probes as bioactive as their parent molecule were designed and synthesized. The fluorescent compound 12 showed a more potent inhibitory activity on RANKL-induced osteoclastogenesis at 2 μM compared with that of QOA-8a. Microscopy experiments revealed that almost all of probe 12 accumulated in the fusing region, with little in the osteoclast precursors or the mature osteoclasts during osteoclast formation. The result suggests the location of the binding target of QOA-8a, which might greatly narrow down the search field of the target protein(s). | 25,147,613 | [
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Discovery and structure-based optimization of adenain inhibitors. | The cysteine protease adenain is the essential protease of adenovirus and, as such, represents a promising target for the treatment of ocular and other adenoviral infections. Through a concise two-pronged hit discovery approach we identified tetrapeptide nitrile 1 and pyrimidine nitrile 2 as complementary starting points for adenain inhibition. These hits enabled the first high-resolution X-ray cocrystal structures of adenain with inhibitors bound and revealed the binding mode of 1 and 2. The screening hits were optimized by a structure-guided medicinal chemistry strategy into low nanomolar drug-like inhibitors of adenain. | 25,147,618 | [
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Cytotaxonomy of two species of genus Chrysolaena H. Robinson, 1988 (Vernonieae, Asteraceae) from Northeast Paraguay. | Chromosome counts and karyotypes of two species of Chrysolaena H. Robinson 1988 are presented in this paper. Mitotic analysis revealed that both taxa have x=10, a basic chromosome number considered characteristic of the genus. The chromosome number and the karyotype of Chrysolaena cristobaliana are reported for the first time, as well as a new cytotype and the karyotype of Chrysolaena sceptrum. Chrysolaena cristobaliana showed heptaploid cytotype with 2n=7x=70 and a karyotype composed of 46 m + 24 sm chromosomes. On the other hand, Chrysolaena sceptrum presented tetraploid cytotype with 2n=4x=40 and a karyotype with 30 m + 10 sm chromosomes. Accessory chromosomes were observed in cells of both species. The chromosome analysis showed that these species differ in the chromosome number and the total chromosome length, although they showed similar chromosome morphology and asymmetry indexes. The results support the use of chromosome data in taxonomic treatments of the American members of the tribe Vernonieae. | 25,147,624 | [
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Chronic pain patients with possible co-morbid post-traumatic stress disorder admitted to multidisciplinary pain rehabilitation-a 1-year cohort study. | Although post-traumatic stress disorder (PTSD) is a common co-morbidity in chronic pain, little is known about the association between PTSD and pain in the context of chronic pain rehabilitation. The aim of the present study was two-fold: (1) to investigate the association of a possible PTSD diagnosis with symptoms of pain, physical and mental functioning, as well as the use of opioids, and (2) to compare the outcome of multidisciplinary chronic pain rehabilitation for patients with a possible PTSD diagnosis at admission with patients without PTSD at admission. A consecutively referred cohort of 194 patients completed a baseline questionnaire at admission covering post-traumatic stress, pain symptoms, physical and mental functioning, as well as self-reported sleep quality and cognitive difficulties. Medication use was calculated from their medical records. A total of 95 were admitted to further multidisciplinary treatment and included in the outcome study. A high prevalence of possible PTSD was found (26.3%). Patients with possible co-morbid PTSD experienced significantly poorer general and mental health, poorer sleep quality, and more cognitive problems as well as inferior social functioning compared to patients without PTSD. Possible co-morbid PTSD did not result in higher use of opioids or sedatives. Surprisingly, possible co-morbid PTSD at admission was not associated with lower levels of symptom reduction from pre- to post-treatment. Possible co-morbid PTSD in chronic pain is a major problem associated with significantly poorer functioning on several domains. Nevertheless, our results indicate that pain-related symptoms could be treated with success despite possible co-morbid PTSD. However, since PTSD was only measured at admission it is not known whether rehabilitation actually reduced PTSD. | 25,147,628 | [
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Antibody-mediated immunity induced by engineered Escherichia coli OMVs carrying heterologous antigens in their lumen. | Outer membrane vesicles (OMVs) from Gram-negative bacteria are gaining increasing attention as vaccine platform for their built-in adjuvanticity and for their potential use as carriers of heterologous antigens. These 2 properties offer the opportunity to make highly effective, easy to produce multi-valent vaccines. OMVs can be loaded with foreign antigens by targeting protein expression either to the outer membrane or to the periplasm of the OMV-producing strain. Periplasmic expression is simple and relatively efficient but leads to the accumulation of recombinant antigens in the lumen of OMVs and the ability of OMVs carrying internalized antigens to induce antigen-specific antibody responses has been only marginally investigated and is considered to be sub-optimal. We have systematically analyzed in qualitative and quantitative terms antibody responses induced by OMVs carrying different heterologous antigens in their lumen. Group A Streptococcus (GAS) Slo, SpyCEP, Spy0269 and Group B Streptococcus (GBS) SAM_1372 were fused to the OmpA leader sequence for secretion and expressed in Escherichia coli. OMVs from the recombinant strains were purified and tested for immunogenicity and protective activity. All proteins were incorporated into the OMVs lumen in their native conformation. Upon mice immunization, OMVs induced high functional antibody titers against the recombinant proteins. Furthermore, immunization with Slo-OMVs and SpyCEP-OMVs protected mice against GAS lethal challenge. The efficiency of antigen delivery to the vesicular lumen via periplasmic expression, and the surprisingly high immunogenicity and protective activity of OMVs carrying internalized recombinant antigens further strengthens the potential of OMVs as vaccine platform. | 25,147,647 | [
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Severe falciparum malaria in iran: a very rare case from an endemic region. | Malaria is a protozoal disease, transmitted to humans by female Anopheles mosquito bite. Plasmodium falciparum, compared to other kinds of Plasmodium, causes more severe malaria and is associated with a higher mortality rate. Annually, one to three million deaths occur due to malaria, especially by P. falciparum. In this report, we introduce an Iranian patient suffering from P. falciparum. Peripheral blood smear for malaria parasites showed severe infection of P. falciparum, with 75 to 85 percent of red blood cells containing one to five parasites per cell. However, the patient revealed a fast response to treatment and a good prognosis, suggesting a high level of relative immunity in the patient. To confirm this hypothesis, we conducted a comparative study by comparing the rate of clinical response to treatment as well as the level of prognosis of our patient with similar patients from different regions around the world. These included some malaria cases (caused by P. falciparum) chosen from endemic and nonendemic regions, such as Africa, South Europe and Canada. The findings revealed that generally, patients from endemic regions significantly show a greater response to treatment and also a better prognosis in comparison to the patients from nonendemic regions. These differences can plausibly be attributed to a high level of relative immunity in endemic regions. Consequently, we would strongly support the hypothesis that response to treatment and prognosis of malaria is a matter of patients' living environment circumstances. In other words, people who live in endemic regions acquire a high relative immunity leading to a greater response to treatment and a better prognosis. | 25,147,660 | [
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Eradication of Pseudomonas aeruginosa Biofilms Using the Combination of n-butanolic Cyclamen coum Extract and Ciprofloxacin. | Biofilm formation is a major pathogenic factor in different bacteria such as Pseudomonas aeruginosa. A number of studies have reported that bacterial biofilms show different levels of antibiotic resistance. In order to re-sensitize the bacterial biofilms to antibiotics, biofilms should be dispersed. In this study, the effect of n-butanolic Cyclamen coum extract in combination with ciprofloxacin was examined on one, three and five day old P. aeruginosa biofilms. The synergistic effect of n-butanolic C. coum extract and ciprofloxacin towards dispersing pre-established P. aeruginosa biofilms was also studied. The ability of biofilm formation by six different P. aeruginosa strains was confirmed by microtiter plate method and PCR assay for the cupA gene. The extraction of C. coum tubers was achieved by fractionation method using different solvents. The minimum inhibitory concentration (MIC) of n-butanolic C. coum extract and ciprofloxacin against planktonic cells was evaluated using agar well diffusion and microdilution methods. The microdilution chequerboard method was used to determine the fractional biofilm eradication concentration index (FBCI), when the combination of n-butanolic C. coum extract and ciprofloxacin were used against P. aeruginosa biofilms. The ability of biofilm formation by P. aeruginosa strains was quantitatively confirmed. The PCR method confirmed the existence of cup A gene (172 bp) in all studied strains. Saponin content of the n-butanolic C. coum extract was 156 µg/mL. The extract revealed antibacterial activity against planktonic cells of P. aeruginosa strains. The results showed that one and three day old biofilms are affected by either ciprofloxacin or n-butanolic C. coum extract. However, n-butanolic C. coum extract in combination with ciprofloxacin was significantly more effective against P. aeruginosa biofilms. Using n-butanolic C. coum extract in combination with ciprofloxacin offers a novel strategy to control biofilm-based infections caused by P. aeruginosa. | 25,147,668 | [
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Production and Screening of High Yield Avermectin B1b Mutant of Streptomyces avermitilis 41445 Through Mutagenesis. | Secondary metabolite production from wild strains is very low for economical purpose therefore certain strain improvement strategies are required to achieve hundred times greater yield of metabolites. Most important strain improvement techniques include physical and chemical mutagenesis. Broad spectrum mutagenesis through UV irradiation is the most important and convenient physical method. The present study was conducted for enhanced production of avermectin B1b from Streptomyces avermitilis 41445 by mutagenesis using ultraviolet (UV) radiation, ethidium bromide (EB), and ethyl methanesulfonate (EMS) as mutagens. S. avermitilis DSM 41445 maintained on yeast extract malt extract glucose medium (YMG) was used as inoculum for SM2 fermentation medium. Spores of S. avermitilis DSM 41445 were exposed to UV radiation for physical broad spectrum mutagenesis and to EMS and EB for chemical mutagenesis. For each mutagen, the lethality rate and mutation rate were calculated along with positive mutation rate. Avermectin B1b-hyper-producing mutant, produced using these three different methods, was selected according to the HPLC results. The mutant obtained after 45 minutes of UV radiation to the spores of S. avermitilis 41445, was found to be the best mutant for the enhanced production of avermectin B1b component (254.14 mg/L). Other avermectin B1b-hyper-producing mutants, were obtained from EMS (1 µL/mL) and EB (30 µL/mL) treatments, and yielded 202.63 mg/L and 199.30 mg/L of B1b, respectively. The hereditary stability analysis of the UV mentioning 45 minutes revealed the UV exposure time for mutants and 3 represented the colony taken from the plate irradiated for 45 minutes mutant showed that the production of avermectin B1b remained constant and no reverse mutation occurred after 15 generations. | 25,147,669 | [
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Evaluating the Efficacy of Achillea millefolium and Thymus vulgaris Extracts Against Newcastle Disease Virus in Ovo. | Nowadays natural products such as pure compounds and plant extract scan provide unlimited opportunities for new antiviral drugs. Newcastle disease virus (NDV) is one of the most important viral diseases in poultry industry. Vaccination could provide protection against NDV outbreaks, but it is not sufficient because infections by NDVs have remained frequent around the world. The current research aimed to study Achillea millefolium and Thymus vulgaris antiviral activity against Newcastle disease virus (NDV). The antiviral activity of the plants was measured by the reduction assay of viral titer, and explained by inhibition percentage (IP). Inhibition percentage was determined as 10 (1.75), which indicated the ability of the extracts to reduce the viral potency by more than 56 folds. Both plants were found effective against Newcastle disease virus. | 25,147,678 | [
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Characterization of Variations in PB2, NS1, M, Neuraminidase and Hemagglutinin of Influenza A (H3N2) Viruses in Iran. | In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. The mechanism of pathogenicity differs among these viruses. Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses. The goal of this study was to find the alterations in genes, which might be responsible in the virus pathogenesis. Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed. In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site. The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. It is important to mention that these changes were at the amino acid level and studies need to be performed on animals to investigate the significance of these findings. | 25,147,684 | [
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The rise of staphylococcal super antigens in psoriatic patients: a case-control study. | Staphylococcus aureus, the major virulence factor of hospital and community acquired infections, secretes numerous exotoxins (super antigens), which may affect immunological and inflammatory status in psoriatic skin lesion. This study is designed to compare the S. aureus super antigens level in sera of psoriatic patients with normal cases (nevus). A case control study was performed in dermatology ward of Rasoul Hospital in Tehran, IR Iran (2008 - 2010). Staphylococcal super antigens (Entrotoxin A, B, D and TSST1) were measured in serum of 41 psoriatic patients and 28 normal persons (Nevus) by ELISA. Chi square values (CI 95%, P value < 0.05) were calculated for all categorical variables. In this study 63.4% (26) of cases were male, 36.6% (15) were female. Age ranged from 4 months to 64 years old, with a mean age of 33.7 ± 15.4 years. Type of skin disease in cases: 20% (8) were inflicted by the Gutate form of the disease; 59% (23) with chronic plaque psoriasis (CPP), 7.7% (3) with erythrodermic and 12.8% (5) had other types of the disease (plaque, pustular, inverse). TSST (toxic shock syndrome toxin) was detected in 47% (20/41) of cases and in 6% (1/28) of the controls with a significant difference. (P value = 0.000) Entrotoxins (A, B, D) were detected in the sera of 48.8% (21/41) of cases; and only 6 %( 1/21) of controls, showed significant differences (P value = 0.000) positive TSST was more common in spring, and correlates with CPP type of psoriasis, but not related to patient`s gender and age. In this study, S. aureus were 25 times more in psoriatic patients. Super antigens should be first detected in the serum samples; if negative, the skin lesions should be examined by PCR especially in chronic types of disease. Adding the antibiotics against S. aureus to other conventional treatments might be helpful. It has a more important and significant role in children with acuteinfection. | 25,147,719 | [
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The Association of Virulence Determinants of Uropathogenic Escherichia coli With Antibiotic Resistance. | The emergence of antimicrobial resistant strains of Escherichia coli has raised considerable interest in understanding the diversity and epidemiology of E. coli infections in humans. Virulence factors of E. coli determine the specific infections caused by this microorganism. This study aimed to determine the prevalence of eight E. coli virulence factors and their association with antimicrobial resistance in bacteria isolated from patients with urinary tract infections (UTI). One thousand patients with UTI were enrolled in this cross-sectional study. Antimicrobial susceptibility was examined by disc diffusion method according to CLSI guidelines. After DNA extraction, the materials were probed by PCR for eight virulence factors genes, namely fimH, hly, iucC, ibeA, sfa/foc, neuC, papC, and afa genes. The frequency of virulence factors papC, afa, sfa/foc, fimH, hly, neuC, ibeA, and iucC were 53.3%, 51.7%, 53.3%, 56.7%, 23.3%, 31.7%, 20%, and 73.3%, respectively. In addition, there was a high degree resistance to cotrimoxazole and nalidixic acid while a high degree of susceptibility to nitrofurantoin was detected. There was a statistically significant association between fimH gene and resistance to ciprofloxacin (P = 0.006), nalidixic acid (P = 0.025), and cotrimoxazole (P = 0.02). Such associations were found between ibeA gene and amikacin (P = 0.02) and cotrimoxazole (P = 0.02) as well as between afa gene and gentamycin (P = 0.05). The results showed that E. coli isolated from patients with UTI had eight virulence factors with high frequencies. Moreover, these results alleged a direct connection between virulence factors and antimicrobial resistance in E. coli. | 25,147,722 | [
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Modern Multicomponent Reactions for better Drug Syntheses** | Multicomponent reaction (MCR) technology is now widely recognized for its impact on drug discovery projects and is strongly endorsed by industry as well as academia. However, still relatively few products based on MCRs are marketed or under development. This provides tremendous opportunities for organic chemists to shorten synthetic pathways thus reducing the cost-of-goods considerably. A recent example of the HCV drug Telaprevir is highlighted where introduction of two MCRs could lead to a shortening of the synthesis route by more than 50%. | 25,147,729 | [
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Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma. | We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma. | 25,147,732 | [
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Mechanical ventilation weaning in inclusion body myositis: feasibility of isokinetic inspiratory muscle training as an adjunct therapy. | Inclusion body myositis is a rare myopathy associated with a high rate of respiratory complications. This condition usually requires prolonged mechanical ventilation and prolonged intensive care stay. The unsuccessful weaning is mainly related to respiratory muscle weakness that does not promptly respond to immunosuppressive therapy. We are reporting a case of a patient in whom the use of an inspiratory muscle-training program which started after a two-week period of mechanical ventilation was associated with a successful weaning in one week and hospital discharge after 2 subsequent weeks. | 25,147,743 | [
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Anandamide inhibits breast tumor-induced angiogenesis. | Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death in women. Great advances in the treatment of primary tumors have led to a significant increment in the overall survival rates, however recurrence and metastatic disease, the underlying cause of death, are still a medical challenge. Breast cancer is highly dependent on neovascularization to progress. In the last years several anti-angiogenic drugs have been developed and administered to patients in combination with chemotherapeutic drugs. Collected preclinical evidence has proposed the endocannabinoid system as a potential target in cancer. The endocannabinoid anandamide has been reported to affect breast cancer growth at multiple levels, by inhibiting proliferation, migration and invasiveness in vitro and in vivo and by directly inhibiting angiogenesis. Aim of the present work is to investigate if anandamide is able to affect the proangiogenic phenotype of the highly invasive and metastatic breast cancer cells MDA-MB-231. We found that following anandamide treatment, MDAMB-231 cells lose their ability to stimulate endothelial cells proliferation in vitro, due to a significant inhibition of all the pro-angiogenic factors produced by these cells. This finding adds another piece of evidence to the anti-tumor efficacy of anandamide in breast cancer. | 25,147,760 | [
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Osteitis pubis: can early return to elite competition be contemplated? | In elite athletes, osteitis pubis is a common painful degenerative process of the pubic symphysis and surrounding soft tissues and tendons. We report the diagnostic pathway and the rehabilitation protocol of six elite athletes with osteitis pubis in three different sports, and compare protocol stages and time to return to competition. 6 athletes (2 soccer, 2 basketball, 2 rugby players) were diagnosed with osteitis pubis stage III and IV according to Rodriguez classification using standard clinical and imaging criteria. After performing a baseline lumbo-pelvic assessment, the rehabilitation protocol described by Verrall was adapted to each individual athlete. The length of time for each stage of the protocol was as follows; Stage 1 (rest from sport) was 26 +/- 5 days, Stage 2 (to achieve pain free running), 18 +/- 5 days, Stage 3 (squad training) 63 +/- 7, Stage 4 (return to competition) 86 +/- 15. Soccer players took longer to return to competition than basketball and rugby players. No recurrences were reported at 2 year follow-up. The protocol presented ensures a safe return to elite athletes. The time from diagnosis to full recovery is longer in football players, and seems to increase with age. | 25,147,768 | [
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Obesity and obesity-associated cardiometabolic risk factors in indigenous Nenets women from the rural Nenets Autonomous Area and Russian women from Arkhangelsk city. | The prevalence of obesity and obesity-related conditions varies by population groups. Indigenous women of the circumpolar north are believed to be at high risk of obesity. We studied, first the obesity prevalence in indigenous Arctic women, Nenets, compared to urban Russian women. Second, the association between obesity and cardiometabolic risk factors in the combined group of Nenets and Russian women. Third, ethnic differences in the association between obesity and cardiometabolic risk factors. Cross-sectional study performed in 2008-2009. 93 Nenets women, aged 19-77 (the indigenous village, the Nenets Autonomous Area) and 132 Russian women, aged 21-72 (Arkhangelsk city). Obesity was defined as body mass index (BMI)≥30 kg/m(2), waist circumference (WC)≥88 cm and or waist-to-hip ratio (WHR)≥0.85%. We assessed associations between obesity and cardiometabolic risk factors by linear and logistic regression models that included covariates of ethnicity, age, smoking and physical activity. We also tested for interaction between obesity measurements and ethnicity. Prevalence of obesity estimated through BMI, WC and WHR were 42.5, 45.3 and 41.9% in Nenets and 34.4, 46.4 and 29.5% in Russians, respectively, with no differences found. BMI, WC and WHR associated positively with triglycerides, fasting insulin and Homeostasis Model Assessment of Insulin Resistance index. In addition, BMI and WC correlated negatively with high-density lipoprotein cholesterol and positively with systolic blood pressure and apolipoprotein B/apoliporotein A-I ratio. WC explained significant variation in fasting glucose (FG) level. BMI predicted type 2 diabetes history. FG level associated strongly with ethnicity and was found to be higher in Russians. We found no differences in prevalence of obesity between Nenets and Russian females. Obesity was associated with cardiometabolic risk factors independently of ethnicity in the sample studied. There was no link between obesity measurements and ethnicity. | 25,147,770 | [
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Targeting Glutathione S-transferase M4 in Ewing sarcoma. | Ewing sarcoma is a malignant pediatric bone and soft tissue tumor. Although the 5-year survival rate of localized disease approaches 75%, the prognosis of metastatic and/or therapy-resistant disease remains dismal despite the wide use of aggressive therapeutic strategies. We previously reported that high expression of glutathione S-transferase M4 (GSTM4) in primary tumors correlates with poor patient outcomes. GSTM4 is required for oncogenic transformation and mediates resistance to chemotherapeutic drugs in Ewing sarcoma cells. Here, we performed RNA-sequencing analyses of Ewing sarcoma cells and combined our results with publicly available datasets to demonstrate that GSTM4 is a major GST specifically expressed in Ewing sarcoma. Pharmacological inhibition of GSTM4 activity using a pan GST inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX), significantly limited cellular proliferation and oncogenic transformation of Ewing sarcoma cells. Moreover, combined use of NBDHEX and etoposide synergistically increased cytotoxicity, suggesting a role for GSTM4 as an inhibitor of apoptosis. Mechanistic studies revealed that GSTM4 limits apoptosis owing to its ability to interact with Apoptosis Signal-regulating Kinase 1 (ASK1) and inhibit signaling via the c-Jun N-terminal Kinase axis. To exploit our observation that GSTM4 expression is specifically up-regulated in Ewing sarcoma, we tested the effect of a GSTM4-activated anti-cancer agent, O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate or JS-K, on tumor growth and survival. We found that JS-K robustly decreased Ewing sarcoma cell viability and xenograft tumor growth and improved overall survival of xenograft mice. Our data suggest that GSTM4 is a novel therapeutic target for the treatment of high GSTM4-expressing Ewing sarcoma. Strategies that combine standard chemotherapy with agents that inhibit GSTM4, that are activated by GSTM4, or that block GSTM4/ASK1 interactions, can potentially be more specific and/or efficacious than standard therapeutic approaches. | 25,147,782 | [
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Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial. | B vitamins play an important role in homocysteine metabolism, with vitamin deficiencies resulting in increased levels of homocysteine and increased risk for stroke. We performed a genome-wide association study (GWAS) in 2,100 stroke patients from the Vitamin Intervention for Stroke Prevention (VISP) trial, a clinical trial designed to determine whether the daily intake of high-dose folic acid, vitamins B6, and B12 reduce recurrent cerebral infarction. Extensive quality control (QC) measures resulted in a total of 737,081 SNPs for analysis. Genome-wide association analyses for baseline quantitative measures of folate, Vitamins B12, and B6 were completed using linear regression approaches, implemented in PLINK. Six associations met or exceeded genome-wide significance (P ≤ 5 × 10(-08)). For baseline Vitamin B12, the strongest association was observed with a non-synonymous SNP (nsSNP) located in the CUBN gene (P = 1.76 × 10(-13)). Two additional CUBN intronic SNPs demonstrated strong associations with B12 (P = 2.92 × 10(-10) and 4.11 × 10(-10)), while a second nsSNP, located in the TCN1 gene, also reached genome-wide significance (P = 5.14 × 10(-11)). For baseline measures of Vitamin B6, we identified genome-wide significant associations for SNPs at the ALPL locus (rs1697421; P = 7.06 × 10(-10) and rs1780316; P = 2.25 × 10(-08)). In addition to the six genome-wide significant associations, nine SNPs (two for Vitamin B6, six for Vitamin B12, and one for folate measures) provided suggestive evidence for association (P ≤ 10(-07)). Our GWAS study has identified six genome-wide significant associations, nine suggestive associations, and successfully replicated 5 of 16 SNPs previously reported to be associated with measures of B vitamins. The six genome-wide significant associations are located in gene regions that have shown previous associations with measures of B vitamins; however, four of the nine suggestive associations represent novel finding and warrant further investigation in additional populations. | 25,147,783 | [
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Peptide-ligand binding modeling of siRNA with cell-penetrating peptides. | The binding affinity of a series of cell-penetrating peptides (CPP) was modeled through docking and making use of the number of intermolecular hydrogen bonds, lipophilic contacts, and the number of sp3 molecular orbital hybridization carbons. The new ranking of the peptides is consistent with the experimentally determined efficiency in the downregulation of luciferase activity, which includes the peptides' ability to bind and deliver the siRNA into the cell. The predicted structures of the complexes of peptides to siRNA were stable throughout 10 ns long, explicit water molecular dynamics simulations. The stability and binding affinity of peptide-siRNA complexes was related to the sidechains and modifications of the CPPs, with the stearyl and quinoline groups improving affinity and stability. The reranking of the peptides docked to siRNA, together with explicit water molecular dynamics simulations, appears to be well suited to describe and predict the interaction of CPPs with siRNA. | 25,147,791 | [
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Studying the complex expression dependences between sets of coexpressed genes. | Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments. | 25,147,825 | [
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Upregulation of pluripotency markers in adipose tissue-derived stem cells by miR-302 and leukemia inhibitory factor. | The expression pattern of pluripotency markers in adipose tissue-derived stem cells (ADSCs) is a subject of controversy. Moreover, there is no data about the signaling molecules that regulate these markers in ADSCs. In the present study, we studied the roles of leukemia inhibitory factor (LIF) and miR-302 in this regard. Freshly isolated mouse ADSCs expressed hematopoietic, mesenchymal, and pluripotency markers. One day after plating, ADSCs expressed OCT4 and Sox2 proteins. After three passages, the expression of hematopoietic and pluripotency markers decreased, while the expression of mesenchymal stem cell markers exhibited a striking rise. Both supplementation of culture media with LIF and transfection of the ADSCs with miR-302 family upregulated the expression levels of OCT4, Nanog, and Sox2 mRNAs. These findings showed that mouse adipose tissue contains a population of cells with molecular resemblance to embryonic stem cells, and LIF and miR-302 family positively affect the expression of pluripotency markers. | 25,147,827 | [
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Antiviral action of synthetic stigmasterol derivatives on herpes simplex virus replication in nervous cells in vitro. | Polyfunctionalized stigmasterol derivatives, (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2), inhibit herpes simplex virus type 1 (HSV-1) replication and spreading in human epithelial cells derived from ocular tissues. Both compounds reduce the incidence and severity of lesions in a murine model of herpetic stromal keratitis when administered in different treatment modalities. Since encephalitis caused by HSV-1 is another immunopathology of viral origin, we evaluate here the antiviral effect of both compounds on HSV-1 infected nervous cell lines as well as their anti-inflammatory action. We found that both stigmasterol derivatives presented low cytotoxicity in the three nervous cell lines assayed. Regarding the antiviral activity, in all cases both compounds prevented HSV-1 multiplication when added after infection, as well as virus propagation. Additionally, both compounds were able to hinder interleukin-6 and Interferon-gamma secretion induced by HSV-1 infection in Neuro-2a cells. We conclude that compounds 1 and 2 have exerted a dual antiviral and anti-inflammatory effect in HSV-1 infected nervous cell lines, which makes them interesting molecules to be further studied. | 25,147,828 | [
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δ-Cut decision-theoretic rough set approach: model and attribute reductions. | Decision-theoretic rough set is a quite useful rough set by introducing the decision cost into probabilistic approximations of the target. However, Yao's decision-theoretic rough set is based on the classical indiscernibility relation; such a relation may be too strict in many applications. To solve this problem, a δ-cut decision-theoretic rough set is proposed, which is based on the δ-cut quantitative indiscernibility relation. Furthermore, with respect to criterions of decision-monotonicity and cost decreasing, two different algorithms are designed to compute reducts, respectively. The comparisons between these two algorithms show us the following: (1) with respect to the original data set, the reducts based on decision-monotonicity criterion can generate more rules supported by the lower approximation region and less rules supported by the boundary region, and it follows that the uncertainty which comes from boundary region can be decreased; (2) with respect to the reducts based on decision-monotonicity criterion, the reducts based on cost minimum criterion can obtain the lowest decision costs and the largest approximation qualities. This study suggests potential application areas and new research trends concerning rough set theory. | 25,147,847 | [
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A cuckoo search algorithm for multimodal optimization. | Interest in multimodal optimization is expanding rapidly, since many practical engineering problems demand the localization of multiple optima within a search space. On the other hand, the cuckoo search (CS) algorithm is a simple and effective global optimization algorithm which can not be directly applied to solve multimodal optimization problems. This paper proposes a new multimodal optimization algorithm called the multimodal cuckoo search (MCS). Under MCS, the original CS is enhanced with multimodal capacities by means of (1) the incorporation of a memory mechanism to efficiently register potential local optima according to their fitness value and the distance to other potential solutions, (2) the modification of the original CS individual selection strategy to accelerate the detection process of new local minima, and (3) the inclusion of a depuration procedure to cyclically eliminate duplicated memory elements. The performance of the proposed approach is compared to several state-of-the-art multimodal optimization algorithms considering a benchmark suite of fourteen multimodal problems. Experimental results indicate that the proposed strategy is capable of providing better and even a more consistent performance over existing well-known multimodal algorithms for the majority of test problems yet avoiding any serious computational deterioration. | 25,147,850 | [
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Effect of codon optimisation on the production of recombinant fish growth hormone in Pichia pastoris. | This study was established to test the hypothesis of whether the codon optimization of fish growth hormone gene (FGH) based on P. pastoris preferred codon will improve the quantity of secreted rFGH in culture supernatant that can directly be used as fish feed supplements. The optimized FGH coding sequence (oFGH) and native sequence (nFGH) of giant grouper fish (Epinephelus lanceolatus) were cloned into P. pastoris expression vector (pPICZαA) downstream of alcohol oxidase gene (AOX1) for efficient induction of extracellular rFGH by adding 1% of absolute methanol. The results showed that recombinant P. pastoris was able to produce 2.80 ± 0.27 mg of oFGH compared to 1.75 ± 0.25 of nFGH in one litre of culture supernatant. The total body weight of tiger grouper fingerlings fed with oFGH increased significantly at third (P < 0.05) and fourth weeks (P < 0.01) of four-week experiment period compared to those fed with nFGH. Both oFGH and nFGH significantly enhanced the final biomass and fish survival percentage. In conclusion, codon optimization of FGH fragment was useful to increase rFGH quantity in the culture supernatant of P. pastoris that can be directly used as fish feed supplements. Further studies are still required for large scale production of rFGH and practical application in aquaculture production. | 25,147,851 | [
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Stress-strain relationship of Ca(OH)2-activated Hwangtoh concrete. | This study examined the stress-strain behavior of 10 calcium hydroxide (Ca(OH)2)-activated Hwangtoh concrete mixes. The volumetric ratio of the coarse aggregate (V agg) and the water-to-binder (W/B) ratio were selected as the main test variables. Two W/B ratios (25% and 40%) were used and the value of V agg varied between 0% and 40.0%, and 0% and 46.5% for W/B ratios of 25% and 40%, respectively. The test results demonstrated that the slope of the ascending branch of the stress-strain curve of Ca(OH)2-activated Hwangtoh concrete was smaller, and it displayed a steeper drop in stress in the descending branch, compared with those of ordinary Portland cement (OPC) concrete with the same compressive strength. This trend was more pronounced with the increase in the W/B ratio and decrease in V agg. Based on the experimental observations, a simple and rational stress-strain model was established mathematically. Furthermore, the modulus of elasticity and strain at peak stress of the Ca(OH)2-activated Hwangtoh concrete were formulated as a function of its compressive strength and V agg. The proposed stress-strain model predicted the actual behavior accurately, whereas the previous models formulated using OPC concrete data were limited in their applicability to Ca(OH)2-activated Hwangtoh concrete. | 25,147,869 | [
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DPPA3 prevents cytosine hydroxymethylation of the maternal pronucleus and is required for normal development in bovine embryos. | Dppa3 has been described in mice as an important maternal factor contributed by the oocyte that participates in protecting the maternal genome from oxidation of methylated cytosines (5mC) to hydroxymethylated cytosines (5hmC). Dppa3 is also required for normal mouse preimplantation development. This gene is poorly conserved across mammalian species, with less than 32% of protein sequence shared between mouse, cow and human. RNA-seq analysis of bovine oocytes and preimplantation embryos revealed that DPPA3 transcripts are some of the most highly abundant mRNAs in the oocyte, and their levels gradually decrease toward the time of embryonic genome activation (EGA). Knockdown of DPPA3 by injection of siRNA in germinal vesicle (GV) stage oocytes was used to assess its role in epigenetic remodeling and embryo development. DPPA3 knockdown resulted in increased intensity of 5hmC staining in the maternal pronucleus (PN), demonstrating a role for this factor in the asymmetric remodeling of the maternal and paternal PN in bovine zygotes. Also, DPPA3 knockdown decreased the developmental competence of parthenogenetic and in vitro fertilized embryos. Finally, DPPA3 knockdown embryos that reached the blastocyst stage had significantly fewer ICM cells as compared with control embryos. We conclude that DPPA3 is a maternal factor important for correct epigenetic remodeling and normal embryonic development in cattle, indicating that the role of DPPA3 during early development is conserved between species. | 25,147,917 | [
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Selenite enhances immune response against Pseudomonas aeruginosa PA14 via SKN-1 in Caenorhabditis elegans. | Selenium (Se) is an important nutrient that carries out many biological processes including maintaining optimal immune function. Here, inorganic selenite (Se(IV)) was evaluated for its pathogen resistance and potential-associated factors in Caenorhabditis elegans. The immune effects of Se(IV) were investigated by examining the responses of C. elegans to Pseudomonas aerugonisa PA14 strain. Se(IV)-treated C. elegans showed increased survival under PA14 infection compared with untreated controls. The significant pathogen resistance of Se(IV) on C. elegans might not be attributed to the effects of Se(IV) on PA14 as Se(IV) showed no effect on bacterial quorum-sensing and virulence factors of PA14. This study showed that Se(IV) enhanced the expression of a gene pivotal for the innate immunity in C. elegans. The study found that the pathogen-resistant phenotypes contributed by Se(IV) was absent from the skn-1 mutant worms. Moreover, Se(IV) influenced the subcellular distribution of SKN-1/Nrf in C. elegans upon PA14 infection. Furthermore, Se(IV) increased mRNA levels of SKN-1 target genes (gst-4 and gcs-1). This study found evidence of Se(IV) protecting C. elegans against P. aeruginosa PA14 infection by exerting effects on the innate immunity of C. elegans that is likely mediated via regulation of a SKN-1-dependent signaling pathway. | 25,147,937 | [
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A Case of Orbital Metastasis of Uterine Leiomyosarcoma With Intracranial Extension Presenting With Proptosis. | A 57-year-old woman presented with protrusion of the OS 2 months in duration and decreased vision 1 month in duration. The patient was diagnosed with uterine leiomyosarcoma approximately 3 years before presentation. Lung and liver metastases were diagnosed by biopsy 1 year prior to this visit. CT revealed a solid mass with central necrosis in the left lateral orbit that resulted in orbital shifting, bony destruction, and intracranial extension. The diagnosis was left orbital metastatic leiomyosarcoma, and the patient died 2 months after receiving the diagnosis. | 25,147,935 | [
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Spectroscopic and permeation studies of phospholipid bilayers supported by a soft hydrogel scaffold. | Polarized attenuated total reflection infrared (ATR-IR) spectroscopy, fluorescence microscopy, and fluorescence spectroscopy were used to characterize a lipid coating composed of 70 mol % 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 30 mol % cholesterol, supported on a spherical hydrogel scaffold. The fluorescence microscopy images show an association between the lipid coating and the hydrogel scaffold. Fluorescence permeability measurements revealed that the phospholipid coating acts as a permeability barrier, exhibiting characteristics of a lamellar bilayer coating structure. Variable evanescent wave penetration depth ATR-IR spectroscopy studies validated the determination of quantitative molecular orientation information for a lipid coating supported on a spherical scaffold. These polarized ATR-IR studies measured an average DMPC acyl chain tilt angle of ∼21-25°, with respect to the surface normal. | 25,147,944 | [
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CSF biomarkers and neuropsychological profiles in patients with cerebral small-vessel disease. | Despite existing criteria, differential diagnosis of Vascular Dementia (VD) and Alzheimer's disease (AD) remains difficult. The aim of this study is to figure out cognitive and biomarker profiles that may help to distinguish between VD, AD and AD + Cerebral Small Vessel Disease (CSVD). We examined a cohort of patients with CSVD (n = 92). After stratification of cognitive impaired patients (n = 59) using the standard CSF beta-amyloid 42/40 ratio cut-off point of 0.975, we obtained two groups which differed with respect to several features: 32 patients with normal beta-amyloid 42/40 ratio (>0.975) showed markedly impaired blood-brain-barrier function as indicated by an elevated albumin ratio (median 8.35). They also differed in cognitive profiles when compared to 27 patients with AD typical beta-amyloid ratio and normal albumin ratio. We also enrolled an additional group of patients with AD (no significant CSVD on MRI, n = 27) which showed no impairment of the blood-brain-barrier. We showed a negative correlation between the albumin ratio and executive cognitive function (p = 0.016) and a negative correlation between memory function and typical AD markers like Tau (p = 0.004) and p181-Tau (p = 0.023) in our cohort. We suppose that the group of patients with normal beta-amyloid ratio represents VD while patients in the other groups represent AD+CSVD and pure AD. Our results support the idea that a dysfunction of the blood-brain-barrier might be contributing factor in the development of cognitive decline in CSVD as it seems to be of more importance than the severity of white matter lesions. | 25,147,945 | [
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Investigation and control of anthrax outbreak at the human-animal interface, Bhutan, 2010. | In 2010, we investigated anthrax outbreak in Bhutan. A total of 43 domestic animals died, and cutaneous anthrax developed in 9 persons, and 1 died. All affected persons had contact with the carcasses of infected animals. Comprehensive preparedness and response guidelines are needed to increase public awareness of anthrax in Bhutan. | 25,147,965 | [
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Sign inversion of circularly polarized luminescence by geometry manipulation of four naphthalene units introduced into a tartaric acid scaffold. | Tethering four 1- versus 2-naphthyls to the same chiral scaffold derived from tartaric acid led to oppositely signed circularly polarized luminescence (CPL) and circular dichroism (CD) in solution, which not only reveals the decisive role of the spatial arrangement of chromophores/fluorophores in determining the chiroptical behaviors but also provides us with a versatile tool for switching the signs of CPL and CD without using the antipodal scaffold. | 25,147,969 | [
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What I need to start my job: a wish list (positioning yourself for success in an academic or nonacademic environment). | Beginning practice as an orthopaedic traumatologist is an important event, when the groundwork is set up for the next few years of hard work. Plans must be made, resources allocated, staff hired, etc. to optimally support the newly practicing surgeon. Academic and nonacademic practice settings are possible, where the facets of practice (i.e., clinic, operating room, floor work, education, and research) may be quite different. The goal of this article is to discuss these differences between relatively academic and nonacademic practices, ultimately to allow the young orthopaedic traumatologist to form a "wish list" with which to start planning the logistics of his or her career. | 25,147,999 | [
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Improving business IQ in medicine through mentorship and education. | Business intelligence in the field of medicine, particularly with physicians, has been an abstract concept at best with no objective metric. Furthermore, in many arenas, it was taboo for medical students, residents, and physicians to discuss the business and finances of their work for fear that it would interfere with their sacred duties as health care providers. There has been a substantial shift in this philosophy over the last few decades with the growth and evolution of the health care industry in the United States. In 2012, health care expenditures accounted for 17.2% of the United States Gross Domestic Product, averaging $8915 per person. The passage of the Affordable Care Act in March of 2010 sent a clear message to all that change is coming, and it is more important now than ever to have physician leaders whose skills and knowledge in business, management, and health care law rival their acumen within their medical practice. Students, residents, and fellows all express a desire to gain more business knowledge throughout their education and training, but many do not know where to begin or have access to programs that can further their knowledge. Whether you are an employed or private practice physician, academic or community based, improving your business intelligence will help you get a seat at the table where decisions are made and give you the skills to influence those decisions. | 25,148,000 | [
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The stereotactic approach for mapping epileptic networks: a prospective study of 200 patients. | Stereoelectroencephalography (SEEG) is a methodology that permits accurate 3D in vivo electroclinical recordings of epileptiform activity. Among other general indications for invasive intracranial electroencephalography (EEG) monitoring, its advantages include access to deep cortical structures, its ability to localize the epileptogenic zone when subdural grids have failed to do so, and its utility in the context of possible multifocal seizure onsets with the need for bihemispheric explorations. In this context, the authors present a brief historical overview of the technique and report on their experience with 2 SEEG techniques (conventional Leksell frame-based stereotaxy and frameless stereotaxy under robotic guidance) for the purpose of invasively monitoring difficult-to-localize refractory focal epilepsy. Over a period of 4 years, the authors prospectively identified 200 patients with refractory epilepsy who collectively underwent 2663 tailored SEEG electrode implantations for invasive intracranial EEG monitoring and extraoperative mapping. The first 122 patients underwent conventional Leksell frame-based SEEG electrode placement; the remaining 78 patients underwent frameless stereotaxy under robotic guidance, following acquisition of a stereotactic ROSA robotic device at the authors' institution. Electrodes were placed according to a preimplantation hypothesis of the presumed epileptogenic zone, based on a standardized preoperative workup including video-EEG monitoring, MRI, PET, ictal SPECT, and neuropsychological assessment. Demographic features, seizure semiology, number and location of implanted SEEG electrodes, and location of the epileptogenic zone were recorded and analyzed for all patients. For patients undergoing subsequent craniotomy for resection, the type of resection and procedure-related complications were prospectively recorded. These results were analyzed and correlated with pathological diagnosis and postoperative seizure outcomes. The epileptogenic zone was confirmed by SEEG in 154 patients (77%), of which 134 (87%) underwent subsequent craniotomy for epileptogenic zone resection. Within this cohort, 90 patients had a minimum follow-up of at least 12 months; therein, 61 patients (67.8%) remained seizure free, with an average follow-up period of 2.4 years. The most common pathological diagnosis was focal cortical dysplasia Type I (55 patients, 61.1%). Per electrode, the surgical complications included wound infection (0.08%), hemorrhagic complications (0.08%), and a transient neurological deficit (0.04%) in a total of 5 patients (2.5%). One patient (0.5%) ultimately died due to intracerebral hematoma directly ensuing from SEEG electrode placement. Based on these results, SEEG methodology is safe, reliable, and effective. It is associated with minimal morbidity and mortality, and serves as a practical, minimally invasive approach to extraoperative localization of the epileptogenic zone in patients with refractory epilepsy. | 25,148,007 | [
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Correlation between magnetic resonance imaging grading and pathological grading in meningioma. | This study investigated the specific preoperative MRI features of patients with intracranial meningiomas that correlate with pathological grade and provide appropriate preoperative planning. From 2006 to 2012, 120 patients (36 men and 84 women, age range 20-89 years) with newly diagnosed symptomatic intracranial meningiomas undergoing resection were retrospectively analyzed in terms of radiological features of preoperative MRI. There were 90 WHO Grade I and 30 WHO Grade II or III meningiomas. The relationships between MRI features and WHO histopathological grade were analyzed and scored quantitatively. According to the results of multivariate logistic regression analysis, age ≥ 75 years, indistinct tumorbrain interface, positive capsular enhancement, and heterogeneous tumor enhancement were identified factors in the prediction of advanced histopathological grade. The prediction model was quantified as a scoring scale: 2 × (age) + 5 × (tumor-brain interface) + 3 × (capsular enhancement) + 2 × (tumor enhancement). The calculated score correlated positively with the probability of high-grade meningioma. This scoring approach may be useful for clinicians in determining therapeutic strategy and in surgical planning for patients with intracranial meningiomas. | 25,148,010 | [
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Preference for women's body mass and waist-to-hip ratio in Tsimane' men of the Bolivian Amazon: biological and cultural determinants. | The issue of cultural universality of waist-to-hip ratio (WHR) attractiveness in women is currently under debate. We tested men's preferences for female WHR in traditional society of Tsimane'(Native Amazonians) of the Bolivian rainforest (N = 66). Previous studies showed preferences for high WHR in traditional populations, but they did not control for the women's body mass.We used a method of stimulus creation that enabled us to overcome this problem. We found that WHR lower than the average WHR in the population is preferred independent of cultural conditions. Our participants preferred the silhouettes of low WHR, but high body mass index (BMI), which might suggest that previous results could be an artifact related to employed stimuli. We found also that preferences for female BMI are changeable and depend on environmental conditions and probably acculturation (distance from the city). Interestingly, the Tsimane' men did not associate female WHR with age, health, physical strength or fertility. This suggests that men do not have to be aware of the benefits associated with certain body proportions - an issue that requires further investigation. | 25,148,034 | [
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Optogenetic recruitment of dorsal raphe serotonergic neurons acutely decreases mechanosensory responsivity in behaving mice. | The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses. | 25,148,042 | [
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Pharmacophore and docking-based virtual screening approach for the design of new dual inhibitors of Janus kinase 1 and Janus kinase 2. | Janus kinase 1 and 2, non-receptor protein tyrosine kinases, are implicated in various cancerous diseases. Involvement of these two enzymes in the pathways that stimulate cell proliferation in cancerous conditions makes them potential therapeutic targets for designing new dual-targeted agents for the treatment of cancer. In the present study, two separate pharmacophore models were developed and the best models for JAK1 (AAADH.25) and JAK2 (ADRR.92) were selected on the basis of their external predictive ability. Both models were subjected to a systematic virtual screening (VS) protocol using a PHASE database of 1.5 million molecules. The hits retrieved in VS were investigated for ADME properties to avoid selection of molecules with a poor pharmacokinetic profile. The molecules considered to be within the range of acceptable limits of ADME properties were further employed for docking simulations with JAK1 and JAK2 proteins to explore the final hits that possess structural features of both pharmacophore models as well as display essential interactions with both of them. Thus, the new molecules obtained in this way should show inhibitory activity against JAK1 and JAK2 and may serve as novel therapeutic agents for the treatment of cancerous disease conditions. | 25,148,044 | [
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Parenting and the behavior problems of young children with an intellectual disability: concurrent and longitudinal relationships in a population-based study. | We examined parenting behaviors, and their association with concurrent and later child behavior problems. Children with an intellectual disability (ID) were identified from a UK birth cohort (N = 516 at age 5). Compared to parents of children without an ID, parents of children with an ID used discipline less frequently, but reported a more negative relationship with their child. Among children with an ID, discipline, and home atmosphere had no long-term association with behavior problems, whereas relationship quality did: closer relationships were associated with fewer concurrent and later child behavior problems. Increased parent-child conflict was associated with greater concurrent and later behavior problems. Parenting programs in ID could target parent-child relationship quality as a potential mediator of behavioral improvements in children. | 25,148,056 | [
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The purported association between depression, aggression, and self-injury in people with intellectual disability: a critical review of the literature. | The prevalence of depression in individuals with an intellectual disability is estimated to lie between 3% and 6%. It has been suggested that symptoms of depression in this population might be atypical and include unusual features such as challenging behavior. However, there is significant disagreement regarding the use of challenging behavior as "depressive equivalent" symptomatology. The aim of this review is to evaluate published research reporting on the association between challenging behavior, specifically aggression and self-injury, and depression in people with an intellectual disability as a first step toward evaluating whether challenging behaviors might be considered as depressive equivalent symptoms. The results of the studies identified indicated that the association between depression and aggression, and depression and self-injury are equivocal and the interpretations of the results limited by threats to validity. Based on this analysis, there is insufficient evidence to support the use of challenging behavior as a depressive equivalent symptom. Further research to examine potentially confounding variables and the association between challenging behaviour and depression using methodologically robust designs and measures is clearly warranted. | 25,148,058 | [
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Visibility through atmospheric haze and its relation to macular pigment. | A major factor limiting the visibility of distant targets is veiling attributed to atmospheric scattering, known commonly as haze. It has been suggested that yellow filters (in this case, the macular pigments, MPs) could selectively absorb this haze, thus extending visual range. This study is an empirical test of the visibility hypothesis. Twelve subjects had their full contrast sensitivity function (CSF) (represented by six spatial frequencies) assessed in the presence of two background conditions: simulated blue haze and short wave-deficient light. Contrast sensitivity at the peak of the CSF (7.5 cycles per degree) was measured in the presence of the same two backgrounds as the full CSF, with the addition of a broadband xenon background condition in a separate sample of 25 subjects. Simulated blue haze was found to uniformly reduce the CSF in the 12 subjects for whom the full CSF was assessed. Therefore, only the peak was measured in the larger sample of 25 subjects. Macular pigment density was significantly related to energy at threshold for both the haze and xenon backgrounds but not the short wave-deficient background. Thus, subjects with higher levels of MP could withstand more light before losing sight of the target. This result is consistent with previous modeling of the visibility hypothesis as well as visual range improvements seen when using an artificial MP filter. | 25,148,065 | [
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Microbial communities of three sympatric Australian stingless bee species. | Bacterial symbionts of insects have received increasing attention due to their prominent role in nutrient acquisition and defense. In social bees, symbiotic bacteria can maintain colony homeostasis and fitness, and the loss or alteration of the bacterial community may be associated with the ongoing bee decline observed worldwide. However, analyses of microbiota associated with bees have been largely confined to the social honeybees (Apis mellifera) and bumblebees (Bombus spec.), revealing--among other taxa--host-specific lactic acid bacteria (LAB, genus Lactobacillus) that are not found in solitary bees. Here, we characterized the microbiota of three Australian stingless bee species (Apidae: Meliponini) of two phylogenetically distant genera (Tetragonula and Austroplebeia). Besides common plant bacteria, we find LAB in all three species, showing that LAB are shared by honeybees, bumblebees and stingless bees across geographical regions. However, while LAB of the honeybee-associated Firm4-5 clusters were present in Tetragonula, they were lacking in Austroplebeia. Instead, we found a novel clade of likely host-specific LAB in all three Australian stingless bee species which forms a sister clade to a large cluster of Halictidae-associated lactobacilli. Our findings indicate both a phylogenetic and geographical signal of host-specific LAB in stingless bees and highlight stingless bees as an interesting group to investigate the evolutionary history of the bee-LAB association. | 25,148,082 | [
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Consumer e-health solutions: the cure for Baumol's disease? | Baumol's disease is the fact that costs in persistently labour-intensive sectors such as healthcare do not drop, despite increased use of technology. The idea of consumer e-health solutions is seductive, because it provides one option for treating Baumol's disease. However, barriers to the implementation of these solutions exist, and the successful treatment of Baumol's disease with consumer e-health solutions rests on more than their removal. In this introduction, the editor-in-chief adds to the conversation four shifts that are critical to reaping the benefits of consumer e-health solutions: moving the focus from privacy to protection; from mere access to the use of information in decision-making; from the patient-provider dyad to one that includes a full formal and informal care team; and from structural solutions in healthcare to ones designed around the goals we have for our health system. | 25,148,118 | [
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Facilitating the appropriate use of e-health solutions. | In this issue, the lead article proposes that e-health technologies should be used more broadly and that patients should have greater access to their information through such technologies. The Canadian Medical Protective Association (CMPA) agrees with this statement and suggests that to facilitate the timely and appropriate adoption of new technologies among healthcare providers to enhance patient care, barriers in the existing regulatory, legislative and legal frameworks must be addressed. While much of the discussion to date on e-health has focused primarily on high-level issues regarding regulatory compliance, "privacy by design" and the e-health "panacea," CMPA suggests that there needs to be a refocus on achieving more concrete change and gains through consideration of the specific impact on the drivers of healthcare delivery. An integrated or holistic approach is required involving healthcare providers, regulators, legislators, stakeholders, ministries of health, privacy commissioners and the courts. To better leverage potential advantages, efficiencies and enhanced, safer care for our healthcare system, all parties must work together to develop an acceptable and flexible approach to the "appropriate use" of e-health technologies that will facilitate adoption by healthcare professionals in a manner that is consistent with the expectations of the profession and applicable standards of practice. | 25,148,123 | [
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Solutions for patient activation will yield the greatest benefit. | In the context of fiscal scarcity and abundant consumer health technologies, robust choices must be made. In this article, the authors assert that technologies that will yield the greatest return on investment for patients, providers and health system payers should be prioritized. They present three technology solutions that enable high-needs patients and their advocates to actively participate in their care: an audiovisual record of patient-education that can be accessed and shared post-consultation to improve retention; patient-friendly care plans that enable more active participation in shared decision-making; and personal health coaching to foster sustainable behaviour change. | 25,148,125 | [
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Node fingerprinting: an efficient heuristic for aligning biological networks. | With the continuing increase in availability of biological data and improvements to biological models, biological network analysis has become a promising area of research. An emerging technique for the analysis of biological networks is through network alignment. Network alignment has been used to calculate genetic distance, similarities between regulatory structures, and the effect of external forces on gene expression, and to depict conditional activity of expression modules in cancer. Network alignment is algorithmically complex, and therefore we must rely on heuristics, ideally as efficient and accurate as possible. The majority of current techniques for network alignment rely on precomputed information, such as with protein sequence alignment, or on tunable network alignment parameters, which may introduce an increased computational overhead. Our presented algorithm, which we call Node Fingerprinting (NF), is appropriate for performing global pairwise network alignment without precomputation or tuning, can be fully parallelized, and is able to quickly compute an accurate alignment between two biological networks. It has performed as well as or better than existing algorithms on biological and simulated data, and with fewer computational resources. The algorithmic validation performed demonstrates the low computational resource requirements of NF. | 25,148,127 | [
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Contractile force is enhanced in Aortas from pendrin null mice due to stimulation of angiotensin II-dependent signaling. | Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation. | 25,148,130 | [
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An alumina stabilized ZnO-graphene anode for lithium ion batteries via atomic layer deposition. | Atomic layer deposition (ALD) was applied to deposit ZnO on graphene aerogel, and this composite was used as an anode material for lithium ion batteries. This electrode material was further modified by an ultrathin Al2O3 layer via ALD to stabilize its electrochemical stability. These two metal oxides were uniformly immobilized on graphene frameworks, and the Al2O3 coating strongly improved the electrochemical performances of ZnO-graphene aerogel composite anodes. Particularly, the composite with 10 ALD cycles of Al2O3 coating (denoted as ZnO-G-10) exhibited a high initial discharge capacity of 1513 mA h g(-1) and maintained a reversible capacity of 490 mA h g(-1) after 100 cycles at a current density of 100 mA g(-1). Furthermore, the capacity retention rate increased from 70% to 90% in comparison with its uncoated counterpart after 100 cycles. The ZnO-G-10 anode also showed good rate-capability, delivering a discharge capacity of 415 mA h g(-1) at 1000 mA g(-1). The improved electrochemical performance is attributed to the formation of an artificial solid electrolyte interphase layer, stabilizing ZnO and the electrolyte by preventing the aggregation of Zn/ZnO nanograins and the side reaction that would cause the degradation of anodes. | 25,148,141 | [
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Conformationally switchable non-cyclic tetrapyrrole receptors: synthesis of tetrakis(1H-pyrrole-2-carbaldehyde) derivatives and their anion binding properties. | A series of tetrakis(1H-pyrrole-2-carbaldehyde) receptors (2, 4, and 6) were synthesized in two steps from commercially available starting materials. The anion binding properties of these receptors can be tuned through electronic switching to stabilize a conformation displaying high affinity for the dihydrogenphosphate and pyrophosphate anions (as the tetrabutylammonium salts) in chloroform. | 25,148,146 | [
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Pitfalls and pearls in MRI of the knee. | The purpose of this article is to review the common pitfalls in MRI of the knee and pearls on how to avoid them. MRI of the knee is highly accurate in evaluation of internal derangements of the knee. However, a variety of potential pitfalls in interpretation of abnormalities related to the knee have been identified, particularly in evaluation of the menisci, ligaments, and articular cartilage. | 25,148,154 | [
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Outpatient falls prevention program outcome: an increase, a plateau, and a decrease in incident reports. | We implemented an outpatient falls guideline in 2008 in the department of radiology. Here, we describe our multiyear experience. This was a retrospective study conducted between April 2006 and September 2013 to investigate outpatient falls. The span of the study was divided into eight periods. The incident reporting system was searched for the falls and the fall-related variables. A total of 327 falls occurred during 5,080,512 radiology examinations (rate, 0.64/10,000 total examinations). The highest rate was in period 6 (0.83/10,000 examinations). The average for periods 1 and 2 is 0.39/10,000 examinations (37 falls/945,427 examinations), and the average for periods 3-6 is 0.77/10,000 examinations (204 falls/2,656,805 examinations). The average rate for periods 7 and 8 is 0.58/10,000 examinations (86 falls/1,478,280 examinations). There was a statistically significant increase in the total number of falls reported between period 2 and period 3 (p = 0.02). There was a statistically significant decrease in outpatient falls between period 6 and period 7 (p = 0.01). The number of falls among patients 60 years old or older was 177 falls/2,180,093 examinations (rate, 0.81/10,000 examinations), and that among patients younger than 60 years was 150 falls/2,900,419 examinations (rate, 0.52/10,000 examinations), with a statistically significant difference (p = 0.007). Although the rate of falls was higher among female patients, there was no statistically significant difference between the sexes (p = 0.18). The outcome of the outpatient falls guideline was characterized by an increase, a plateau, and a decrease in incident reports. The initial increase may be due to the Hawthorne effect. The plateau may represent the value closest to the true incidence. The decrease may represent the effect of the program. | 25,148,166 | [
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Retrospective research in radiology from concept to publication: a stepwise guide for trainees and mentors. | The purpose of this article is to describe a step-by-step approach to the successful mentorship of trainees completing retrospective radiology research projects. The topics addressed include selection of a mentor and mentee and the selection, planning, initiation, and completion of a retrospective research project. Mentoring a trainee in the completion of a retrospective research project is an ideal way to introduce a trainee to academics. The goals of such a project given the time constraints of radiology residents include completion of an educational exhibit, an oral scientific presentation, and a published manuscript. | 25,148,188 | [
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Differences between wavefront and subjective refraction for infrared light. | To determine the accuracy of objective wavefront refractions for predicting subjective refractions for monochromatic infrared light. Objective refractions were obtained with a commercial wavefront aberrometer (COAS, Wavefront Sciences). Subjective refractions were obtained for 30 subjects with a speckle optometer validated against objective Zernike wavefront refractions on a physical model eye (Teel et al., Design and validation of an infrared Badal optometer for laser speckle, Optom Vis Sci 2008;85:834-42). Both instruments used near-infrared (NIR) radiation (835 nm for COAS, 820 nm for the speckle optometer) to avoid correction for ocular chromatic aberration. A 3-mm artificial pupil was used to reduce complications attributed to higher-order ocular aberrations. For comparison with paraxial (Seidel) and minimum root-mean-square (Zernike) wavefront refractions, objective refractions were also determined for a battery of 29 image quality metrics by computing the correcting lens that optimizes retinal image quality. Objective Zernike refractions were more myopic than subjective refractions for 29 of 30 subjects. The population mean discrepancy was -0.26 diopters (D) (SEM = 0.03 D). Paraxial (Seidel) objective refractions tended to be hyperopically biased (mean discrepancy = +0.20 D, SEM = 0.06 D). Refractions based on retinal image quality were myopically biased for 28 of 29 metrics. The mean bias across all 31 measures was -0.24 D (SEM = 0.03). Myopic bias of objective refractions was greater for eyes with brown irises compared with eyes with blue irises. Our experimental results are consistent with the hypothesis that reflected NIR light captured by the aberrometer originates from scattering sources located posterior to the entrance apertures of cone photoreceptors, near the retinal pigment epithelium. The larger myopic bias for brown eyes suggests that a greater fraction of NIR light is reflected from choroidal melanin in brown eyes compared with blue eyes. | 25,148,218 | [
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Identification of oncogenic mutations and gene fusions in the follicular variant of papillary thyroid carcinoma. | The diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) is increasingly common. Recent studies have suggested that FVPTC is heterogeneous and comprises multiple tumor types with distinct biological behaviors and underlying genetics. The purpose of this work was to identify the prevalence of mutations and gene fusions in known oncogenes in a panel representative of the common spectrum of FVPTC diagnosed at an academic medical center and correlate the clinical and pathological features obtained at the initial diagnosis with the tumor genotype. We performed SNaPshot genotyping on a panel of 129 FVPTCs of ≥1 cm for 90 point mutations or small deletions in known oncogenes and tumor suppressors and identified gene fusions using an anchored multiplex PCR assay targeting a panel of rearranged oncogenes. We identified a mutation or gene fusion in 70% (89 of 127) of cases. Mutations targeting the RAS family of oncogenes were the most frequently observed class of alterations, present in 36% (46 of 127) of cases, followed by BRAF mutation, present in 30% (38 of 127). We also detected oncogenic rearrangements not previously associated with FVPTC, including TFG-ALK and CREB3L2-PPARγ. BRAF mutation was significantly associated with unencapsulated tumor status. These data support the hypothesis that FVPTC is composed of distinct biological entities, with one class being identified by BRAF mutation and support the use of clinical genotyping assays that detect a diverse array of rearrangements involving ALK and PPARγ. Additional studies are necessary to identify genetic drivers in the 30% of FVPTCs with no known oncogenic alteration and to better predict behavior in tumors with known genotypes. | 25,148,236 | [
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Evaluation of naturally acquired IgG antibodies to a chimeric and non-chimeric recombinant species of Plasmodium vivax reticulocyte binding protein-1: lack of association with HLA-DRB1*/DQB1* in malaria exposed individuals from the Brazilian Amazon. | The development of modular constructs that include antigenic regions targeted by protective immune responses is an attractive approach for subunit vaccine development. However, a main concern of using these vaccine platforms is how to preserve the antigenic identity of conformational B cell epitopes. In the present study we evaluated naturally acquired antibody responses to a chimeric protein engineered to contain a previously defined immunodominant domain of the Plasmodium vivax reticulocyte binding protein-1 located between amino acid positions K435-I777. The construct also includes three regions of the cognate protein (F571-D587, I1745-S1786 and L2235-E2263) predicted to contain MHC class II promiscuous T cell epitopes. Plasma samples from 253 naturally exposed individuals were tested against this chimeric protein named PvRMC-RBP1 and a control protein that includes the native sequence PvRBP123-751 in comparative experiments to study the frequency of total IgG and IgG subclass reactivity. HLA-DRB1 and HLA-DQB1 allelic groups were typed by PCR-SSO to evaluate the association between major HLA class II alleles and antibody responses. We found IgG antibodies that recognized the chimeric PvRMC-RBP1 and the PvRBP123-751 in 47.1% and 60% of the studied population, respectively. Moreover, the reactivity index against both proteins were comparable and associated with time of exposure (p<0.0001) and number of previous malaria episodes (p<0.005). IgG subclass profile showed a predominance of cytophilic IgG1 over other subclasses against both proteins tested. Collectively these studies suggest that the chimeric PvRMC-RBP1 protein retained antigenic determinants in the PvRBP1435-777 native sequence. Although 52.9% of the population did not present detectable titers of antibodies to PvRMC-RBP1, genetic restriction to this chimeric protein does not seem to occur, since no association was observed between the HLA-DRB1* or HLA-DQB1* alleles and the antibody responses. This experimental evidence strongly suggests that the identity of the conformational B cell epitopes is preserved in the chimeric protein. | 25,148,251 | [
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Chronic HCV infection affects the NK cell phenotype in the blood more than in the liver. | Although epidemiological and functional studies have implicated NK cells in protection and early clearance of HCV, the mechanism by which they may contribute to viral control is poorly understood, particularly at the site of infection, the liver. We hypothesized that a unique immunophenotypic/functional NK cell signature exists in the liver that may provide insights into the contribution of NK cells to viral control. Intrahepatic and blood NK cells were profiled from chronically infected HCV-positive and HCV-negative individuals. Baseline expression of activating and inhibitory receptors was assessed, as well as functional responses following stimulation through classic NK cell pathways. Independent of HCV infection, the liver was enriched for the immunoregulatory CD56(bright) NK cell population, which produced less IFNγ and CD107a but comparable levels of MIP1β, and was immunophenotypically distinct from their blood counterparts. This profile was mostly unaltered in chronic HCV infection, though different expression levels of NKp46 and NKG2D were associated with different grades of fibrosis. In contrast to the liver, chronic HCV infection associated with an enrichment of CD161(low)perforin(high) NK cells in the blood correlated with increased AST and 2B4 expression. However, the association of relatively discrete changes in the NK cell phenotype in the liver with the fibrosis stage nevertheless suggests an important role for the NK response. Overall these data suggest that tissue localization has a more pervasive effect on NK cells than the presence of chronic viral infection, during which these cells might be mostly attuned to limiting immunopathology. It will be important to characterize NK cells during early HCV infection, when they should have a critical role in limiting infection. | 25,148,254 | [
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Protective effects of the sodium/calcium exchanger inhibitor on endothelial dysfunction induced by high glucose. | This study was designed to investigate the protective effects of KB-R7943, an inhibitor of sodium/calcium exchanger (NCX) on endothelial dysfunction induced by high glucose in endothelial cells. NCX expression, NCX activity and oxidative stress index were determined after endothelial cells were exposed to high glucose in the absence and presence of KB-R7943. Coincubation of endothelial cells with high glucose for 6, 12, 24 and 48 h resulted in a significant decrease in NCX expression, superoxide dismutase (SOD) activity and the release of nitric oxide (NO), and increased NCX activity and malondialdehyde (MDA) production. These effects were abolished by KB-R7943. A similar effect was observed after treatment of endothelial cells with H-7, a protein kinase C (PKC) inhibitor and NADPH oxidase inhibitor (DPI). These results suggest that the sodium/calcium exchanger inhibitor exerts beneficial effects on high glucose-induced endothelial dysfunction, which may be related to PKC signal pathway. | 25,148,264 | [
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DRUGS system enhancing adherence of Chinese surgeons to antibiotic use guidelines during perioperative period. | Irrational use of antimicrobial agents for preventing postoperative SSIs is a common phenomenon in China, which results in more bacterial resistance, higher hospital infection rates, extra costs of antimicrobial agents. The aim of the study is to evaluate the effect of Drug Rational Usage Guidelines System (DRUGS) on the surgeon's prescription behavior of antimicrobial agents. 10 common surgical operations which included 1543 cases (where 778 cases using paper-based guidelines and 765 cases using DRUGS) were selected and their demographic and clinical data were collected. The selected operations include thyroid resection, breast mass resection, myomectomy, etc. The evaluation criteria were antibiotic administrative categories, the time of initial dose, duration of administration, length of stay, the costs of antibiotics, SSIs and drug adverse reactions(ADR). The antimicrobial agents were mostly administrated within 0.5 h to 2 h before incision, 656 patients (85.75%) were intervened with DRUGS and 256 (32.90%) with paper-based guidelines according to the protocol. For the clean wounds incision, 547 patients (91.62%) were within 24 h of withdrawal antibiotics with using paper-based guidelines versus 91 (14.79%) with using DRUGS. A total of 19 kinds of antibiotics were used in the 1543 cases. The leading three on the list of frequency were piperacillin and sulbactam sodium, cefathiamidine and cefoperazone. While after the intervention, the list of frequency changed to cefazolin, cefathiamidine, cefoperazone. The average hospital stay was (7.00±4.31)d with paper-based guidelines and (2.54±1.57)d with DRUGS, respectively. The average cost of antibiotics was ¥(3481.36±2584.46) with paper-based guidelines and ¥(1693.39±1478.27) with DRUGS, respectively. However, there were no significant differences in the incidence of SSIs and ADR between two groups. In this study, the increased availability of antibiotic guidelines at the time of drug ordering, combined with DRUGS, was associated with an enhanced surgeon adherence to guidelines. | 25,148,306 | [
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Silk damping at a redshift of a billion: new limit on small-scale adiabatic perturbations. | We study the dissipation of small-scale adiabatic perturbations at early times when the Universe is hotter than T≃0.5 keV. When the wavelength falls below the damping scale k(D)(-1), the acoustic modes diffuse and thermalize, causing entropy production. Before neutrino decoupling, k(D) is primarily set by the neutrino shear viscosity, and we study the effect of acoustic damping on the relic neutrino number, primordial nucleosynthesis, dark-matter freeze-out, and baryogenesis. This sets a new limit on the amplitude of primordial fluctuations of Δ(R)(2)<0.007 at 10(4) Mpc(-1)≲k≲10(5) Mpc(-1) and a model-dependent limit of Δ(R)(2)≲0.3 at k≲10(20-25) Mpc(-1). | 25,148,313 | [
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Determination of the η(')-proton scattering length in free space. | Taking advantage of both the high mass resolution of the COSY-11 detector and the high energy resolution of the low-emittance proton beam of the cooler synchrotron COSY, we determine the excitation function for the pp→ppη(') reaction close to threshold. Combining these data with previous results, we extract the scattering length for the η(')-proton potential in free space to be Re(a(pη(')))=0±0.43 fm and Im(a(pη(')))=0.37(-0.16)(+0.40) fm. | 25,148,320 | [
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Engineering frequency-time quantum correlation of narrow-band biphotons from cold atoms. | The nonclassical photon pair, generated via a parametric process, is naturally endowed with a specific form of frequency-time quantum correlations. Here, we report complete control of frequency-time quantum correlations of narrow-band biphotons generated via spontaneous four-wave mixing in a cold atomic ensemble. We have experimentally confirmed the generation of frequency-anticorrelated, frequency-correlated, and frequency-uncorrelated narrow-band biphoton states, as well as verifying the strong nonclassicality of the correlations. Our work opens up new possibilities for engineering narrow-band entangled photons for various quantum optical and quantum information applications. | 25,148,327 | [
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Interfacing superconducting qubits and telecom photons via a rare-earth-doped crystal. | We propose a scheme to couple short single photon pulses to superconducting qubits. An optical photon is first absorbed into an inhomogeneously broadened rare-earth doped crystal using controlled reversible inhomogeneous broadening. The optical excitation is then mapped into a spin state using a series of π pulses and subsequently transferred to a superconducting qubit via a microwave cavity. To overcome the intrinsic and engineered inhomogeneous broadening of the optical and spin transitions in rare-earth doped crystals, we make use of a special transfer protocol using staggered π pulses. We predict total transfer efficiencies on the order of 90%. | 25,148,328 | [
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TL1A increases expression of CD25, LFA-1, CD134 and CD154, and induces IL-22 and GM-CSF production from effector CD4 T-cells. | Elevated levels of the cytokine TL1A is associated with several autoimmune diseases e.g. rheumatoid arthritis and inflammatory bowel disease. However, the exact role of TL1A remains elusive. In this study, we investigated the function of TL1A in a pro-inflammatory setting. We show that TL1A together with IL-12, IL-15 and IL-18 increases expression of the co-stimulatory molecules CD154 (CD40 ligand) and CD134 (OX40) on previously activated CD4+ T cells. This indicates that TL1A functions as a co-stimulatory molecule, decreasing the activation threshold of T-cells. We have previously shown that TL1A co-stimulation strongly induces IL-6 in human healthy leukocytes. Interestingly, the cytokine-activated effector T-cells did not produce IL-6 in response to TL1A, indicating distinct effects of TL1A on different cell populations. We further show that this co-stimulation increases the expression of CD25 (IL-2Rα) and CD11a (α-chain of LFA-1) on CD4 T-cells, likely governing increased IL-2/IL-15 sensitivity and cell-cell contact. Along with this, TL1A co-stimulation caused a specific induction of IL-22 and GM-CSF from the activated T-cells. These results substantially contribute to the explanation of TL1A's role in inflammation. Our results suggest that TL1A should be considered as a target for immunotherapeutic treatment of rheumatoid arthritis and inflammatory bowel disease. | 25,148,371 | [
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Efficacy and safety of intravesical onabotulinumtoxinA injection on elderly patients with chronic central nervous system lesions and overactive bladder. | Intravesical injection of onabotulinumtoxinA is an effective treatment for overactive bladder (OAB). Nonetheless, the treatment outcome is unclear in OAB patients with central nervous system (CNS) lesions. This study evaluated the efficacy and safety of intravesical onabotulinumtoxinA treatment in elderly patients with chronic cerebrovascular accidents (CVAs), Parkinson's disease (PD) and dementia. Patients with CVA, PD, dementia, and OAB refractory to antimuscarinic therapy were consecutively enrolled in the study group. Age-matched OAB patients without CNS lesions were selected to serve as a control group. OnabotulinumtoxinA (100 U) was injected into the bladder suburothelium at 20 sites. The clinical effects, adverse events, and urodynamic parameters were assessed at baseline and 3 months post-treatment. The Kaplan-Meier method was used to compare long-term success rates between groups. A total of 40 patients with OAB due to CVA (23), PD (9), dementia (8) and 160 control patients were included in this retrospetive analysis. Improvement of urgency severity scale, increased bladder capacity and increased post-void residual volume were comparable between the groups at 3 months. Patients with CNS lesions did not experience increased risks of acute urinary retention and urinary tract infection; nonetheless, patients with CVA experienced a higher rate of straining to void. Long-term success rates did not differ between the patients with and without CNS lesions. Intravesical injection of 100 U of onabotulinumtoxinA effectively decreased urgency symptoms in elderly OAB patients with CNS lesions. The adverse events were acceptable, and long-term effects were comparable to OAB patients in general. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization need careful evaluation for this very vulnerable population before choosing intravesical onabotulinumtoxinA treatment. | 25,148,378 | [
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Outcomes of pancreas retransplantation after simultaneous kidney-pancreas transplantation are comparable to pancreas after kidney transplantation alone. | There is a paucity of contemporary data describing the results of pancreas retransplantation (PRT). As a measure of utility, we wished to determine whether PRT could produce equivalent short-term and long-term recipient outcomes to primary pancreas after kidney (PAK) transplantation. Retrospective analysis of 96 consecutive pancreas only transplants performed from 2003 to May 2012. Primary PAK transplants (n = 78) were compared to PRT (n=18). Donor and recipient demographics were similar. Pancreas graft survival was similar for PAK and PRT at 1 year (88.2% vs. 100%) and 3 years (85.1% vs. 85.1%). Pancreas graft failure occurred in 14 PAK and two PRT patients with a mean follow-up of 61.6 ± 38.7 and 37.8 ± 26.1 months, respectively. There were no differences in postoperative length of stay (9.9 days vs. 8.7 days; P = 0.9) or postoperative complications in the first 3 months (47.4% vs. 38.9%, P = 0.6). At 3-year follow-up, both groups had comparable HBA1c (0.06 vs. 0.05; P = 0.8), serum creatinine (116.6 μmol/L v 131.7 μmol/L; P = 0.09), and oral glucose tolerance tests. Pancreas retransplantation is a safe and effective therapy for select recipients after graft loss. Pancreas retransplantation is associated with the same risk of postoperative complications and has similar intermediate-term graft survival compared to primary PAK transplantation. | 25,148,379 | [
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American Organization of Nurse Executives Care Innovation and Transformation program: improving care and practice environments. | The American Organization of Nurse Executives conducted an evaluation of the hospitals participating in the Care Innovation and Transformation (CIT) program. A total of 24 hospitals participated in the 2-year CIT program from 2012 to 2013. Reported outcomes include increased patient satisfaction, decreased falls, and reductions in nurse turnover and overtime. Nurses reported statistically significant improvements in 4 domains of the principles and elements of a healthful practice environment developed by the Nursing Organizations Alliance. | 25,148,395 | [
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Designing tomorrow from the other side of the bed. | The author poses insights about transitions in the development of collaborative relationships between medical students and nurses. | 25,148,397 | [
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Magnet nurse administrator attitudes and opportunities: toward improving lesbian, gay, bisexual, or transgender-specific healthcare. | This study explored Magnet® hospital chief nursing officers' (CNOs') attitudes toward gays and lesbians and the impact that these attitudes have on providing advocacy for lesbian, gay, bisexual, or transgender (LGBT) patients and staff. Homonegativity encompasses both heterosexism and homophobia and has profound effects on the health of LGBT populations. Little has been reported about the attitudes of CNOs toward LGBT populations and how these might impact advocacy for LGBT healthcare. Surveys were electronically mailed to 343 Magnet CNOs. The Modern Homonegativity Scale was used to assess attitudes, and additional statements were developed to assess the comfort level of the respondent in advocating for LGBT populations. Attitudes among CNOs toward LGBT populations and comfort with advocating for LGBT populations were positively correlated. Those demonstrating less homonegative attitudes were more likely to feel comfortable advocating for LGBT patients and staff. Recognizing and addressing bias among nurse leaders through education are important to ensure equitable healthcare for patients and employees. | 25,148,402 | [
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0.1031639,
0.057... |
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