title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Proximal thoracic endograft displacement rescued by balloon-assisted pull-back, external shunting, and in situ fenestration of the left carotid artery. | Proximal displacement of thoracic aortic endografts is a catastrophic adverse event, which rarely occurs but is associated with extremely high morbidity and mortality. We describe herein the case of a patient with accidental proximal displacement of a thoracic endograft with occlusion of all supra-aortic branches, successfully rescued by the combination of three advanced endovascular techniques: (1) aggressive pull-back maneuver with a compliant balloon; (2) establishment of an arterio-arterial temporary shunt to the occluded carotid artery over sheaths; and (3) in-situ fenestration of the occluded carotid artery. | 25,080,881 | [
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SGI-1776, an imidazo pyridazine compound, inhibits the proliferation of ovarian cancer cells by inactivating Pim-1. | To investigate the antitumor effect of SGI-1776 on human ovarian cancer HO-8910 cells and its molecular mechanism. HO-8910 cells were cultured in vitro, and the proliferation inhibitory effects of SGI- 1776 were determined by MTT assay and colony formation assay. The effect of SGI-1776 on the distribution of cell cycle phase was observed by flow cytometry with propidium iodide (PI) staining. The inhibition rate of migration and invasion were valued by transwell cell assay. Multiple molecular techniques, such as ELISA, Western blot, siRNA and cDNA transfection were used to explore the molecular mechanism. SGI-1776 presented dramatic anti-tumor activity against HO-8910 cells in vitro, inhibited the cells proliferation and colony formation, and attenuated the migration and invasion in a dosedependent manner, accompanied by cell cycle arrest in G1 phase. SGI-1776 caused the proliferation inhibition with concomitant decrease in Pim-1 kinase activity, down-regulated the expression of Pim-1 protein and and its downstream genes, such as CDK6, pCDK6, CDK4, pCDK4, CDK2 and pCDK2, and increased the expression of P21 and P27. Down-regulation expression of Pim-1 by siRNA followed SGI-1776 treatment resulted in enhanced cell proliferation inhibition rate and attenuated migration/invasion. Up-regulation of Pim-1 by cDNA transfection attenuated SGI- 1776-induced cell proliferation inhibition and its migration/invasion. Pim-1 mediates the biological effect of SGI-1776 in human ovarian cancer HO-8910 cells, suggesting Pim-1 might be a novel target for human ovarian cancer. | 25,080,901 | [
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[Inhibition on the proliferation of human endometrial cancer cells by RNAi inhibiting HMGB1 gene expression and its possible molecular mechanism]. | To investigate the effect of HMGB1 small interfering RNA (siRNA) on the proliferation, cell cycle and apoptosis of human endometrial cancer cell line HEC-1A, and its possible molecular mechanism. Lentivirus vector with HMGB1 shRNA was constructed and infected the endometrial cancer cell line HEC-1A. After viral infection for 72 h, real time PCR and Western blot were performed to investigate HMGB1 mRNA and protein expression. The cell proliferation was determined with methyl thiazolyl tetrazolium (MTT) method. Flow cytometry was performed to analyze the cell cycle progression of propidium iodide (PI)-stained HEC-1A cells and the apoptotic rate of annexinV/PI-stained cells. Western blot was used to detect the protein expression of AKT, pAKT and CyclinD1. Lentivirus vector with HMGB1 shRNA inhibited the mRNA (P<0.05) and protein (P<0.01) expression of HMGB1 in the cell line HEC-1A. The MTT assay demonstrated that HMGB1 knockdown significantly reduced the cell proliferation. FCM results showed that HMGB1 knockdown significantly resulted in the disruption of the cell cycle at G0/G1 phase and the induction of apoptosis. The apoptotic rate was (17.89±0.23)%, (4.69±0.20)% and (4.62±0.17)% in the HMGB1 knockdown group, the blank group and the negative group respectively. There was significance difference between the 3 groups (P<0.01). The protein expressions of pAKT and cyclinD1 were down-regulated after the HMGB1 knockdown for 72 h. Knockdown of HMGB1 expression can significantly inhibit the proliferation and induce the cell cycle arrest and apoptosis in the endometrial cancer cell line HEC-1A. PI3K/ AKT pathway and down-regulation of the protein expression of cyclinD1 may be involved in its therapeutic mechanism. | 25,080,914 | [
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The dynamics of correlated novelties. | Novelties are a familiar part of daily life. They are also fundamental to the evolution of biological systems, human society, and technology. By opening new possibilities, one novelty can pave the way for others in a process that Kauffman has called "expanding the adjacent possible". The dynamics of correlated novelties, however, have yet to be quantified empirically or modeled mathematically. Here we propose a simple mathematical model that mimics the process of exploring a physical, biological, or conceptual space that enlarges whenever a novelty occurs. The model, a generalization of Polya's urn, predicts statistical laws for the rate at which novelties happen (Heaps' law) and for the probability distribution on the space explored (Zipf's law), as well as signatures of the process by which one novelty sets the stage for another. We test these predictions on four data sets of human activity: the edit events of Wikipedia pages, the emergence of tags in annotation systems, the sequence of words in texts, and listening to new songs in online music catalogues. By quantifying the dynamics of correlated novelties, our results provide a starting point for a deeper understanding of the adjacent possible and its role in biological, cultural, and technological evolution. | 25,080,941 | [
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Frequent KIT mutations in human gastrointestinal stromal tumors. | Identifying gene mutations in individual tumors is critical to improve the efficacy of cancer therapy by matching targeted drugs to specific mutations. Gastrointestinal stromal tumors (GIST) are stromal or mesenchymal subepithelial neoplasms affecting the gastrointestinal tract and frequently contain activating gene mutations in either KIT or platelet-derived growth factor A (PDGFRA). Although GIST is highly responsive to several selective tyrosine kinase inhibitors, combined use of inhibitors targeting other mutations is needed to further prolong survival in patients with GIST. In this study, we aim to screen and identify genetic mutations in GIST for targeted therapy using the new Ion Torrent next-generation sequencing platform. Utilizing the Ion Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes using DNA extracted from formalin-fixed and paraffin-embedded (FFPE) samples of 121 human gastrointestinal stromal tumors, set up stringent parameters for reliable variant calling by filtering out potential raw base calling errors, and identified frequent mutations in the KIT gene. This study demonstrates the utility of using Ion Torrent sequencing to efficiently identify human cancer mutations. This may provide a molecular basis for clinically developing new drugs targeting these gene mutations for GIST therapy. | 25,080,996 | [
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Shock wave lithotripsy: the new phoenix? | Following its introduction in 1980, shock wave lithotripsy (SWL) rapidly emerged as the first-line treatment for the majority of patients with urolithiasis. Millions of SWL therapies have since been performed worldwide, and nowadays, SWL still remains to be the least invasive therapy modality for urinary stones. During the last three decades, SWL technology has advanced in terms of shock wave generation, focusing, patient coupling and stone localization. The implementation of multifunctional lithotripters has made SWL available to urology departments worldwide. Indications for SWL have evolved as well. Although endoscopic treatment techniques have improved significantly and seem to take the lead in stone therapy in the western countries due to high stone-free rates, SWL continues to be considered as the first-line therapy for the treatment of most intra-renal stones and many ureteral stones. This paper reviews the fundamentals of SWL physics to facilitate a better understanding about how a lithotripter works and should be best utilized. Advances in lithotripsy technology such as shock wave generation and focusing, advances in stone localization (imaging), different energy source concepts and coupling modalities are presented. Furthermore adjuncts to improve the efficacy of SWL including different treatment strategies are reviewed. If urologists make use of a more comprehensive understanding of the pathophysiology and physics of shock waves, much better results could be achieved in the future. This may lead to a renaissance and encourage SWL as first-line therapy for urolithiasis in times of rapid progress in endoscopic treatment modalities. | 25,081,010 | [
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Evaluation of the PI-RADS scoring system for mpMRI of the prostate: a whole-mount step-section analysis. | Evaluation of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system for classifying multi-parametric magnetic resonance imaging findings of the prostate using whole-mount step-section slides as reference standard. Prospective inclusion of 50 consecutive patients with biopsy-proven prostate cancer (PCa). All patients received a multi-parametric MRI of the prostate, consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. After prostatectomy, all prostates were prepared as whole-mount step-section slides. For each patient, six lesions were predefined on whole-mount step-sections according to a distinct scheme and the corresponding regions were identified on MRI. Each lesion then was scored on MRI according to PI-RADS by an experienced blinded uro-radiologist and compared with histopathological findings. PCa received significant (p < 0.01) higher overall PI-RADS scores (4.10 ± 0.75) compared with benign changes (2.00 ± 0.74). In the peripheral zone, each single modality score showed good diagnostic accuracy for PCa detection (area under the curve [AUC] > 0.90). When combining all single modality scores, an even higher discriminative ability of PCa detection (AUC = 0.97, 95 % CI 0.95-0.99) could be achieved. In contrast, in the transitional zone, dynamic contrast-enhanced MRI (DCE) showed very low diagnostic accuracy (AUC = 0.60). Regarding tumor malignancy, no high-grade PCa (Gleason >7a) was present at PI-RADS scores <4 and no Gleason 6 PCa at a PI-RADS score of 5. The PI-RADS scoring system showed good diagnostic accuracy: Only PI-RADS 4 and 5 showed high-grade PCa. However, it seems necessary to revise the PI-RADS scoring system concerning DCE in the transitional zone. | 25,081,011 | [
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HOXB9 promotes epithelial-to-mesenchymal transition via transforming growth factor-β1 pathway in hepatocellular carcinoma cells. | The function of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established. However, the regulatory mechanisms modulating this phenomenon remain unclear. Homeobox B9 (HOXB9) has been proposed as an oncogene in many cancer developments, but its function and underlying mechanisms in HCC metastasis remain unknown. HOXB9 modulates EMT through the transforming growth factor-β1 (TGF-β1) pathway, which is a recognized regulator of EMT in HCC cells. The knockdown of HOXB9 decreased the migration and invasion of HCC cells. Conversely, the HOXB9 overexpression led to an increase in the above-mentioned phenotypes in HCC cells. Further analysis of HOXB9-regulated cellular functions showed the ability of this transcription factor to induce EMT. Moreover, we demonstrated that the TGF-β1 pathway is important in HOXB9-induced EMT in HCC cells. These findings define a novel cellular mechanism regulated by HOXB9, which controls EMT phenotype in HCC. This study is the first to illustrate the pivotal function of HOXB9 in regulating the metastatic behavior of HCC cells. | 25,081,022 | [
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Distribution of permanent canine agenesis in Down syndrome: 15 cases from a Centre for Special Care Dentistry. | The purpose of this study was to investigate the distribution of permanent canine agenesis in subjects with Down syndrome (DS). Subjects with canine agenesis were determined by means of panoramic radiographs from 150 DS subjects attending a center for special care dentistry. Our results confirm the high prevalence of agenetic canines in DS (21 canines, 14%). We found specific effects on the distribution both of phenotype and of location (jaw). In subjects with a mild expression of hypodontia (phenotype nonoligodontia) agenetic canines primarily occurred in the mandibula, whereas in subjects with severe hypodontia (phenotype oligodontia) agenetic canines virtually only occurred in the maxilla. In both phenotypes cooccurrence of an agenetic lateral incisor with an agenetic canine was observed in the maxilla. It was striking that canine agenesis in the mandibula did not cooccur with agenesis of other teeth. These results can be important for treatment planning. | 25,081,021 | [
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OsWRKY42 represses OsMT1d and induces reactive oxygen species and leaf senescence in rice. | We isolated a rice (Oryza sativa L.) WRKY gene which is highly upregulated in senescent leaves, denoted OsWRKY42. Analysis of OsWRKY42-GFP expression and its effects on transcriptional activation in maize protoplasts suggested that the OsWRKY42 protein functions as a nuclear transcriptional repressor. OsWRKY42-overexpressing (OsWR KY42OX) transgenic rice plants exhibited an early leaf senescence phenotype with accumulation of the reactive oxygen species (ROS) hydrogen peroxide and a reduced chlorophyll content. Expression analysis of ROS producing and scavenging genes revealed that the metallothionein genes clustered on chromosome 12, especially OsMT1d, were strongly repressed in OsWRKY42OX plants. An OsMT1d promoter:LUC construct was found to be repressed by OsWRKY42 overexpression in rice protoplasts. Finally, chromatin immunoprecipitation analysis demonstrated that OsWRKY42 binds to the W-box of the OsMT1d promoter. Our results thus suggest that OsWRKY42 represses OsMT1d-mediated ROS scavenging and thereby promotes leaf senescence in rice. | 25,081,037 | [
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New links between mRNA polyadenylation and diverse nuclear pathways. | The 3' ends of most eukaryotic messenger RNAs must undergo a maturation step that includes an endonuc-leolytic cleavage followed by addition of a polyadenylate tail. While this reaction is catalyzed by the action of only two enzymes it is supported by an unexpectedly large number of proteins. This complexity reflects the necessity of coordinating this process with other nuclear events, and growing evidence indicates that even more factors than previously thought are necessary to connect 3' processing to additional cellular pathways. In this review we summarize the current understanding of the molecular machinery involved in this step of mRNA maturation, focusing on new core and auxiliary proteins that connect polyadenylation to splicing, DNA damage, transcription and cancer. | 25,081,038 | [
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Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model. | Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1(+/-) mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (<P19). Seizures are generated intracortically in the granular layer of the neocortex. Slow kinetics of aberrant GluN2C-mediated currents in spiny stellate cells promotes excessive temporal integration of persistent NMDAR-mediated recurrent excitation and seizure generation. Accordingly, specific GluN2C/D antagonists block seizures in Tsc1(+/-) mice in vivo and in vitro. Likewise, GluN2C expression is upregulated in TSC human surgical resections, and a GluN2C/D antagonist reduces paroxysmal hyperexcitability. Thus, GluN2C receptor constitutes a promising molecular target to treat epilepsy in TSC patients. | 25,081,057 | [
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Ocular Involvement in Juvenile Idiopathic Arthritis: Classification and Treatment. | Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in childhood with a prevalence of 4 in 1,000 children. Anterior uveitis is a well-known threatening comorbid condition of JIA and affects around 10 % of the patients depending on JIA subtype. A large proportion of children with JIA develop uveitis in the first year of disease and 73 to 90 % after 4 years. Uveitis can progress into adulthood and usually occurs as 'white uveitis', while in the JIA related to the enthesitis subtype that is symptomatic. Current studies reinforced the previous observations that early age of JIA onset, oligoarticular subtype and ANA reactivity are the main risk factors for the development of uveitis. Factors associated to worse prognosis are as follows: findings of 1+ or more vitreous cells at presentation and initial visual acuity of 20/200 or worse. The Standardization of Uveitis Nomenclature (SUN) Group took the first step to define outcome measures for uveitis, but it was established for adults. The Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC) proposed outcome measures for JIA-associated uveitis incorporating the SUN criteria in 2011. The current suggested management recommends to start early a steroid-sparing effective immunomodulatory systemic treatment. Methylprednisolone intravenous pulse therapy, rituximab, tocilizumab and abatacept are promising agents. Because JIA-associated uveitis is a potentially threatening comorbidity, it is important to recognize and treat it early to prevent any visual damage that could impair visual acuity. | 25,081,063 | [
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Current Approach to Dry Eye Disease. | Dry eye disease (DED) is a multifactorial disease of the tears and ocular surface that causes tear film instability with potential damage to the ocular surface. The prevalence of dry eye in the world population ranges from 6 to 34 %. It is more common in those aged over 50, and affects mainly women. Since the introduction of the Schirmer's test in 1903, other tests have been developed to evaluate dry eye, such as biomicroscopy, the tear film breakup time (BUT), vital dyes (lissamine green and rose bengal), fluorescein, leaf fern test, corneal sensitivity test, conjunctiva impression cytology, optical coherence tomography (OCT), and tear osmolarity measurement. Although there is no gold standard, it is advisable to combine at least two tests. Strategies for treating DED have recently been modified and include patient education, tear substitute, corticosteroids, secretagogues, fatty acids, immunomodulators, occlusion of lacrimal puncta surgery and, tarsorrhaphy. Biological therapy and new topical immunomodulators such as tacrolimus, tofacitinib and IL-1 receptor inhibitor are being tested. In this review, the evaluation tests for dry eye are compared and the main studies on treatment are presented, with emphasis on studies in patients with Sjögren's syndrome. The authors propose an approach for the management of dry eye. | 25,081,064 | [
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Efficacy of interventions for prevention of chemotherapy-induced alopecia: a systematic review and meta-analysis. | Chemotherapy-induced alopecia (CIA) is a highly distressing event for cancer patients, and hence, we here aimed to assess the efficacy of various interventions in the prevention of CIA. We searched PubMed, EMBASE and the Cochrane Library, from June 20, 2013 through August 31, 2013. Two of the authors independently reviewed and selected clinical trials that reported the efficacy of any intervention for prevention of CIA compared with that of controls. Two authors extracted data independently on dichotomized outcome in terms of CIA occurrence. Relative risks (RRs) and 95% confidential intervals (CIs) were calculated for efficacy of CIA prevention by using random-effect or fixed-effect models. Out of 691 articles retrieved, a total of eight randomized controlled trials and nine controlled clinical trials involving 1,098 participants (616 interventions and 482 controls), were included in the final analyses. Scalp cooling, scalp compression, a combination of cooling and compression, topical minoxidil and Panicum miliaceum were used as interventions. The participants were mainly breast cancer patients receiving doxorubicin- or epirubicin-containing chemotherapy. Scalp cooling, which is the most popular preventive method, significantly reduced the risk of CIA (RR = 0.38, 95% CI = 0.32-0.45), whereas topical 2% minoxidil and other interventions did not significantly reduce the risk of CIA. No serious adverse effects associated with scalp cooling were reported. Our results suggest that scalp cooling can prevent CIA in patients receiving chemotherapy. However, the long-term safety of scalp cooling should be confirmed in further studies. | 25,081,068 | [
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Archaeal abundance in post-mortem ruminal digesta may help predict methane emissions from beef cattle. | Methane produced from 35 Aberdeen-Angus and 33 Limousin cross steers was measured in respiration chambers. Each group was split to receive either a medium- or high-concentrate diet. Ruminal digesta samples were subsequently removed to investigate correlations between methane emissions and the rumen microbial community, as measured by qPCR of 16S or 18S rRNA genes. Diet had the greatest influence on methane emissions. The high-concentrate diet resulted in lower methane emissions (P < 0.001) than the medium-concentrate diet. Methane was correlated, irrespective of breed, with the abundance of archaea (R = 0.39), bacteria (-0.47), protozoa (0.45), Bacteroidetes (-0.37) and Clostridium Cluster XIVa (-0.35). The archaea:bacteria ratio provided a stronger correlation (0.49). A similar correlation was found with digesta samples taken 2-3 weeks later at slaughter. This finding could help enable greenhouse gas emissions of large animal cohorts to be predicted from samples taken conveniently in the abattoir. | 25,081,098 | [
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Structural investigation of donor age effect on human bone marrow mesenchymal stem cells: FTIR spectroscopy and imaging. | Stem cell studies hold enormous potential for development of new therapies for tissue regeneration and repair. Bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into a variety of non-hematopoietic tissues and contribute maintenance of healthy hematopoiesis by providing supportive cellular microenvironment into BM. Here, we investigated age-related differences in BM-MSCs by using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and FTIR imaging together with hierarchical clustering as a novel methods to clarify global alterations in the structure and function of macromolecules in characterized BM-MSCs of different aged donors. The results may contribute to identification of age-related new molecular marker(s) to determine the effects of donor age on MSCs. The spectral results reflected that there were significant increases in the concentration of saturated lipids, proteins, glycogen, and nucleic acids in children and adolescent group BM-MSCs when compared to the infants and early and mid adults. The concentration of mentioned macromolecules in adult (early and mid) BM-MSCs were significantly lower than the concentrations in the children and adolescents. These results were attributed to the increase in the proliferation activity in younger BM-MSCs. The distribution of macromolecules into the cells was shown as in the form of chemical maps by FTIR imaging, and the results are in agreement with the ATR-FTIR spectroscopy results. The cellular activity degree was determined by the thiazolyl blue tetrazolium bromide (MTT) proliferation assay to support ATR-FTIR spectroscopy results. BM-MSCs of five different age groups were discriminated by making the hierarchical cluster analysis where the spectral data according to alterations in structure and composition of macromolecules were considered. | 25,081,108 | [
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An active-core/active-shell structure with enhanced quantum-cutting luminescence in Pr-Yb co-doped monodisperse nanoparticles. | Monodisperse Pr(3+)/Yb(3+):NaGdF₄@NaYF₄ active-core/inert-shell nanoparticles, which exhibit efficient near-infrared quantum-cutting luminescence, are successfully prepared. In order to relieve the adverse effect caused by concentration quenching in the core, the extra Yb(3+) ions are introduced into the shell, forming an active-core/active-shell structure which leads to a much intensified near-infrared emission. | 25,081,139 | [
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Two new species of Aulospongus Norman, 1878 with a key to the Atlantic species (Poecilosclerida; Demospongiae; Porifera). | We describe two new species: Aulospongus trirhabdostylus sp. nov. and Aulospongus mandela sp. nov. from Potiguar Basin (Rio Grande do Norte State, Northeastern Brazil). Both species were compared with their congeners and an identification key for the Atlantic species of Aulospongus is provided. The genus Aulospongus now contains 16 species. | 25,081,159 | [
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The parerigonine genus Paropesia Mesnil (Diptera, Tachinidae), with descriptions of three new species from East Asia. | Three new species of Paropesia Mesnil (Phasiinae, Parerigonini) are described: P. discalis sp. nov. from China and Myanmar, P. grisea sp. nov. from Japan and P. tessellata sp. nov. from Myanmar and China. The type species of Paropesia, P. nigra Mesnil, is redescribed. The male and female terminalia of the new species are described and illustrated and characteristics of the genus Paropesia are briefly discussed. | 25,081,178 | [
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Architectural proteins CTCF and cohesin have distinct roles in modulating the higher order structure and expression of the CFTR locus. | Higher order chromatin structures across the genome are maintained in part by the architectural proteins CCCTC binding factor (CTCF) and the cohesin complex, which co-localize at many sites across the genome. Here, we examine the role of these proteins in mediating chromatin structure at the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encompasses nearly 200 kb flanked by CTCF-binding enhancer-blocking insulator elements and is regulated by cell-type-specific intronic enhancers, which loop to the promoter in the active locus. SiRNA-mediated depletion of CTCF or the cohesin component, RAD21, showed that these two factors have distinct roles in regulating the higher order organization of CFTR. CTCF mediates the interactions between CTCF/cohesin binding sites, some of which have enhancer-blocking insulator activity. Cohesin shares this tethering role, but in addition stabilizes interactions between the promoter and cis-acting intronic elements including enhancers, which are also dependent on the forkhead box A1/A2 (FOXA1/A2) transcription factors (TFs). Disruption of the three-dimensional structure of the CFTR gene by depletion of CTCF or RAD21 increases gene expression, which is accompanied by alterations in histone modifications and TF occupancy across the locus, and causes internalization of the gene from the nuclear periphery. | 25,081,205 | [
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Drosophila Brahma complex remodels nucleosome organizations in multiple aspects. | ATP-dependent chromatin remodeling complexes regulate nucleosome organizations. In Drosophila, gene Brm encodes the core Brahma complex, the ATPase subunit of SWI/SNF class of chromatin remodelers. Its role in modulating the nucleosome landscape in vivo is unclear. In this study, we knocked down Brm in Drosophila third instar larvae to explore the changes in nucleosome profiles and global gene transcription. The results show that Brm knockdown leads to nucleosome occupancy changes throughout the entire genome with a bias in occupancy decrease. In contrast, the knockdown has limited impacts on nucleosome position shift. The knockdown also alters another important physical property of nucleosome positioning, fuzziness. Nucleosome position shift, gain or loss and fuzziness changes are all enriched in promoter regions. Nucleosome arrays around the 5' ends of genes are reorganized in five patterns as a result of Brm knockdown. Intriguingly, the concomitant changes in the genes adjacent to the Brahma-dependent remodeling regions have important roles in development and morphogenesis. Further analyses reveal abundance of AT-rich motifs for transcription factors in the remodeling regions. | 25,081,211 | [
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The yeast prefoldin-like URI-orthologue Bud27 associates with the RSC nucleosome remodeler and modulates transcription. | Bud27, the yeast orthologue of human URI/RMP, is a member of the prefoldin-like family of ATP-independent molecular chaperones. It has recently been shown to mediate the assembly of the three RNA polymerases in an Rpb5-dependent manner. In this work, we present evidence of Bud27 modulating RNA pol II transcription elongation. We show that Bud27 associates with RNA pol II phosphorylated forms (CTD-Ser5P and CTD-Ser2P), and that its absence affects RNA pol II occupancy of transcribed genes. We also reveal that Bud27 associates in vivo with the Sth1 component of the chromatin remodeling complex RSC and mediates its association with RNA pol II. Our data suggest that Bud27, in addition of contributing to Rpb5 folding within the RNA polymerases, also participates in the correct assembly of other chromatin-associated protein complexes, such as RSC, thereby modulating their activity. | 25,081,216 | [
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Validation of a new questionnaire to assess the impact of Whiplash Associated Disorders: The Whiplash Activity and participation List (WAL). | Valid questionnaires for measuring functional limitations in patients with Whiplash Associated Disorders (WAD) are lacking, since existing measures are not suitable for addressing the specific limitations of these patients and because of cross contamination between theoretical constructs. The objective of this study was to evaluate dimensionality, test-retest reliability, measurement error, construct validity, and responsiveness of a new condition-specific questionnaire for WAD as well as to estimate the minimally important change score. Patients with WAD grade I or II were recruited from physical therapy practices and rehabilitation centers. Dimensionality was examined by internal consistency analysis (Cronbach's alpha) and factor analysis. Test-retest reliability was estimated by intraclass correlations and measurement error was calculated by the minimal detectable change (MDC) scores. Construct validity was investigated by testing predefined hypotheses on correlations of the WAL scores with generic health measures and by using the known group method. Responsiveness was expressed as the minimal clinically important change (MCIC) score. 73 patients (53 women) were included. Cronbach's alpha was high (0.95) and unidimensionality was plausible because factor analysis showed 40.3% variance explained by one dominant factor, which was more than 4.5 times larger than the second largest factor. Test-retest reliability was excellent (0.92, 95% CI 0.87-0.95). Construct validity was supported by 14 out of 15 confirmed hypotheses and the WAL showed statistically significant differences between known groups. MDC was 16 points while the MCIC was 18 points. In conclusion, the present study suggests that the WAL has adequate measurement properties, but additional research is needed. | 25,081,220 | [
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Decreases in activated CD8+ T cells in patients with severe hepatitis B are related to outcomes. | Many studies on T helper (Th)1, Th2, T regulatory and Th17 cells have been carried out in acute-on-chronic liver failure (ACLF). However, CD8(+) T cell, as a main participant in immune-mediated injuries and defense against microorganisms, has seldom been studied in ACLF. The purpose of this study was to investigate the CD8(+) T cell function, and the outcomes of patients with severe hepatitis [SH; serum bilirubin (SB) ≥ 10 mg/dl and prothrombin activity (PTA) < 60 %]. Thirty-six patients with chronic HBV-associated SH were included. Twenty normal chronic hepatitis B (CHB) patients (2 < SB < 10 (mg/dl) and PTA ≥ 60 %) and 28 healthy volunteers were enrolled as control groups. Twenty-six patients with SH were diagnosed with ACLF (SB ≥ 10 mg/dl and PTA ≤ 40 %). The non-recovered ACLFs (NR-ACLF) had higher HBV DNA loads than recovered ACLFs (R-ACLF) (6.03 ± 1.79 vs. 4.36 ± 1.61 (log10, IU/L)). The NR-ACLFs had the highest neutrophil:lymphocyte ratios (5.10 ± 2.37) (all P < 0.001; a = 0.05). The CHBs had higher perforin(+) and TCM (CD45RA(-)CD62L(hi)CCR7(+)) proportions [31.28 ± 19.51, 5.32 ± 3.57 (%)] compared to R-ACLFs (11.75 ± 15.35, 0.78 ± 0.76 (%); P = 0.004, 0.001, respectively), or NR-ACLFs (11.61 ± 5.79, 1.14 ± 0.67 (%); P = 0.006, 0.003). The non-ACLF SHs had higher CD38(+) proportions than R-ACLFs or NR-ACLFs (25.46 ± 8.02 vs. 16.24 ± 7.77 or 16.81 ± 6.30 (%), P = 0.039, 0.023). High neutrophil:lymphocyte ratios and a decrease in activated CD8(+) T cells may be related to poor outcomes in patients with SH. | 25,081,223 | [
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Optical coherence tomography for guiding wire into a side branch coronary artery with flush total occlusion. | We report a case of flush occlusion, where a novel use of optical coherence tomography (OCT) helped in successful crossing and stenting of the lesion. | 25,081,229 | [
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Disparities in reported and substantiated infant maltreatment by maternal Hispanic origin and nativity: a birth cohort study. | We followed Latino infants prospectively through age 1 to determine whether maternal foreign-born status conferred a protective advantage against reported and substantiated maltreatment across Hispanic-origin groups, and whether the likelihood an infant was reported or substantiated for maltreatment varied by Hispanic origin. We drew data for all Latino infants born in California between 2000 and 2006 (N = 1,909,155) from population-based birth records linked to child protective services data. We used χ(2) tests to assess distributional differences in covariates and utilized generalized linear models to estimate the adjusted relative risk of report and substantiation in models stratified by nativity. We observed significant health advantages in reported and substantiated maltreatment for infants of foreign-born mothers within every Hispanic-origin group. Risks of report and substantiation among infants of Mexican and Central/South American mothers were consistently lower than Puerto Rican and Cuban mothers despite socioeconomic disadvantage. The presence of disparities among Hispanic-origin groups in child maltreatment report and substantiation during infancy has implications for the health of Latinos across the life course. Further research is warranted to unravel the complex processes underlying observed relationships. | 25,081,241 | [
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Impact of sex on the survival of patients with hepatocellular carcinoma: a Surveillance, Epidemiology, and End Results analysis. | Men are 4 to 8 times more likely to develop hepatocellular carcinoma (HCC) than women. Preclinical models have suggested a role for sex hormones in the development of HCC. In the current study, the authors investigated the impact of age, sex, race, and ethnicity on the survival of patients with HCC using the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with HCC from 1988 through 2010 were identified from the SEER registry. Hazard ratios (HR) for overall survival (OS) were derived using the Cox regression model adjusted for race, year of diagnosis, marital status, treatment, birthplace, tumor differentiation, and tumor size. A total of 39,345 patients were identified; 76% were men and 34% were women (50% white, 12% African American, 21% Asian, 16% Hispanic, and 1% Native American). The median age at the time of diagnosis was 61 years for men and 67 years for women. Approximately 84% of patients had liver-limited disease and 16% had metastatic disease. Treatment information was available for patients diagnosed after 1998 (34,674 patients): 11% received liver-directed therapy, 11% underwent surgical resection, and 7% underwent liver transplantation. The HR for the OS of women versus men was 0.83 (95% confidence interval [95% CI], 0.77-0.88) for patients aged <55 years. The protective effect of sex on OS was found to be greatest in patients aged 18 to 44 years (HR, 0.75; 95% CI, 0.65-0.86 [P<.001]), especially those with surgically resected tumors (HR, 0.68; 95% CI, 0.54-0.86 [P = .001]) and those who were African American (HR, 0.85; 95% CI, 0.78-0.92 [P<.001]). There was no survival difference between sexes noted among Hispanics or patients aged >65 years. Sex appears to be associated with survival in patients with HCC. The role of androgens and estrogens in the development and progression of HCC warrants further investigation. | 25,081,299 | [
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Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain. | Direct intracellular delivery of intact proteins has been successfully achieved by tagging cell-penetrating peptide (CPP), which consists of short positively charged amino acids, such as 11 poly-arginine (11R); however, in vivo delivery of the proteins to the brain has remained challenging because it is unclear whether CPP would enable proteins to cross the blood-brain barrier (BBB). In this study, we conducted an in vivo kinetic study to investigate the efficiency of 11R-mediated peptide delivery in the normal and ischemic brain. The 11R was observed in the microvessels and neurons surrounding the microvessels throughout the brain 1 hour after systemic administration, but the signal of the peptide was faint after 2 hours. In a transient middle cerebral artery occlusion mouse model, 11R was markedly enhanced and remained detectable in the cells on the ipsilateral side for as long as 8 hours after administration compared with the contralateral side. These results suggest that 11R is capable of in vivo delivery to the brain by passing through the BBB. Furthermore, 11R-mediated protein transduction could be used for the delivery of therapeutic molecules in cerebral ischemia. | 25,081,308 | [
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Elevated international normalized ratio as a manifestation of post-thrombolytic coagulopathy in acute ischemic stroke. | A serious complication of intravenous tissue plasminogen activator (tPA) in acute ischemic stroke is hemorrhage. Coagulation factors that may potentially increase the risk of bleeding after tPA are not well understood. We retrospectively reviewed 284 acute ischemic stroke patients who received tPA. Post-tPA coagulopathy was defined as a documented elevation of international normalized ration (INR) > 1.5 within 24 hours after IV tPA without a known cause. We identified 21 (7.4%) patients with an elevated INR post-thrombolysis. The mean age was 68.3 years (standard deviation ± 11.9) and 57% were male. The mean initial National Institutes of Health Stroke Scale (pre-tPA) was 15.8 (range, 4-35). Liver disease or alcohol abuse was noted in 19%. There were 2 tPA protocol violations who received more than 90 mg tPA. The mean post-tPA INR was 2.03 (range, 1.5-4.7) and the elevation in INR was documented within a mean 5.4 hours (range, 1-15) after tPA initiation. Repeat INR levels returned to normal during their hospital stay in 19 patients. Hypofibrinogenemia was noted in 10 of 12 patients who had fibrinogen levels drawn within 48 hours after tPA initiation and in all 7 patients with fibrinogen levels drawn the same time as the elevated INR. Among the 6 patients with bleeding complications, 2 patients had symptomatic intracerebral hemorrhage. We report an under-recognized early transient coagulopathy associated with elevated INR in stroke patients after treatment with tPA. | 25,081,309 | [
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Pre-procedural combined coronary angiography and stress myocardial perfusion imaging using 320-detector CT in unprotected left main and ostial left anterior descending artery intervention. | Pre-procedural anatomic and functional coronary assessment plays a crucial role in selection of patients suitable for unprotected left main percutaneous coronary intervention. Combined coronary computed tomography angiography and adenosine stress computed tomography myocardial perfusion imaging is a non-invasive technique which may provide this information. This is the first report describing its use to assist patient selection and procedural planning prior to elective left main and ostial left anterior descending artery coronary intervention. | 25,081,314 | [
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Clinically insignificant residual fragments after flexible ureterorenoscopy: medium-term follow-up results. | The characteristics of clinically insignificant residual fragments (CIRFs) are well described after percutaneous nephrolithonomy (PCNL) and shock wave lithotripsy (SWL). In follow-up procedures, CIRFs are associated with obstruction, infectious conditions, and recurrent stone development. In this study, we aim to determine the medium-term outcomes of CIRF. Between May 2009 and January 2013, 384 patients underwent flexible ureterorenoscopy (F-URS). In 44 patients, CIRFs were diagnosed with abdominal CT between 3 weeks and 3 months after the operation. Periodic follow-up, including clinical examination, serum biochemistry, urine culture, and radiological imaging, was performed for all patients. Also, 24 h urine analysis and stone composition were evaluated. Asymptomatic patients with stable stone sizes or patients with spontaneous clearance were classified in group 1 and patients with increasing stone sizes or those who became symptomatic were classified in group 2. The variables affecting stone recurrence between the two groups were compared. A total of 15 patients showed symptoms and/or stone development in the median 30.5 ± 8.809 months follow-up period. Additional treatment modalities-including F-URS in five patients, URS in three patients, SWL in two patients, and PCNL in one patient-were performed in 11 patients. The pre-operative stone burden and the number of patients with metabolic abnormalities were significantly higher in group 2 than in group 1. Medium-term follow-up of CIRF after F-URS demonstrated that recurrence is common within 2 years. The presence of a pre-operative high stone burden and metabolic abnormalities in 24 h urine analysis were predictive factors for stone recurrence. | 25,081,327 | [
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Association study of DGKH gene polymorphisms with calcium oxalate stone in Chinese population. | Diacylglycerol kinase eta (DGKH) participates in regulating the intracellular concentrations of two bioactive lipids, diacylglycerol and phosphatidic acid. With the emerging evidence of a novel regulatory function for diacylglycerol kinase and diacylglycerol in transplasmalemmal calcium ion influx, the present study was designed to investigate the association between DGKH genetic polymorphisms and calcium oxalate stone. 507 patients with calcium oxalate stone and 505 healthy cohorts as control were entered in this prospective study. Three tag single nucleotide polymorphisms (rs4142110, rs180870 and rs17646069) were investigated. Genotyping was carried out by iPLEX Gold for MassARRAY system. Our results showed that rs4142110 was associated with risk of calcium oxalate stone and hypercalciuria (P < 0.05). The T allele, CT genotype, TT genotype, and the combined T variant genotype (TT + CT) of rs4142110 significantly decreased calcium oxalate stone risk (P < 0.05). Rs180870 also showed significant association in genotype distributions between cases and controls (P = 0.042). Hypercalciuria was more prevalent in stone formers (P = 0.010). These findings implicate a link between nucleotide variant of DGKH and a cause for a complex-trait disease, calcium oxalate stone. Similar relationship might also exist between polymorphism of DGKH and hypercalciuria. | 25,081,328 | [
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Use of photovoice to integrate a community-engaged scholarship model of research into an undergraduate clinical nursing course. | For undergraduate nursing students to appreciate the underpinnings of research, it is essential to bring research to real-life clinical practice. This article reports on an innovative educational experience integrating qualitative research into the sophomore-level clinical setting. The elements of this pedagogical approach within the context of faculty-mentored and student-led community-based participatory research are described. | 25,081,330 | [
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The downregulation of ErbB3 binding protein 1 (EBP1) is associated with poor prognosis and enhanced cell proliferation in hepatocellular carcinoma. | ErbB3 binding protein 1 (EBP1) has been recently reported to function as a tumor suppressor in the progression of multiple cancers, including breast cancer, prostate cancer, salivary adenoid cystic carcinoma (ACC), and oral squamous cell carcinoma (OSCC). However, the expression and physiological significance of EBP1 in hepatocellular carcinoma (HCC) remain unclear. In the study, we showed that EBP1 was significantly downregulated in clinical HCC specimens, and that decreased expression of EBP1 was associated with enhanced proliferation in HCC cells. Western blot and immunohistochemical analyses revealed that EBP1 was remarkably downregulated in HCC tissues compared with the adjacent normal ones. The levels of EBP1 were significantly associated with histological grade (P = 0.034), tumor size (P = 0.001), and Ki67 expression (P < 0.001) in HCC specimens. Univariate and multivariate analyses showed that EBP1 could serve as an independent prognostic indicator of patients' survival. Serum starvation and refeeding assay indicated that EBP1 was accumulated in growth-arrested HCC cells, and was progressively decreased when cells entered into S phase. Moreover, the depletion of EBP1 induced growth acceleration and cell cycle progression in L02 hepatocytes. On the basis of these findings, we conclude that EBP1 may be a valuable prognostic marker and promising therapeutic target of HCC. | 25,081,333 | [
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Margins: a status report from the Annual Meeting of the American Society of Breast Surgeons. | Since the emergence of breast conserving surgery (BCS) as an alternative to mastectomy in the 1980's, there has been little consensus on what constitutes acceptable margins for cases of invasive breast cancer, how best to evaluate margins in the operating room, or an understanding of the challenging process of margin assessment by pathologists. The program committee for the 15th Annual Meeting of The American Society of Breast Surgeons organized a plenary session to discuss the latest thinking and guidelines for these important issues. The SSO/ASTRO Consensus Guideline on Margins for BCS was an important focus of discussion. The SSO/ASTRO consensus panelists concluded that "no ink on tumor" is an adequate surgical margin for BCS in patients with invasive breast cancers. Intraoperative strategies to decrease the incidence of positive margins include intraoperative localization techniques (wire-localization, ultrasound, radioactive seed) and intraoperative margin assessments with specimen radiography, imprint cytology, and frozen section. Studies also demonstrate the positive effect of shave margins with or without intraoperative margin assessment. The College of American Pathologists protocols for breast specimen margin evaluation consider multiple variables that can impact the proper assessment of margins. These variables include: tissue fixation time, specimen orientation, cold ischemia time, leaking ink, specimen pancaking and others that surgeons need to be aware of. Determining when "enough is enough" should not only be the application of guidelines and national standards, but also a multidisciplinary discussion between breast cancer specialists for what is right for the individual patient's unique circumstances. | 25,081,342 | [
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Higher rate of breast surgery complications in patients with metastatic breast cancer: an analysis of the NSQIP database. | Four percent of breast cancer patients present with metastatic disease. To date, no one has examined whether these patients are at higher risk of postoperative complications. The objective of this study was to determine morbidity and mortality associated with breast surgery in the metastatic setting. We analyzed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, including breast cancer patients undergoing primary breast surgery from 2005 to 2012. Patients with bilateral surgery or severe comorbidities were excluded. Multivariable logistic regression was performed to determine the independent effect of metastatic breast cancer on postoperative morbidity and mortality. We identified 68,316 patients who underwent breast surgery for invasive breast cancer; 1,031 (1.5 %) had metastatic disease. The 30-day unadjusted morbidity was significantly higher in the metastatic cohort (7.5 vs. 3.7 %; p < 0.001), as was the all-cause 30-day mortality (1.8 vs. 0.06 %; p < 0.001). The metastatic cohort was more likely to experience an: infectious, respiratory, thromboembolic, cardiac, or bleeding complication than non-metastatic patients. However, preoperative chemo- and radiation therapy did not contribute to an overall increased complication rate. The adjusted odds ratio for postoperative complications in the setting of metastatic disease was 1.6 (95 % confidence limit 1.2-2.1). This is the first study documenting the morbidity and mortality associated with breast surgery in metastatic breast cancer. The 30-day morbidity and mortality in this population is higher than in patients with stage I-III disease. Although the complication rate is increased, operating on the primary in metastatic breast cancer is relatively safe. | 25,081,343 | [
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The exon junction complex is required for definition and excision of neighboring introns in Drosophila. | Splicing of pre-mRNAs results in the deposition of the exon junction complex (EJC) upstream of exon-exon boundaries. The EJC plays crucial post-splicing roles in export, translation, localization, and nonsense-mediated decay of mRNAs. It also aids faithful splicing of pre-mRNAs containing large introns, albeit via an unknown mechanism. Here, we show that the core EJC plus the accessory factors RnpS1 and Acinus aid in definition and efficient splicing of neighboring introns. This requires prior deposition of the EJC in close proximity to either an upstream or downstream splicing event. If present in isolation, EJC-dependent introns are splicing-defective also in wild-type cells. Interestingly, the most affected intron belongs to the piwi locus, which explains the reported transposon desilencing in EJC-depleted Drosophila ovaries. Based on a transcriptome-wide analysis, we propose that the dependency of splicing on the EJC is exploited as a means to control the temporal order of splicing events. | 25,081,352 | [
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Geographic disparity: the dilemma of lower socioeconomic status, multiple listing, and death on the liver transplant waiting list. | Due to the current regionally based allocation system, some patients list for and are transplanted away from home in regions with shorter waits and higher transplant rates. Of 147 included patients, 120 died waiting and 27 received transplants at outside centers during the study (32.5 months). Those transplanted elsewhere had higher median incomes than patients dying on the waitlist ($84 946 vs. $55 250, p = 0.0001). Those with median incomes <$60 244 were more likely to die than those with incomes >$60 244 (94% vs. 70%, RR: 1.35, 95% CI: 1.14-1.59). Patients with Medicaid were more likely to die waiting than those with other insurance (100% vs. 77%, RR: 1.30, 95% CI: 1.18-1.44). Our analysis demonstrates that those who died waiting were more likely to have lower incomes and Medicaid compared with those transplanted elsewhere. Even when we controlled for Medicaid status, patients who died waiting had lower incomes compared with those transplanted elsewhere. Increased organ sharing over geographically broader regions, as recommended by the Institute of Medicine in 1999, may reduce incentives for patients to travel to receive a liver and reduce inequities. Current efforts to address this disparity continue to fall short of the Institute of Medicine recommendations, United States Department of Health and Human Services regulations and the Final Rule. | 25,081,356 | [
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Liquid-metal electrode to enable ultra-low temperature sodium-beta alumina batteries for renewable energy storage. | Commercial sodium-sulphur or sodium-metal halide batteries typically need an operating temperature of 300-350 °C, and one of the reasons is poor wettability of liquid sodium on the surface of beta alumina. Here we report an alloying strategy that can markedly improve the wetting, which allows the batteries to be operated at much lower temperatures. Our combined experimental and computational studies suggest that addition of caesium to sodium can markedly enhance the wettability. Single cells with Na-Cs alloy anodes exhibit great improvement in cycling life over those with pure sodium anodes at 175 and 150 °C. The cells show good performance even at as low as 95 °C. These results demonstrate that sodium-beta alumina batteries can be operated at much lower temperatures with successfully solving the wetting issue. This work also suggests a strategy to use liquid metals in advanced batteries that can avoid the intrinsic safety issues associated with dendrite formation. | 25,081,362 | [
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Delayed argon administration provides robust protection against cardiac arrest-induced neurological damage. | Argon at a dosage of 70 % is neuroprotective, when given 1 h after cardiac arrest (CA) in rats. We investigated if a neuroprotective effect of argon would also be observed, when administration was delayed. Twenty-four male Sprague-Dawley rats, weighing between 400 and 500 g were subjected to 7 min of CA and 3 min of cardiopulmonary resuscitation. Animals were randomized to receive either 1 h of 70 % argon ventilation 1 h (n = 8) or 3 h (n = 8) after return of spontaneous circulation or no argon treatment (n = 8). For all animals, a neurological deficit score (NDS) was calculated daily for 7 days following the experiment. On day 8, rats were re-anesthetized and transcardially perfused before brains were harvested for histopathological analyses. All animals survived. Control animals exhibited severe neurologic dysfunction at all time points as measured with the NDS. Argon-treated animals showed significant improvements in the NDS through all postoperative days, even when argon administration was delayed for 3 h. This was paralleled by a significant reduction in the neuronal damage index in the neocortex and the hippocampal CA 3/4 region in argon-treated animals, regardless of the timing of argon administration. However, animals of the delayed argon administration group additionally showed significant reductions in the basal ganglia in comparison with control animals. Our study demonstrates that a 1-h application of argon provided a significant reduction in histopathological damage, associated with a marked improvement in functional neurologic recovery even when treatment was delayed for 3 h. This is highly significant with regard to clinical situations, where argon treatment cannot be provided timely. | 25,081,369 | [
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[Clinical criteria of involuntary psychiatric treatment: a literature review and a synthesis of recommendations]. | Though the carrying out of involuntary psychiatric care (IPC) mainly follows from a subjective appraisal of the patient's state, some specific clinical criteria have been proposed on regards to the underlying disorder. French national recommendations are synthesized hereby, and completed by a literature review. In psychotic disorders, the level of insight and the impact of delusion(s) are the essential criteria that should recommend to carry out IPC. In mood disorders, the appraisal is different depending on the underlying clinical state. In depressive or mixed states, IPC should be considered mainly in case of suicidal risk or jeopardizing physical consequences. In mania, IPC should result from a poor level of insight, or from the onset of significant social or occupational aftermaths. For suicidal states, it is necessary to appreciate suicidal risk and underlying psychiatric disorder. In addictive disorders, repeated risk-taking and denial should be the main criteria for considering IPC. In eating disorders, the occurring of both danger of death and denial of care should lead to possible IPC. Personality disorders are severity factors of emergency psychiatric states which can result in IPC. They are not criteria for IPC by themselves. For patients with dementia, mostly behavioural disturbances can require IPC. | 25,081,393 | [
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Impact of echocardiographic left ventricular geometry on clinical prognosis. | Abnormal left ventricular (LV) geometry, including LV hypertrophy (LVH), is associated with increased risk of major cardiovascular (CV) events and all-cause mortality and may be an independent predictor of morbid CV events. Patients with LVH have increased risk of congestive heart failure, coronary heart disease, sudden cardiac death and stroke. We review the risk factors for LVH and its consequences, as well as the risk imposed by concentric remodeling (CR). We also examine evidence supporting the benefits of LVH regression, as well as evidence regarding the risk of CR progressing to LVH, as opposed to normalization of CR. We also briefly review the association of abnormal LV geometry with left atrial enlargement and the combined effects of these structural cardiac abnormalities. | 25,081,397 | [
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Rare functional variants in genome-wide association identified candidate genes for nonsyndromic clefts in the African population. | Nonsyndromic clefts of the lip and palate (NSCLP) are complex genetic traits. Together, they are classified as one of the most common birth defects with a prevalence of 1/700 live births. Genome-wide association studies (GWAS) for nonsyndromic cleft lip with or without cleft palate (NSCL[P]) revealed significant association for common single nucleotide polymorphisms near genes involved in craniofacial development i.e., MAFB, PAX7, VAX1, ARHGAP29 (ABCA4 locus), and IRF6. Sequencing of protein coding regions of the NSCL(P) GWAS candidate genes or adjacent genes suggest a role for rare functional variants. Replication studies in the African population did not observe any significant association with the GWAS candidate genes. On the other hand, the role of rare functional variants in GWAS candidate genes has not been evaluated in the African population. We obtained saliva samples from case triads in Nigeria and Ethiopia for Sanger sequencing of the GWAS candidate genes (MAFB, PAX7, VAX1, ARHGAP29, and IRF6) in order to identify rare functional variants. A total of 220 African samples (140 Nigerians and 80 Ethiopians) were sequenced and we found the following new rare variants- p.His165Asn in the MAFB gene, p.Asp428Asn in the PAX7, a splice-site variant that creates a new donor splice-site in PAX7. We also found three previously reported missense variants p.Gly466Ser in PAX7; p.Leu913Ser and Arg955His in ARHGAP29. No de novo mutations were found. Future genome-wide association and sequencing studies should be conducted using samples from Africa in order to identify new molecular genetic factors that contribute to the etiology of NSCLP. | 25,081,408 | [
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Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing. | Immunohistochemistry (IHC) for mismatch repair protein expression, microsatellite instability (MSI) testing, tumor morphology, and family history were compared to determine which screening strategy is superior in identifying Lynch syndrome (LS) in unselected women with newly diagnosed endometrial cancer (EC) who have undergone universal germline mutation testing. A prospective cohort study was performed that recruited women with newly diagnosed EC. Participants completed a family history assessment with molecular characterization of EC with IHC and MSI testing and EC assessment for LS-associated morphologic features and underwent universal germline mutation testing for mutations in the mismatch repair pathway. The sensitivity, specificity, and positive and negative predictive values were compared between the screening strategies. A total of 118 (65%) of 182 consecutive women with EC participated. Of these, 34 women (29%) had tumors that were IHC deficient and 27 women (23%; N = 117) had tumors that were positive for MSI. Twenty women (17%) met IHC criteria and 16 women (15.2%, N = 105) met family history criteria based on Ontario Ministry of Health Criteria for the genetic assessment for LS. Seven women (5.9%) had a germline mutation: 4 had MLH1 (mutL homolog 1), 2 had MSH6 (mutS homolog 6), and 1 had MSH2 (mutS homolog 2). IHC in women aged <60 years had the best performance characteristics, with a sensitivity of 100%, a specificity of 86.1%, a positive predictive value of 58.3%, and a negative predictive value of 100%. Family history and tumor morphology both had the lowest sensitivity at 71.4%. Overall tumor morphology had the poorest performance, with a specificity of 42.1%. The mutation rate of 5.9% was higher than expected in this unselected cohort of women with EC. The superior screening strategy to identify women presenting with EC is universal IHC screening in women aged <60 years. | 25,081,409 | [
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Echocardiographic assessment of prosthetic heart valves. | Valvular heart disease is a global health problem. It is estimated that more than 280,000 prosthetic heart valves are implanted worldwide each year. As the world's population is aging, the incidence of prosthetic heart valve implantation and the prevalence of prosthetic heart valves continue to increase. Assessing heart valve prosthesis function remains challenging, as prosthesis malfunction is unpredictable but not uncommon. Transthoracic two-dimensional and Doppler echocardiography is the preferred method for assessing prosthetic valve function. Clinically useful Doppler-derived measures for assessing prosthetic valve hemodynamic profiles have been reported for aortic, mitral, and tricuspid valve prostheses, but echocardiographic data regarding pulmonary valve prostheses remain limited. Complete prosthetic valve evaluation by transthoracic echocardiography (TTE) is sometimes challenging due to acoustic shadowing and artifacts. In these cases, further imaging with transesophageal echocardiography, fluoroscopy and/or gated CT may be warranted, particularly if prosthetic valve dysfunction is suspected. Being able to differentiate pathologic versus functional obstruction of an individual prosthesis is extremely important, as this distinction affects management decisions. Transprosthetic and periprosthetic regurgitation may be difficult to visualize on TTE, so careful review of Doppler-derived data combined with a high index of suspicion is warranted, particularly in symptomatic patients. A baseline TTE soon after valve implantation is indicated in order to "fingerprint" the prosthesis hemodynamic profile. It remains unclear how frequently serial imaging should be performed in order to assess prosthetic valve function, as this issue has not been systematically studied. | 25,081,405 | [
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Early development and growth in captive-born Iberian lynx (Lynx pardinus). | Knowledge on the growth and early development patterns of endangered species can become a useful conservation tool because it may allow detecting anomalous growth in newborns, both in captivity breeding and in the wild. We studied the growth and early development of 40 Iberian lynx (Lynx pardinus) cubs belonging to 21 litters born in captivity between 2005 and 2012 at "El Acebuche" Iberian Lynx Breeding Centre. This is the first study on growth in this critically endangered species. The Iberian lynx cubs were not fully developed at birth. During the first 3 weeks of life, cubs underwent many of the physical changes that allowed them to improve their interaction with the environment, such as the opening of eye and auditory channels, teeth eruptions, and the ability to walk. When the cubs were 1 month old, they were ready to leave the den and develop new behaviors such as the exploration of their environment, play, or hunt. Three different models had been fitted to the body mass growth of the Iberian lynx. The von Bertalanffy curve provided the best fit. The asymptotic adult mass was the only parameter that differed between males and females (males being 8% larger), due to the higher growth rate of males. The adult weight of hand-reared cubs (i.e., those abandoned at born) did not differ from that of cubs reared by their mothers. Both growth and development showed differences from other lynx species. | 25,081,419 | [
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A high-speed brain speller using steady-state visual evoked potentials. | Implementing a complex spelling program using a steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) remains a challenge due to difficulties in stimulus presentation and target identification. This study aims to explore the feasibility of mixed frequency and phase coding in building a high-speed SSVEP speller with a computer monitor. A frequency and phase approximation approach was developed to eliminate the limitation of the number of targets caused by the monitor refresh rate, resulting in a speller comprising 32 flickers specified by eight frequencies (8-15 Hz with a 1 Hz interval) and four phases (0°, 90°, 180°, and 270°). A multi-channel approach incorporating Canonical Correlation Analysis (CCA) and SSVEP training data was proposed for target identification. In a simulated online experiment, at a spelling rate of 40 characters per minute, the system obtained an averaged information transfer rate (ITR) of 166.91 bits/min across 13 subjects with a maximum individual ITR of 192.26 bits/min, the highest ITR ever reported in electroencephalogram (EEG)-based BCIs. The results of this study demonstrate great potential of a high-speed SSVEP-based BCI in real-life applications. | 25,081,427 | [
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Description of the tadpoles of three rare species of megophryid frogs (Amphibia: Anura: Megophryidae) from Gunung Mulu, Sarawak, Malaysia. | The megophryid frogs Leptobrachella brevicrus, Leptolalax dringi and Megophrys dringi are species exclusively known from highly localised areas in isolated mountain ranges on Borneo. The tadpoles and adults in this study were collected at the shared type locality for the three species in Gunung Mulu National Park, Sarawak, Malaysia (Borneo). The species identities of larvae were determined via comparison to syntopic adults using DNA barcoding techniques based on partial 16S rRNA mitochondrial gene sequences. The genetic data supported the status of the three taxa as valid species. Descriptions of colouration in life and after preservation, external morphological features, morphometric measurements and ecological notes in comparison to congeneric species are supplied. The tadpoles of L. brevicrus and L. dringi show similar adaptations to a fossorial lifestyle. These include an elongated, vermiform body, a relatively long tail and small eyes. Both were found in the gravel beds of a small mountain stream. In contrast, the larvae of M. dringi are adapted to occupying and feeding at the surface of pools within the stream. | 25,081,435 | [
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Taxonomic Revision of the genus Mesomphalia Hope, 1839 (Insecta, Coleoptera, Chrysomelidae). | A revision of the genus Mesomphalia Hope, 1839, is presented based on a detailed morphological study of all species, except M. ampliata Boheman, 1850 and M. albofasciculata Boheman, 1856. The genus and species are redescribed. One species is transferred to Stolas Billberg, 1820, as S. scrobiculata (Boheman, 1850) comb. nov.; one species is transferred to Cyrtonota Chevrolat, 1836, as C. pyramidata (Boheman, 1850) comb. nov.; M. sexmaculata Boheman, 1850 syn. nov. is a junior subjective synonym of M. turrita (Illiger, 1801); one new species M. spaethi Simões & Monné, sp. nov. is described. Following this revision, Mesomphalia now contains fourteen species. A key to the species, photographs and distribution maps are provided. | 25,081,443 | [
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Apochrysinae (Neuroptera: Chrysopidae): new larval description and subfamilial comparisons. | Although Apochrysinae is considered an important, ancient clade of Chrysopidae, its immature stages are very poorly known. Larvae are rarely seen, and descriptions are limited to the third instar of only one species in the genus Apochrysa. Herein, the larvae (all instars) of a second species, Apochrysa voeltzkowi (Weele), are described, and the features of the two Apochrysa species are compared with those of other chrysopids. The results provide support (one potential synapomorphy) for a phylogenetic relationship between Apochrysinae and Nothochrysinae and additional support for two synapomorphies previously proposed for Nothochrysinae. Diagnostic larval characteristics are proposed for the genus Apochrysa, and species-specific features are identified for the two known Apochrysa larvae. | 25,081,444 | [
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A review of the louse genus Tinamotaecola (Insecta: Phthiraptera: Philopteridae sensu lato), with description of a new species. | We studied a collection of lice from Argentina, Brazil, Paraguay and Chile containing all four known species and one new species (described herein) in the genus Tinamotaecola, parasites of birds of the families Cariamidae and Tinamidae. We also (1) describe previously unknown second and third nymphal instars of two Tinamotaecola species, (2) discuss hosts and geographical ranges for all Tinamotaecola species, and (3) speculate on possible macroevolutionary events that may explain the current distribution of these lice on their respective avian hosts. | 25,081,457 | [
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An extraordinary new blind catfish, Xiurenbagrus dorsalis (Teleostei: Siluriformes: Amblycipitidae), from Guangxi, China. | Xiurenbagrus dorsalis, a new cave-dwelling amblycipitid catfish species, is described based on one specimen collected from the Pearl River drainage in Guangxi, China. The new species can be distinguished from congeners in having a unique combination of features, including the absence of eyes, long barbels, dorsal-fin origin posterior to vertical line at tip of pectoral fins and an adipose fin confluent with caudal fin. This is the first record of a blind catfish in China. | 25,081,460 | [
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[Orthognathic surgery: specific aspects of surgical-orthodontic preparations]. | Orthodontic preparation, mandatory before surgery, has benefited from great innovations in periodontics and implantology. The objectives of current orthodontics are short procedures and compliance with dental capital. Using bone anchorage changes treatment modalities for dental compensation. Piezo-electric surgery has become the first line procedure for osteotomies by improving surgical precision and downgrading nerve complications. Alveolar corticotomy has allowed decreasing orthodontic preparation time by causing an acceleration of tooth displacement. Primary transverse and sagittal surgery allow improving or protecting periodontal and muscular systems during orthodontic preparation. Normalization of oro-facial functions is an essential factor of surgical stability. The initial dysfunction justifies an appropriate and rapid management. | 25,081,489 | [
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Association of interleukin-6-572C/G gene polymorphism and serum or cerebrospinal fluid interleukin-6 level with enterovirus 71 encephalitis in Chinese Han patients with hand, foot, and mouth disease. | Interleukin-6 (IL-6), as one of pro-inflammatory cytokines, plays a key role in Enterovirus 71 (EV71) encephalitis. We investigated the association of IL-6-572C/G polymorphism and serum or cerebrospinal fluid (CSF) IL-6 level with EV71 encephalitis in patients with hand, foot, and mouth disease (HFMD). This study was carried out in 59 Chinese Han patients with EV71 encephalitis, 128 EV71-related HFMD without complications, and 232 controls. The IL-6-572C/G polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism gene analysis. Serum or CSF IL-6 levels were determined using a commercial enzyme-linked immunosorbent assay. The patients with EV71 encephalitis had a higher frequency of IL-6-572GG/GC genotype compared to the patients with EV71-related HFMD without encephalitis complications (40.7 vs. 15.6 %, odds ratio (OR)=3.70, 95 % confidence interval (CI)=1.83-7.50, p=0.001). Similarly, the frequency of IL-6-572 G allele among the patients with EV71 encephalitis was also higher than that of patients with EV71-related HFMD without encephalitis complications (23.7 vs. 8.6 %, OR=3.31, 95 % CI=1.80-6.08, p<0.001). Serum IL-6 levels in G carries (CG + GG) (195.1 ± 11.8 pg/ml) elevated significantly compared to CC homozygotes (167.7 ± 6.7 pg/ml) in EV71-infected patients (p<0.001), but no significant differences were observed in CSF IL-6 levels among different genotypes in patients with EV71 encephalitis. Furthermore, G carriers (GG + GC) (10.6 ±.29 mg/l) had significantly higher blood CRP levels compared to CC homozygotes (9.31 ± 1.93 mg/l) in patients with EV71 encephalitis (p=0.005). These findings suggested that IL-6-572 G allele was significantly associated with the susceptibility to EV71 encephalitis in Chinese Han patients, and IL-6-572 G allele might elevate the risk to EV71 encephalitis. | 25,081,498 | [
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The use of osteochondral allograft with bone marrow-derived mesenchymal cells and hinge joint distraction in the treatment of post-collapse stage of osteonecrosis of the femoral head. | Osteonecrosis of the femoral head is an entity which occurs mainly in young and active patients aged between 20 and 50. The success of hip joint preserving treatments ranges from 15% to 50% depending on the stage and amount of osteonecrotic lesion. Total hip replacement is indicated in late post-collapse hips but it has unsatisfactory survival because of the wear and osteolysis in young and active patients. Osteochondral allografts have been reported in the treatment of large articular lesions with defects in underlying bone in knee, talus and shoulder. By combining osteoconductive properties of osteochondral allograft with osteogenic abilities of bone marrow-derived mesenchymal cells it has a potential to be an alternative to an autologous graft. The adjunct of hinged joint distraction should minimize stresses in subchondral bone to promote creeping substitution and prevent femoral head collapse. Unlike current treatment modalities, it would provide both structural support and allow bony and articular substitution. | 25,081,504 | [
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Functional relationship between matrix metalloproteinase-11 and matrix metalloproteinase-14. | MMP-11 is a key factor in physiopathological tissue remodeling. As an active form is secreted, its activity must be tightly regulated to avoid detrimental effects. Although TIMP-1 and TIMP-2 reversibly inhibit MMP-11, another more drastic scenario, presumably via hydrolysis, could be hypothesized. In this context, we have investigated the possible implication of MMP-14, since it exhibits a spatiotemporal localization similar to MMP-11. Using native HFL1-produced MMP-11 and HT-1080-produced MMP-14 as well as recombinant proteins, we show that MMP-11 is a MMP-14 substrate. MMP-14 cleaves MMP-11 catalytic domain at the PGG(P1)-I(P1')LA and V/IQH(P1)-L(P1')YG scissile bonds, two new cleavage sites. Interestingly, a functional test showed a dramatical reduction in MMP-11 enzymatic activity when incubated with active MMP-14, whereas inactive point-mutated MMP-14 had no effect. This function is conserved between human and mouse. Thus, in addition to the canonical reversible TIMP-dependent inhibitory system, irreversible MMP proteolytic inactivation might occur by cleavage of the catalytic domain in a MMP-dependent manner. Since MMP-14 is produced by HT-1080 cancer cells, whereas MMP-11 is secreted by HFL1 stromal cells, our findings support the emerging importance of tumor-stroma interaction/cross-talk. Moreover, they highlight a Janus-faced MMP-14 function in the MMP cascade, favoring activation of several pro-MMPs, but limiting MMP-11 activity. Finally, both MMPs are active at the cell periphery. Since MMP-14 is present at the cell membrane, whereas MMP-11 is soluble into the cellular microenvironment, this MMP-14 function might represent one critical regulatory mechanism to control the extent of pericellular MMP-11 bioavailability and protect cells from excessive/inappropriate MMP-11 function. | 25,081,520 | [
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Emerging roles for hyaluronidase in cancer metastasis and therapy. | Hyaluronidases are a family of five human enzymes that have been differentially implicated in the progression of many solid tumor types, both clinically and in functional studies. Advances in the past 5 years have clarified many apparent contradictions: (1) by demonstrating that specific hyaluronidases have alternative substrates to hyaluronan (HA) or do not exhibit any enzymatic activity, (2) that high-molecular weight HA polymers elicit signaling effects that are opposite those of the hyaluronidase-digested HA oligomers, and (3) that it is actually the combined overexpression of HA synthesizing enzymes with hyaluronidases that confers tumorigenic potential. This review examines the literature supporting these conclusions and discusses novel mechanisms by which hyaluronidases impact invasive tumor cell processes. In addition, a detailed structural and functional comparison of the hyaluronidases is presented with insights into substrate selectivity and potential for therapeutic targeting. Finally, technological advances in targeting hyaluronidase for tumor imaging and cancer therapy are summarized. | 25,081,524 | [
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Targeting hyaluronic acid family for cancer chemoprevention and therapy. | Hyaluronic acid or hyaluronan (HA) is perhaps one of the most uncomplicated large polymers that regulates several normal physiological processes and, at the same time, contributes to the manifestation of a variety of chronic and acute diseases, including cancer. Members of the HA signaling pathway (HA synthases, HA receptors, and HYAL-1 hyaluronidase) have been experimentally shown to promote tumor growth, metastasis, and angiogenesis, and hence each of them is a potential target for cancer therapy. Furthermore, as these members are also overexpressed in a variety of carcinomas, targeting of the HA family is clinically relevant. A variety of targeted approaches have been developed to target various HA family members, including small-molecule inhibitors and antibody and vaccine therapies. These treatment approaches inhibit HA-mediated intracellular signaling that promotes tumor cell proliferation, motility, and invasion, as well as induction of endothelial cell functions. Being nontoxic, nonimmunogenic, and versatile for modifications, HA has been used in nanoparticle preparations for the targeted delivery of chemotherapy drugs and other anticancer compounds to tumor cells through interaction with cell-surface HA receptors. This review discusses basic and clinical translational aspects of targeting each HA family member and respective treatment approaches that have been described in the literature. | 25,081,525 | [
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Hyaluronan in the healthy and malignant hematopoietic microenvironment. | The fate of both endogenous and transplanted stem cells is dependent on the functional status of the regulatory local microenvironment, which is compromised by disease and therapeutic intervention. The glycosaminoglycan hyaluronan (HA) is a critical component of the hematopoietic microenvironment. We summarize recent advances in our understanding of the role of HA in regulating mesenchymal stem cells, osteoblasts, fibroblasts, macrophages, and endothelium in bone marrow (BM) and their crosstalk within the hematopoietic microenvironment. HA not only determines the volume, hydration, and microfluidics of the BM interstitial space, but also, via interactions with specific receptors, regulates multiple cell functions including differentiation, migration, and production of regulatory factors. The effects of HA are dependent on the polymer size and are influenced by the formation of complexes with other molecules. In healthy BM, HA synthases and hyaluronidases form a molecular network that maintains extracellular HA levels within a discrete physiological window, but HA homeostasis is often perturbed in pathological conditions, including hematological malignancies. Recent studies have suggested that HA synthases may have functions beyond HA production and contribute to the intracellular regulatory machinery. We discuss a possible role for HA synthases, intracellular and extracellular HA in the malignant BM microenvironment, and resistance to therapy. | 25,081,529 | [
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Hyaluronan/RHAMM interactions in mesenchymal tumor pathogenesis: role of growth factors. | Fibrosarcoma belongs to the sarcoma cancer group, which are spindle cell malignancies of mesenchymal origin, and owe their name to the predominant cell line that is present within the tumor. The extracellular matrix (ECM) is a complicated structure that surrounds and supports cells within tissues. Its main components are proteoglycans, collagens, glycoproteins, hyaluronan (HA), and several matrix-degrading enzymes. During cancer progression, significant changes can be observed in the structural and mechanical properties of ECM components. The ECM provides a physical scaffold to which tumor cells attach and migrate. Thus, it is required for key cellular events such as cell motility, adhesion, proliferation, invasion, and metastasis. Importantly, fibrosarcomas were shown to have a high content and turnover of ECM components including HA, proteoglycans, collagens, fibronectin, and laminin. In this review, we will focus on the HA component of fibrosarcoma ECM and critically discuss its role and involved mechanisms during fibrosarcoma pathogenesis. | 25,081,535 | [
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CD147: regulator of hyaluronan signaling in invasiveness and chemoresistance. | Major determinants that influence negative outcome in cancer patients are the abilities of cancer cells to resist current therapies and to invade surrounding host tissue, consequently leading to local and metastatic dissemination. Hyaluronan (HA), a prominent constituent of the tumor microenvironment, not only provides structural support but also interacts with cell surface receptors, especially CD44, that influence cooperative signaling pathways leading to chemoresistance and invasiveness. CD147 (emmprin; basigin) is a member of the Ig superfamily that has also been strongly implicated in chemoresistance and invasiveness. CD147 both regulates HA synthesis and interacts with the HA receptors, CD44, and LYVE-1. Increased CD147 expression induces formation of multiprotein complexes containing CD44 (or LYVE-1) as well as members of the membrane-type matrix metalloproteinase, receptor tyrosine kinase, ABC drug transporter, or monocarboxylate transporter families, which become assembled in specialized lipid raft domains along with CD147 itself. In each case, multivalent HA-receptor interactions are essential for formation or stabilization of the lipid raft complexes and for downstream signaling pathways or transporter activities that are driven by these complexes. We conclude that cooperativity between HA, HA receptors, and CD147 may be a major driver of the interconnected pathways of invasiveness and chemoresistance widely critical to malignancy. | 25,081,536 | [
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Combined application of plasma mutagenesis and gene engineering leads to 5-oxomilbemycins A3/A4 as main components from Streptomyces bingchenggensis. | Milbemycin oxime has been commercialized as effective anthelmintics in the fields of animal health, agriculture, and human infections. Currently, milbemycin oxime is synthesized by a two-step chemical reaction, which involves the ketonization of milbemycins A3/A4 to yield the intermediates 5-oxomilbemycins A3/A4 using CrO3 as catalyst. Due to the low efficiency and environmental unfriendliness of the ketonization of milbemycins A3/A4, it is imperative to develop alternative strategies to produce 5-oxomilbemycins A3/A4. In this study, the atmospheric and room temperature plasma (ARTP) mutation system was first employed to treat milbemycin-producing strain Streptomyces bingchenggensis, and a mutant strain BC-120-4 producing milbemycins A3, A4, B2, and B3 as main components was obtained, which favors the construction of genetically engineered strains producing 5-oxomilbemycins. Importantly, the milbemycins A3/A4 yield of BC-120-4 reached 3,890 ± 52 g/l, which was approximately two times higher than that of the initial strain BC-109-6 (1,326 ± 37 g/l). The subsequent interruption of the gene milF encoding a C5-ketoreductase responsible for the ketonization of milbemycins led to strain BCJ60 (∆milF) with the production of 5-oxomilbemycins A3/A4 and the elimination of milbemycins A3, A4, B2, and B3. The high 5-oxomilbemycins A3/A4 yield (3,470 ± 147 g/l) and genetic stability of BCJ60 implied the potential use in industry to prepare 5-oxomilbemycins A3/A4 for the semisynthesis of milbemycins oxime. | 25,081,559 | [
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STOP-Bang and prediction of difficult airway in obese patients. | To determine if a high score (≥ 3) on the STOP-Bang screening questionnaire for obstructive sleep apnea (OSA) predicts whether obese patients are at high risk for OSA and increased risk of difficult airway. Prospective, questionnaire-based clinical assessment. University-affiliated hospital. 127 ASA physical status 2 and 3 patients, who were scheduled for elective bariatric surgery. Patients were allocated to three groups. Group 1 patients had a previous history of OSA, Group 2 patients had no history of OSA but did have a high STOP-Bang score (≥ 3), and Group 3 patients had no history of OSA but did have a low STOP-Bang score (< 3). Groups 2 and 3 only were assessed using the STOP-Bang questionnaire. After induction and intubation of the patient, an anesthesiologist who was blinded to the three study group allocations completed an airway questionnaire on the three study groups. The frequency of difficult airway, difficult mask ventilation with or without muscle relaxation, poor visualization of the vocal cords, difficulty in blade insertion, and difficult intubation were compared. The group of patients with high STOP-Bang scores (Group 2) and those patients previously diagnosed with OSA (Group1) showed a higher risk for difficult airway than the patients with low STOP-Bang scores (Group 3; P < 0.001). The STOP-Bang score may be used as an effective predictor of difficult airway in obese patients. Obese surgical patients with unknown/undiagnosed OSA status should be evaluated using the STOP-Bang questionnaire score. | 25,081,584 | [
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Emergence of apospory and bypass of meiosis via apomixis after sexual hybridisation and polyploidisation. | Hybridisation and polyploidy are major forces contributing to plant speciation. Homoploid (2x) and heteroploid (3x) hybrids, however, represent critical stages for evolution due to disturbed meiosis and reduced fertility. Apomixis--asexual reproduction via seeds--can overcome hybrid sterility, but requires several concerted alterations of developmental pathways to result in functional seed formation. Here, we analyse the reproductive behaviours of homo- and heteroploid synthetic hybrids from crosses between sexual diploid and tetraploid Ranunculus auricomus species to test the hypothesis that developmental asynchrony in hybrids triggers the shift to apomictic reproduction. Evaluation of male and female gametophyte development, viability and functionality of gametes shows developmental asynchrony, whereas seed set and germinability indicate reduced fitness in synthetic hybrids compared to sexual parents. We present the first experimental evidence for spontaneous apospory in most hybrids as an alternative pathway to meiosis, and the appearance of functional apomictic seeds in triploids. Bypassing meiosis permits these triploid genotypes to form viable seed and new polyploid progeny. Asynchronous development causes reduced sexual seed set and emergence of apospory in synthetic Ranunculus hybrids. Apomixis is functional in triploids and associated with drastic meiotic abnormalities. Selection acts to stabilise developmental patterns and to tolerate endosperm dosage balance shifts which facilitates successful seed set and establishment of apomictic lineages. | 25,081,588 | [
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Probing the structural and electronic properties of bimetallic chromium-gold clusters CrmAun(m+n≤6): comparison with pure chromium and gold clusters. | Bimetallic chromium-gold CrmAun(m+n≤6) clusters are systematically investigated using the density functional theory at PW91P86 level with LanL2TZ basis set to understand the evolution of various structural, electronic, magnetic, and energetic properties as a function of size (m+n) and composition (m/n) of the system. Theoretical results show a logical evolution of the properties depending on the size and the composition of the system. Cr m clusters clearly prefer 3D structures while Au n clusters favor planar configurations. The geometry of the bimetallic Cr m Au n clusters mainly depends on their composition, i.e., clusters enriched in Cr atoms prefer 3D structures while increasing Au contents promotes planar configurations. The stability is maximized when the composition of binary Cr m Au n clusters is nearly balanced. Meanwhile, the number of hetero Cr-Au bonds and charge transfer from Cr to Au are maximized for clusters with m≈n. The most probable dissociation channels of the Cr m Au n clusters are calculated and analyzed. Natural population analysis reveals that Au atoms tend to be negatively charged while Cr atoms tend to be positively charged. Combined with the trend that Au atoms favor the surface/edges/vertices and Cr atoms tend to be inside, the outer part of the cluster tends to be negatively charged, and the inner part tends to be positively charged. | 25,081,608 | [
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Validation of a questionnaire on hand hygiene in the construction industry. | Construction workers are at risk of developing occupational contact dermatitis. Gloves, when used properly, may protect against chemicals and coarse materials. We investigated the prevalence and determinants of contact dermatitis in a population of Dutch construction workers and aimed at validating questionnaire items on hand hygiene. A cross-sectional study was conducted at 13 construction sites, yielding data of 177 subjects (95% response rate). A questionnaire covering questions on hand hygiene and contact dermatitis symptoms was used. Agreement between workplace observations and a number of questionnaire items was assessed by calculating Cohen's kappa. Log-binomial regression analysis was used to assess the association between contact dermatitis and various hand hygiene-related determinants. The 1-year prevalence of self-reported contact dermatitis in our study sample was 46.9%. Multiple regression analysis showed a positive association with difficulties with hand cleaning (prevalence ratio [PR]: 1.26, 95% confidence interval [CI]: 1.05-1.52), hand contamination at the end of the working day (PR: 2.30, 95% CI: 1.14-4.65), and intensive hand cream use (PR: 2.07, 95% CI: 1.42-3.01). Observations of hand contamination, glove use, and glove types were found to agree well with the self-reported data from the questionnaire (Cohen's kappa's 0.75, 0.97, and 0.88). Self-reported contact dermatitis prevalence in construction workers was high and related to hand hygiene. A strong agreement was found between workplace observations and self-reported questionnaire data. | 25,081,611 | [
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A prospective trial comparing FDG-PET/CT and CT to assess tumor response to cetuximab in patients with incurable squamous cell carcinoma of the head and neck. | Computed tomography (CT), the standard method to assess tumor response to cetuximab in incurable squamous cell carcinoma of the head and neck (SCCHN), performs poorly as judged by the disparity between high disease control rate (46%) and short time to progression (TTP) (70 days). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT is an alternative method to assess tumor response. The primary objective of this prospective trial was to evaluate the metabolic response of target lesions, assessed as the change in maximum standardized uptake value (SUV(max)) on FDG-PET/CT before and after 8 weeks (cycle 1) of cetuximab. Secondary objectives were to compare tumor response by CT (RECIST 1.0) and FDG-PET/CT (EORTC criteria) following cycle 1, and determine TTP with continued cetuximab administration in patients with disease control by CT after cycle 1 but stratified for disease control or progression by FDG-PET/CT. Among 27 patients, the mean percent change of SUV(max) of target lesions after cycle 1 was -21% (range: +72% to -81%); by FDG-PET/CT, partial response (PR)/stable disease (SD) occurred in 15 patients (56%) and progression in 12 (44%), whereas by CT, PR/SD occurred in 20 (74%) and progression in 7 (26%). FDG-PET/CT and CT assessments were discordant in 14 patients (P = 0.0029) and had low agreement (κ = 0.30; 95% confidence interval [CI]: 0.12, 0.48). With disease control by CT after cycle 1, median TTP was 166 days (CI: 86, 217) if the FDG-PET/CT showed disease control and 105 days (CI: 66, 159) if the FDG-PET/CT showed progression (P < 0.0001). Median TTP of the seven patients whose post cycle 1 CT showed progression compared to the 12 whose FDG-PET/CT showed progression were similar (53 [CI: 49, 56] vs. 61 [CI: 50, 105] days, respectively). FDG-PET/CT may be better than CT in assessing benefit of cetuximab in incurable SCCHN. | 25,081,631 | [
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Reprogramming nonribosomal peptide synthetases for "clickable" amino acids. | Nonribosomal peptide synthetases (NRPSs) are multifunctional enzymes that produce a wide array of bioactive peptides. Here we show that a single tryptophan-to-serine mutation in phenylalanine-specific NRPS adenylation domains enables the efficient activation of non-natural aromatic amino acids functionalized with azide and alkyne groups. The resulting 10(5)-fold switch in substrate specificity was achieved without appreciable loss of catalytic efficiency. Moreover, the effective communication of the modified A domains with downstream modules in dipeptide synthetases permitted incorporation of O-propargyl-L-tyrosine into diketopiperazines both in vitro and in vivo, even in the presence of competing phenylalanine. Because azides and alkynes readily undergo bioorthogonal click reactions, reprogramming NRPSs to accept non-natural amino acids that contain these groups provides a potentially powerful means of isolating, labeling, and modifying biologically active peptides. | 25,081,643 | [
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Analysis of immune-related ESTs and differential expression analysis of few important genes in lines of rohu (Labeo rohita) selected for resistance and susceptibility to Aeromonas hydrophila infection. | A total of 137,629 contigs generated via de novo transcriptome assembly from resistant and susceptible lines of rohu (first generation) raised against aeromoniasis were further analyzed in terms of defence-related genes. Out of 1,939 contigs showing homology to genes involved in immune processes, 1,866 were further categorised into different functional subgroups. Comparative analysis revealed five genes for the first time in any carp species out of which apolipoprotein h, septin 4 isoform 3 and septin isoform cra_c were identified for the first time in fish. Differential expression analysis of ten genes viz., heat shock proteins (Hsps) (Hsp30, Hsp70 and Hsp90), serum lectin isoform 1 (SLI1), linker histone H1M (LHH1M), NAD(P)H quinone 1 (NQO1), zona pellucida 2 (ZP2) and three unknown genes that were highly up-expressed in first generation resistant line fish from mRNA-seq coverage data, was carried out using susceptible and resistant individuals of the second generation selected populations in eight different tissues viz. liver, kidney, intestine, gill, brain, spleen, skin and muscle using qPCR. Significant up-regulation in Hsp90, NQO1, C_116914 and C_22454 in specific tissues of resistant line and variable expression in Hsp30 and LHH1M genes in different tissues of both lines were noticed. The expression of Hsp70 was lower in many tissues of the resistant line than in susceptible line rohu. The expression of ZP2, SLI1 and C_94589 genes was not significantly different in terms of fold difference between the two lines. Differentially expressed genes need further characterisation to explore their role in resistance to Aeromonas hydrophila infection in rohu. | 25,081,649 | [
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Initiation of home mechanical ventilation at home: a randomised controlled trial of efficacy, feasibility and costs. | Home mechanical ventilation (HMV) in the Netherlands is normally initiated in hospital, but this is expensive and often a burden for the patient. In this randomised controlled study we investigated whether initiation of HMV at home in patients with chronic respiratory failure is non-inferior to an in hospital based setting. Seventy-seven patients were included, of which 38 patients started HMV at home. All patients were diagnosed with chronic respiratory failure due to a neuromuscular or thoracic cage disease. Primary outcome was the arterial carbon dioxide (PaCO2) while quality of life and costs were secondary outcomes. Telemonitoring was used in the home group to provide therapeutic information, for example; transcutaneous carbon dioxide, oxygen saturation and ventilator information, to the caregivers. Follow-up was six months. PaCO2, improved by 0.72 (SE ± 0.16) kPa in the hospital group and by 0.91 (±0.20) in the home group, both improvements being significant and the latter clearly not inferior. There were also significant improvements in quality of life in both groups, again not being inferior with home treatment. This study is the first to show that initiation of HMV at home in a selective group of patients with chronic respiratory failure is as effective for gas exchange and quality of life as hospital initiation. In addition we found that it is safe, technically feasible and that more than € 3000 per patient can be saved compared to our standard care. | 25,081,652 | [
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Breast cancer recurrence according to molecular subtype. | To evaluate the location of tumor relapse and imaging modality for detection according to the breast cancer subtype: luminal A, luminal B, HER2 positive luminal B, nonluminal HER2 positive, and triple negative. A total of 1244 patients with breast cancer with known estrogen receptor (ER), progesterone receptor (PR), Ki-67 and human epidermal growth factor receptor 2 (HER2), who underwent breast surgery from 2009 to 2012 were analyzed. Patients were classified into the following categories: luminal A (n=458), luminal B (n=241), HER2 positive luminal B (n=227), nonluminal HER2 positive (n=145) and triple negative (n=173). A total of 105 cases of relapse were detected in 102 patients: locoregional recurrence (n=46), recurrence in the contralateral breast (n=28) and distant metastasis (n=31). Comparison of proportions was used to determine the difference between subtypes. Relapse rates by subtypes are as follows: luminal A 23 of 458 (5.02%), luminal B 19 of 241 (7.88%), HER2 positive luminal B 15 of 227 (6.61%), nonluminal HER2 postive 19 of 145 (13.10%) and triple negative 29 of 173 (16.76%). Luminal A tumors had the lowest rate of recurrence and had significantly lower recurrence rate in comparison with nonluminal HER2 postive (p=0.0017) and triple negative subtypes (p<0.0001). Compared with all other subtypes except nonluminal HER2 positive, triple negative tumors had the highest rate of tumor recurrence (p<0.01). Triple negatives were most likely to develop contralateral recurrence against all subtypes (p<0.05). Detection rate of locoregional and contralateral tumor recurrence were 28.3% on mammography (n=17/60). Luminal A tumors are associated with a low risk of recurrence while triple negative lesions have a high risk. In case of triple negative tumors, the contralateral breast has much more recurrence as compared with all other subtype. In terms of detection rates, breast USG was the best modality for detecting tumor recurrence, compared with other modalities (p<0.05). Subtyping of breast tumors using a molecular gene expression panel can identify patients who have increased risk of recurrence and allow prediction of locations of tumor recurrence for each subtype. | 25,081,661 | [
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Analysis of different ways of drainage for obstructive jaundice caused by hilar cholangiocarcinoma. | To evaluate the prognosis of different ways of drainage for patients with obstructive jaundice caused by hilar cholangiocarcinoma. During the period of January 2006- March 2012, percutaneous transhepatic catheter drainage (PTCD)/ percutaneous transhepatic biliary stenting (PTBS) were performed for 89 patients. According to percutaneous transhepatic cholangiography (PTC), external drainage was selected if the region of obstruction could not be passed by guide wire or a metallic stent was inserted if it could. External drainage was the first choice if infection was diagnosed before the procedure, and a metallic stent was inserted in one week after the infection was under control. Selection by new infections, the degree of bilirubin decrease, the change of ALT, the time of recurrence of obstruction, and the survival time of patients as the parameters was conducted to evaluate the methods of different interventional treatments regarding prognosis of patients with hilar obstruction caused by hilar cholangiocarcinoma. PTCD was conducted in 6 patients and PTBS in 7 (p<0.05). Reduction of bilirubin levels and ALT levels was obvious after the procedures (p<0.05). The average survival time with PTCD was 161 days and with PTBS was 243 days (p<0.05). With both drainage procedures for obstructive jaundice caused by hilar cholangiocarcinoma improvement in liver function was obvious. PTBS was found to be better than PTCD for prolonging the patient survival. | 25,081,675 | [
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Assessment of midwifery student preparation for performing the role of breast cancer educator. | Our research project aimed at presenting midwifery student self-assessment of performing the role of breast cancer prevention educator. Investigations were carried out in 2011 at the Medical University of Lublin in Poland, and Katolieke Hogeschool of Kortrijk in Belgium, after obtaining approval of the ethical committee of Polish Midwives Association (III/EC/2011/PMA). The project involved a total of 155 midwifery students, made up of 95 from Poland, and 60 from Belgium. Relations between opposing characteristics were tested with Chi-square (x2) test for independent traits. To assess the dependence relation between the examined variables Pearson's corrected coefficient was used. Data base and statistics were carried out with computer software STATISTICA 9.0 (StatSoftPoland). Student knowledge on prevention against breast cancer was unsatisfactory.The students place of residence determined their self-estimation of personal knowledge of breast cancer prevention and diagnosing methods to assess the incidence of the disease, this knowledge being better with the students of Lublin. Better self-estimation in the students of Lublin of their personal knowledge on factors rising the risk of breast cancer, such as alimentation method, application of oral contraceptives and breast feeding was found than in Belgian students. | 25,081,678 | [
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Association between cigarette smoking history and mortality in 36,446 health examinees in Korea. | It is well known that smoking is a preventable factor for all-cause mortality; however, it is still questionable how many years after smoking cessation that people will have reduced risk for mortality, in particular in those with a high interest in their own health. We aimed to examine the association between time since quitting smoking and total mortality among past-smokers relative to current smokers. We enrolled 36,446 health examinees that voluntarily taken with diverse health check-up packages of high cost burden in 1995-2003 and followed them till death by 2004. The history of cigarette smoking consumption was collected using a self-administrative questionnaire at the first visit time. Mortality risk by smoking cessation years was analyzed using Cox's proportional hazard model. Compared to non-smokers, male smokers over 15 pack-years had higher risk for total mortality (HR=1.49, 95%CI 1.02-2.18). The mortality risk in female smokers with same pack-years was more pronounced than that in male smokers (HR=2.83, 95%CI 1.17-7.04) despite a small number of cases. Compared to current smokers, a decrease of total mortality was observed among those who ceased smoking, and inverse dose-response was found with years after cessation: RR 0.98 (95%CI, 0.64-1.41) (<2 yrs), 0.60 (95%CI, 0.43-0.83) (3-9 yrs), and 0.58 (95%CI, 0.43-0.79) (≥10 yrs). A reduced risk of total mortality was observed after 3 years of smoking cessation. Our findings suggest that at least 3 years of smoking cessation may contribute to reduce premature mortality among Asian men. | 25,081,686 | [
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Single-laboratory validation for the determination of caffeic acid and seven caffeoylquinic acids in sweet potato leaves. | A single-laboratory validation study was conducted on an HPLC method for the detection and quantification of caffeic acid (CA) and seven species of caffeoylquinic acids (CQAs) in lyophilized sweet potato leaves. The procedure for extraction of the analytes from the matrix and the HPLC conditions for the efficient separation of CA and CQAs were optimized. In the proposed method, a relative response factor to one of the CQAs (5-CQA) was used to quantify the others. The method performed well in terms of precision when carried out on five different days and demonstrated Horwitz ratio (HorRat) scores ranging from 0.5 to 1.0 for all analytes, which were well within the limits of performance acceptability. Accuracy testing at three levels showed an overall recovery of 94% when duplicated on five different days. Moreover, a stability study revealed that all analytes in both standard solution and sample extract were stable for 28 days. | 25,081,737 | [
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Tetra detector analysis of membrane proteins. | Well-characterized membrane protein detergent complexes (PDC) that are pure, homogenous, and stable, with minimized excess detergent micelles, are essential for functional assays and crystallization studies. Procedural steps to measure the mass, size, shape, homogeneity, and molecular composition of PDCs and their host detergent micelles using size-exclusion chromatography (SEC) with a Viscotek Tetra Detector Array (TDA; absorbance, refractive index, light scattering, and viscosity detectors) are presented in this unit. The value of starting with a quality PDC sample, the precision and accuracy of the results, and the use of a digital benchtop refractometer are emphasized. An alternate and simplified purification and characterization approach using SEC with dual absorbance and refractive index detectors to optimize detergent and lipid concentration while measuring the PDC homogeneity is also described. Applications relative to purification and characterization goals are illustrated as well. | 25,081,744 | [
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TERT promoter mutations contribute to subset prognostication of lower-grade gliomas. | Recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) have been found in various cancers including diffuse gliomas. Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. However, the clinical significance of TERT promoter mutations in lower-grade gliomas remains undetermined. The aim of this study is to evaluate the status of TERT promoter and the respective prognostic significance in a cohort of 237 lower-grade gliomas comprising grades II and III astrocytomas, oligodendrogliomas, and oligoastrocytomas. Mutually exclusive mutations in TERT promoter, C228T and C250T, were identified in 16/105 (15%) diffuse astrocytomas, 16/63 (25%) anaplastic astrocytomas, 13/18 (72%) oligodendrogliomas, 3/3 (100%) anaplastic oligodendrogliomas, 17/45 (38%) oligoastrocytomas, and 2/3 (67%) anaplastic oligoastrocytomas. Mutations co-occurred with 1p/19q codeletion (P<0.001) and are associated with oligodendroglial histology (P<0.001). Kaplan-Meier's survival analysis showed that TERT promoter mutation (P=0.037), Isocitrate dehydrogenase (IDH) mutation (P<0.001), and 1p/19q codeletion (P<0.001) were associated with favorable overall survival (OS). In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). Consistent with this observation, in the subset of 97 IDH-mutated astrocytomas, 14 TERT promoter-mutated tumors showed longer PFS (P=0.001) and OS (P=0.001). In contrast, among the subset of 74 IDH wild-type lower-grade gliomas with intact 1p/19q, TERT promoter mutation was associated with shorter PFS (P=0.001) and OS (P=0.001). Similarly, in the subset of 65 IDH wild-type astrocytomas, 16 TERT promoter-mutated tumors exhibited unfavorable PFS (P=0.007) and OS (P=0.008). Our results indicate that when combined with IDH status, TERT promoter mutation contributes to prognostic subgroups of lower-grade astrocytic tumors or 1p/19q intact lower-grade gliomas and this may further refine future molecular classification of lower-grade gliomas. | 25,081,751 | [
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A new species and five new records of chewing lice (Insecta: Phthiraptera: Ischnocera) from an isolated population of the solitary tinamou Tinamus solitarius (Aves: Tinamiformes). | We report the first records of chewing lice from an isolated population of the solitary tinamou (formerly known as Tinamus solitarius pernambucensis Berla, 1946) in the Pernambuco Centre of Endemism (PCE), Brazil. All louse records previously published from the solitary tinamou came from the populations south of the São Francisco River, formerly known as Tinamus solitarius solitarius (Vieillot, 1819). Five known species of the family Heptapsogasteridae were identified from the northern population of this host: Heptarthrogaster grandis Carriker, 1936; Ornicholax alienus (Giebel, 1874); Pterocotes solitarius Guimarães & Lane, 1937; Rhopaloceras oniscus (Nitzsch [in Giebel], 1866); and Strongylocotes wernecki Guimarães & Lane, 1937. Also, the new species Heptagoniodes guimaraesi is described and illustrated from the northern population of this host, and a key for identification of all the species of Heptagoniodes Carriker, 1936 is included. The discovery of H. guimaraesi is the first Brazilian example of a bird ectoparasite represented by two different species of the same genus living on two distinct populations of the same host species. Records of eight louse species and 31 new localities from the southern population of the solitary tinamou in Brazil are given, and an updated list of all the chewing lice known from both host populations [subspecies] is included. | 25,081,764 | [
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Species of Neoperla (Plecoptera: Perlidae) from Henan Province, China. | A new species, Neoperla jigongshana Li & Li, sp. nov., is proposed from Henan Province, China and compared with related congeners. Two additional species, N. cavaleriei (Navás, 1922) and N. forcipata Yang & Yang, 1992, are reported from the Province for the first time and descriptions of female and egg of N. baotianmana Li & Wang, 2011 are also presented. A provisional key to the known species of the Henan Province is presented. | 25,081,767 | [
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First description of imago and redescription of nymph for Cloeodes irvingi Waltz & McCafferty, 1987 (Ephemeroptera: Baetidae). | The male imago of Cloeodes irvingi Waltz & McCafferty, 1987 is described for the first time based on reared nymphs collected from the state of Pernambuco, northeastern Brazil. It is differentiated from Neotropical congeners, among other characteristics, by the marginal intercalary veins being paired, except between veins ICu1-ICu2 and ICu2-CuP where they are single and between Sc-R1 and CuP-A where they are absent; segment II of forceps with a medial constriction; and the posterior margin of the subgenital plate being rounded. The nymph of this species is redescribed based on new and original specimens. It is differentiated from Neotropical congeners, among others characteristics, by having a labrum with a dorsal arc composed of 2 + 0 + 2 long, spine-like setae, a labial palp segment III that is subquadrangular, and the fore femur with an apex that is not projected, with 2 blunt setae. | 25,081,799 | [
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Ultra-broadband and efficient surface plasmon polariton launching through metallic nanoslits of subwavelength period. | Ultra-broadband, efficient and unidirectional surface plasmon polariton (SPP) launching is of great concern in plasmonic devices and circuits. To address this challenge, a novel method adopting deep-subwavelength slits of subwavelength period (λSPP/4 ~ λSPP/3) in a thick metal film and under backside illumination is proposed. A new band pattern featuring broadband and wide angular characteristics, which is due to the coupling of the zeroth-order SPP resonance at the superstrate-metal interface and the first-order SPP resonance at the metal-substrate interface, is observed for the first time in the dispersion diagram. Unidirectional SPP launching efficiency of ~50%, ultra-broad bandwidth of up to 780 nm, covering the entire optical fiber communication bands, and relatively wide angular range of 7° are achieved. This remarkable efficient, ultra-broadband and wide angular performance is demonstrated by carefully designed experiments in the near infrared regime, showing good agreement with numerical results. | 25,081,812 | [
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Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1. | G protein-coupled receptors (GPCRs) are the major transducers of external stimuli and key therapeutic targets in many pathological conditions. When activated by different ligands, one receptor can elicit multiple signalling cascades that are mediated by G proteins or β-arrestin, a process defined as functional selectivity or ligand bias. However, the dynamic mechanisms underlying β-arrestin signalling remain unknown. Here by studying the cannabinoid receptor 1 (CB1R), we identify ligand-specific endocytic dwell times, that is, the time during which receptors are clustered into clathrin pits together with β-arrestins before endocytosis, as the mechanism controlling β-arrestin signalling. Agonists inducing short endocytic dwell times produce little or no β-arrestin signalling, whereas those eliciting prolonged dwell times induce robust signalling. Remarkably, extending CB1R dwell times by preventing endocytosis substantially increased β-arrestin signalling. These studies reveal how receptor activation translates into β-arrestin signalling and identify a mechanism to control this pathway. | 25,081,814 | [
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Alexithymia and brain gray matter volumes in a general population sample. | Alexithymia is perceived as a personality construct involving deficits in the cognitive processing of emotion. Brain areas that process emotions might be structurally altered in affected people. Subjects from the Study of Health in Pomerania who underwent whole body magnetic resonance imaging were investigated. After quality control procedures 2,589 subjects with Toronto Alexithymia Scale 20 (TAS-20) data and interview-based information on major depressive disorder (MDD) were available. After exclusion of study participants who were older than 65 years or had MDD in their lifetime, 1,685 subjects were included in the voxel-based morphometric (VBM 8) analyses. In whole-brain analyses, the TAS-20 total score was associated with less gray matter (GM) volumes of the bilateral dorsal anterior cingulate cortex (dACC). The TAS-20 factor scale difficulty identifying feelings (DIF) was associated with less GM volume in three clusters: dACC, left middle and inferior temporal gyrus, left fusiform gyrus and cerebellum. The lower GM volume in the left fusiform gyrus was specific for females. Absolute GM volume analyses also revealed associations between the factor scales difficulty describing feelings, external orientated thinking and the dACC. Adjustment for current symptoms of anxiety and depression did not change the effects sizes substantially. In conclusion, lower GM volume in the dACC represents the major structural correlate of alexithymia. Associations with DIF suggest a prominent involvement of left temporal areas. These areas represent language and semantic processing and might be involved in the cognitive processing of emotions and the conscious identification of feelings. | 25,081,815 | [
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The use and utility of specific nonpharmacological interventions for behavioral symptoms in dementia: an exploratory study. | This study compares different nonpharmacological interventions for persons with behavioral symptoms and dementia on frequency of use and perceived efficacy in terms of change in behavior and interest. Participants were 89 nursing home residents from six Maryland nursing homes with a mean age of 85.9 years (SD: 8.6 years). Research assistants presented interventions tailored to the participants' needs and preferences in a pre-intervention trial phase and in an intervention phase. The impact of each intervention on behavioral symptoms and on the person's interest was rated immediately after the intervention by a research assistant. The most utilized interventions in both trial and treatment phases were the social intervention of one-on-one interaction, simulated social interventions such as a lifelike doll and respite video, the theme intervention of magazine, and the sensory stimulation intervention of music. In contrast, the least utilized interventions in both phases were sewing, fabric book, and flower arrangement. Interventions with the highest impact on behavioral symptoms included one-on-one social interaction, hand massage, music, video, care, and folding towels. Other high impact interventions included walking, going outside, flower arranging, food or drink, sewing, group activity, book presentation, ball toss, coloring or painting, walking, and family video. The results provide initial directions for choosing specific interventions for persons with dementia and also demonstrate a methodology for increasing knowledge through ongoing monitoring of practice. | 25,081,819 | [
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Oxidative stress participates in age-related changes in rat lumbar intervertebral discs. | Aging is a major factor associated with lumber intervertebral disc degeneration, and oxidative stress is known to play an essential role in the pathogenesis of many age-related diseases. In this study, we investigated oxidative stress in intervertebral discs of Wistar rats in three different age groups: youth, adult, and geriatric. Age-related intervertebral disc changes were examined by histological analysis. In addition, oxidative stress was evaluated by assessing nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPPs). Intervertebral disc, but not serum, NO concentrations significantly differed between the three groups. Serum and intervertebral disc SOD activity gradually decreased with age. Furthermore, both serum and intervertebral disc MDA and AOPP levels gradually increased with age. Our studies suggest that oxidative stress is associated with age-related intervertebral disc changes. | 25,081,833 | [
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Seagrass ecosystem response to long-term high CO2 in a Mediterranean volcanic vent. | We examined the long-term effect of naturally acidified water on a Cymodocea nodosa meadow growing at a shallow volcanic CO2 vent in Vulcano Island (Italy). Seagrass and adjacent unvegetated habitats growing at a low pH station (pH = 7.65 ± 0.02) were compared with corresponding habitats at a control station (pH = 8.01 ± 0.01). Density and biomass showed a clear decreasing trend at the low pH station and the below- to above-ground biomass ratio was more than 10 times lower compared to the control. C content and δ(13)C of leaves and epiphytes were significantly lower at the low pH station. Photosynthetic activity of C. nodosa was stimulated by low pH as seen by the significant increase in Chla content of leaves, maximum electron transport rate and compensation irradiance. Seagrass community metabolism was intense at the low pH station, with significantly higher net community production, respiration and gross primary production than the control community, whereas metabolism of the unvegetated community did not differ between stations. Productivity was promoted by the low pH, but this was not translated into biomass, probably due to nutrient limitation, grazing or poor environmental conditions. The results indicate that seagrass response in naturally acidified conditions is dependable upon species and geochemical characteristics of the site and highlight the need for a better understanding of complex interactions in these environments. | 25,081,848 | [
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Citrus essential oils and their influence on the anaerobic digestion process: an overview. | Citrus waste accounts for more than half of the whole fruit when processed for juice extraction. Among valorisation possibilities, anaerobic digestion for methane generation appears to be the most technically feasible and environmentally friendly alternative. However, citrus essential oils can inhibit this biological process. In this paper, the characteristics of citrus essential oils, as well as the mechanisms of their antimicrobial effects and potential adaptation mechanisms are reviewed. Previous studies of anaerobic digestion of citrus waste under different conditions are presented; however, some controversy exists regarding the limiting dosage of limonene for a stable process (24-192 mg of citrus essential oil per liter of digester and day). Successful strategies to avoid process inhibition by citrus essential oils are based either on recovery or removal of the limonene, by extraction or fungal pre-treatment respectively. | 25,081,855 | [
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Genome analysis of NDM-1 producing Morganella morganii clinical isolate. | To analyze the resistome and virulence genes of Morganella morganii F675, a multidrug-resistant clinical isolate using whole genome sequencing (WGS). M. morganii F675 was isolated from a patient from Jerusalem, Israel. WGS was performed using both 454 and SOLiD sequencing technologies. Analyses of the bacterial resistome and other virulence genes were performed in addition to comparison with other available M. morganii genomes. The assembled sequence had a genome size of 4,127,528 bp with G+C content of 51%. The resistome consisted of 13 antibiotic resistance genes including blaNDM-1 located in a plasmid likely acquired from Acinetobacter spp. Moreover, we characterized for the first time the whole lipid A biosynthesis pathway in this species along with the O-antigen gene cluster, the urease gene cluster and several other virulence genes. The WGS analysis of this pathogen further provides insight into its pathogenicity and resistance to antibiotics. | 25,081,858 | [
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Male access to emergency contraception in pharmacies: a mystery shopper survey. | Pharmacy access to emergency contraception (EC) could involve men in pregnancy prevention. The objectives were to assess the availability and cost of EC. Male mystery shoppers visited 158 pharmacies in three neighborhoods in New York City. They asked for EC and its cost and noted weekend hours. Twenty-two (73.3%) of 30 pharmacies created barriers to get EC. The cost of EC was higher in the higher-socioeconomic status (SES) neighborhood (p<.001), and the higher-SES neighborhood pharmacies had a greater number of weekend hours (p<.001). Overall, males had a 20% probability of not being able to access EC. The national dialogue should include males. | 25,081,865 | [
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Subcellular localisation of retromer in post-endocytic pathways of polarised Madin-Darby canine kidney cells. | Retromer is required for endosome-to-Golgi retrieval of the cation-independent mannose 6-phosphate receptor (CI-MPR), allowing delivery of hydrolases into lysosomes. It is constituted by a conserved heterotrimer formed by vacuolar protein sorting (Vps) gene products Vps26, Vps35 and Vps29, which is in charge of cargo selection, and a dimer of phosphoinositide-binding sorting nexins (SNXs), which has a structural role. Retromer has been implicated in sorting of additional cargo. Thus, retromer also promotes polymeric immunoglobulin A (pIgA) transcytosis by the pIgA receptor (pIgR) in polarised cells, and considerable evidence implicates retromer in controlling epithelial cell polarity. However, the precise localisation of retromer along the endocytic pathway of polarised cells has not been studied in detail. Our biochemical analysis using rat liver endosome fractions suggests a distinct distribution pattern. Although subunits of the cargo-selective complex were enriched in early endosomes (EEs), levels of SNX2 were greater in sorting endosomes. We then immunolocalised the retromer subunits in polarised Madin-Darby canine kidney (MDCK) cells by confocal microscopy. An estimated 25% of total Vps26 and SNX2 localised to EEs, with negligible portions in recycling endosomes as well as in late endosomes and lysosomes. Although Vps26 was in structures of more heterogeneous size and shape than SNX2, these markedly overlapped. In consequence, the two retromer subcomplexes mostly colocalised. When we analysed retromer overlap with its cargo, we found that structures retromer and pIgA(+) are independent of those structures retromer and CI-MPR(+) . Remarkably, retromer localised preferentially at the transcytotic pathway. Pharmacological inhibition of phosphoinositide 3-kinase affected the co-distribution of retromer with pIgA and the CI-MPR, delaying pIgA progress to the apical surface. In polarised MDCK cells, we found retromer associated with certain specialised EE-derived pathways. Our data imply that retromer is largely engaged in pIgA transcytosis in pIgR-expressing MDCK cells, as opposed to endosome-to-Golgi retrieval. | 25,081,925 | [
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Cytomegalovirus upregulates expression of CCR5 in central memory cord blood mononuclear cells, which may facilitate in utero HIV type 1 transmission. | Administration of combination antiretroviral therapy to human immunodeficiency virus type 1 (HIV-1)-infected pregnant women significantly reduces vertical transmission. In contrast, maternal co-opportunistic infection with primary or reactivated cytomegalovirus (CMV) or other pathogens may facilitate in utero transmission of HIV-1 by activation of cord blood mononuclear cells (CBMCs). Here we examine the targets and mechanisms that affect fetal susceptibility to HIV-1 in utero. Using flow cytometry, we demonstrate that the fraction of CD4(+)CD45RO(+) and CD4(+)CCR5(+) CBMCs is minimal, which may account for the low level of in utero HIV-1 transmission. Unstimulated CD4(+) CBMCs that lack CCR5/CD45RO showed reduced levels of HIV-1 infection. However, upon in vitro stimulation with CMV, CBMCs undergo increased proliferation to upregulate the fraction of T central memory cells and expression of CCR5, which enhances susceptibility to HIV-1 infection in vitro. These data suggest that activation induced by CMV in vivo may alter CCR5 expression in CD4(+) T central memory cells to promote in utero transmission of HIV-1. | 25,081,935 | [
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Ice packs reduce postoperative midline incision pain and narcotic use: a randomized controlled trial. | Postoperative pain is an unavoidable consequence of open abdominal surgery. Although cryotherapy, the application of ice to a surgical wound site, has been shown to be effective in reducing postoperative pain in orthopaedic, gynecologic, and hernia operations, it has not been assessed in patients who undergo major open abdominal operations. We hypothesized that patients who receive cryotherapy would report lower pain scores as a primary outcomes measure. Patients undergoing abdominal operations with midline incisions were randomized to receive cryotherapy for a minimum of 24 hours in time intervals dictated by patient preference vs no cryotherapy. The primary outcome of pain relief was assessed with visual analog pain scores (VAS). The study was powered to detect a clinically significant difference in VAS between the control and cryotherapy group. Comparisons between groups were measured by Student's t-test or Mann-Whitney U test for parametric and nonparametric data, respectively. There were 55 patients randomized: 28 to the control group and 27 to the cryotherapy group. For the primary measure, mean postoperative pain score on postoperative days (PODs) 1 and 3 after surgery was significantly lower between the control and cryotherapy groups on the visual analog pain scale (p < 0.005). Narcotic use was decreased in the cryotherapy group on POD 1 by 3.9 morphine equivalents (p = 0.008). No statistically significant difference was found between the 2 treatment groups with respect to length of hospital stay, pulmonary complications, and wound infection rate in terms of secondary measures. Ice packs are a simple, cost-effective adjuvant for decreasing postoperative pain and narcotic use in patients undergoing major abdominal operations. | 25,081,937 | [
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An exceptionally stable and water-resistant metal-organic framework with hydrophobic nanospaces for extracting aromatic pollutants from water. | A novel hydrophobic metal-organic framework (MOF), namely Cu2 L (L = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate), is synthesized through a stepwise method, and exhibits an unprecedented 3,4-c net. The exceptionally thermal, chemical, and air stability of this MOF, especially in water and under acidic or basic conditions, and its selective and fast sorption capacity for hydrocarbons over water warrant its direct use for efficient removal of trace organic wastes (e.g. benzene, toluene, xylene, and mixtures thereof) from contaminated water. | 25,081,943 | [
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Perioperative morbidity and mortality comparison in circumferential cervical fusion for osteomyelitis versus cervical spondylotic myelopathy. | The most common indications for circumferential cervical decompression and fusion are cervical spondylotic myelopathy (CSM) and cervical osteomyelitis (COM). Currently, the informed consent process prior to circumferential cervical fusion surgery is not different for these two groups of patients, as details of their diagnosis-specific risk profiles have not been quantified. The authors compared two patient cohorts with either CSM or COM treated using circumferential fusion. They sought to quantify perioperative morbidity and postoperative mortality in these two groups to assist with a diagnosis-specific informed consent process for future patients undergoing this type of surgery. Perioperative and follow-up data from two cohorts of patients who had undergone circumferential cervical decompression and fusion were analyzed. Estimated blood loss (EBL), length of stay (LOS), perioperative complications, hospital readmission, 30-day reoperation rates, change in Nurick grade, and mortality were compared between the two groups. Twenty-two patients were in the COM cohort, and 24 were in the CSM cohort. Complications, hospital readmission, 30-day reoperation rates, EBL, and mortality were not statistically different, although patients with COM trended higher in each of these categories. There was a significantly greater LOS (p < 0.001) in the COM group and greater improvement in Nurick grade in the CSM group (p < 0.001). When advising patients undergoing circumferential fusion about perioperative risk factors, it is important for those with COM to know that they are likely to have a higher rate of complications and mortality than those with CSM who are undergoing similar surgery. Furthermore, COM patients have less neurological improvement than CSM patients after surgery. This information may be useful to surgeons and patients in providing appropriate informed consent during preoperative planning. | 25,081,967 | [
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An X-linked sex ratio distorter in Drosophila simulans that kills or incapacitates both noncarrier sperm and sons. | Genomic conflict occurs when a genomic component gains a reproductive advantage at the expense of the organism as a whole. X-linked segregation distorters kill or incapacitate Y-bearing sperm, thereby gaining a transmission advantage but also reducing male fertility and generating a female-biased sex ratio. When some damaged, Y-bearing sperm survive and fertilize eggs, then the segregation distortion phenotype could be expanded by harming or killing sons in the next generation. X-linked son-killers are predicted by theory to be favored by natural selection and evolve when brothers and sisters compete for shared limiting resources and/or when brothers reduce the inclusive fitness of their sisters via sib-mating-a phenomenon called SA-zygotic drive. Here I develop and use a process-of-elimination screen to show that an unclassified X-linked sex ratio distorter (skew) in Drosophila simulans kills or incapacitates noncarrier sperm and also kills a substantial proportion of sons, i.e., it has both a segregation distortion and a SA-zygotic drive phenotype. There are three unique X-linked segregation distorters known to occur in D. simulans named Winters, Durham, and Paris. Autosomal-dominant suppressors of Winters (Nmy) and Durham (Tmy) failed to suppress skew. A Y-linked suppressor of Paris, however, did suppress skew, and a recombination test failed to detect recombinants between these two sex ratio distorters, indicating that they are tightly linked and plausibly identical or allelic. Son-killing may be an important yet unrecognized component of other X-linked segregation distorters. | 25,081,980 | [
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Regulation of centromere localization of the Drosophila Shugoshin MEI-S332 and sister-chromatid cohesion in meiosis. | The Shugoshin (Sgo) protein family helps to ensure proper chromosome segregation by protecting cohesion at the centromere by preventing cleavage of the cohesin complex. Some Sgo proteins also influence other aspects of kinetochore-microtubule attachments. Although many Sgo members require Aurora B kinase to localize to the centromere, factors controlling delocalization are poorly understood and diverse. Moreover, it is not clear how Sgo function is inactivated and whether this is distinct from delocalization. We investigated these questions in Drosophila melanogaster, an organism with superb chromosome cytology to monitor Sgo localization and quantitative assays to test its function in sister-chromatid segregation in meiosis. Previous research showed that in mitosis in cell culture, phosphorylation of the Drosophila Sgo, MEI-S332, by Aurora B promotes centromere localization, whereas Polo phosphorylation promotes delocalization. These studies also suggested that MEI-S332 can be inactivated independently of delocalization, a conclusion supported here by localization and function studies in meiosis. Phosphoresistant and phosphomimetic mutants for the Aurora B and Polo phosphorylation sites were examined for effects on MEI-S332 localization and chromosome segregation in meiosis. Strikingly, MEI-S332 with a phosphomimetic mutation in the Aurora B phosphorylation site prematurely dissociates from the centromeres in meiosis I. Despite the absence of MEI-S332 on meiosis II centromeres in male meiosis, sister chromatids segregate normally, demonstrating that detectable levels of this Sgo are not essential for chromosome congression, kinetochore biorientation, or spindle assembly. | 25,081,981 | [
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Lessons learned: feasibility and acceptability of a telehealth-delivered exercise intervention for rural-dwelling individuals with dementia and their caregivers. | Until dementias can be prevented or cured, interventions that maintain or maximize cognitive and functional abilities will remain critical healthcare and research priorities. Best practice guidelines suggest that individualized exercise programs may improve fitness, cognition, and function for people with mild to moderate dementia; however, few high quality exercise intervention trials exist for this population. Increasingly, telehealth is being used to improve the delivery and availability of healthcare services for individuals living in rural areas, including exercise. This article describes the feasibility of a telehealth-delivered exercise intervention for rural, community-dwelling individuals diagnosed with dementia and their caregivers. A mixed-methods two-phase exploratory approach was used. In phase 1, Rural and Remote Memory Clinic (RRMC; Saskatoon, Saskatchewan, Canada) patients and caregivers were surveyed about current exercise levels, perceptions about exercise, exercise preferences, and perceived barriers to exercise; community resources, acceptability of telehealth exercise interventions, and physical activity and exercise attitudes (Older Persons Attitudes Toward Physical Activity and Exercise Questionnaire). Data were analyzed using descriptive statistics and factors associated with willingness to participate in a telehealth exercise intervention were explored using hierarchical linear regression. In phase 2, acceptability, practicality, and implementation were examined. Two RRMC patient-caregiver dyads completed a 4-week exercise program delivered via telehealth. Observed engagement in the telehealth-based exercise intervention, using a revised version of the Menorah Park Engagement Scale (by Hearthstone Alzheimer Care), and attendance were monitored. Patient-caregiver dyads were interviewed at the end of the intervention phase and completed a telehealth and intervention satisfaction questionnaire. Interviews were thematically analyzed and questionnaire data were analyzed descriptively. Phase 1: Survey response rate was 50% (n=77). Patients (n=42) and caregivers (n=35) were equally likely to express interest in participating in the telehealth-based intervention. Willingness to participate in group exercise was the only significant predictor of willingness to participate in a telehealth-based intervention, accounting for 24.4% of the variance (F-statistic=16.14, p<0.001). Phase 2: Attendance rates were high for the telehealth-delivered exercise sessions. Engagement scale data indicated that the caregivers helped the patient participants during the intervention and that, overall, all participants were engaged in the target activity during the sessions. Ease of getting to the telehealth department, how well privacy was respected, ability to focus without distraction due to telehealth, ability to engage with group, and ability to engage with facilitator over telehealth were rated highly, as was the overall intervention experience. Telehealth voice and visual quality, ease of room set-up and conduciveness of the room to exercise were rated as good. Thematic analysis found that both dyads liked participating in the intervention together as a couple, and that participating in an exercise intervention with persons who were in a similar situations was deemed beneficial. Study results identified that although there are barriers to overcome, the development and evaluation of telehealth-delivered exercise interventions is a timely and important research activity that has the potential to facilitate improved healthcare services for individuals with dementia and their caregivers. | 25,081,991 | [
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Nanomechanical assessment of human and murine collagen fibrils via atomic force microscopy cantilever-based nanoindentation. | The nanomechanical assessment of collagen fibrils via atomic force microscopy (AFM) is of increasing interest within the biomedical research community. In contrast to conventional nanoindentation there exists no common standard for conducting experiments and analysis of data. Currently used analysis approaches vary between studies and validation of quantitative results is usually not performed, which makes comparison of data from different studies difficult. Also there are no recommendations with regards to the maximum indentation depth that should not be exceeded to avoid substrate effects. Here we present a methodology and analysis approach for AFM cantilever-based nanoindentation experiments that allows efficient use of captured data and relying on a reference sample for determination of tip shape. Further we show experimental evidence that maximum indentation depth on collagen fibrils should be lower than 10-15% of the height of the fibril to avoid substrate effects and we show comparisons between our and other approaches used in previous works. While our analysis approach yields similar values for indentation modulus compared to the Oliver-Pharr method we found that Hertzian analysis yielded significantly lower values. Applying our approach we successfully and efficiently indented collagen fibrils from human bronchi, which were about 30 nm in size, considerably smaller compared to collagen fibrils obtained from murine tail-tendon. In addition, derived mechanical parameters of collagen fibrils are in agreement with data previously published. To establish a quantitative validation we compared indentation results from conventional and AFM cantilever-based nanoindentation on polymeric samples with known mechanical properties. Importantly we can show that our approach yields similar results when compared to conventional nanoindentation on polymer samples. Introducing an approach that is reliable, efficient and taking into account the AFM tip shape, we anticipate that the present work may act as a guideline for conducting AFM cantilever-based nanoindentation of collagen fibrils. This may aid understanding of collagen-related diseases such as asthma, lung fibrosis or bone disease with potential alterations of collagen fibril mechanics. | 25,081,997 | [
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A memory-efficient algorithm to obtain splicing graphs and de novo expression estimates from de Bruijn graphs of RNA-Seq data. | The recent advance of high-throughput sequencing makes it feasible to study entire transcriptomes through the application of de novo sequence assembly algorithms. While a popular strategy is to first construct an intermediate de Bruijn graph structure to represent the transcriptome, an additional step is needed to construct predicted transcripts from the graph. Since the de Bruijn graph contains all branching possibilities, we develop a memory-efficient algorithm to recover alternative splicing information and library-specific expression information directly from the graph without prior genomic knowledge. We implement the algorithm as a postprocessing module of the Velvet assembler. We validate our algorithm by simulating the transcriptome assembly of Drosophila using its known genome, and by performing Drosophila transcriptome assembly using publicly available RNA-Seq libraries. Under a range of conditions, our algorithm recovers sequences and alternative splicing junctions with higher specificity than Oases or Trans-ABySS. Since our postprocessing algorithm does not consume as much memory as Velvet and is less memory-intensive than Oases, it allows biologists to assemble large libraries with limited computational resources. Our algorithm has been applied to perform transcriptome assembly of the non-model blow fly Lucilia sericata that was reported in a previous article, which shows that the assembly is of high quality and it facilitates comparison of the Lucilia sericata transcriptome to Drosophila and two mosquitoes, prediction and experimental validation of alternative splicing, investigation of differential expression among various developmental stages, and identification of transposable elements. | 25,082,000 | [
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... |
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