title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Ultrastructure of the Algivorous Amoeboflagellate Viridiraptor invadens (Glissomonadida, Cercozoa). | The family Viridiraptoridae represents a morphologically and ecologically distinct lineage of glissomonad flagellates (Cercozoa, Rhizaria). It currently comprises two highly specialised, algivorous genera inhabiting freshwater ecosystems, Orciraptor and Viridiraptor, for which ultrastructural data were lacking. In this study, the ultrastructure of Viridiraptor invadensHess et Melkonian, the sole described species of the viridiraptorid type genus, has been studied by transmission and scanning electron microscopy. In particular the flagellar transitional region and basal apparatus, both reconstructed from serial sections, revealed ultrastructural traits, that agree with the phylogenetic placement of the viridiraptorids within Glissomonadida: The transitional region contains a distal plate/collar complex and the basal apparatus comprises two ventral posterior roots and an anterior root, all known from other glissomonads. However, two additional small microtubular roots, two conspicuous rhizoplasts and probasal bodies present during interphase represent novel characteristics. Furthermore, an acorn/V-shaped filament system was discovered at the proximal end of the flagellar transitional region and used to establish a basal body triplet numbering system for flagellate cells of the Rhizaria. Finally, ultrastructural data on perforated algal cell walls suggest that the previously described reticulocyst of Viridiraptor represents an extrusome-derived, mesh-like coat supporting the invasion/feeding process. | 25,150,610 | [
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Proteomics analysis of altered cellular metabolism induced by insufficient copper level. | Insufficient copper level in the mammalian cell culture medium resulted in lactate accumulation while maintaining similar growth and culture viability profiles. Label-free, LC-MS/MS-based shotgun proteomics method was applied to compare the protein expression profiles obtained from the cultures exposed to suboptimal copper level to those provided with sufficient amount of copper. Under copper deficient condition, a substantial reduction of the protein levels of the multiple subunits of Complex IV, also known as cytochrome c oxidase, of the mitochondrial electron transport chain was observed for all three different Chinese Hamster Ovary (CHO) cell lines expressing therapeutic monoclonal antibodies tested. Additional proteins affected by suboptimal copper level included peroxiredoxin (PRDX) and hepatocyte-derived growth factor (HDGF), which were affected during early phase of the fed-batch production, several days prior to initiation of lactate accumulation. In contrast, proteins such as syntenin (SDCBP) and integral membrane 2C (ITM2C) showed altered expression patterns toward the end of culture duration, after lactate divergence had occurred. For all conditions tested, time was the most predominant factor facilitating the direction of global protein expression trend, with substantial number of proteins subjected to time-dependent changes in expression, independent of copper. | 25,150,618 | [
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Concordant B-cell precursor acute lymphoblastic leukemia in non-twinned siblings. | Associating the risk of childhood acute lymphoblastic leukemia (ALL) with genetic predisposition is still a challenge. Here, we discuss two non-twinned sibs (girl and boy) diagnosed with B-cell precursor (BCP-ALL) and ETV6-RUNX1. BCP-ALL clinical onset occurred 10months apart from each diagnosis. One child is alive in complete continuous remission, whereas, the other relapsed and evolved to death with resistance to ALL treatment. Despite the fact that BCP-ALL with ETV6-RUNX1 usually results in a very good prognosis, the sibs experienced divergent outcomes; a remarkable difference in one child that presented a more aggressive disease was higher leukocytosis associated with IKZF1 deletion. The familial history of cancer and genetic susceptibility was explored. The sibs were absolutely identical in all 17 loci of genes tested; GSTM1, GSTT1, NQO1, TP53, and TP63 were wild-type, whereas at least one copy of the variant allele for IKZF1, ARID5B, PTPRJ and CEBPE was present. The familial pattern of ETV6 was tested by the 12p microsatellite analysis and demonstrated that deletions occurred in one child but not the other, while heterozygous patterns were found in the parents. Altogether, our data suggest that genetic predisposition aligned with chance haa an additive effect in BCP-ALL outcome. | 25,150,625 | [
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An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields. | Adaptive radiotherapy (ART) has considerable potential in treatment of bladder cancer due to large inter-fractional changes in shape and size of the target. The aim of this study was to compare our clinically applied method for plan library creation that involves manual bladder delineations (Clin-ART) with a method using the deformation vector fields (DVFs) resulting from intensity-based deformable image registrations (DVF-based ART). The study included thirteen patients with urinary bladder cancer who had daily cone beam CTs (CBCTs) acquired for set-up. In both ART strategies investigated, three plan selection volumes were generated using the CBCTs from the first four fractions; in Clin-ART boolean combinations of delineated bladders were used, while the DVF-based strategy applied combinations of the mean and standard deviation of patient-specific DVFs. The volume ratios (VRs) of the course-averaged PTV for the two ART strategies relative the non-adaptive PTV were calculated. Both Clin-ART and DVF-based ART considerably reduced the course-averaged PTV, compared to non-adaptive RT. The VR for DVF-based ART was lower than for Clin-ART (0.65 vs. 0.73; p<0.01). DVF-based ART for bladder irradiation has a considerable normal tissue sparing potential surpassing our already highly conformal clinically applied ART strategy. | 25,150,634 | [
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Risk factors for radiotherapy incidents and impact of an online electronic reporting system. | To ascertain the rate, type, significance, trends and the potential risk factors associated with radiotherapy incidents in a large academic department. Data for all radiotherapy activities from July 2001 to January 2011 were reviewed from radiotherapy incident reporting forms. Patient and treatment data were obtained from the radiotherapy record and verification database (MOSAIQ) and the patient database (HOSPRO). Logistic regression analyses were performed to determine variables associated with radiotherapy incidents. In that time, 65,376 courses of radiotherapy were delivered with a reported incident rate of 2.64 per 100 courses. The rate of incidents per course increased (1.96 per 100 courses to 3.52 per 100 courses, p<0.001) whereas the proportion of reported incidents resulting in >5% deviation in dose (10.50 to 2.75%, p<0.001) had decreased after the introduction of an online electronic reporting system. The following variables were associated with an increased rate of incidents: afternoon treatment time, paediatric patients, males, inpatients, palliative plans, head-and-neck, skin, sarcoma and haematological malignancies. In general, complex plans were associated with higher incidence rates. Radiotherapy incidents were infrequent and most did not result in significant dose deviation. A number of risk factors were identified and these could be used to highlight high-risk cases in the future. Introduction of an online electronic reporting system resulted in a significant increase in the number of incidents being reported. | 25,150,636 | [
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Assessing patterns of spatial behavior in health studies: their socio-demographic determinants and associations with transportation modes (the RECORD Cohort Study). | Prior epidemiological studies have mainly focused on local residential neighborhoods to assess environmental exposures. However, individual spatial behavior may modify residential neighborhood influences, with weaker health effects expected for mobile populations. By examining individual patterns of daily mobility and associated socio-demographic profiles and transportation modes, this article seeks to develop innovative methods to account for daily mobility in health studies. We used data from the RECORD Cohort Study collected in 2011-2012 in the Paris metropolitan area, France. A sample of 2062 individuals was investigated. Participants' perceived residential neighborhood boundaries and regular activity locations were geocoded using the VERITAS application. Twenty-four indicators were created to qualify individual space-time patterns, using spatial analysis methods and a geographic information system. Three domains of indicators were considered: lifestyle indicators, indicators related to the geometry of the activity space, and indicators related to the importance of the residential neighborhood in the overall activity space. Principal component analysis was used to identify main dimensions of spatial behavior. Multilevel linear regression was used to determine which individual characteristics were associated with each spatial behavior dimension. The factor analysis generated five dimensions of spatial behavior: importance of the residential neighborhood in the activity space, volume of activities, and size, eccentricity, and specialization of the activity space. Age, socioeconomic status, and location of the household in the region were the main predictors of daily mobility patterns. Activity spaces of small sizes centered on the residential neighborhood and implying a large volume of activities were associated with walking and/or biking as a transportation mode. Examination of patterns of spatial behavior by individual socio-demographic characteristics and in relation to transportation modes is useful to identify populations with specific mobility/accessibility needs and has implications for investigating transportation-related physical activity and assessing environmental exposures and their effects on health. | 25,150,652 | [
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Social capital and adolescent smoking in schools and communities: a cross-classified multilevel analysis. | We sought to determine whether social capital at the individual-, school- and community-level can explain variance in adolescent smoking and accounts for social inequalities in smoking. We collected data as part of the 2005/6 Health Behavior in School-aged Children survey, a nationally representative survey of the health and well-being of high school pupils in Belgium (Flanders). Social capital was assessed by structural and cognitive components of family social capital, a four-factor school social capital scale and a cognitive community social capital scale. We fitted non-hierarchical multilevel models to the data, with 8453 adolescents nested within a cross-classification of 167 schools and 570 communities. Significant variation in adolescent regular smoking was found between schools, but not between communities. Only structural family social capital and cognitive school social capital variables negatively related to regular smoking. No interactions between socio-economic status and social capital variables were found. Our findings suggest that previously observed community-level associations with adolescent smoking may be a consequence of unmeasured confounding. Distinguishing nested contexts of social capital is important because their associations with smoking differ. | 25,150,654 | [
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Bucking social norms: examining anomalous fertility aspirations in the face of HIV in Lusaka, Zambia. | In settings of high fertility and high HIV prevalence, individuals are making fertility decisions while simultaneously trying to avoid or manage HIV. We sought to increase our understanding of how individuals dually manage HIV risk while attempting to achieve their fertility goals as part of the project entitled HIV Status and Achieving Fertility Desires conducted in Zambia in 2011. Using multivariate regression to predict fertility patterns based on socio-demographic characteristics for respondents from facility-based and community-based surveys, we employed Anomalous Case Analysis (ACA) whereby in-depth interview respondents were selected from the groups of outliers amongst the survey respondents who reported lower or higher fertility preferences than predicted as well as those who adhered to predicted patterns, and lived in Lusaka (n=45). All of the facility-based respondents were HIV-positive. We utilize the Theory of Conjunctural Action (TCA) to categorize domains of influence on individuals' preferences and behavior. Both community-based and facility-based right-tail respondents (outliers whose fertility intentions indicated that they wanted a/nother child when we predicted that they did not) expressed comparatively less control over their fertility and gave more weight to pressures from others to continue childbearing. Partner communication about fertility desires was greater among left-tail respondents (outliers whose fertility intentions indicated that they did not want a/nother child when we predicted that they did). HIV-positive right-tail respondents were more likely to see anti-retroviral therapies (ARTs) which prevent mother to child transmission of HIV as highly effective, mitigating inhibitions to further childbearing. Drug interactions between ARTs and contraceptives were identified as a limitation to HIV-positive individuals' contraceptive options on both sides of the distribution. Factors that should be taken into account in the future to understand fertility behavior in high HIV-prevalent settings include couples' communication around fertility and perception of the efficacy of ARTs. | 25,150,655 | [
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Selecting measures for balance and mobility to improve assessment and treatment of individuals after stroke. | Assessment of individuals with stroke using reliable and valid outcome measures is a key component of the treatment planning process. Health care professionals may have difficulty selecting balance and mobility measures given the large number of measures to choose from. This article utilizes a case-based approach to describe the benefits of using a common set of outcome measures and a process for selecting optimal measures across body structure/function, activity, and participation domains of the International Classification of Functioning, Disability and Health (ICF) model and stages of stroke recovery. Specific measures for use in acute care, rehabilitation, outpatient, and home health care settings are discussed based on StrokEDGE task force recommendations by the Neurology Section of the American Physical Therapy Association. | 25,150,662 | [
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Task matters: influence of different cognitive tasks on cognitive-motor interference during dual-task walking in chronic stroke survivors. | The impact of unilateral brain damage, such as that caused by stroke, on the interaction between higher cognitive functions and walking remains uncertain. We compared cognitive-motor interference (CMI) during dual-task (DT) walking between chronic stroke survivors and young adults performing explicitly different cognitive tasks. Ten community-dwelling chronic stroke survivors and 10 young adults performed 3 cognitive tasks - visuomotor reaction time (VMRT), serial subtraction (SS), and Stroop test (STR) - while sitting and walking. Gait velocity was recorded using an electronic walkway. Cognitive variables included reaction time and number of correct responses. Motor and cognitive costs were computed. DT walking led to significant declines in motor and cognitive performance. Significant main effect of task (P < .01) and group (P < .01) was observed for motor cost. The stroke group showed highest motor cost for SS task, whereas the young group showed highest motor cost for STR task (Group × Task interaction, P < .05). Although cognitive costs for both groups was highest for VMRT and lowest for STR tasks, cognitive cost for SS task was significantly greater for the stroke group compared with the young group (Group × Task interaction, P < .05). CMI pattern in chronic stroke survivors differs significantly with type of cognitive task. Gradual cognitive decline with chronicity of condition might have a role in altering the CMI pattern in this population. Future studies of DT interventions for stroke survivors might benefit from incorporating working memory tasks in their protocols. | 25,150,667 | [
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Impacts of powdered activated carbon addition on trihalomethane formation reactivity of dissolved organic matter in membrane bioreactor effluent. | Characteristics and trihalomethane (THM) formation reactivity of dissolved organic matter (DOM) in effluents from two membrane bioreactors (MBRs) with and without powdered activated carbon (PAC) addition (referred to as PAC/MBR and MBR, respectively) were examined to investigate the effects of PAC addition on THM formation of MBR effluent during chlorination. PAC addition increased the specific UV absorbance. Hydrophobic DOM especially hydrophobic acids in PAC/MBR effluent (50%) were more than MBR effluent (42%). DOM with molecular weight <1 kDa constituted 12% of PAC/MBR effluent DOM, which was less than that of MBR effluent (16%). Data obtained from excitation and emission matrix fluorescence spectroscopy revealed that PAC/MBR effluent DOM contained more simple aromatic protein, but had less fulvic acid-like and soluble microbial by-product-like. PAC addition reduced the formation of bromine-containing THMs during chlorination of effluents, but increased THM formation reactivity of effluent DOM. | 25,150,685 | [
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A comparative protein profile of mammalian erythrocyte membranes identified by mass spectrometry. | A comparative analysis of erythrocyte membrane proteins of economically important animals, goat (Capra aegagrus hircus), buffalo (Bubalus bubalis), pig (Sus scrofa), cow (Bos tauras), and human (Homo sapiens) was performed. Solubilized erythrocyte membrane proteins were separated by sodium dodecyl sulfate-polyacryamide gel electrophoresis (SDS-PAGE), visualized by staining the gels with Commassie Brilliant Blue (CBB), and identified by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Emerging results show that all major erythrocyte membrane proteins present in human are also seen in all the animals except for band 4.5 which could not be identified. Band 3 is seen as more intense and compact, band 4.1 appears as a doublet in all the animal erythrocyte membranes, band 4.2 exhibits a slightly higher molecular weight (Mr) in buffalo, and cow and band 4.9 has a higher Mr in all the animals relative to the human protein. In addition, there are two new bands in the goat membrane, band G1, identified as HSP 90α, and band G2 identified as HSP 70. A new band C2 identified as HSP 70 is also seen in cow membranes. Peroxiredoxin II is of lower intensity and/or higher Mr in the animals. The difference in size of the proteins possibly indicates the variations in the composition of the amino acids. The difference in intensity of the proteins among these mammalians highlights the presence of less or more number of copies of that protein per cell. This data complement the earlier observations of differences in the sialoglycoprotein profile and effect of proteases and neuraminidase on agglutination among the mammalian erythrocytes. This study provides a platform to understand the molecular architecture of the individual erythrocytes, and in turn the dependent disorders, their phylogenetic relationship and also generates a database of erythrocyte membrane proteins of mammals. The animals selected for this study are of economic importance as they provide milk for the dairy industry and raw material for leather industry and are routinely sacrificed to obtain non vegetarian food worldwide. | 25,150,706 | [
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The use of biomarkers for the etiologic diagnosis of MCI in Europe: an EADC survey. | We investigated the use of Alzheimer's disease (AD) biomarkers in European Alzheimer's Disease Consortium centers and assessed their perceived usefulness for the etiologic diagnosis of mild cognitive impairment (MCI). We surveyed availability, frequency of use, and confidence in diagnostic usefulness of markers of brain amyloidosis (amyloid positron emission tomography [PET], cerebrospinal fluid [CSF] Aβ42) and neurodegeneration (medial temporal atrophy [MTA] on MR, fluorodeoxyglucose positron emission tomography [FDG-PET], CSF tau). The most frequently used biomarker is visually rated MTA (75% of the 37 responders reported using it "always/frequently") followed by CSF markers (22%), FDG-PET (16%), and amyloid-PET (3%). Only 45% of responders perceive MTA as contributing to diagnostic confidence, where the contribution was rated as "moderate". Seventy-nine percent of responders felt "very/extremely" comfortable delivering a diagnosis of MCI due to AD when both amyloid and neuronal injury biomarkers were abnormal (P < .02 versus any individual biomarker). Responders largely agreed that a combination of amyloidosis and neuronal injury biomarkers was a strongly indicative AD signature. | 25,150,733 | [
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Comparison of operative and non-operative outcomes based on surgical selection criteria for patients with Chiari I malformations. | Few studies have directly compared operative and non-operative outcomes in Chiari I patients. We evaluated risk factors for clinical improvement in 177 patients in order to help determine the optimal treatment of these often difficult to treat patients. The mean age at surgery for the operative treatment group was 29.9 years. The most common presenting signs and symptoms included cough headache (63.0%), migraine and non-cough type headaches (23.9%), paresthesias (32.1%), and abnormal reflexes or clonus (27.5%). The mean age of diagnosis for the non-operative treatment group was 30.2 years. The most common presenting signs or symptoms included migraine and other types of non-cough-associated headache (57.4%), paresthesias (45.6%), cough headache (44.1%), cerebellar signs or symptoms (41.2%), and dysphagia or apnea (15.7%). A propensity score was generated using cough headache, any headache, other headache, syrinx, abnormal reflexes or clonus, cerebellar symptoms, and miscellaneous symptoms as independent predictors of selection for surgery. The propensity score-adjusted odds of overall improvement for patients treated with surgery were 16.5 times the odds of overall improvement for patients treated conservatively (95% confidence interval 5.5-57.1, p<0.0001). Overall 94.5% and 47.1% of operative and conservatively treated patients reported improvement, respectively. Only 26.5% of conservatively treated patients reported worsening of any of their symptoms. In conclusion, we provided further evidence for the use of cough headache as surgical indication for suboccipital decompression in patients with Chiari I malformation. | 25,150,760 | [
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Arterial fenestrations and their association with cerebral aneurysms. | Fenestrations of intracranial arteries and associated aneurysms are rare. The significance of these fenestrations in relation to aneurysms remains unclear. We present four patients with fenestration-associated aneurysms and a comprehensive review of associations with aneurysms and other vascular lesions. A PubMed search of the literature was conducted from 1970-2012 reporting cases of intracranial aneurysms associated with arterial fenestration or duplications. Data were collected on patient presentation, sex, age, aneurysm and fenestration location, aneurysm treatment, and presence of other vascular lesions. We performed a retrospective review of four patients with intracranial fenestrations associated with aneurysms at our institution from 2012-2013. There were 59 cases of fenestrations and associated aneurysms in the literature. Aneurysms were reported as either arising from (n=50) or adjacent to but distinct from (n=13) fenestrations. The most common single fenestration location was at the basilar artery (n=23, 36.5%); however the majority of fenestrations were in the carotid circulation (n=34, 54.0%). The majority of patients with aneurysms and fenestrations at all locations except those at the anterior communicating artery (70.5%) presented with subarachnoid hemorrhage. Patients with aneurysms arising from a fenestration or adjacent to a fenestration presented with an additional intracranial vascular lesion in 38% and 31% of cases, respectively. The majority of all aneurysms were treated with microsurgical clipping. Aneurysms associated with cerebral arterial fenestrations are most commonly discovered after subarachnoid hemorrhage and are most often located in the carotid circulation. A high index of suspicion must be maintained for an associated vascular lesion if an intracranial fenestration is discovered. | 25,150,765 | [
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Relationships among cognitive impairment, sleep, and fatigue in Parkinson's disease using the MDS-UPDRS. | Non-motor complications of Parkinson's disease (PD), specifically cognitive impairment, sleep disturbances, and fatigue, are recognized as important contributors to poor patient outcomes and quality of life. How sleep problems and fatigue interrelate and impact cognitive function, however, has not systematically been investigated across the stages of PD. The aim of our study was to investigate the relationships among cognitive impairment, night-time sleep problems, daytime sleepiness, and fatigue across all severities of PD. We examined these non-motor problems using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) in a study of 1319 PD patients drawn from three large cohort studies: the Parkinson's Progressive Markers Initiative, the Rush University PD Cognitive-Behavioral-Imaging study, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Clinimetric testing program study, which spanned the gamut of disease, from early to advanced PD. Generalized linear mixed models with logit linking functions and covariates including study cohort, age, PD duration, and presence/absence of PD medications were used to examine relationships between these three non-motor symptoms and cognitive impairment. Of these three frequent, and often inter-twined, non-motor complications, greater daytime sleepiness and fatigue were associated with worse cognitive impairment across the full spectrum of PD (F[16,1158] = 2.40 and F[16,1158] = 3.45 respectively, p's < 0.0005), but an association with night-time sleep was not detected (p = 0.83). Given this association of daytime sleepiness and fatigue with cognitive impairment, clinical monitoring for these problems should be considered across all points in the PD spectrum, from early to more advanced disease. | 25,150,770 | [
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Photoinduced electron transfer (PET) based label-free aptasensor for platelet-derived growth factor-BB and its logic gate application. | Platelet-derived growth factor-BB (PDGF-BB) is often overexpressed in human malignant tumors as an indicator for tumor angiogenesis. Here by the photoinduced electron transfer (PET) between DNA-Ag fluorescent nanoclusters (NCs) and G-quadruplex/hemin complexes, we present a sensitive label-free fluorescent sensor for PDGF-BB. In the presence of PDGF-BB, the specific conjugation with its aptamer induced the conformational change of the duplex-like DNA sequence, releasing the G-quadruplex sequence part. Then in the presence of hemin and K(+), the horseradish peroxidase mimicking DNAzyme (HRP-DNAzyme) was formed. With the electron transfer between the DNA-Ag NCs to the hemin Fe (III) center of HRP-DNAzyme, the PET occurred with a decrease in the fluorescence intensity of the DNA-Ag NCs. The detection performance such as selectivity, linear dynamic range, sensitivity, and the quenching capability of HRP-DNAzyme were estimated. The detection range for PDGF-BB is from 5×10(-13) to 1×10(-8) M and the detection limit is 1×10(-13) M. The experimental results confirmed that the novel fluorescent aptasensor possessed a good sensitivity and high selectivity for PDGF-BB. In addition, the developed probe is nontoxic, label-free only involving one-step hybridization without sophisticated fabrication process. Furthermore, based on this quenching mode occurred by PDGF-BB and hemin, using PDGF-BB and hemin as inputs and the fluorescence signal as an output, a logic gate has been fabricated. | 25,150,781 | [
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Mental testing in the early twentieth century: internationalizing the mental testing story. | This article suggests a possible approach to analyzing the global history of intelligence testing in light of some recent work in the history of science and science studies. In particular, it uses work in metrology and subaltern studies to develop possible models for the dissemination, appropriation, and transformation of mental testing in the early 20th century. It draws on the accounts presented in the other articles in this collection to substantiate its claims. (PsycINFO Database Record (c) 2014 APA, all rights reserved). | 25,150,810 | [
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The role of central and peripheral muscle fatigue in postcancer fatigue: a randomized controlled trial. | Postcancer fatigue is a frequently occurring problem, impairing quality of life. Little is known about (neuro)physiological factors determining postcancer fatigue. It may be hypothesized that postcancer fatigue is characterized by low peripheral muscle fatigue and high central muscle fatigue. The aims of this study were to examine whether central and peripheral muscle fatigue differ between fatigued and non-fatigued cancer survivors and to examine the effect of cognitive behavioral therapy (CBT) on peripheral and central muscle fatigue of fatigued cancer survivors in a randomized controlled trial. Sixteen fatigued patients in the intervention group (CBT) and eight fatigued patients in the waiting list group were successfully assessed at baseline and six months later. Baseline measurements of 20 fatigued patients were compared with 20 non-fatigued patients. A twitch interpolation technique and surface electromyography were applied, respectively, during sustained contraction of the biceps brachii muscle. Muscle fiber conduction velocity (MFCV) and central activation failure (CAF) were not significantly different between fatigued and non-fatigued patients. Change scores of MFCV and CAF were not significantly different between patients in the CBT and waiting list groups. Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group. Postcancer fatigue is neither characterized by abnormally high central muscle fatigue nor by low peripheral muscle fatigue. These findings suggest a difference in the underlying physiological mechanism of postcancer fatigue vs. other fatigue syndromes. | 25,150,812 | [
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The Notch γ-secretase inhibitor ameliorates kidney fibrosis via inhibition of TGF-β/Smad2/3 signaling pathway activation. | Kidney fibrosis is a common feature of chronic kidney disease (CKD). A recent study suggests that abnormal Notch signaling activation contributes to the development of renal fibrosis. However, the molecular mechanism that regulates this process remains unexplored. Unilateral ureteral obstruction (UUO) or sham-operated C57BL6 mice (aged 10 weeks) were randomly assigned to receive dibenzazepine (DBZ, 250 μg/100g/d) or vehicle for 7 days. Histologic examinations were performed on the kidneys using Masson's trichrome staining and immunohistochemistry. Real-time PCR and western blot analysis were used for detection of mRNA expression and protein phosphorylation. The expression of Notch 1, 3, and 4, Notch intracellular domain (NICD), and its target genes Hes1 and HeyL were upregulated in UUO mice, while the increase in NICD protein was significantly attenuated by DBZ. After 7 days, the severity of renal fibrosis and expression of fibrotic markers, including collagen 1α1/3α1, fibronectin, and α-smooth muscle actin, were markedly increased in UUO compared with sham mice. In contrast, administration of DBZ markedly attenuated these effects. Furthermore, DBZ significantly inhibited UUO-induced expression of transforming growth factor (TGF)-β, phosphorylated Smad 2, and Smad 3. Mechanistically, Notch signaling activation in tubular epithelial cells enhanced fibroblast proliferation and activation in a coculture experiment. Our study provides evidence that Notch signaling is implicated in renal fibrogenesis. The Notch inhibitor DBZ can ameliorate this process via inhibition of the TGF-β/Smad2/3 signaling pathway, and might be a novel drug for preventing chronic kidney disease. | 25,150,830 | [
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Asymmetric mRNA localization contributes to fidelity and sensitivity of spatially localized systems. | Although many proteins are localized after translation, asymmetric protein distribution is also achieved by translation after mRNA localization. Why are certain mRNA transported to a distal location and translated on-site? Here we undertake a systematic, genome-scale study of asymmetrically distributed protein and mRNA in mammalian cells. Our findings suggest that asymmetric protein distribution by mRNA localization enhances interaction fidelity and signaling sensitivity. Proteins synthesized at distal locations frequently contain intrinsically disordered segments. These regions are generally rich in assembly-promoting modules and are often regulated by post-translational modifications. Such proteins are tightly regulated but display distinct temporal dynamics upon stimulation with growth factors. Thus, proteins synthesized on-site may rapidly alter proteome composition and act as dynamically regulated scaffolds to promote the formation of reversible cellular assemblies. Our observations are consistent across multiple mammalian species, cell types and developmental stages, suggesting that localized translation is a recurring feature of cell signaling and regulation. | 25,150,862 | [
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Whole blood transcriptomic analysis to identify clinical biomarkers of drug response. | Since most immunological and hematological conditions might be expected to alter whole blood gene expression, its examination can lead to insights into disease processes, and biomarkers to assess molecular phenotypes, disease states, progression and response to therapy. In this chapter we describe collection and storage of RNA from whole blood, techniques to measure gene expression, and analytical approaches to identify the dysregulated gene expression using pathway and clustering analysis, gene set enrichment, heat map approaches, and cell subset deconvolution. | 25,150,865 | [
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Management of side effects in the personalized medicine era: chemotherapy-induced peripheral neuropathy. | Pharmacogenomics has been establishing itself as a powerful tool to predict individual response to treatment, in order to personalize therapy management; this field has been explored in particular in Oncology. Not only efficacy on the malignant disease has been investigated, but also the possibility to predict adverse effects due to drug administration. Chemotherapy-Induced Neurotoxicity (CIPN) is one of those. This potentially severe and long-lasting/permanent side effect of commonly administered anticancer drugs can severely impair Quality of Life (QoL) in a large cohort of long survival patients. So far, a pharmacogenomics-based approach in CIPN regard has been quite delusive, making a methodological improvement warranted in this field of interest: even the most refined genetic analysis cannot be effective if not applied correctly. Here, we try to devise why it is so, suggesting how THE "bench-side" (Pharmacogenomics) might benefit from and should cooperate with THE "bed-side" (Clinimetrics), in order to make genetic profiling effective if applied to CIPN. | 25,150,874 | [
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Specificity of emotion regulation difficulties related to anxiety in early adolescence. | Etiological models identify difficulties in emotion regulation as potential contributors to the development and maintenance of anxiety. To date, studies with adolescents have not tested whether different types of anxiety symptoms are related to different emotion regulation difficulties. The current study aimed to examine specificity of associations between emotion regulation difficulties and symptoms of social and generalized anxiety in early adolescence. Ninety adolescents (ages 11-14 years) completed measures of emotion regulation and anxiety symptoms. Social and generalized anxiety symptoms showed similar bivariate correlations with emotion regulation. However, when controlling for generalized anxiety, social anxiety symptoms were uniquely related to emotion understanding, acceptance, evaluation, and reactivity. Generalized anxiety symptoms were uniquely related to emotion modification. The current study suggests that social and generalized anxiety symptoms have both common and unique associations with emotion regulation difficulties in early adolescence, and has implications for which emotion regulation skills to target in clinical interventions. | 25,150,890 | [
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High-affinity GABA uptake by neuronal GAT1 transporters provokes release of [(3)H]GABA by homoexchange and through GAT1-independent Ca(2+)-mediated mechanisms. | High-affinity uptake of GABA into nerve terminals may have functions other than recapture of the neurotransmitter. Synaptosomes purified from mouse cerebellum were prelabelled with [(3)H]GABA and then superfused with GABA and drugs selective for some presynaptic targets. Influx of GABA through GAT1 transporters stimulated efflux of [(3)H]GABA in a concentration-dependent manner (EC50 ∼ 3 μM). The efflux of the transmitter occurred in part by GAT1 reversal through the so called homoexchange. The ion fluxes (particularly Na(+) influx) accompanying GABA uptake triggered intraterminal Ca(2+) signals through both plasmalemmal Na(+)/Ca(2+) exchangers, sensitive to KB-R7943 or to ifenprodil and mitochondrial Na(+)/Ca(2+) exchangers, sensitive to CGP37157. These Ca(2+) signals likely facilitated GABA release from nerve terminals via niflumic acid- and NPPB-sensitive anion channels. The results show that GABA, at concentrations corresponding to the high-affinity uptake, can evoke GABA release which occurs in part by the expected GAT1-mediated homoexchange, while the transporter-independent component of the GABA uptake-evoked GABA release takes place by hitherto unsuspected mechanisms which include Na(+)/Ca(2+) exchangers and anion channels. The significance of the novel function of the GABA high-affinity uptake here identified deserves further multidisciplinary investigation. | 25,150,942 | [
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Health status and fatigue of postpartum anemic women: a prospective cohort study. | The incidence of postpartum anemia is high. Current therapy consists of iron supplementation or blood transfusions, based on the assumption that these treatments improve health status (HS) and reduce fatigue. The aim of this study was to compare HS and fatigue in postpartum women with and without anemia. This prospective cohort study was performed in The Netherlands between April 2008 and August 2010 and involved 112 anemic (hemoglobin [Hb]<10.5g/dL) and 108 non-anemic (Hb≥10.5g/dL) women. The anemic women received oral iron supplementation. Within 48h and 5 weeks after delivery, HS was measured using the 36 item Short-Form Health Survey (SF-36) and fatigue was measured using the Checklist Individual Strength (CIS). ANOVA for repeated measures was used to compare HS and fatigue scores among groups and across time. After adjustment for confounding variables, there were no differences in any of the HS and fatigue scores. HS and fatigue seem to be more influenced by a complicated delivery than by anemia. HS and fatigue scores significantly improved over time in all women. HS and fatigue were not different among women with and without postpartum anemia. | 25,150,948 | [
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Evaluation of pesticide toxicity at their field recommended doses to honeybees, Apis cerana and A. mellifera through laboratory, semi-field and field studies. | A series of experiments were carried out to determine the acute toxicity of pesticides in the laboratory, toxicity through spray on flowering plants of mustard (Tier II evaluation) and field on both Apis cerana and A. mellifera bees. The overall mortality of honey bees through topical (direct contact) were found significantly higher than that of indirect filter paper contamination assays. Insecticides viz., chlorpyriphos, dichlorvos, malathion, profenofos, monocrotophos and deltamethrin when exposed directly or indirectly at their field recommended doses caused very high mortality up to 100% to both the bees at 48 HAT. The insecticides that caused less mortality through filter paper contamination viz., flubendiamide, methyl demeton, imidacloprid and thiamethoxam caused very high morality through direct exposure. Apart from all the fungicides tested, carbendazim, mancozeb, chlorothalonil and propiconazole, insecticides acetamiprid and endosulfan were found safer to both the bees either by direct or indirect exposures. Tier II evaluation by spray of pesticides at their field recommended doses on potted mustard plants showed monocrotophos as the highly toxic insecticide with 100% mortality even with 1h of exposure followed by thiamethoxam, dichlorvos, profenofos and chlorpyriphos which are not to be recommended for use in pollinator attractive flowering plants. Acetamiprid and endosulfan did not cause any repellent effect on honey bees in the field trials endorse the usage of acetamiprid against sucking pest in flowering plants. | 25,150,969 | [
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T cell isolation from mouse kidneys. | The kidneys contain very few lymphocytes under homeostatic conditions. One kidney from a healthy mouse per average contains only 1-5 × 10(3) CD4(+) T cells. In immune-mediated kidney disease, γδ T cells, NKT cells, CD4(+) T cells, CD8(+) T cells, and regulatory T cells (Treg) infiltrate the kidney. Their numbers and subset composition of infiltrating T cells varies between the different forms of nephritis. For example, in glomerulonephritis CD4(+) T cells mediate renal injury, by local cytokine production, effector cell activation and/or by helping B cells to produce nephritogenic antibodies. A better understanding of the pathomechanisms of immune-mediated kidney diseases requires a method to isolate T cells from the kidney for ex vivo analysis. Here we describe an effective and specific isolation protocol for T cells from the murine kidney. | 25,150,994 | [
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In vitro generation of microbe-specific human Th17 cells. | Th17 cells represent a T helper cell subset with major implications for the pathogenesis of autoimmune diseases and the clearance of extracellular bacteria and fungi. The in vitro generation of human Th17 cells has been subject to many debates concerning the minimal cytokine requirements for IL-17 induction. This is partly due to the low Th17 cell priming efficiencies that have been reported so far for human as compared to murine T cells. In addition, human T helper cell priming is primarily performed using polyclonal stimulation even though it has recently been reported that cytokine requirements for the generation of Th17 cells may differ depending on the microbial antigen specificities of naïve T cells. Here, we present a detailed procedure on how to efficiently generate microbe-specific Th17 cells from naïve T helper cells. | 25,151,000 | [
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Mouse models of allergic airway disease. | In the last decades there has been a substantial increase in the prevalence of allergic diseases such as asthma. Hence there is a basic necessity to investigate disease mechanisms of allergic disorders and to trace novel treatment approaches. Indeed, allergic asthma is a disorder which is characterized by airway inflammation, airway obstruction, and hyperresponsiveness. Several of these features can be studied in models of allergic airway disease. In this chapter different mouse models of allergic diseases are described. These include frequently models of allergic airway disease utilizing sensitization and challenge towards ovalbumin. Furthermore a model using the human-relevant allergen-specific house dust mite is described. In addition, information about DC-induced models and analysis of in vitro-generated T cell following transfer into recipients are described as well as analysis of a humanized mouse model is provided. | 25,151,003 | [
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Induction of colitis in mice (T-cell transfer model). | Animal model of intestinal inflammation is essential for the understanding of the pathomechanisms of inflammatory bowel diseases like Crohn's disease and ulcerative colitis. Typically, naïve T-cells were transferred into immunocompromised mice and develop gut inflammation because of inappropriate downregulation. Here, we describe the isolation, purification, and transfer of CD4(+)CD25(-) T-cells into recipients to obtain an experimental colitis model for the analysis of pathogenesis. | 25,151,004 | [
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Inflammatory biomarkers and bladder cancer prognosis: a systematic review. | Host immune response has an impact on tumour development and progression. There is interest in the use of inflammatory biomarkers (InfBMs) in cancer care. Although several studies assessing the potential prognostic value of InfBMs in cancer have been published in the past decades, they have had no impact on the management of patients with urothelial bladder carcinoma (UBC). To review and summarise the scientific literature on the prognostic value of tumour, serum, urine, and germline DNA InfBMs on UBC. A systematic review of the literature was performed searching the Medline and Embase databases for original articles published between January 1975 and November 2013. The main inclusion criterion was the provision of a survival analysis (Kaplan-Meier and/or Cox) according to the Reporting Recommendations for Tumor Marker Prognostic Studies guidelines for the assessment of prognostic markers. We focused on markers assessed at least twice in the literature. Findings are reported following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Overall, 34 publications, mostly retrospective, fulfilled the main inclusion criterion. Main limitations of these studies were missing relevant information about design or analysis and heterogeneous methodology used. Inflammatory cells, costimulatory molecules in tumour cells, and serum cytokines showed prognostic significance, mainly in univariable analyses. High C-reactive protein values were consistently reported as an independent prognostic factor for mortality in invasive UBC. There is a dearth of studies on InfBMs in UBC compared with other tumour types. Evidence suggests that InfBMs may have an impact on the management of patients with UBC. Currently, methodological drawbacks of the studies limit the translational potential of results. In this review, we analysed studies evaluating the impact of inflammatory response on bladder cancer progression. Despite methodological limitations, some inflammatory biomarkers should be further analysed because they hold promise to improve patient care. | 25,151,017 | [
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Coupling of comprehensive two-dimensional gas chromatography with quadrupole mass spectrometry: application to the identification of atmospheric volatile organic compounds. | Observation data of atmospheric volatile organic compounds (VOCs) are highly needed in air quality assessment, photochemical mechanism study, and emission control policy-making, while it has been a challenge to accurately and comprehensively measure them. Comprehensive two-dimensional gas chromatography (GC×GC) is one of the advanced techniques in analysis of complex mixtures, providing a good choice for measurement of VOCs. However, the requirement for a fast detector limits the application of quadrupole mass spectrometry (qMS) in GC×GC analysis. This paper presents a method of a common qMS detector coupled with GC×GC to the identification of atmospheric VOCs. About 125 VOCs including alkanes, alkenes, aromatics, oxygenated hydrocarbons, and halocarbons were identified in the measurement of standard gas mixtures and/or urban air samples from Beijing. The results were applied to the analysis of GC×GC-FID by one to one correspondence of peaks of the equivalent compounds between the GC×GC-FID and GC×GC-qMS chromatograms, and the retention times of the identified components in GC×GC-FID in turn undertake the qualitative analysis without the further help of MS. The wrap-around phenomenon which may confuse the match of peaks was discussed in detail. The cooperation of GC×GC-FID and GC×GC-qMS which assists the identification makes the GC×GC exploration more affordable and yet practical on both qualitative and quantitative analysis. The method and the identified results can be expanded to analyze other volatiles. | 25,151,040 | [
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Coming of age: orphan genes in plants. | Sizable minorities of protein-coding genes from every sequenced eukaryotic and prokaryotic genome are unique to the species. These so-called ‘orphan genes’ may evolve de novo from non-coding sequence or be derived from older coding material. They are often associated with environmental stress responses and species-specific traits or regulatory patterns. However, difficulties in studying genes where comparative analysis is impossible, and a bias towards broadly conserved genes, have resulted in underappreciation of their importance. We review here the identification, possible origins, evolutionary trends, and functions of orphans with an emphasis on their role in plant biology. We exemplify several evolutionary trends with an analysis of Arabidopsis thaliana and present QQS as a model orphan gene. | 25,151,064 | [
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Cadmium recovery by coupling double microbial fuel cells. | Cr(VI)-MFC of the double microbial fuel cell (d-MFC) arrangement could successfully complement the insufficient voltage and power needed to recover cadmium metal from Cd(II)-MFC, which operated as a redox-flow battery. It was also possible to drain electrical energy from the d-MFC by an additional passage. The highest maximum utilization power density (22.5Wm(-2)) of Cr(VI)-MFC, with the cathode optimized with sulfate buffer, was 11.3times higher than the highest power density directly supplied to Cd(II)-MFC (2.0Wm(-2)). Cr(VI)-MFC could generate 3times higher power with the additional passage than without it; and the current density for the former was 4.2times higher than the latter at the same maximum power point (38.0Am(-2) vs. 9.0Am(-2)). This boosting phenomenon could be explained by the Le Chatelier's principle, which addresses the rate of electron-hole pair formation that can be accelerated by quickly removing electrons generated by microorganisms. | 25,151,082 | [
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Blood donation fears inventory: development and validation of a measure of fear specific to the blood donation setting. | Although individual differences in fear of stimuli related to blood donation is a key determinant of donor recruitment and retention, a donation-specific fear measure has yet to be developed. A donation-related fear measure was developed and tested on an initial sample of donors and non-donors, and then re-evaluated on a second sample to confirm the observed factor structure. Analyses supported a four-factor structure, with subscales related to fear of: (1) syncopal symptoms, (2) blood and needles, (3) social evaluation, and (4) health screen results. The Blood Donation Fears Inventory is a novel measure to assess fears held by current and potential blood donors. | 25,151,096 | [
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Public willingness to pay for CO2 mitigation and the determinants under climate change: a case study of Suzhou, China. | This study explored the factors that influence respondents' willingness to pay (WTP) for CO2 mitigation under climate change. A questionnaire survey combined with contingent valuation and psychometric paradigm methods were conducted in the city of Suzhou, Jiangsu Province in China. Respondents' traditional demographic attributes, risk perception of greenhouse gas (GHG), and attitude toward the government's risk management practices were established using a Tobit model to analyze the determinants. The results showed that about 55% of the respondents refused to pay for CO2 mitigation, respondent's WTP increased with increasing CO2 mitigation percentage. Important factors influencing WTP include people's feeling of dread of GHGs, confidence in policy, the timeliness of governmental information disclosure, age, education and income level. | 25,151,109 | [
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An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: a proteomics approach. | Down syndrome (DS) is one of the most common causes of intellectual disability, owing to trisomy of all or part of chromosome 21. DS is also associated with the development of Alzheimer disease (AD) neuropathology after the age of 40 years. To better clarify the cellular and metabolic pathways that could contribute to the differences in DS brain, in particular those involved in the onset of neurodegeneration, we analyzed the frontal cortex of DS subjects with or without significant AD pathology in comparison with age-matched controls, using a proteomics approach. Proteomics represents an advantageous tool to investigate the molecular mechanisms underlying the disease. From these analyses, we investigated the effects that age, DS, and AD neuropathology could have on protein expression levels. Our results show overlapping and independent molecular pathways (including energy metabolism, oxidative damage, protein synthesis, and autophagy) contributing to DS, to aging, and to the presence of AD pathology in DS. Investigation of pathomechanisms involved in DS with AD may provide putative targets for therapeutic approaches to slow the development of AD. | 25,151,119 | [
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Nicotine mediates oxidative stress and apoptosis through cross talk between NOX1 and Bcl-2 in lung epithelial cells. | Nicotine contributes to the onset and progression of several pulmonary diseases. Among the various pathophysiological mechanisms triggered by nicotine, oxidative stress and cell death are reported in several cell types. We found that chronic exposure to nicotine (48h) induced NOX1-dependent oxidative stress and apoptosis in primary pulmonary cells. In murine (MLE-12) and human (BEAS-2B) lung epithelial cell lines, nicotine acted as a sensitizer to cell death and synergistically enhanced apoptosis when cells were concomitantly exposed to hyperoxia. The precise signaling pathway was investigated in MLE-12 cells in which NOX1 was abrogated by a specific inhibitor or stably silenced by shRNA. In the early phase of exposure (1h), nicotine mediated intracellular Ca(2+) fluxes and activation of protein kinase C, which in its turn activated NOX1, leading to cellular and mitochondrial oxidative stress. The latter triggered the intrinsic apoptotic machinery by modulating the expression of Bcl-2 and Bax. Overexpression of Bcl-2 completely prevented nicotine's detrimental effects, suggesting Bcl-2as a downstream key regulator in nicotine/NOX1-induced cell damage. These results suggest that NOX1 is a major contributor to the generation of intracellular oxidative stress induced by nicotine and might be an important molecule to target in nicotine-related lung pathologies. | 25,151,121 | [
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Complete resection of a giant mediastinal teratoma occupying the entire right hemithorax in a 14-year-old boy. | Mature teratomas are the most common histological type of germ cell tumors. A 14-year-old boy was referred to our hospital with a giant mature teratoma occupying the entire right hemithorax compressed the superior vena cava (SVC) and total atelectasis of the right lung. He was misdiagnosed as malignant teratoma by a fine-needle biopsy in a hospital. After 4-cycle of chemotherapy without effect, he underwent an unsuccessful exploratory thoracotomy. Venous conduit bypass between the right jugular vein and right femoral vein was established in the operating room for superior vena cava (SVC) replacement if needed. En bloc resection of the huge tumor, wedge resection of the dense adhesions of the right lung and partial pericardectomy were successfully performed, and lung function was recovered. To the best of our knowledge, this is the first report of complete resection of the teratoma occupying the whole right hemithorax combined with wedge resection of the right upper, middle and lower lobes and partial resection of the pericardium. | 25,151,139 | [
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Evolving possible link between PI3K and NO pathways in neuroprotective mechanism of ischemic postconditioning in mice. | The present study was conducted to pharmacologically investigate the influence of NO signaling pathway in PI3K mediated neuroprotective mechanism of ischemic postconditioning (iPoCo). Bilateral carotid artery occlusion (BCAO) of 12 min followed by reperfusion for 24 h was employed to produce ischemia/reperfusion-induced cerebral injury in male Swiss mice. Memory was assessed using Morris water maze test. Degree of motor incoordination was evaluated using inclined beam walk test, rotarod test, and lateral push test. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Brain acetylcholinesterase activity, thiobarbituric acid reactive species (TBARS), nitrite/nitrate and reduced glutathione (GSH) levels were also estimated. BCAO followed by reperfusion produced significant rise in cerebral infarct size, acetylcholinesterase activity, and TBARS levels along with fall in nitrite/nitrate and GSH levels. A significant impairment of memory and motor coordination was also noted. iPoCo consisting of three episodes of 10 s carotid artery occlusion and reperfusion significantly attenuated infarct size, memory impairment, motor incoordination, and altered biochemicals. iPoCo-induced neuroprotective effects were significantly abolished by wortmannin (a selective PI3K inhibitor). However, administration of L-Arginine (a NO precursor) in the presence of wortmannin restored the protective effect of ischemic postconditioning. It may be concluded that neuroprotective mechanism of iPoCo involves PI3K-mediated pathway with NO signaling as an important downstream step. | 25,151,147 | [
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Discovery and classification of homeobox genes in animal genomes. | The diversification of homeobox genes is of great interest to evolutionary and developmental biology. To generate a catalogue of all homeobox genes within species of interest, it is necessary to sequence complete genomes. It is now possible for small research projects and individual laboratories to determine near-complete genome sequences of animal species. We provide bioinformatic methods for assembling draft genome sequences from any animal species, including read filtering and error correction, plus methods for extracting and classifying all homeobox sequences. | 25,151,154 | [
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How to study HOX gene expression and function in mammalian oocytes and early embryos. | Mammalian oocytes and early embryos have unique characteristics and can only be obtained in small amounts. As a consequence, the techniques to be used to characterize gene expression and function have to be adapted. It is also important to keep in mind that differences exist between mammalian species. Here we describe a set of techniques useful to analyze gene expression in oocytes and early bovine embryos, including techniques to quantify maternal and embryonic transcripts by RT-qPCR, to evaluate the translation potential of maternal transcripts, to knock down HOX transcripts by injection of siRNA, and to localize HOX proteins by whole-mount immunofluorescence. | 25,151,155 | [
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Ertapenem prophylaxis of surgical site infections in elective colorectal surgery in China: a multicentre, randomized, double-blind, active-controlled study. | Our purpose was to evaluate ertapenem versus ceftriaxone/metronidazole for prophylaxis of surgical site infections (SSIs) following elective colorectal surgery in Chinese adult patients. Eligible Chinese adults aged 18-80 years scheduled to undergo elective colorectal surgery by laparotomy were randomized to receive a 30 min infusion of 1 g of ertapenem/metronidazole placebo or 2 g of ceftriaxone/500 mg of metronidazole within 2 h before initial incision. The study endpoint was the proportion of patients with successful prophylaxis at 4 weeks after treatment. The primary analysis was based on the evaluable population (PP population) and the pre-specified non-inferiority margin was set at -15%. ClinicalTrials.gov: NCT01254344. Of 599 patients randomized, 499 (251 ertapenem and 248 ceftriaxone) were eligible for inclusion in the PP population. The proportions of patients with successful prophylaxis in the ertapenem and ceftriaxone groups were 90.4% (227/251) and 90.3% (224/248), respectively. The difference in the proportion of successful outcomes was 0.1% (95% CI -5.2%, 5.5%). Unexplained antibiotic use was the most frequent reason for prophylaxis failure in both groups [ertapenem 4.8% (12/251), ceftriaxone 4.4% (11/248); difference 0.3%; 95% CI -3.6, 4.3]. Pathogen species isolated from SSI sources were consistent with previously conducted studies and the product package insert. The incidence of adverse events (AEs) was similar between the groups, with the most common AE being pyrexia [ertapenem 7.6% (22/290), ceftriaxone 5.7% (17/297)]. Ertapenem is as effective as ceftriaxone/metronidazole for SSI prophylaxis in patients undergoing elective colorectal surgery, and is well tolerated. | 25,151,205 | [
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A revised model of ex-vivo reduction of hexavalent chromium in human and rodent gastric juices. | Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function of Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. | 25,151,221 | [
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Modeling the drugs' passive transfer in the body based on their chromatographic behavior. | One of the most challenging aims in modern analytical chemistry and pharmaceutical analysis is to create models for drugs' behavior based on simulation experiments. Since drugs' effects are closely related to their molecular properties, numerous characteristics of drugs are used in order to acquire a model of passive absorption and transfer in the human body. Importantly, such direction in innovative bioanalytical methodologies is also of stressful need in the area of personalized medicine to implement nanotechnological and genomics advancements. Simulation experiments were carried out by examining and interpreting the chromatographic behavior of 113 analytes/drugs (400 observations) in RP-HPLC. The dataset employed for this purpose included 73 descriptors which are referring to the physicochemical properties of the mobile phase mixture in different proportions, the physicochemical properties of the analytes and the structural characteristics of their molecules. A series of different software packages was used to calculate all the descriptors apart from those referring to the structure of analytes. The correlation of the descriptors with the retention time of the analytes eluted from a C4 column with an aqueous mobile phase was employed as dataset to introduce the behavior models in the human body. Their evaluation with a Partial Least Squares (PLS) software proved that the chromatographic behavior of a drug on a lipophilic stationary and a polar mobile phase is directly related to its drug-ability. At the same time, the behavior of an unknown drug in the human body can be predicted with reliability via the Artificial Neural Networks (ANNs) software. | 25,151,230 | [
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Modified ensemble Kalman filter for nuclear accident atmospheric dispersion: prediction improved and source estimated. | Atmospheric dispersion models play an important role in nuclear power plant accident management. A reliable estimation of radioactive material distribution in short range (about 50 km) is in urgent need for population sheltering and evacuation planning. However, the meteorological data and the source term which greatly influence the accuracy of the atmospheric dispersion models are usually poorly known at the early phase of the emergency. In this study, a modified ensemble Kalman filter data assimilation method in conjunction with a Lagrangian puff-model is proposed to simultaneously improve the model prediction and reconstruct the source terms for short range atmospheric dispersion using the off-site environmental monitoring data. Four main uncertainty parameters are considered: source release rate, plume rise height, wind speed and wind direction. Twin experiments show that the method effectively improves the predicted concentration distribution, and the temporal profiles of source release rate and plume rise height are also successfully reconstructed. Moreover, the time lag in the response of ensemble Kalman filter is shortened. The method proposed here can be a useful tool not only in the nuclear power plant accident emergency management but also in other similar situation where hazardous material is released into the atmosphere. | 25,151,237 | [
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A greater proportion of liver transplant candidates have colorectal neoplasia than in the healthy screening population. | Various types of liver disease are associated with an increased prevalence of colorectal adenomas. We investigated whether cirrhosis is a risk factor for colorectal neoplasia by analyzing colonoscopy findings from 2 cohorts of patients awaiting liver transplantation. We performed a retrospective analysis to compare findings from colorectal cancer screenings of 567 adult patients with cirrhosis placed on the waitlist for liver transplantation with those from controls (matched for age, sex, body mass index, smoking, and diabetes). Rates of adenoma and advanced adenoma detection were adjusted owing to differences in rates of polypectomies performed in the 2 cohorts. Adenomas were detected in a significantly higher percentage of patients with cirrhosis (29.3%) than in controls (21.5%) (P = .0057; relative risk [RR], 1.36; 95% confidence interval [CI], 1.09-1.69); and patients with cirrhosis had a higher rate of advanced adenoma detection than controls (13.9% vs 7.7%; P = .0015; relative risk, 1.82; 95% CI, 1.25-2.64). A greater percentage of patients with alcoholic cirrhosis had neoplasias (34.3%) than controls (25.3%; P = .0350; RR, 1.36), and rates of advanced adenoma detection were 16.7% vs 10.2% (P = .0409; RR, 1.63). Adenomas were detected in 27.8% of patients with viral cirrhosis vs 15.9% of controls (P = .0061; RR, 1.74), with rates of advanced adenoma detection of 13.6% vs 5.0% (P = .0041; RR, 2.73). Similar proportions of patients with cirrhosis of other etiologies and controls were found to have colorectal neoplasias. Based on a retrospective analysis of colonoscopy findings from patients awaiting liver transplantation, those with alcoholic or viral cirrhosis are at higher risk of developing colorectal neoplasia and should be considered for earlier colonoscopy examination. | 25,151,257 | [
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Dietary acid load and chronic kidney disease among adults in the United States. | Diet can markedly affect acid-base status and it significantly influences chronic kidney disease (CKD) and its progression. The relationship of dietary acid load (DAL) and CKD has not been assessed on a population level. We examined the association of estimated net acid excretion (NAE(es)) with CKD; and socio-demographic and clinical correlates of NAE(es). Among 12,293 U.S. adult participants aged >20 years in the National Health and Nutrition Examination Survey 1999-2004, we assessed dietary acid by estimating NAE(es) from nutrient intake and body surface area; kidney damage by albuminuria; and kidney dysfunction by eGFR < 60 ml/min/1.73 m(2) using the MDRD equation. We tested the association of NAE(es) with participant characteristics using median regression; while for albuminuria, eGFR, and stages of CKD we used logistic regression. Median regression results (β per quintile) indicated that adults aged 40-60 years (β [95% CI] = 3.1 [0.3-5.8]), poverty (β [95% CI] = 7.1 [4.01-10.22]), black race (β [95% CI] = 13.8 [10.8-16.8]), and male sex (β [95% CI] = 3.0 [0.7- 5.2]) were significantly associated with an increasing level of NAE(es). Higher levels of NAE(es) compared with lower levels were associated with greater odds of albuminuria (OR [95% CI] = 1.57 [1.20-2.05]). We observed a trend toward greater NAE(es) being associated with higher risk of low eGFR, which persisted after adjustment for confounders. Higher NAE(es) is associated with albuminuria and low eGFR, and socio-demographic risk factors for CKD are associated with higher levels of NAE(es). DAL may be an important target for future interventions in populations at high risk for CKD. | 25,151,260 | [
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Gamma-range synchronization of fast-spiking interneurons can enhance detection of tactile stimuli. | We tested the sensory impact of repeated synchronization of fast-spiking interneurons (FS), an activity pattern thought to underlie neocortical gamma oscillations. We optogenetically drove 'FS-gamma' while mice detected naturalistic vibrissal stimuli and found enhanced detection of less salient stimuli and impaired detection of more salient ones. Prior studies have predicted that the benefit of FS-gamma is generated when sensory neocortical excitation arrives in a specific temporal window 20-25 ms after FS synchronization. To systematically test this prediction, we aligned periodic tactile and optogenetic stimulation. We found that the detection of less salient stimuli was improved only when peripheral drive led to the arrival of excitation 20-25 ms after synchronization and that other temporal alignments either had no effects or impaired detection. These results provide causal evidence that FS-gamma can enhance processing of less salient stimuli, those that benefit from the allocation of attention. | 25,151,266 | [
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Evolution in functionality of a metastatic pancreatic neuroendocrine tumour (pNET) causing Cushing's syndrome: treatment response with chemotherapy. | We report the case of a patient who had a non-functional metastatic pancreatic neuroendocrine tumour (pNET), which changed in functionality during the course of the disease. This case demonstrates the effectiveness of conventional cytotoxic chemotherapy in the management of select group of patients with this rare, challenging condition. Our patient was a 34 year old man under oncology follow up, diagnosed with a non-functional metastatic pancreatic neuroendocrine tumour treated with a Whipple's procedure two years ago. Despite treatment with somatostatin analogues and sunitinib, a tyrosine kinase inhibitor, he had demonstrated radiological progression of his metastatic disease. He now presented with a short history of Cushing's syndrome. A presumptive diagnosis of a rapidly progressive, metastatic, functional pNET with ectopic ACTH production was made, confirmed biochemically and with liver biopsy. The proliferative index, Ki-67 of 20% of the liver biopsy prompted us to treat him with conventional cytotoxic chemotherapy using streptozocin, 5-fluorouracil and doxorubicin. Prior to its administration clinical and biochemical control of the hypercortisolemic state was achieved with metyrapone. However the clinical, biochemical and radiological response to chemotherapy was so dramatic obviating the need for metyrapone therapy. Non-functional pNETs may evolve in their clinical and biologic behaviour producing functional hormonal syndromes. Chemotherapy may be an effective therapeutic modality in such circumstances. | 25,151,270 | [
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Left ventricular remodelling in aortic stenosis. | Aortic stenosis (AS) is a progressive condition associated with high mortality if not treated. The hemodynamic effects of AS have serious implications for the left ventricle. In this review, we describe the responses of the left ventricle to AS by highlighting the process of adaptive remodelling, which begins as a beneficial compensatory mechanism but ultimately transitions to a maladaptive process with potentially irreversible consequences. We discuss the impact of left ventricular (LV) remodelling on diastolic and systolic function and on the development of symptoms. In addition, we review the adverse consequences of maladaptive LV remodelling on clinical outcomes before and after aortic valve replacement. The relative irreversibility of maladaptive remodelling and the clear relationship between its progression and clinical outcomes suggest a need to incorporate measures of LV performance beyond simply systolic function when deciding on the timing of valve replacement. | 25,151,283 | [
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Tumor cell dissemination to the bone marrow and blood is associated with poor outcome in patients with metastatic breast cancer. | The purpose of this study was to assess the impact of disseminated tumor cells (DTCs) on progression-free and overall survival (OS) in patients with metastatic breast cancer (MBC) and to compare it to simultaneous detection of circulating tumor cells (CTCs) from the blood in a subgroup. Disseminated tumor cells were identified in bone marrow (BM) aspirates by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology prior to the beginning of a new-line therapy. CTCs were enumerated by the CellSearch® technology. BM was obtained from 178 patients with MBC; 64/178 (36 %) patients were DTC-positive. Disseminated tumor cells occurred more frequently in patients with visceral metastases (p = 0.020) and ≥2 lines of therapy (p = 0.017). CTCs were assessed in 33 of these patients and 17/33 (52 %) patients had CTC counts ≥5 CTCs/7.5 ml blood. There was no significant association between the DTC and CTC status. Univariate analysis revealed DTC detection as a significant predictor of poor OS (p < 0.001); median OS in DTC-negative versus DTC-positive patients was 52 [95 % confidence interval (CI) 38-67] versus 28 [95 % CI 19-37] months. Moreover, as described previously, patients with ≥5 CTCs/7.5 ml blood were at an increased risk of disease progression (p = 0.026) and death (p = 0.025). Disseminated tumor cells are predictors of poor prognosis in MBC, highlighting the role of tumor cell dissemination into the BM for breast cancer progression. The absence of a significant association between concurrent DTCs and CTCs suggests they might represent different aspects of systemic BC spread. | 25,151,295 | [
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Role of calpain-1 in the early phase of experimental ALS. | Elevation in [Ca(2+)]i and activation of calpain-1 occur in central nervous system of SOD1(G93A) transgenic mice model of amyotrophic lateral sclerosis (ALS), but few data are available about the early stage of ALS. We here investigated the level of activation of the Ca(2+)-dependent protease calpain-1 in spinal cord of SOD1(G93A) mice to ascertain a possible role of the protease in the aetiology of ALS. Comparing the events occurring in the 120 day old mice, we found that [Ca(2+)]i and activation of calpain-1 were also increased in the spinal cord of 30 day old mice, as indicated by the digestion of some substrates of the protease such as nNOS, αII-spectrin, and the NR2B subunit of NMDA-R. However, the digestion pattern of these proteins suggests that calpain-1 may play different roles depending on the phase of ALS. In fact, in spinal cord of 30 day old mice, activation of calpain-1 produces high amounts of nNOS active species, while in 120 day old mice enhanced-prolonged activation of calpain-1 inactivates nNOS and down-regulates NR2B. Our data reveal a critical role of calpain-1 in the early phase and during progression of ALS, suggesting new therapeutic approaches to counteract its onset and fatal course. | 25,151,305 | [
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A meta-analysis of randomized trials of telmisartan versus active controls for insulin resistance in hypertensive patients. | To determine whether telmisartan improves insulin resistance compared with other antihypertensive drugs, we performed a meta-analysis of randomized controlled trials (RCTs) of telmisartan. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through December 2013. Eligible studies were prospective RCTs of telmisartan versus other antihypertensive drugs, enrolling individuals with hypertension and reporting insulin levels and/or homeostasis model assessment-insulin resistance (HOMA-IR) as outcomes. Of 67 potentially relevant articles screened initially, 33 reports of RCTs enrolling a total of 2033 patients with hypertension were identified and included. Pooled analyses of only the eight double-blind-design trials demonstrated statistically significant reductions in percent changes of insulin levels (mean difference, -5.19%; 95% confidence interval, -8.94% to -1.43%; P = .007) and HOMA-IR (-15.34%; -26.39% to -4.28%; P = .007) with telmisartan relative to other antihypertensive drugs. When data from all the 33 trials were pooled, telmisartan was associated with statistically significant reductions in percent changes of insulin levels (-10.92%; -15.60% to -6.23%; P < .00001) and HOMA-IR (-15.89%; -22.01% to -9.78%; P < .00001) relative to other antihypertensive drugs. In conclusion, telmisartan appears to significantly improve insulin resistance compared with other antihypertensive drugs in patients with hypertension. | 25,151,319 | [
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Illusions of truths in the Symplicity HTN-3 trial: generic design strengths but neuroscience failings. | The Achilles heel in catheter-based studies of renal denervation for severe hypertension is the almost universal failure to apply a confirmatory test for renal denervation. When renal denervation efficacy was assessed, using measurements of the spillover of norepinephrine from the renal sympathetic nerves to plasma, the only test validated to this point, denervation was found to be incomplete and nonuniform between patients. It is probable that the degree of denervation has typically been suboptimal in renal denervation trials. This criticism applies with special force to the Symplicity HTN-3 trial, where the proceduralists, although expert interventional cardiologists, had no prior experience with the renal denervation technique. Their learning curve fell during the trial, a shortcoming accentuated by the fact that one-third of operators performed one procedure only. Recently presented results from the Symplicity HTN-3 trialists confirm that renal denervation was not effectively or consistently achieved in the trial. | 25,151,320 | [
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Analysis of combined detection of N-terminal pro-B-type natriuretic peptide and left ventricular ejection fraction in heart function in patients with acute CO poisoning. | N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been used in the evaluation on heart function in many heart diseases. However, little is known in patients with acute carbon monoxide poisoning (ACOP). Left ventricular ejection fraction (LVEF) can be applied as a preliminary test method to measure the left ventricular function. In the present study, we investigate the clinical significance of NT-proBNP combined with LVEF on heart function in 68 patients with ACOP. A total of 68 ACOP patients hospitalized were divided into 3 groups: the mild, the moderate, and the severe group. During the same period, 30 healthy volunteers were chosen to represent the control group. The serum NT-proBNP was immediately measured and LVEF was monitored by an echocardiogram within 24 hours after admission. All data were analyzed and compared for the groups investigated. N-terminal pro-B-type natriuretic peptide showed a significant increase and LVEF a considerable decrease in all 3 clinic groups (P < .01) when compared with the control group. Levels of NT-proBNP are increased and levels of LVEF are decreased when the clinic group changed from mild, moderate, to severe. N-terminal pro-B-type natriuretic peptide is negatively correlated with LVEF (r = -0.955, P = .045). Combined detection of NT-proBNP and LVEF in the diagnosis of heart function was found to be more sensitive compared with the single index after ACOP (χ(2) = 14.636, P < .05). There are an increased level of NT-proBNP and a decrease of LVEF, which represents a clear sign of heart malfunction by ACOP. Combined NT-proBNP and LVEF detection technique has a significant advantage in the diagnosis of patients with myocardial contraction function damage after ACOP. | 25,151,325 | [
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Tracheal intubation difficulties in the setting of face and neck burns: myth or reality? | Face and/or neck burn (FNB) exposes patients to the double respiratory risk of obstruction and hypoxia, and these risks may require a tracheal intubation. This study aims to describe the incidence and the characteristics of difficult intubation in FNB patients. We conducted a 5-year retrospective, single-center study including all patients meeting the following criteria: 18 years of age or older, an FNB at least 1% of burned surface area with a severity equal to or greater than the superficial second degree, and intubation and a burn center admission within the first 24 hours after the burn. Patients were compared according to the difficulty of their intubation. Between January 2007 and December 2011, we included 134 patients. The incidence of difficult intubation was 11.2% but was greater in the burn center than in the pre-burn center: 16.9% vs 3.5% (P = .02). The most important difference between patients with or without difficult intubation was the time between the burn injury and the intubation: 210 (105-290) vs 120 (60-180) minutes (P = .047). After multivariate analysis, an intubation performed at a burn center was independently associated with difficult intubation: odds ratio = 3.2; 95% confidence interval, 1.1-528. This study underlines the high incidence of difficult intubation in FNB patients, greater than 11.2%, and demonstrates that intubation is more difficult when realized at a burn center, probably because it is performed later, allowing for development of cervical and laryngeal edema. | 25,151,328 | [
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Metabolic profiling of Gynostemma pentaphyllum extract in rat serum, urine and faeces after oral administration. | Folk drug Gynostemma pentaphyllum (Thunb.) Makino contains many biologically active phytochemicals which have been demonstrated to be effective against chronic diseases. As in vivo anti-tumor experiments of G. pentaphyllum extract (GP) show much stronger antitumor activities than in vitro, it is important and necessary to understand the metabolic study of GP. A sensitive and specific U-HPLC-MS method was utilized for the first time to rapidly identify gypenosides and its possible metabolites in rat serum, urine, and faeces after oral administration. Solid phase extraction was utilized in the sample preparation. Negative Electrospray ionisation (ESI) mass spectrometry was used to discern gypenosides and its possible metabolites in rat samples. As a result, after oral administration, a total of seven metabolites of G. pentaphyllum extract were assigned, two from the rat serum and seven both from the rat urine and faeces. As metabolites of G. pentaphyllum extract, all of them have never been reported before. | 25,151,329 | [
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Gangliosides and cell surface ganglioside glycohydrolases in the nervous system. | Gangliosides are a large group of complex lipids found predominantly on the outer layer of the plasma membranes of cells, and they are particularly concentrated in nerve endings. Their half-life in the nervous system is short, and their membrane composition and content are strictly connected to their metabolism. Their neobiosynthesis starts in the endoplasmic reticulum and is completed in the Golgi; catabolism occurs primarily in the lysosomes. However, the final content of gangliosides in the plasma membrane is affected by other cellular processes.In this chapter structural changes in the oligosaccharide chains of gangliosides induced by the activity of glycohydrolases and in some cases by glycosyltransferases that are associated with plasma membranes are discussed. Some of the plasma membrane enzymes arise from fusion processes between intracellular fractions and the plasma membrane; however, other plasma membrane enzymes display a structure different from that of the intracellular enzymes. Several of these plasma membrane enzymes have been characterized and some of them seem to have a specific role in the nervous system. | 25,151,381 | [
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Role of galactosylceramide and sulfatide in oligodendrocytes and CNS myelin: formation of a glycosynapse. | The two major glycosphingolipids of myelin, galactosylceramide (GalC) and sulfatide (SGC), interact with each other by trans carbohydrate-carbohydrate interactions in vitro. They face each other in the apposed extracellular surfaces of the multilayered myelin sheath produced by oligodendrocytes and could also contact each other between apposed oligodendrocyte processes. Multivalent galactose and sulfated galactose, in the form of GalC/SGC-containing liposomes or silica nanoparticles conjugated to galactose and galactose-3-sulfate, interact with GalC and SGC in the membrane sheets of oligodendrocytes in culture. This interaction causes transmembrane signaling, loss of the cytoskeleton and clustering of membrane domains, similar to the effects of cross-linking by anti-GalC and anti-SGC antibodies. These effects suggest that GalC and SGC could participate in glycosynapses, similar to neural synapses or the immunological synapse, between GSL-enriched membrane domains in apposed oligodendrocyte membranes or extracellular surfaces of mature myelin. Formation of such glycosynapses in vivo would be important for myelination and/or oligodendrocyte/myelin function. | 25,151,383 | [
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Roles of carbohydrates in the interaction of pathogens with neural cells. | Numerous pathogens that can affect neural function utilize oligosaccharide-protein interactions as a first step in the infection process. The variability in carbohydrate structures as well as the presence of carbohydrate binding receptors on the surface of cells provides a plethora of potential binding sites for viruses, bacteria, and bacterial toxins. This chapter discusses scenarios for how carbohydrates may affect the ability of infectious agents to interact with neural cells, provides examples of problems that may result from development of antibodies to carbohydrate antigens found on pathogens that are similar to epitopes expressed on mammalian cells, and presents approaches either in use or under consideration for translational uses of this information. | 25,151,389 | [
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N-glycosylation in regulation of the nervous system. | Protein N-glycosylation can influence the nervous system in a variety of ways by affecting functions of glycoproteins involved in nervous system development and physiology. The importance of N-glycans for different aspects of neural development has been well documented. For example, some N-linked carbohydrate structures were found to play key roles in neural cell adhesion and axonal targeting during development. At the same time, the involvement of glycosylation in the regulation of neural physiology remains less understood. Recent studies have implicated N-glycosylation in the regulation of neural transmission, revealing novel roles of glycans in synaptic processes and the control of neural excitability. N-Glycans were found to markedly affect the function of several types of synaptic proteins involved in key steps of synaptic transmission, including neurotransmitter release, reception, and uptake. Glycosylation also regulates a number of channel proteins, such as TRP channels that control responses to environmental stimuli and voltage-gated ion channels, the principal determinants of neuronal excitability. Sialylated carbohydrate structures play a particularly prominent part in the modulation of voltage-gated ion channels. Sialic acids appear to affect channel functions via several mechanisms, including charge interactions, as well as other interactions that probably engage steric effects and interactions with other molecules. Experiments also indicated that some structural features of glycans can be particularly important for their function. Since glycan structures can vary significantly between different cell types and depend on the metabolic state of the cell, it is important to analyze glycan functions using in vivo approaches. While the complexity of the nervous system and intricacies of glycosylation pathways can create serious obstacles for in vivo experiments in vertebrates, recent studies have indicated that more simple and experimentally tractable model organisms like Drosophila should provide important advantages for elucidating evolutionarily conserved functions of N-glycosylation in the nervous system. | 25,151,388 | [
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Galectins and neuroinflammation. | Galectins, β-galactoside-binding lectins, play multiple roles in the regulation of immune and inflammatory responses. The major galectins expressed in the CNS are galectins 1, 3, 4, 8, and 9. Under normal physiological conditions, galectins maintain CNS homeostasis by participating in neuronal myelination, neuronal stem cell proliferation, and apical vesicle transport in neuronal cells. In neuronal diseases and different experimental neuroinflammatory disease models, galectins may serve as extracellular mediators or intracellular regulators in controlling the inflammatory response or conferring the remodeling capacity in damaged CNS tissues. In general, galectins 1 and 9 attenuate experimental autoimmune encephalomyelitis (a model of multiple sclerosis), while galectin-3 promotes inflammation in this model. In brain ischemic lesions, both galectins 1 and 3 are induced to help neuronal regeneration. The expression of galectin-1 is required for astrocyte-derived neurotrophic factor secretion, and recombinant galectin-1 promotes neuronal regeneration. Galectin-3 promotes microglial cell proliferation and attenuates ischemic damage and neuronal apoptosis after cerebral ischemia. In amyotrophic lateral sclerosis models, galectin-3 is deleterious to neuroregeneration, while intramuscular administration of oxidized galectin-1 can improve neuromuscular disorders. In axotomy and Wallerian degeneration, galectin-3 helps phagocytosis of macrophages to clear degenerate myelin in the injured PNS or CNS. Thus, galectins are important modulators participating in homeostasis of the CNS and neuroinflammation. Continued investigations of the roles of galectins in neuroinflammation promise to provide a better understanding of the mechanism of this process and lead to new therapeutic approaches. | 25,151,395 | [
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Glycoconjugates and neuroimmunological diseases. | A wide range of neuroimmunological diseases affect the central and peripheral nervous systems. These disorders are caused by autoimmune attack directed against structurally and functionally diverse nervous system antigens. One such category comprises peripheral nervous system (PNS) diseases, termed peripheral neuropathies, in which the target antigens for autoantibody-directed nerve injury are glycan structures borne by glycoproteins and glycolipids, particularly gangliosides that are concentrated in peripheral nerve. The archetypal PNS disorder is the acute paralytic disease, Guillain-Barré syndrome (GBS) in which autoantibodies against glycolipids arise in the context of acute infections that precede the clinical onset, notably Campylobacter jejuni enteritis. In addition, several chronic autoimmune neuropathies are associated with IgM antibodies directed against nerve glycans including sulphated glucuronic acid epitopes present on myelin-associated glycoprotein and sulphated glucuronyl paragloboside, a range of disialylated gangliosides including GD1b and GD3, and GM1 ganglioside. This chapter describes the immunological, pathological and clinical features of these disorders in the context of our broader knowledge of the glycobiology underpinning this neuroimmunological field. | 25,151,396 | [
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An alternative measurement tool for the identification of hysteretic responses in biological joints. | In structural engineering, sophisticated multi-dimensional analysis techniques, such as the Restoring Force Method (RFM), have been established for complex, nonlinear hysteretic systems. The purpose of the present study was to apply the RFM to quantify nonlinear spine hysteresis responses under applied moments. First, synthetic hysteretic spine responses (n=50) were generated based on representative results from pure moment flexion-extension loading of a human cadaveric lumbar spine segment. Then, the RFM was applied to each hysteresis response to describe the flexion-extension rotation as a function of applied moment and simulated axial displacement using a set of 16 unique coefficients. Range of motion, neutral zone, elastic zone, and stiffness were also measured. The RFM coefficient corresponding to the 1st-order linear dependence of rotation on applied moment was dominant, and paralleled changes in elastic zone. The remaining RFM coefficients were not captured from the traditional biomechanical analysis. Therefore, the RFM may potentially supplement the traditional analysis to develop a more comprehensive, quantitative description of spine hysteresis. The results suggest the potential for more thorough and specific characterization of spine kinematics, and may lead to future applications of such techniques in characterizing biological structures. | 25,151,448 | [
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Agrin requires specific proteins to selectively activate γ-aminobutyric acid neurons for pain suppression. | Agrin, a heparan sulfate proteoglycan functioning as a neuro-muscular junction inducer, has been shown to inhibit neuropathic pain in sciatic nerve injury rat models, via phosphorylation of N-Methyl-d-aspartate receptor NR1 subunits in gamma-aminobutyric acid neurons. However, its effects on spinal cord injury-induced neuropathic pain, a debilitating syndrome frequently encountered after various spine traumas, are unknown. In the present investigation, we studied the 50kDa agrin isoform effects in a quisqualic acid dorsal horn injection rat model mimicking spinal cord injury-induced neuropathic pain. Our results indicate that 50kDa agrin decreased only in the dorsal horn of neuropathic animals and increased 50kDa agrin expression in the dorsal horn, via intra-spinal injection of adeno-associated virus serum type two, suppressed spinal cord injury-induced neuropathic pain. Also, the reason why 50kDa agrin only activates the N-Methyl-d-aspartate receptor NR1 subunits in the GABA neurons, but not in sensory neurons, is unknown. Using immunoprecipitation and Western-blot analysis, two dimensional gel separation, and mass spectrometry, we identified several specific proteins in the reaction protein complex, such as neurofilament 200 and mitofusin 2, that are required for the activation of the NR1 subunits of gamma-aminobutyric acid inhibitory neurons by 50kDa agrin. These findings indicate that 50kDa agrin is a promising agent for neuropathic pain treatment. | 25,151,458 | [
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Sometimes it hurts when supervisors don't listen: the antecedents and consequences of safety voice among young workers. | We examined the relationship among having ideas about how to improve occupational safety, speaking up about them (safety voice), and future work-related injuries. One hundred fifty-five employed teenagers completed 3 surveys with a 1-month lag between each survey. We found that participants who were more likely to have ideas about how to improve occupational safety and had high affective commitment to the organization reported the highest level of safety voice. In turn, supervisor openness to voice moderated the relationship between safety voice and future work-related injuries. Specifically, future work-related injuries were most frequent when high levels of safety voice were combined with low supervisor openness to voice. The tested model clarifies the conditions under which workers share safety-related ideas with a supervisor and the real consequences of speaking up about them. We discuss the implications of these findings for safety management. (PsycINFO Database Record (c) 2014 APA, all rights reserved). | 25,151,463 | [
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Mutation of the mitochondrial large ribosomal RNA can provide pentamidine resistance to Saccharomyces cerevisiae. | Pentamidine is used to treat several trypanosomal diseases, as well as opportunistic infection by pathogenic fungi. However, the relevant targets of this drug are unknown. We isolated dominant mutations providing pentamidine resistance to Saccharomyces cerevisiae, one of which was localized to mitochondrial DNA. Next-generation sequencing revealed alteration of a widely conserved base at the peptidyl transferase center of the mitochondrial 21S ribosomal RNA. Our results provide a potential rationale for the toxicity of this drug to patients, and we discuss whether blockade of mitochondrial translation is the mechanism by which pathogenic fungi or protists are killed by pentamidine. | 25,151,477 | [
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Is age associated with risk of malignancy in thyroid cancer? | Many predictive models for risk of malignancy in well-differentiated thyroid cancer (WDTC) have been proposed, and many scoring systems for thyroid cancer prognosis have been established. Age is taken in consideration in all. Our main goal is to establish whether patients' age has a correlation with the rate of malignancy, size, and aggressiveness of the tumor. Case series with chart review. McGill University Thyroid Teaching Hospitals. A retrospective analysis of 1022 patients undergoing consecutive thyroidectomy was performed. The patients were divided based on age (<45 and ≥ 45 years). Data were gathered for the size of thyroid nodules, the presence of lymph node (LN) metastasis, and the final thyroid pathology, including the presence of extrathyroidal extension. There were 396 patients younger than 45 years and 626 patients 45 years or older. The rates of malignancy were 67.2% in the first group and 68.7% in the second group (P = .111). When patients were stratified according to different age cutoffs, WDTC and LN metastasis occurred more often in patients younger than 50 years (50.2% vs 43.2%, P = .031 and 18.9% vs 14.1%, P = .0496, respectively). Micropapillary carcinoma occurred more often in patients 50 years or older (23.6% vs 16.1%, P = .0035). Tumor behavior and rates of WDTC were similar in patients aged <45 and ≥ 45 years. Well-differentiated thyroid cancer occurred more often in patients younger than 50 years, whereas the rate of micropapillary carcinoma occurred more often in patients 50 years or older. | 25,151,485 | [
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OSL and photo-transferred TL of quartz single crystals sensitized by high-dose of gamma-radiation and moderate heat-treatments. | This study investigates the optically stimulated luminescence (OSL) and the photo-transferred thermoluminescence (PTTL) signals in quartz single crystals showing a strong TL peak near 300°C after being sensitized by irradiation with 25kGy of gamma rays and heating at 400°C. Natural and sensitized samples were prepared from two crystals with different sensitivity levels in the 300°C TL region. Continuous-wave (CW) and linearly-modulated (LM) OSL signals were stimulated with blue light-emitting diodes during 40 and 1000s, respectively. Two components were isolated from the CW-OSL signals of sensitized samples. These components were clearly seen in LM-OSL measurements together with two long-term components. LM-OSL showed that the sensitization process considered in this study sensitized an ultrafast OSL component of these crystals. The similar behavior found for the thermal stabilities of OSL and TL signals and the dependence of these signals with sample origins suggested that the trapping site related to the ultrafast component is also related to the TL process of the sensitized peak. The PTTL signal induced by blue LEDs increased the intensity of the sensitized glow peak. On the other hand, a remarkable reduction in the intensity of this peak as a result of the accumulated effect of blue light exposure was clearly seen in both kinds of crystals. These results were explained by a mechanism of competition between optically unstable deep traps and trap levels responsible to the sensitized TL peak. | 25,151,496 | [
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Social disorder, physical activity and adiposity in Mexican adults: evidence from a longitudinal study. | This study analyzed the prospective relationship of community social disorder with sedentary behavior, sport participation, and adiposity in Mexican adults from the National Mexican Family Life Survey (MxFLS). The sample included 8307 adults (aged ≥20 years) from 145 communities. During a three-year follow-up, participants from communities with high social disorder had a 1.36cm larger increase in waist circumference than participants from communities with low social disorder. However, there were no differences in body mass index, television, or sport participation. These findings emphasize the need to promote healthy social environments in local communities. | 25,151,499 | [
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Symptoms and medication management in the end of life phase of high-grade glioma patients. | During the end of life (EOL) phase of high-grade glioma (HGG) patients, care is primarily aimed at reducing symptom burden while maintaining quality of life as long as possible. In this study, we evaluated the prevalence of symptoms and medication management in HGG patients during the EOL phase. We analyzed disease-specific symptoms, general EOL symptoms, symptom frequency, and medication use at 3 months and 1 week before death in a cohort of 178 HGG patients, based on questionnaires completed by physicians responsible for EOL care. In addition, information on patient's perceived quality of care (QOC) was derived from 87 questionnaires completed by patient's relatives. Somnolence, focal neurological deficits and cognitive disturbances were the most prevalent symptoms during the EOL phase. Overall, disease-specific symptoms occurred more often than general EOL symptoms at both 3 months and 1 week before death. Somnolence and/or dysphagia were present in 81 % of patients whose medication was withdrawn and 96 % of patients in whom antiepileptic drugs (AEDs) were withdrawn. One week before death, 65.9 % of patients with high symptom frequency experienced good QOC, compared to 87.5 % of patients with low symptom frequency (p = 0.032). Disease-specific symptoms are the main concern in EOL care for HGG patients. Somnolence and dysphagia may hamper the regular oral administration of drugs, and particularly AEDs, during the EOL phase. High symptom frequency at 1 week before death negatively affects patient's perceived QOC. | 25,151,506 | [
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A content and structural assessment of oxidative motifs across a diverse set of life forms. | Exposure to weightlessness (microgravity) or other protein stresses are detrimental to animal and human protein tissue health. Protein damage has been associated with stress and is linked to aging and the onset of diseases such as Alzheimer׳s, Parkinson׳s, sepsis, and others. Protein stresses may cause alterations to physical protein structure, altering its functional identity. Alterations from stresses such as microgravity may be responsible for forms of muscle atrophy (as noted in returning astronauts), however, protein stresses come from other sources as well. Oxidative carbonylation is a protein stress which is a driving force behind protein decay and is attracted to protein segments enriched in R, K, P, T, E and S residues. Since mitochondria apply oxidative processes to produce ATP, their proteins may be placed in the same danger as those that are exposed to stresses. However, they do not appear to be impacted in the same way. Across 14 diverse organisms, we evaluate the coverage of motifs which are high in the amino acids thought to be affected by protein stresses such as oxidation. For this study, we study RKPT and PEST motifs which are both responsible for attracting forms of oxidation across mitochondrial and non-mitochondrial proteins. We show that mitochondrial proteins have fewer of these oxidative sites compared to non-mitochondrial proteins. Additionally, we analyze the oxidative regions to determine that their motifs preferentially tend to make up the connection points between the four kinds of structures of folded proteins (helices, turns, sheets, and coils). | 25,151,511 | [
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Deformable image registration for adaptive radiation therapy of head and neck cancer: accuracy and precision in the presence of tumor changes. | To compare deformable image registration (DIR) accuracy and precision for normal and tumor tissues in head and neck cancer patients during the course of radiation therapy (RT). Thirteen patients with oropharyngeal tumors, who underwent submucosal implantation of small gold markers (average 6, range 4-10) around the tumor and were treated with RT were retrospectively selected. Two observers identified 15 anatomical features (landmarks) representative of normal tissues in the planning computed tomography (pCT) scan and in weekly cone beam CTs (CBCTs). Gold markers were digitally removed after semiautomatic identification in pCTs and CBCTs. Subsequently, landmarks and gold markers on pCT were propagated to CBCTs, using a b-spline-based DIR and, for comparison, rigid registration (RR). To account for observer variability, the pair-wise difference analysis of variance method was applied. DIR accuracy (systematic error) and precision (random error) for landmarks and gold markers were quantified. Time trend of the precisions for RR and DIR over the weekly CBCTs were evaluated. DIR accuracies were submillimeter and similar for normal and tumor tissue. DIR precision (1 SD) on the other hand was significantly different (P<.01), with 2.2 mm vector length in normal tissue versus 3.3 mm in tumor tissue. No significant time trend in DIR precision was found for normal tissue, whereas in tumor, DIR precision was significantly (P<.009) degraded during the course of treatment by 0.21 mm/week. DIR for tumor registration proved to be less precise than that for normal tissues due to limited contrast and complex non-elastic tumor response. Caution should therefore be exercised when applying DIR for tumor changes in adaptive procedures. | 25,151,537 | [
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Establishing high-quality prostate brachytherapy using a phantom simulator training program. | To design and implement a unique training program that uses a phantom-based simulator to teach the process of prostate brachytherapy (PB) quality assurance and improve the quality of education. Trainees in our simulator program were practicing radiation oncologists, radiation oncology residents, and fellows of the American Brachytherapy Society. The program emphasized 6 core areas of quality assurance: patient selection, simulation, treatment planning, implant technique, treatment evaluation, and outcome assessment. Using the Iodine 125 ((125)I) preoperative treatment planning technique, trainees implanted their ultrasound phantoms with dummy seeds (ie, seeds with no activity). Pre- and postimplant dosimetric parameters were compared and correlated using regression analysis. Thirty-one trainees successfully completed the simulator program during the period under study. The mean phantom prostate size, number of seeds used, and total activity were generally consistent between trainees. All trainees met the V100 >95% objective both before and after implantation. Regardless of the initial volume of the prostate phantom, trainees' ability to cover the target volume with at least 100% of the dose (V100) was not compromised (R=0.99 pre- and postimplant). However, the V150 had lower concordance (R=0.37) and may better reflect heterogeneity control of the implant process. Analysis of implants from this phantom-based simulator shows a high degree of consistency between trainees and uniformly high-quality implants with respect to parameters used in clinical practice. This training program provides a valuable educational opportunity that improves the quality of PB training and likely accelerates the learning curve inherent in PB. Prostate phantom implantation can be a valuable first step in the acquisition of the required skills to safely perform PB. | 25,151,539 | [
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Statistical modeling of CTV motion and deformation for IMRT of early-stage rectal cancer. | To derive and validate a statistical model of motion and deformation for the clinical target volume (CTV) of early-stage rectal cancer patients. For 16 patients, 4 to 5 magnetic resonance images (MRI) were acquired before each fraction was administered. The CTV was delineated on each MRI. Using a leave-one-out methodology, we constructed a population-based principal component analysis (PCA) model of the CTV motion and deformation of 15 patients, and we tested the model on the left-out patient. The modeling error was calculated as the amount of the CTV motion-deformation of the left-out-patient that could not be explained by the PCA model. Next, the PCA model was used to construct a PCA target volume (PCA-TV) by accumulating motion-deformations simulated by the model. A PCA planning target volume (PTV) was generated by expanding the PCA-TV by uniform margins. The PCA-PTV was compared with uniform and nonuniform CTV-to-PTV margins. To allow comparison, geometric margins were determined to ensure adequate coverage, and the volume difference between the PTV and the daily CTV (CTV-to-PTV volume) was calculated. The modeling error ranged from 0.9 ± 0.5 to 2.9 ± 2.1 mm, corresponding to a reduction of the CTV motion-deformation between 6% and 60% (average, 23% ± 11%). The reduction correlated with the magnitude of the CTV motion-deformation (P<.001, R=0.66). The PCA-TV and the CTV required 2-mm and 7-mm uniform margins, respectively. The nonuniform CTV-to-PTV margins were 4 mm in the left, right, inferior, superior, and posterior directions and 8 mm in the anterior direction. Compared to uniform and nonuniform CTV-to-PTV margins, the PCA-based PTV significantly decreased (P<.001) the average CTV-to-PTV volume by 128 ± 20 mL (49% ± 4%) and by 35 ± 6 mL (20% ± 3.5%), respectively. The CTV motion-deformation of a new patient can be explained by a population-based PCA model. A PCA model-generated PTV significantly improved sparing of organs at risk compared to uniform and nonuniform CTV-to-PTV margins. | 25,151,540 | [
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Factors relating to the perceived management of emergency situations: a survey of former Advanced Life Support course participants' clinical experiences. | This study explored individual, team, and setting factors associated with the quality of management of in-hospital emergency situations experienced by former Advanced Life Support (ALS) course participants. This study was a survey of former ALS course participants' long-term experience of management of in-hospital, emergency situations. The survey was carried out in 2012 in Denmark and Norway. A questionnaire was send to 526 potential responders and (281/479 × 100) 58.7% responded. The results demonstrated that 75% of the emergency situations were perceived as "managed well". In general, the responders' confidence in being ALS providers was high, mean 4.3 (SD 0.8), scale 1-5. Significant differences between the perceived "well" and "not well" managed situations were found for all questions, p<0.001. The largest differences related to perception of co-workers' ability to apply ALS principles, the team atmosphere and communication. Responders' ratings of quality of management of emergency situations increased with intensity of setting. However, the 'clinical setting' was rated significantly lower as attributor to ability to apply ALS principles compared to 'co-workers familiarity with ALS principles', 'own confidence as ALS-provider' and 'own social/inter-personal skills'. The results of this survey emphasise that ALS providers' perceived ability to apply ALS skills were substantially affected by teamwork skills and co-workers' skills. Team related factors associated with successful outcome were related to clear role distribution, clear inter-personal communication and attentive listening, as well as respectful behaviour and positive team atmosphere. Although intensity of setting was attributed to ability to apply ALS principles, this did not affect management of emergency situations to the same extent as individual and team factors. | 25,151,548 | [
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Performing under pressure: quiet eye training improves surgical knot-tying performance. | We examined the effectiveness of traditional technical training (TT) and quiet eye training (QET) on the performance of 1-handed square knot tying among first-year surgery residents under normal and high-anxiety conditions. Twenty surgery residents were assigned randomly to 1 of 2 groups and completed pretest, training, and simple and complex retention tests under conditions of high and low anxiety. The TT group received traditional instruction on improving hand movements; the QET group received feedback on their gaze behaviors. Participants wore an eye tracker that recorded simultaneously their gaze and hand movements. Dependent variables were knot tying performance (%), quiet eye duration (%), number of fixations, and total movement time (s). Both groups improved their knot tying performance (P < .05) from pretest to the low anxiety conditions (mean difference: QET, 28%; TT, 17%); however, only the QET group maintained their knot tying performance under the high-anxiety conditions (mean difference: QET, 18%; P < .05), with the TT group decreasing their performance close to pretest levels (P > .05). The QET group also demonstrated more efficient gaze and hand movements post training. These data demonstrate the effectiveness of training gaze behaviors, not only to improve the effectiveness and efficiency of performance, but also to mediate negative effects of anxiety on performance. These findings may have important implications for medical educators and practitioners, as well as surgeons who may be (re)training or learning new procedures. | 25,151,552 | [
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Global epidemiology of HIV. | The number of persons living with HIV worldwide reached approximately 35.3 million in 2012. Meanwhile, AIDS-related deaths and new HIV infections have declined. Much of the increase in HIV prevalence is from rapidly increasing numbers of people on antiretroviral treatment who are now living longer. There is regional variation in epidemiologic patterns, major modes of HIV transmission, and HIV program response. It is important to focus on HIV incidence, rather than prevalence, to provide information about HIV transmission patterns and populations at risk. Expanding HIV treatment will function as a preventive measure through decreasing horizontal and vertical transmission of HIV. | 25,151,559 | [
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Cost-effectiveness of insulin glargine versus sitagliptin in insulin-naïve patients with type 2 diabetes mellitus. | In the EASIE (Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-Naïve Patients) trial, insulin glargine found a significant reduction in glycosylated hemoglobin compared with sitagliptin in patients with type 2 diabetes who are inadequately controlled with metformin. The objective of this study was to assess the cost-effectiveness of insulin glargine compared with sitagliptin in type 2 diabetes patients, from the perspective of the publicly funded Canadian health care system. The IMS CORE Diabetes Model, a standard Markov structure and Monte Carlo simulation model, was used. The model used a lifetime horizon to capture the long-term complications associated with type 2 diabetes. The efficacy of insulin glargine and sitagliptin in terms of glycosylated hemoglobin reduction and corresponding rates of hypoglycemia were obtained from the EASIE trial. Health utility and cost data were obtained from recently published Canadian publications. Univariate and probabilistic sensitivity analyses were conducted. In the lifetime base-case analysis, treatment with insulin glargine resulted in cost savings of $1434 CAD in 2012 and a gain of 0.08 quality-adjusted life years per patient. A probabilistic sensitivity analysis found the robustness of the base-case analysis, with 88% probability of insulin glargine being dominant (ie, cost savings and more quality-adjusted life years). Insulin glargine is a clinically superior and cost-effective alternative to sitagliptin in patients with type 2 diabetes who are inadequately controlled with metformin. | 25,151,573 | [
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Assessment of the effective dose in supine, prone, and oblique positions in the maxillofacial region using a novel combined extremity and maxillofacial cone beam computed tomography scanner. | The objectives of this study were to assess the organ and effective doses (International Commission on Radiological Protection [ICRP] 103 standard) resulting from supine, prone, and oblique phantom positions in the maxillofacial region using a novel cone beam computed tomography (CBCT) device and to compare the results with conventional dental CBCT and multislice computed tomography (MSCT) devices. Measurements were performed using an anthropomorphic RANDO head phantom (Radiation Analogue Dosimetry System) with 20 MOSFET (metal-oxide-semiconductor field-effect transistor) dosimeters placed in the most radiosensitive maxillofacial organs. Effective doses were measured in 3 phantom positions using a combined extremity and maxillofacial CBCT device: the Planmed Verity CBCT scanner. Reference values were measured in the upright position with 2 CBCT devices and in the prone position with one MSCT scanner. The Planmed Verity CBCT scanner effective doses were 247 μSv in supine, 192 μSv in prone, and 134 μSv in oblique position. The effective dose with ProMax 3D MAX CBCT was 168 μSv; with i-CAT Next Generation, 170 μSv; and with Philips Brilliance 64 MSCT, 781 μSv. Head positioning has an important effect on the organ and effective doses. The Planmed Verity CBCT scanner effective dose results were comparable with those attained on 2 conventional CBCT devices and were considerably lower than the MSCT scanner results. | 25,151,590 | [
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Mechanisms underlying sleep-wake disturbances in alcoholism: focus on the cholinergic pedunculopontine tegmentum. | Sleep-wake (S-W) disturbances are frequently associated with alcohol use disorders (AUD), occurring during periods of active drinking, withdrawal, and abstinence. These S-W disturbances can persist after months or even years of abstinence, suggesting that chronic alcohol consumption may have enduring negative effects on both homeostatic and circadian sleep processes. It is now generally accepted that S-W disturbances in alcohol-dependent individuals are a significant cause of relapse in drinking. Although significant progress has been made in identifying the socio-economic burden and health risks of alcohol addiction, the underlying neurobiological mechanisms that lead to S-W disorders in AUD are poorly understood. Marked progress has been made in understanding the basic neurobiological mechanisms of how different sleep stages are normally regulated. This review article in seeking to explain the neurobiological mechanisms underlying S-W disturbances associated with AUD, describes an evidence-based, easily testable, novel hypothesis that chronic alcohol consumption induces neuroadaptive changes in the cholinergic cell compartment of the pedunculopontine tegmentum (CCC-PPT). These changes include increases in N-methyl-d-aspartate (NMDA) and kainate receptor sensitivity and a decrease in gamma-aminobutyric acid (GABAB)-receptor sensitivity in the CCC-PPT. Together these changes are the primary pathophysiological mechanisms that underlie S-W disturbances in AUD. This review is targeted for both basic neuroscientists in alcohol addiction research and clinicians who are in search of new and more effective therapeutic interventions to treat and/or eliminate sleep disorders associated with AUD. | 25,151,622 | [
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Tailored atrial substrate modification based on low-voltage areas in catheter ablation of atrial fibrillation. | Reduced electrogram amplitude has been shown to correlate with diseased myocardium. We describe a novel individualized approach for catheter ablation of atrial fibrillation (AF) based on low-voltage areas (LVAs) in the left atrium (LA). We sought to assess (1) the incidence of LVAs in patients undergoing AF catheter ablation, (2) the distribution of LVAs within the LA, and (3) the effect of an individualized ablation strategy on long-term rhythm outcomes. In 178 patients with paroxysmal or persistent AF, LA voltage maps were created during sinus rhythm after circumferential pulmonary vein isolation. Subsequent substrate modification was confined to the presence of LVA (<0.5 mV) and inducible regular atrial tachycardias. LVAs were identified in 35% and 10% of patients with persistent and paroxysmal AF, respectively. The LA roof and the anterior, septal, and posterior wall LA were most often affected. The 12-month atrial tachycardias/AF-free survival was 62% for patients without LVAs and 70% for patients with LVAs and tailored substrate modification (P=0.3). Success rate in a comparison group of 26 LVA patients without further substrate modification was 27%. LVAs can be found at preferred sites in 10% of patients with paroxysmal AF and in 35% of patients with persistent AF. This is the first clinical report describing a consistent voltage-based approach for substrate modification in addition to circumferential pulmonary vein isolation irrespective of AF type. Application of this limited individualized approach may have the potential to compensate for the impaired 12-month outcome of patients with endocardial structural defects. | 25,151,631 | [
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Multimeric states of starch phosphorylase determine protein-protein interactions with starch biosynthetic enzymes in amyloplasts. | Protein-protein interactions between starch phosphorylase (SP) and other starch biosynthetic enzymes were investigated using isolated maize endosperm amyloplasts and a recombinant maize enzyme. Plastidial SP is a stromal enzyme existing as a multimeric protein in amyloplasts. Biochemical analysis of the recombinant maize SP indicated that the tetrameric form was catalytically active in both glucan-synthetic and phosphorolytic directions. Protein-protein interaction experiments employing the recombinant SP as an affinity ligand with amyloplast extracts showed that the multimeric state of SP determined interactions with other enzymes of the starch biosynthetic pathway. The monomeric form of SP interacts with starch branching enzyme I (SBEI) and SBEIIb, whereas only SBEI interacts with the tetrameric form of SP. In all cases, protein-protein interactions were broken when amyloplast lysates were dephosphorylated in vitro, and enhanced following pre-treatment with ATP, suggesting a mechanism of protein complex formation regulated by protein phosphorylation. In vitro protein phosphorylation experiments with [γ-(32)P]-ATP show that SP is phosphorylated by a plastidial protein kinase. Evidence is presented which suggests SBEIIb modulates the catalytic activity of SP through the formation of a heteromeric protein complex. | 25,151,633 | [
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Vitamin K antagonists and cognitive impairment: results from a cross-sectional pilot study among geriatric patients. | Vitamin K is involved in brain physiology, suggesting that its deficiency induces cognitive decline. Our objective was to determine whether using vitamin K antagonists (VKAs) was associated with cognitive impairment among geriatric patients. Two hundred sixty-seven older patients (mean, 83.4 ± 8.1 years; 56.9% female) were categorized according to cognitive impairment (ie, Mini-Mental State Examination ≤ 25). The regular use of VKAs was sought by questioning the patients, relatives, and family physicians. Age, gender, body mass index, comorbidity burden, mood and executive functioning, history of atrial fibrillation, ischemic stroke, intracranial hemorrhage and transient ischemic attack, use of other anticoagulants and antiplatelet medications, and severe renal failure were used as potential confounders. Compared with participants without cognitive impairment (n = 70), those with Mini-Mental State Examination ≤ 25 used more frequently VKAs (p = .038). The risk of cognitive impairment was 15% higher with VKAs, specifically with fluindione. Using VKAs was independently associated with cognitive impairment (fully adjusted odds ratio = 17.4 [95% CI: 1.4-224.2], p = .028). We found more frequent cognitive impairment associated with the use of VKAs, specifically fluindione, among geriatric patients. | 25,151,653 | [
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Identification of fluoride contamination with the interaction of physico-chemical characteristics in groundwater of Jodhpur (India). | A hydrogeochemical investigation has been carried out in Jodhpur district of western Rajasthan in India. The investigated area has been classified into four types with reference to concentration of F(-) prescribed for drinking: low-F(-) (< 1.0 mgl(-1)), moderate-F(-) (1.0-1.50 mgl(-1)) , high-F(-) (1.5-3.0 mgl-(1)) and very high-F(-) ( > 3.0 mgl(-1)). Twenty three percent of the total groundwater samples belong to the very high-F(-) category, Twenty two percent samples belong to the high-F(-) category, Thirty four percent samples belong to the moderate-F(-) category and twenty one percent samples belong to the low-F(-) category. The correlation study suggests a positive correlation (r = 0.396) between the pH and fluoride concentration, indicating that higher alkalinity of the water promotes the leaching of fluoride and thus affect the concentration of fluoride in groundwaters. Highest positive correlation coefficient was observed between fluoride and alkalinity (r = 0.516) indicating that alkalinity favors the higher values of fluoride in the study area. The regression equations have been developed by taking fluoride as dependent variable and other water quality parameters as independent variable. Possible sources of fluoride (F(-)) are weathering and leaching of F(-) bearing minerals under the alkaline environment. Arid environment, high rate of evapotranspiration and longer residence time of waters in the aquifer zone are the supplementary factors to further increase the F(-) content in the ground waters. | 25,151,715 | [
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Noise monitoring and modeling on four lanning of national highways corridor. | Noise emitted from traffic contributes to about 55% of total noise pollution in India. This paper is an effort of a research conducted to quantify and analyze the traffic noise emissions along the Salem-Namakkal NH 7 corridor with an ultimate objective of setting up a traffic noise model based on the traffic noise conditions of Indian cities. Noise levels and other variables have been measured in 15 locations to develop a statistical regression model based on A-weighted equivalent noise level for Indian road conditions. The ambient noise levels recorded represent the higher noise levels prevailing along the NH 7 corridor. The Receptor Oriented Technique adopted proves to be helpful in characterizing the ambient noise levels along the study area. The newly developed road traffic noise model can be effectively used as a decision support tool for predicting equivalent noise levels in the cities of India. The present analysis also reveals that the magnitude of noise levels has an increasing trend due to the increased traffic flow and presents the attention needed for minimization. The mitigation measures and the future evaluations are discussed. | 25,151,718 | [
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Assessment of traffic noise at Kolar Gold Fields, India. | Traffic noise produces environmental problems on surroundings. At Kolar Gold Fields (KGF), traffic load at different locations can cause noise pollution. Therefore, a detailed study was carried out at KGF in commercial, residential and silence zone. Different monitoring locations were identified in these zones and A-weighted equivalent sound pressure levels (L(eq)) were measured. The study was conducted on different weekdays and weekend for different periods of the day and compared with ambient noise standards. Since many variables were noted during noise monitoring, therefore, a multiple regression analysis was also carried out to develop a regression model for prediction of L(eq). Stepwise regression procedure was followed for the selection of most influencing variables. Model adequacy was checked using normal distribution with zero mean and constant variance, difference between F-observed and F-critical, and correlation between measured and predicted noise levels. | 25,151,719 | [
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[A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth]. | Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents. | 25,151,731 | [
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[The impurity profiling of simvastatin and its tablets by UPLC-MS/MS]. | Investigation of simvastatin and its related substances was carried out using a reversed phase ultra performance liquid chromatography/tandem mass spectrometry method. The identification of impurities in simvastatin was performed with a triple-quadrupole mass spectrometer, with an electrospray ionization (ESI) source in the negative/positive ion mode. A total of 12 compounds were characterized in commercial samples, among which 2 impurities had never been reported. All the impurities were deduced based on the MS fragment pathways of simvastatin and the biosynthetic pathway of lovastatin. This work provides very useful information for quality control of simvastatin. | 25,151,740 | [
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[Vitro study on gene transfection efficiency of hyaluronic acid modified core-shell liponanoparticles in human retinal pigment epithelium cells]. | The aim of this study is to prepare hyaluronic acid (HA) modified core-shell liponanoparticles (pHA-LCS-NPs) as gene delivery system and investigate its gene transfection efficiency in human retinal pigment epithelium (ARPE-19) cells in vitro. The pHA-LCS-NPs was prepared by firstly hydrating dry lipid film with CS-NPs suspension to get LCS-NPs, then modifying the lipid bilayer with HA by amidation reaction between HA and dioleoyl phosphatidylethanolamine (DOPE). Its morphology, particle size and zeta potential were investigated. XTT assay was used to evaluate the cell safety of different vectors in vitro. The gene transfection efficiency of pHA-LCS-NPs modified with different contents of HA was investigated in ARPE-19 cells with green fluorescent protein (pEGFP) as the reporter gene. The results showed that the obtained pHA-LCS-NPs exhibited a clear core-shell structure with the average particles size of (214.9 +/- 7.2) nm and zeta potential of (-35 +/- 3.7) mV. The 24 h cumulative release of gene from pHA-LCS-NPs was less than 30%. After 48 h incubation, gene transfection efficiency of pHA-LCS-NPs/pEGFP was 1.81 times and 3.75 times higher than that of CS-NPs/pEGFP and naked pEGFP, respectively. Also no obvious cytotoxicity was observed on pHA-LCS-NPs. It suggested that the pHA-LCS-NPs might be promising non-viral gene delivery systems with high efficiency and low cytotoxicity. | 25,151,745 | [
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[Antitumor efficacy of irinotecan-loaded galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles against hepatocellular carcinoma cells]. | The purpose of this study is to prepare galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles (GPEM) to enhance the antitumor efficacy against hepatocellular carcinoma cells. The irinotecan (CPT-11) loaded mesoporous silica nanoparticles (MSNs) was coated with the Gal-P123 modified functional lipid bilayer by thin-film dispersion method. Nanoparticles were characterized with particle size, zeta potential, morphology and drug release in vitro. Afterwards, the cell uptake, intracellular concentration of CPT-11, cell apoptosis rate and cytotoxicity were evaluated on human hepatocellular carcinoma cell line Huh-7. The results showed that MSNs were coated with intact lipid bilayers and the nanoparticles had clear core-shell structure. GPEM is stable with the mean particle size of (78.01 +/- 2.04) nm. The low leakage rate in normal physiological conditions in vitro is contributed to the protection of stable lipid bilayer, and the fast drug release in acid environment due to the destruction of the lipid bilayer. On the cell level, the vector could improve the intracellular CPT-11 concentration by 4 times because of the functional lipid bilayer. The high CPT-11 concentration led to the increasement of apoptosis rate by 48.6%, and the reduction of half maximal inhibitory concentration (IC50) values of CPT-11 by 2 times, indicating stronger cell cytotoxicity. | 25,151,746 | [
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[Surveillance report of drug-resistant bacteria from 2007 to 2012 in Saga Prefecture, Japan (the second report)]. | Drug-resistant bacteria are a problematic issue in Japan. Surveillance of drug-resistant bacteria is important because the frequency of isolation and kinds of such bacteria vary between hospitals and local areas. This study summarizes the results of detection of drug-resistant bacteria in Saga Prefecture from July 2007 to June 2012. Data presented in this study were collected through questionnaire survey that was conducted in 12 hospitals. Frequency of drug-resistant bacteria are as follows: 62.5% of Staphylococcus aureus was methicillin-resistant S. aureus (MRSA); 62.2% of Streptococcus pneumoniae was penicillin-intermediate S. pneumoniae (PISP) or penicillin-resistant S. pneumoniae (PRSP); 26.4% of Haemophilus influenzae was beta-lactamase negative ampicillin-resistant H. influenzae (BLNAR); 0.5% of Pseudomonas aeruginosa was metallo-beta-lactamase (MBL) P. aeruginosa; 0.5% of P. aeruginosa was multi-drug resistant P. aeruginosa (MDRP); 12.9% and 5.1% of Escherichia coli and Klebsiella pneumoniae, respectively, were extended-spectrum beta-lactamase (ESBL) producing organisms. While the isolation frequencies of MRSA and PISP/PRSP were unchanged, those of BLNAR, ESBL producing E. coli and ESBL producing K. pneumoniae raised from 15.4% to 34.2%, from 5.7% to 18.4% and from 2.6% to 8.2%, respectively, over the past 5 years. The frequencies of isolation of MDRP and two drug resistant P. aeruginosa declined. This study revealed that the overall trend in the long-term changes of isolation frequency of drug-resistant bacteria in Saga Prefecture is similar to the trend in the national data. It also showed that the frequency and kinds of drug-resistant bacteria are variable between hospitals and local areas. Further study, such as examination of the usage and MIC value of antimicrobial drugs, will enable us to gain more detailed information on the drug-resistant bacteria. | 25,151,773 | [
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[A 10-year retrospective--from the achievement of ISO 15189 accreditation toward the next stage--chairman's introductory remarks]. | More than 10 years have passed since ISO 15189 was issued in February 2003, and ISO 15189:2012 (bilingual edition published in April 2013) was issued in November 2012. In order to provide useful laboratory services, standardizing examination results performed by medical laboratories is very important. The accreditation of medical laboratories is one of the way to implement such standardization. After publishing ISO 15189 in 2003, many economies started the accreditation program for medical laboratories using its criteria. There are 5,500 accredited medical laboratories in the world, including 2,200 accredited in the Asia-pacific region. In Japan, the JAB (Japan Accreditation Board) started its accreditation service in August 2005. The service is now in its eighth year. As of the end of fiscal year (FY) 2013, the total number of accredited medical laboratories was 69, consisting of 18 university hospitals, 2 clinical trial laboratories, 3 health-checking laboratories, 12 other medical institutes, and 34 registered clinical laboratories. In this symposium, we look back over the more than 10 years since ISO 15189 was issued, and subjects of speeches entitled 'the next stage' will be given by five speakers. | 25,151,781 | [
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[Update to ISO 15189:2012, and future prospects]. | ISO (the International Organization for Standardization) is a worldwide federation of national standard bodies (ISO member bodies). The work of preparing international standards is normally carried out through ISO technical committees. ISO 15189 was prepared by Technical Committee ISO/TC 212, clinical laboratory testing, and in vitro diagnostic test systems. This third edition replaces the second edition (ISO 15189:2007), which was technically revised. Medical laboratory services are essential for patient care and, therefore, have to be available to meet the needs of all patients and the clinical personnel responsible for the care of those patients. | 25,151,783 | [
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Genetic diversity of Mycosphaerella graminicola isolates from a single field. | Septoria tritici blotch caused by Mycosphaerella graminicola is currently one of the most economically damaging diseases on wheat crops worldwide. Two hundred and sixty single-conidial isolates of this fungus were sampled in April 2012 in the Nord-Pas de Calais region (France). They have all been collected from 13 distinct plots in a single field. The corresponding isolates were then fingerprinted using 8 microsatellite markers in order to assess the genetic diversity and population structure of M. graminicola at the single field scale. The results revealed a high genotypic diversity within the collected population, with the detection of 83% of unique haplotypes among the isolates tested (clonal fraction = 17%). A high genic diversity was also found as indicated by the Nei's index value (0.50) and strong allele diversity obtained (number of alleles per locus ranged from 7 to 17, with an average of 10 alleles per locus). Further analyses showed a low population differentiation (G(ST) = 0.08) and a high gene flow (Nm = 5.64) between the 13 sampled plots. Our study suggests that sexual reproduction, by its frequency, plays a major role in the genetic diversification of M. graminicola at the field level and in the distribution and homogenization of this diversity in the field via wind-born ascospores. | 25,151,819 | [
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Quantifying the non-fungicidal effects of foliar applications of fluxapyroxad (Xemium) on stomatal conductance, water use efficiency and yield in winter wheat. | The active ingredient fluxapyroxad belongs to the chemical group of carboxamides and is a new generation succinate dehydrogenase inhibitor (SDHI) in complex II of the mitochondrial respiratory chain. It has strong efficacy against the key foliar diseases of winter wheat in the UK: Septoria leaf blotch, yellow stripe rust and brown rust. Fluxapyroxad is marketed under the brand name of Xemium, was launched in 2012 and is available in the UK as a solo product (Imtrex) for co-application with triazoles, in co-formulation with epoxiconazole (Adexar), or in a three way formulation with epoxiconazole and pyraclostrobin (Ceriax). The objective of the study was to quantify the direct effects of Xemium on stomatal conductance and yield, mediated through stimulation of host physiology. Three field experiments and two controlled environment (CE) experiments were conducted across three cropping seasons (2010-2012) in Herefordshire and Cambridge, in the UK. Xemium was evaluated against boscalid, pyraclostrobin (F500), epoxiconazole and an untreated control. Across site-seasons, disease severity was significantly reduced when Xemium was applied as a foliar spray. Healthy canopy size and duration was increased by Xemium and canopy greening effects were seen shortly after application. Stomatal conductance was found to be consistently lower in Xemium treated plants but reduced stomatal opening was not found to be detrimental to yield in these experiments. Large, beneficial effects of Xemium on water use efficiency were found at the canopy level and this finding was supported by measurements of instantaneous water use efficiency at the leaf level. Effects on season long water use efficiency were largely driven by improvements in yield for a given amount of water uptake. Foliar applications of Xemium reduced the water required to produce 1.0 t grain per hectare by 82,330 L(82 t) when compared with an untreated crop. Yield was significantly higher in Xemium treatments and this was achieved primarily through increases in grains ear. Evidence is presented hereto show that in addition to controlling visible disease symptoms, Xemium is able to exert positive physiological effects on the host. The yield increase from plots treated with Xemium applied at standard commercial timings was shown to exceed that which can be explained solely through good disease control and the associated loss of healthy canopy area. Approximately 1.0 t ha(-1) (12%) yield was produced by Xemium treatments which could not be accounted for through the control of visible disease symptoms. | 25,151,827 | [
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Silky bent grass resistance to herbicides: one year of monitoring in Belgium. | Silky bent grass (Apera spica-venti (L.) P. Beauv.) is a common weed of cereal crops widely spread in Northern and Easthern Europe (Germany, Czech Republic,...), Northern Asia, Siberia and Canada. Up to now, no resistant case has been detected in Belgium but some chemical weeding failures have been observed in Wallonia fields. During summer 2011, 37 seed samples of Apera spica-venti were collected in Wallonia and submitted to resistance tests in controlled conditions. Three modes of action were tested: acetyl coenzyme-A carboxylase inhibitors (pinoxaden and cycloxydim), acetolactate synthase inhibitors (mesosulfuron+iodosulfu-ron, pyroxsulam and sulfometuron) and photosynthesis inhibitors (isoproturon). One susceptible standard population was included in the test in order to validate it and to permit wild populations classification according to "R" rating system developed by Moss et al (2007). Most of populations were susceptible but some populations showed resistance to at least one of the three tested modes of action. | 25,151,844 | [
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Fragment-based docking: development of the CHARMMing Web user interface as a platform for computer-aided drug design. | Web-based user interfaces to scientific applications are important tools that allow researchers to utilize a broad range of software packages with just an Internet connection and a browser. One such interface, CHARMMing (CHARMM interface and graphics), facilitates access to the powerful and widely used molecular software package CHARMM. CHARMMing incorporates tasks such as molecular structure analysis, dynamics, multiscale modeling, and other techniques commonly used by computational life scientists. We have extended CHARMMing's capabilities to include a fragment-based docking protocol that allows users to perform molecular docking and virtual screening calculations either directly via the CHARMMing Web server or on computing resources using the self-contained job scripts generated via the Web interface. The docking protocol was evaluated by performing a series of "re-dockings" with direct comparison to top commercial docking software. Results of this evaluation showed that CHARMMing's docking implementation is comparable to many widely used software packages and validates the use of the new CHARMM generalized force field for docking and virtual screening. | 25,151,852 | [
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