title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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The effect of perceptual grouping on haptic numerosity perception. | We used a haptic enumeration task to investigate whether enumeration can be facilitated by perceptual grouping in the haptic modality. Eight participants were asked to count tangible dots as quickly and accurately as possible, while moving their finger pad over a tactile display. In Experiment 1, we manipulated the number and organization of the dots, while keeping the total exploration area constant. The dots were either evenly distributed on a horizontal line (baseline condition) or organized into groups based on either proximity (dots placed in closer proximity to each other) or configural cues (dots placed in a geometric configuration). In Experiment 2, we varied the distance between the subsets of dots. We hypothesized that when subsets of dots can be grouped together, the enumeration time will be shorter and accuracy will be higher than in the baseline condition. The results of both experiments showed faster enumeration for the configural condition than for the baseline condition, indicating that configural grouping also facilitates haptic enumeration. In Experiment 2, faster enumeration was also observed for the proximity condition than for the baseline condition. Thus, perceptual grouping speeds up haptic enumeration by both configural and proximity cues, suggesting that similar mechanisms underlie perceptual grouping in both visual and haptic enumeration. | 25,248,621 | [
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Ensemble theory for slightly deformable granular matter. | Given a granular system of slightly deformable particles, it is possible to obtain different static and jammed packings subjected to the same macroscopic constraints. These microstates can be compared in a mathematical space defined by the components of the force-moment tensor (i.e. the product of the equivalent stress by the volume of the Voronoi cell). In order to explain the statistical distributions observed there, an athermal ensemble theory can be used. This work proposes a formalism (based on developments of the original theory of Edwards and collaborators) that considers both the internal and the external constraints of the problem. The former give the density of states of the points of this space, and the latter give their statistical weight. The internal constraints are those caused by the intrinsic features of the system (e.g. size distribution, friction, cohesion). They, together with the force-balance condition, determine which the possible local states of equilibrium of a particle are. Under the principle of equal a priori probabilities, and when no other constraints are imposed, it can be assumed that particles are equally likely to be found in any one of these local states of equilibrium. Then a flat sampling over all these local states turns into a non-uniform distribution in the force-moment space that can be represented with density of states functions. Although these functions can be measured, some of their features are explored in this paper. The external constraints are those macroscopic quantities that define the ensemble and are fixed by the protocol. The force-moment, the volume, the elastic potential energy and the stress are some examples of quantities that can be expressed as functions of the force-moment. The associated ensembles are included in the formalism presented here. | 25,248,624 | [
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Symmetric curvature descriptors for label-free analysis of DNA. | High-resolution microscopy techniques such as electron microscopy, scanning tunnelling microscopy and atomic force microscopy represent well-established, powerful tools for the structural characterization of adsorbed DNA molecules at the nanoscale. Notably, the analysis of DNA contours allows mapping intrinsic curvature and flexibility along the molecular backbone. This is particularly suited to address the impact of the base-pairs sequence on the local conformation of the strands and plays a pivotal role for investigations relating the inherent DNA shape and flexibility to other functional properties. Here, we introduce novel chain descriptors aimed to characterize the local intrinsic curvature and flexibility of adsorbed DNA molecules with unknown orientation. They consist of stochastic functions that couple the curvatures of two nanosized segments, symmetrically placed on the DNA contour. We show that the fine mapping of the ensemble-averaged functions along the molecular backbone generates characteristic patterns of variation that highlight all pairs of tracts with large intrinsic curvature or enhanced flexibility. We demonstrate the practical applicability of the method for DNA chains imaged by atomic force microscopy. Our approach paves the way for the label-free comparative analysis of duplexes, aimed to detect nanoscale conformational changes of physical or biological relevance in large sample numbers. | 25,248,631 | [
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Glycoprotein fucosylation is increased in seminal plasma of subfertile men. | Fucose, the monosaccharide frequent in N- and O-glycans, is a part of Lewis-type antigens that are known to mediate direct sperm binding to the zona pellucida. Such interaction was found to be inhibited in vitroby fucose-containing oligo- and polysaccharides, as well as neoglycoproteins. The objective of this study was to screen seminal plasma proteins of infertile/subfertile men for the content and density of fucosylated glycoepitopes, and compare them to samples of fertile normozoospermic subjects. Seminal proteins were separated in polyacrylamide gel electrophoresis and blotted onto nitrocellulose membrane and probed with fucose-specific Aleuria aurantia lectin (AAL). Twelve electrophoretic bands were selected for quantitative densitometric analysis. It was found that the content, and especially the density of fucosylated glycans, were higher in glycoproteins present in seminal plasma of subfertile men. No profound differences in fucosylation density were found among the groups of normozoospermic, oligozoospermic, asthenozoospermic, and oligoasthenozoospermic subfertile men. According to the antibody probing, AAL-reactive bands can be attributed to male reproductive tract glycoproteins, including prostate-specific antigen, prostatic acid phosphatase, glycodelin and chorionic gonadotropin. Fibronectin, α1 -acid glycoprotein, α1 -antitrypsin, immunoglobulin G and antithrombin III may also contribute to this high fucosylation. It is suggested that the abundant fucosylated glycans in the sperm environment could interfere with the sperm surface and disturb the normal course of the fertilization cascade. | 25,248,658 | [
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Antimycobacterial activity generated by the amide coupling of (-)-fenchone derived aminoalcohol with cinnamic acids and analogues. | Aminoethyl substituted 2-endo-fenchol prepared from (-)-fenchone was used as scaffold for the synthesis of series of 31 amide structures by N-acylation applying cinnamic acids and analogues. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed for some of them promising activity-up to 0.2 μg/ml, combined with relatively low cytotoxicity of the selected active compounds. | 25,248,685 | [
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The effect of liposomal bupivacaine injection during total hip arthroplasty: a controlled cohort study. | Multimodal analgesia following total hip arthroplasty has been shown to improve patient satisfaction, participation with physical therapy, and allow early return to self care. Liposomal bupivacaine is a formulation of local anesthetic which has the potential to provide anesthesia for up to 72 hours following administration. The purpose of this study was to compare the effectiveness of liposomal bupivacaine with bupivacaine following total hip arthroplasty. A retrospective chart review was performed on 28 patients undergoing total hip arthroplasty or hip resurfacing who received intraoperative administration of liposomal bupivacaine. A control group of 30 patients who had previously undergone total hip arthroplasty or hip resurfacing and had received intraoperative administration of bupivacaine also underwent a chart review. Length of stay, post-operative opioid use, and pain scores were compared for both groups. The average length of stay in the study group was 1.93 days and the control group length of stay was 2.47 days (p ≤ 0.05). Morphine equivalent use was less in the study group during the first 24 hours compared to the control group (p ≤0.05). During the second and third 24 hours the morphine equivalent use difference was not statistically significant. Visual analogue scores were not significantly different between groups at any time point. Liposomal bupivacaine administration during total hip arthroplasty appears to decrease the need for opioid use post operatively and decrease length of stay. The results of this study justify the need for a well-designed randomized controlled trial utilizing liposomal bupivacaine as part of multimodal analgesia during THA. | 25,248,686 | [
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Immobilization of glucose oxidase on graphene and cobalt phthalocyanine composite and its application for the determination of glucose. | We described a simple and facile chemical reduction strategy for the preparation of graphene (GR)-cobalt phthalocyanine (CoPc) composite and explored it for the enzymatic determination of glucose. CoPc is an active mediator and electrocatalysts for the immobilization of GOx and determination of glucose. However, it is not stable on the electrode surface and also suffers from lack of conductivity. Here, we have employed GR as the suitable support to stabilize CoPc through simple chemical reduction method and the resulting composite has been used for the glucose biosensor application. Scanning electron microscopy, X-ray diffraction and Energy-dispersive X-ray spectroscopy studies confirmed the successful formation of composite. Direct electron transfer of glucose oxidase (GOx) was observed with well defined redox peaks at the formal potential of -0.44 V. The amount of electroactive GOx (Г) and electron transfer rate constant (ks) were calculated to be 3.77×10(-10) mol cm(-2) and 3.57 s(-1), respectively. The fabricated amperometric biosensor detects glucose in wide linear concentration range from 10 μM to 14.8 mM with high sensitivity of 5.0 9μA mM(-1) cm(-2). The sensor offered very low detection limit (LOD) of 1.6 μM. In addition, practical feasibility of the sensor has been explored in screen printing carbon electrode with accurate determination of glucose present in human blood serum and urine samples. Furthermore, the sensor exhibited appreciable stability, repeatability and reproducibility results. | 25,248,701 | [
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[Value of modified POSSUM scoring system on predicting operation risk
in elderly NSCLC patients]. | For the assessment of elderly patients can tolerate lung cancer operation, there is no clear standard. To evaluate the clinical validity of POSSUM (Physiological and Operative Severity Score for the Umeration of Mortality and Morbidity) in elderly non-small cell lung cancer (NSCLC) surgery patients, we want to provide an important basis for operation treatment decisions. A total of 138 patients, with 88 males and 50 females, with elderly NSCLC surgery between December 2007 and December 2013, are included in PLA general hospital. Using the multivariate Logistic regression analysis, we evaluate the value of each factor on the actual postoperative complications mortality and morbidity. The scorings on standard POSSUM and modified POSSUM in the complication group are compared with the non-complication group using the group t test. Drawing receiver operating characteristic (ROC) curve in standard POSSUM group and modified POSSUM group, calculating the area under the curve (AUC), AUC in standard group is compared with modified group using t test. Judge if the modified POSSUM prediction is consistent with the actual mortality and morbidity. Among 138 patients, there were 77 postoperative complications in 59 patients, 2 cases of death. According to the Logistic regression analysis, 17 of 18 factors in standard POSSUM, pulmonary function, different TNM stage are predictors for postoperative complications (P<0.05). Age is a predictor for postoperative death (P<0.05). In the standard POSSUM scoring, actual complication group compared with non-complication group, the difference is statistically significant (P<0.01). In the modified POSSUM scoring, complication group is compared with non-complication group, the difference is statistically significant (P<0.01). Compared with the standard POSSUM, the modified POSSUM has better predictive value on postoperative morbidity, and the comparison of AUC between the two groups is statistically significant. But the latter shows the overpredicted mortality (P<0.01). The modified POSSUM has a good predictive value on postoperative complications in elderly NSCLC surgery patients, so it can provide the basis for decision-making operation treatment. | 25,248,708 | [
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[Immunohistochemical detections of EGFR mutations in NSCLC]. | In recent years, it has been well known that non-small cell lung cancer (NSCLC) patients with mutations of epidermal growth factor receptor (EGFR) response better to EGFR-tyrosine kinase inhibitor treatment. Although DNA-based assays (e.g. DNA sequencing) are the most frequently used and a relatively reliable method to detect EGFR mutations, they are complex, time-consuming and relatively expensive for routine use in clinical laboratories, besides they require high quality tumor samples. In contrast, the immunohistochemistry (IHC) methods make up fully for the above shortcomings and can serve as screening tests for EGFR mutations. However, there are many factors that can influence the results of IHC methods, such as different staining procedures, different antigen retrieval solutions and different sets of criteria, etc. Thus the IHC methods for detecting EGFR mutations have not been widely used in clinic and only in the research stage. This article reviews the use of IHC methods by different researchers and further discusses how to make the IHC methods work best for the detection of EGFR mutations. | 25,248,714 | [
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Antimycobacterial activity of DNA intercalator inhibitors of Mycobacterium tuberculosis primase DnaG. | Owing to the rise in drug resistance in tuberculosis combined with the global spread of its causative pathogen, Mycobacterium tuberculosis (Mtb), innovative anti mycobacterial agents are urgently needed. Recently, we developed a novel primase-pyrophosphatase assay and used it to discover inhibitors of an essential Mtb enzyme, primase DnaG (Mtb DnaG), a promising and unexplored potential target for novel antituberculosis chemotherapeutics. Doxorubicin, an anthracycline antibiotic used as an anticancer drug, was found to be a potent inhibitor of Mtb DnaG. In this study, we investigated both inhibition of Mtb DnaG and the inhibitory activity against in vitro growth of Mtb and M. smegmatis (Msm) by other anthracyclines, daunorubicin and idarubicin, as well as by less cytotoxic DNA intercalators: aloe-emodin, rhein and a mitoxantrone derivative. Generally, low-μM inhibition of Mtb DnaG by the anthracyclines was correlated with their low-μM minimum inhibitory concentrations. Aloe-emodin displayed threefold weaker potency than doxorubicin against Mtb DnaG and similar inhibition of Msm (but not Mtb) in the mid-μM range, whereas rhein (a close analog of aloe-emodin) and a di-glucosylated mitoxantrone derivative did not show significant inhibition of Mtb DnaG or antimycobacterial activity. Taken together, these observations strongly suggest that several clinically used anthracyclines and aloe-emodin target mycobacterial primase, setting the stage for a more extensive exploration of this enzyme as an antibacterial target. | 25,248,725 | [
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Oligomerization of esculin improves its antibacterial activity and modulates antibiotic resistance. | In this particular study, the antibacterial activity of esculin and oligomer fractions was assessed. MIC values of esculin and its oligomer fractions as well as of some antibiotics against Gram-positive and Gram-negative strains and against Escherichia coli multiresistant variants were determined by the standard broth microdilution method. Both esculin and oligoesculin fractions exhibited antibacterial effect against reference strains; Staphylococcus aureus, Enterococcus faecalis, Salmonella enteritidis and Salmonella typhimurium. It appears that E3 oligomer fraction had the greatest antibacterial activity against these reference strains. Besides, as E2 and E3 revealed the best antibacterial effect against multiresistant variants of E. coli, we decided to test the effect of each, combined to the antibiotic against which the variants were resistant. In the interaction study, E2 and E3 oligoesculin fractions were found to be effective in reducing the resistance of E. coli 6574 to ofloxacin and the resistance of E. coli 6228 to amoxicillin. Only E3 oligoesculin fraction showed a synergetic interaction with amoxicillin and tetracyclin against E. coli 6708, but no interaction was found either with E2 or E3 fractions against E. coli 6234. Our study allowed us to conclude that oligomerization of esculin increases its antibacterial potential, according to the degree of polymerization. | 25,248,728 | [
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Regulation of S-adenosylhomocysteine hydrolase by lysine acetylation. | S-Adenosylhomocysteine hydrolase (SAHH) is an NAD(+)-dependent tetrameric enzyme that catalyzes the breakdown of S-adenosylhomocysteine to adenosine and homocysteine and is important in cell growth and the regulation of gene expression. Loss of SAHH function can result in global inhibition of cellular methyltransferase enzymes because of high levels of S-adenosylhomocysteine. Prior proteomics studies have identified two SAHH acetylation sites at Lys(401) and Lys(408) but the impact of these post-translational modifications has not yet been determined. Here we use expressed protein ligation to produce semisynthetic SAHH acetylated at Lys(401) and Lys(408) and show that modification of either position negatively impacts the catalytic activity of SAHH. X-ray crystal structures of 408-acetylated SAHH and dually acetylated SAHH have been determined and reveal perturbations in the C-terminal hydrogen bonding patterns, a region of the protein important for NAD(+) binding. These crystal structures along with mutagenesis data suggest that such hydrogen bond perturbations are responsible for SAHH catalytic inhibition by acetylation. These results suggest how increased acetylation of SAHH may globally influence cellular methylation patterns. | 25,248,746 | [
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Auxin-induced rapid degradation of inhibitor of caspase-activated DNase (ICAD) induces apoptotic DNA fragmentation, caspase activation, and cell death: a cell suicide module. | Caspase-activated DNase (CAD) is a major apoptotic nuclease, responsible for DNA fragmentation and chromatin condensation during apoptosis. CAD is normally activated in apoptosis as a result of caspase cleavage of its inhibitory chaperone ICAD. Other aspects of CAD regulation are poorly understood. In particular, it has been unclear whether direct CAD activation in non-apoptotic living cells can trigger cell death. Taking advantage of the auxin-inducible degron (AID) system, we have developed a suicide system with which ICAD is rapidly degraded in living cells in response to the plant hormone auxin. Our studies demonstrate that rapid ICAD depletion is sufficient to activate CAD and induce cell death in DT40 and yeast cells. In the vertebrate cells, ectopic CAD activation triggered caspase activation and subsequent hallmarks of caspase-dependent apoptotic changes, including phosphatidylserine exposure and nuclear fragmentation. These observations not only suggest that CAD activation drives apoptosis through a positive feedback loop, but also identify a unique suicide system that can be used for controlling gene-modified organisms. | 25,248,749 | [
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Potential role of raltegravir-based therapy to induce rapid viral decay in highly viraemic HIV-infected neonates. | We report safety and tolerability of raltegravir (RAL) as a forth HIV agent in two highly viraemic newborns. Raltegravir (6 mg/kg) was given orally twice daily. The other antiretrovirals were assumed according to standard dose for newborns. The first baby was born at week 36. An antiretroviral therapy consisting of zidovudine, lamivudine, and lopinavir/ritonavir was started 96 hour after delivery. Raltegravir was added at hour 120, being plasma HIV-1 RNA above 10×10(6) copies/ml. HIV RNA declined to 5·000 copies/ml at day 30. The second baby was born at week 40. He was started on zidovudine, lamivudine, and nevirapine at day 0, while RAL was added at day 3. Plasma HIV-1 RNA declined from 6·6×10(6) at birth to 52 copies/ml at day 28. RAL tolerability was good in both patients, one with gamma-glutamyltransferase increase, which normalized after RAL discontinuation. Raltegravir-based four drug regimen may be effective and well tolerated in highly viraemic HIV neonates up to 4 weeks. | 25,248,795 | [
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Effects of lifestyle intervention on dietary intake, physical activity level, and gestational weight gain in pregnant women with different pre-pregnancy Body Mass Index in a randomized control trial. | The objectives of this study were to assess the efficacy of lifestyle intervention on gestational weight gain in pregnant women with normal and above normal body mass index (BMI) in a randomized controlled trial. A total of 116 pregnant women (<20 weeks of pregnancy) without diabetes were enrolled and 113 pregnant women completed the program. Participants were randomized into intervention and control groups. Women in the intervention group received weekly trainer-led group exercise sessions, instructed home exercise for 3-5-times/week during 20-36 weeks of gestation, and dietary counseling twice during pregnancy. Participants in the control group did not receive the intervention. All participants completed a physical activity questionnaire and a 3-day food record at enrolment and 2 months after enrolment. The participants in the intervention group with normal pre-pregnancy BMI (≤24.9 kg/M2, n = 30) had lower gestational weight gain (GWG), offspring birth weight and excessive gestational weight gain (EGWG) on pregnancy weight gain compared to the control group (n = 27, p < 0.05). Those weight related-changes were not detected between the intervention (n = 27) and control group (n = 29) in the above normal pre-pregnancy BMI participants. Intervention reduced total calorie, total fat, saturated fat and cholesterol intake were detected in women with normal or above normal pre-pregnancy BMI compared to the control group (p < 0.05 or 0.01). Increased physical activity and reduced carbohydrate intake were detected in women with normal (p < 0.05), but not above normal, pre-pregnancy BMI at 2 months after the onset of the intervention compared to the control group. The results of the present study demonstrated that the lifestyle intervention program decreased EGWG, GWG, offspring birth weight in pregnant women with normal, but not above normal, pre-pregnancy BMI, which was associated with increased physical activity and decreased carbohydrate intake. NCT00486629. | 25,248,797 | [
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Concordance between digital pathology and light microscopy in general surgical pathology: a pilot study of 100 cases. | (1) A pilot study to determine the accuracy of interpretation of whole slide digital images in a broad range of general histopathology cases of graded complexity. (2) To survey the participating histopathologists with regard to acceptability of digital pathology. Glass slides of 100 biopsies and minor resections were digitally scanned in their entirety, producing digital slides. These cases had been diagnosed by light microscopy at least 1 year previously and were subsequently reassessed by the original reporting pathologist (who was blinded to their original diagnosis) using digital pathology. The digital pathology-based diagnosis was compared with the original glass slide diagnosis and classified as concordant, slightly discordant (without clinical consequence) or discordant. The participants were surveyed at the end of the study. There was concordance between the original light microscopy diagnosis and digital pathology-based diagnosis in 95 of the 100 cases while the remaining 5 cases showed only slight discordance (with no clinical consequence). None of the cases were categorised as discordant. Participants had mixed experiences using digital pathology technology. In the broad range of cases we examined, digital pathology is a safe and viable method of making a primary histopathological diagnosis. | 25,248,822 | [
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Obscure gastrointestinal bleeding: diagnostic performance of 64-section multiphase CT enterography and CT angiography compared with capsule endoscopy. | To compare the diagnostic capabilities between capsule endoscopy (CE) and multislice CT (MSCT) enterography in combination with MSCT angiography for assessment of obscure gastrointestinal bleeding (OGIB). A total of 127 patients with OGIB were looked at in this study. 82 patients (aged 42.7 ± 19.1 years; 34 males) were assigned to receive MSCT diagnosis and 67 patients to (aged 53.9 ± 16.2 years; 28 males) receive CE diagnosis. Among them, 22 patients (aged 54.1 ± 19.1 years; 12 males) received both examinations. Oral isotonic mannitol and intramuscular injection of anisodamine were performed; non-ionic contrast (iopromide, 370 mg I ml(-1)) was intravenously administered; and then multiphase scanning was conducted at arterial, small intestinal and portal venous phases in MSCT. The results were compared with findings of reference standards including double balloon enteroscopy, digital subtraction angiography, intraoperative pathological examination and/or clinical diagnosis. Administration of anisodamine markedly increased the satisfaction rate of bowel filling (94.67% vs 28.57%; p < 0.001) but not the diagnostic yield (p = 0.293) of MSCT. Compared with MSCT, CE showed an improved overall diagnostic yield (68.66% vs 47.56%; p = 0.010), which was also observed in overt bleeding patients (i.e. patients with continued passage of visible blood) (76.19% vs 51.02%; p = 0.013) and in patients aged younger than 40 years of age (85% vs 51.28%; p = 0.024). However, CE had similar positive rates to MSCT (p > 0.05). Among the 22 cases in whom both examinations were conducted, CE showed no significantly different diagnostic capability compared with MSCT (p = 0.4597). Both CE and MSCT are safe and effective diagnostic methods for OGIB. CE is preferred for overt bleeding or patients aged younger than 40 years. The combined use of CE and MSCT is recommended in OGIB diagnosis. | 25,248,830 | [
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Differential Tiam1/Rac1 activation in hippocampal and cortical neurons mediates differential spine shrinkage in response to oxygen/glucose deprivation. | Distinct neuronal populations show differential sensitivity to global ischemia, with hippocampal CA1 neurons showing greater vulnerability compared to cortical neurons. The mechanisms that underlie differential vulnerability are unclear, and we hypothesize that intrinsic differences in neuronal cell biology are involved. Dendritic spine morphology changes in response to ischemic insults in vivo, but cell type-specific differences and the molecular mechanisms leading to such morphologic changes are unexplored. To directly compare changes in spine size in response to oxygen/glucose deprivation (OGD) in cortical and hippocampal neurons, we used separate and equivalent cultures of each cell type. We show that cortical neurons exhibit significantly greater spine shrinkage compared to hippocampal neurons. Rac1 is a Rho-family GTPase that regulates the actin cytoskeleton and is involved in spine dynamics. We show that Rac1 and the Rac guanine nucleotide exchange factor (GEF) Tiam1 are differentially activated by OGD in hippocampal and cortical neurons. Hippocampal neurons express more Tiam1 than cortical neurons, and reducing Tiam1 expression in hippocampal neurons by shRNA enhances OGD-induced spine shrinkage. Tiam1 knockdown also reduces hippocampal neuronal vulnerability to OGD. This work defines fundamental differences in signalling pathways that regulate spine morphology in distinct neuronal populations that may have a role in the differential vulnerability to ischemia. | 25,248,834 | [
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IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice. | Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype. | 25,248,835 | [
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Eflornithine (DFMO) prevents progression of pancreatic cancer by modulating ornithine decarboxylase signaling. | Ornithine decarboxylase (ODC) is the key rate-limiting enzyme in the polyamine synthesis pathway and it is overexpressed in a variety of cancers. We found that polyamine synthesis and modulation of ODC signaling occurs at early stages of pancreatic precursor lesions and increases as the tumor progresses in Kras-activated p48(Cre/+)-LSL-Kras(G12D/+) mice. Interest in use of the ODC inhibitor eflornithine (DFMO) as a cancer chemopreventive agent has increased in recent years since ODC was shown to be transactivated by the c-myc oncogene and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. We tested the effects of DFMO on pancreatic intraepithelial neoplasias (PanIN) and their progression to pancreatic ductal adenocarcinoma (PDAC) in genetically engineered Kras mice. The Kras(G12D/+) mice fed DFMO at 0.1% and 0.2% in the diet showed a significant inhibition (P < 0.0001) of PDAC incidence compared with mice fed control diet. Pancreatic tumor weights were decreased by 31% to 43% (P < 0.03-0.001) with both doses of DFMO. DFMO at 0.1% and 0.2% caused a significant suppression (27% and 31%; P < 0.02-0.004) of PanIN 3 lesions (carcinoma in situ). DFMO-treated pancreas exhibited modulated ODC pathway components along with decreased proliferation and increased expression of p21/p27 as compared with pancreatic tissues derived from mice fed control diet. In summary, our preclinical data indicate that DFMO has potential for chemoprevention of pancreatic cancer and should be evaluated in other PDAC models and in combination with other drugs in anticipation of future clinical trials. | 25,248,858 | [
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Oxidation and reduction processes of platinum nanoparticles observed at the atomic scale by environmental transmission electron microscopy. | Oxidation and reduction of the surfaces of Pt nanoparticles were in situ examined in reactive gases (O2, CO and H2O vapor) by aberration-corrected environmental transmission electron microscopy. Atomic layers of Pt oxides were gradually formed on the surface of Pt nanoparticles at room temperature in O2. The surface Pt oxides were reduced to Pt promptly in both vacuum and gas including CO. We showed that H2O vapor suppressed the surface oxidation. The processes found in this study were induced by gases that were most likely activated by electron irradiation. The observation results provide atomistic insight into the oxidation and reduction process of the surface of Pt nanoparticles that is exposed to activated gases. | 25,248,870 | [
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[Development of novel immunotherapy targeting cancer immune evasion]. | Immunotherapy has been developed as an innovative medical intervention against advanced cancer that is refractory to conventional therapies. In recent years, there have been significant advances in our basic knowledge of tumor immunology and ample experience with the clinical application of novel cancer immunotherapies. Accordingly, many of the molecular and cellular mechanisms of the interaction between cancer cells and the immune system have been elucidated. At the initial stage of cancer occurrence, the immune system constantly surveys for the emergence of cancerous cells in order to eliminate them. For cancers that have evaded immune surveillance, the immune system generates anti-tumor responses by recognizing tumor- associated antigens. In response to such immunological pressure, cancer cells edit their immunogenicity and create immunosuppressive conditions in the tumor microenvironment, resulting in cancer immune evasion. Therefore, in order to achieve effective immunotherapy, it is imperative to inactivate mechanisms used by cancer cells to evade and suppress immune responses. In this article, immune checkpoint blockade, one of the most attractive approaches in cancer immunotherapy, will be discussed. | 25,248,888 | [
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[A case of successful treatment of hepatocellular carcinoma lumbar metastasis by surgery, chemotherapy, and radiation]. | The incidence of bone metastasis in patients with hepatocellular carcinoma (HCC) has reportedly been increasing. We report a progressive case that presented with a solitary HCC lumbar metastasis. A 44-year-old man was referred to us from a local clinic with a complaint of a painful lump. He was diagnosed with HCC due to liver cirrhosis and lumbar metastasis by contrast abdominal computerized tomography and magnetic resonance imaging. Then, he received radiation therapy (3 Gy/ time; total, 39 Gy) and zoledronate. Furthermore, transcatheter arterial embolization and posterior lumbar spinal fusion were performed to treat the lumbar metastasis. This decreased his pain and oxycodone was no longer required. In conclusion, for HCC patients with bone metastasis, combined treatment with radiation, zoledronate, and surgery, may possibly improve their quality of life resulting in a long clinical course. | 25,248,899 | [
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How thermally activated deformation starts in metallic glass. | The studies on dynamics and deformation in glassy materials are particularly challenging because of their strongly disordered atomic structure. Here, by probing the changes in the atomic displacements and stresses at saddle points of the potential energy landscape, we show that thermally activated deformation is triggered by subnano-scale rearrangements of a small number of atoms, typically less than 10 atoms. The individual triggers are invariant of the cooling history or elastic structure of the system. However, the organizations between different trigger centres can be varied and are related to the overall stability of the system. This finding allows a semi-quantitative construction of the potential energy landscape and brings a new perspective to the study of the mechanical properties of glasses. | 25,248,915 | [
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Effects of Training of Affect Recognition on the recognition and visual exploration of emotional faces in schizophrenia. | Schizophrenia patients have impairments in facial affect recognition and display scanpath abnormalities during the visual exploration of faces. These abnormalities are characterized by fewer fixations on salient feature areas and longer fixation durations. The present study investigated whether social-cognitive remediation not only improves performance in facial affect recognition but also normalizes patients' gaze behavior while looking at faces. Within a 2 × 2-design (group × time), 16 schizophrenia patients and 16 healthy controls performed a facial affect recognition task with concomitant infrared oculography at baseline (T0) and after six weeks (T1). Between the measurements, patients completed the Training of Affect Recognition (TAR) program. The influence of the training on facial affect recognition (percent of correct answers) and gaze behavior (number and mean duration of fixations into salient or non-salient facial areas) was assessed. In line with former studies, at baseline patients showed poorer facial affect recognition than controls and aberrant scanpaths, and after TAR facial affect recognition was improved. Concomitant with improvements in performance, the number of fixations in feature areas ('mouth') increased while fixations in non-feature areas ('white space') decreased. However, the change in fixation behavior did not correlate with the improvement in performance. After TAR, patients pay more attention to facial areas that contain information about a displayed emotion. Although this may contribute to the improved performance, the lack of a statistical correlation implies that this factor is not sufficient to explain the underlying mechanism of the treatment effect. | 25,248,938 | [
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A first principles scanning tunneling potentiometry study of an opaque graphene grain boundary in the ballistic transport regime. | We report on a theoretical interpretation of scanning tunneling potentiometry (STP), formulated within the Keldysh non-equilibrium Green's function description of quantum transport. By treating the probe tip as an electron point source/sink, it is shown that this approach provides an intuitive bridge between existing theoretical interpretations of scanning tunneling microscopy and STP. We illustrate this through ballistic transport simulations of the potential drop across an opaque graphene grain boundary, where atomistic features are predicted that might be imaged through high resolution STP measurements. The relationship between the electrochemical potential profile measured and the electrostatic potential drop across such a nanoscale defect is also explored in this model system. | 25,248,965 | [
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Role of primary closure after transoral robotic surgery for tonsillar cancer. | This study was performed to verify the efficacy and feasibility of primary closure for communication defects in the neck after transoral robotic surgery (TORS) for tonsillar cancer, and to verify the necessity of en bloc resection, which can create communication defects during TORS. We applied a new primary closure technique in 13 cases of tonsillar cancer showing a communication defect with the neck after en bloc resection during TORS. This technique is composed of three steps: (1) suturing the remaining superior pharyngeal constrictor muscle and extrinsic tongue muscle complex; (2) suturing the digastric and mylohyoid muscles; and (3) securing reinforcement of the digastric-mylohyoid complex. We analyzed the medical records and pathology reports of these cases. On pathology review, 69.2% of the patients developed invasion of the constrictor muscle. The mean defect size was 3.3 cm; the largest defect was 4.5 cm in diameter. In all patients, primary closure of the defect was possible. With regard to functional results, decannulation was possible within 1 week, oral feeding was possible within 9 days, and none of the patients showed pharyngocutaneous fistula formation. Two patients developed complications independent of the surgery itself. The invasion rate of the pharyngeal constrictor muscle is high. Therefore, en bloc resection creating a communication defect during TORS should be considered in all cases of tonsillar cancer to secure safe margins. In addition, with our primary closure technique, even large defects can be closed without complication and with good preservation of function. | 25,248,970 | [
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Perceived Rewards of Nursing Among Christian Nursing Students in Bangalore, India. | Nurses in India face significant challenges and often migrate to practice nursing abroad. Few studies have focused on the rewards of nursing in India. The aim of this study was to illuminate perceived rewards of nursing among Christian student nurses in Bangalore, India. Photovoice, a participatory action methodology was used, and 14 Christian student nurses participated in the study. Thematic interpretation of photographs, journals, critical group dialog sessions, and observational field notes resulted in the identification of two main themes. These themes included intrinsic rewards and lifelong benefits of nursing in India. | 25,248,979 | [
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Fragmentation of the quinoxaline N-oxide bond to the ˙OH radical upon one-electron bioreduction. | The ˙OH radical is released from 3-trifluoromethyl-quinoxaline 1,4-dioxides upon one-electron reduction by cytochrome P450 oxidoreductase. This process effectively competes with back oxidation of the intermediate radical anion by oxygen and underlies the increased aerobic cytotoxicity of such compounds compared to that seen for the related clinical bioreductive benzotriazine drug, tirapazamine. | 25,248,989 | [
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Mineral composition of the sugarcane juice and its influence on the ethanol fermentation. | In the present work, we evaluated the mineral composition of three sugarcane varieties from different areas in northeast Brazil and their influence on the fermentation performance of Saccharomyces cerevisiae. The mineral composition was homogeneous in the different areas investigated. However, large variation coefficients were observed for concentrations of copper, magnesium, zinc and phosphorus. Regarding the fermentation performances, the sugarcane juices with the highest magnesium concentration showed the highest ethanol yield. Synthetic media supplemented with magnesium also showed the highest yield (0.45 g g(-1)) while the excess of copper led to the lowest yield (0.35 g g(-1)). According to our results, the magnesium is the principal responsible for the increase on the ethanol yield, and it also seems to be able to disguise the inhibitory effects of the toxic minerals present in the sugarcane juice. | 25,248,994 | [
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Expression of ORAII, a plasma membrane resident subunit of the CRAC channel, in rodent and non-rodent species. | We determined the expression of ORAI1 protein in rodent and non-rodent tissues using a monoclonal antibody directed against an extracellular loop of the protein. Previous reports using antibodies directed at the C-terminus of ORAI1 have not detected central nervous system (CNS) expression. Our results demonstrate broad tissue expression that includes the CNS using a unique monoclonal antibody specific to an extracellular loop of ORAI1. In addition, we present in situ hybridization (ISH) results using a probe within the middle of the mouse coding region showing CNS expression of Orai1 RNA. We contrast the patterns of rodent and human tissue expression and conclude that rodents have similar expression of ORAI1 in most tissue types when compared to primates, with an important exception being the male reproductive system, where human-specific expression is observed. | 25,249,026 | [
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Four centuries on from Bacon: progress in building health research systems to improve health systems? | In 1627, Francis Bacon's New Atlantis described a utopian society in which an embryonic research system contributed to meeting the needs of the society. In this editorial, we use some of the aspirations described in New Atlantis to provide a context within which to consider recent progress in building health research systems to improve health systems and population health. In particular, we reflect on efforts to build research capacity, link research to policy, identify the wider impacts made by the science, and generally build fully functioning research systems to address the needs identified. In 2014, Health Research Policy and Systems has continued to publish one-off papers and article collections covering a range of these issues in both high income countries and low- and middle-income countries. Analysis of these contributions, in the context of some earlier ones, is brought together to identify achievements, challenges and possible ways forward. We show how 2014 is likely to be a pivotal year in the development of ways to assess the impact of health research on policies, practice, health systems, population health, and economic benefits.We demonstrate how the increasing focus on health research systems will contribute to realising the hopes expressed in the World Health Report, 2013, namely that all nations would take a systematic approach to evaluating the outputs and applications resulting from their research investment. | 25,249,030 | [
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Pharmacotherapy of type 2 diabetes mellitus: an update on drug-drug interactions. | The incidence of type 2 diabetes mellitus is increasing rapidly, as are the associated co-morbidities. Consequently, it has become necessary for a diabetic patient to take multiple medications at the same time to delay progression of the disease. This can put patients at an increased risk of moderate to severe drug interactions, which may threaten patients' life or may deteriorate the quality of their life. Hence, managing drug-drug interactions is the cornerstone of anti-diabetic therapy. Most of the clinically important drug-drug interactions of anti-diabetic agents are related to their metabolic pathways, but drugs that compete for renal excretion or impair renal status can also play an important role. In this review, we have examined the clinical implications and underlying mechanisms of drugs that are likely to alter the pharmacologic response of or cause adverse events with antidiabetic drugs, and we have outlined safe and efficacious treatment modalities. | 25,249,046 | [
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Innovations in non-communicable diseases management in ASEAN: a case series. | Non-communicable diseases (NCDs) are reaching epidemic proportions worldwide and present an unprecedented challenge to economic and social development globally. In Southeast Asia, the challenges are exacerbated by vastly differing levels of health systems development and funding availability. In addressing the burden of NCDs, ASEAN nations need to fundamentally re-examine how health care services are structured and delivered and discover new models as undiscerning application of models from other geographies with different cultures and resources will be problematic. We sought to examine cases of innovation and identify critical success factors in NCD management in ASEAN. A qualitative design, focusing on in-depth interviews and site visits to explore the meanings and perceptions of participants regarding innovations in NCD against the backdrop of the overall context of delivering health care within the country's context was adopted. In total 12 case studies in six ASEAN countries were analysed. Primary interventions accounted for five of the total cases, whereas secondary interventions comprised four, and tertiary interventions three. Five core themes contributing to successful innovation for NCD management were identified. They include: 1) encourage better outcomes through leadership and support, 2) strengthen inter-disciplinary partnership, 3) community ownership is key, 4) recognise the needs of the people and what appeals to them, and 5) raise awareness through capacity building and increasing health literacy. Innovation is vital in enabling ASEAN nations to successfully address the growing crisis of NCDs. More of the same or wholesale transfers of developed world models will be ineffective and lead to financially unsustainable programmes or programmes lacking appropriate human capital. The case studies have demonstrated the transformative impact of innovation and identified key factors in successful implementation. Beyond pilot success, the bigger challenge is scaling up. Medical technologies are crucial but insufficient; passionate and engaged leaders and communities enabled by enlightened policy makers and funding agencies matter more. | 25,249,061 | [
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The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study. | Histamine plays important roles in inflammation and nervous irritability in allergic disorders, including atopic dermatitis (AD). It has been shown to regulate the expression of pruritic factors, such as nerve growth factor and semaphorin 3A, in skin keratinocytes via histamine H1 receptor (H1R). Furthermore, H1R antagonist reduced the level of IL-31, a cytokine involving the skin barrier and pruritus, in chronic dermatitis lesions in NC/Nga mice and patients with AD. Histamine plays roles in the induction of allergic inflammation by activating eosinophils, mast cells, basophils, and Th2 cells via histamine H4 receptor (H4R). H4R, in addition to H1R, is expressed on sensory neurons, and a decrease in scratching behaviors was observed in H4R-deficient mice and mice treated with a H4R antagonist. We found that the combined administration of H1R and H4R antagonists inhibited the itch response and chronic allergic inflammation, and had a pharmacological effect similar to that of prednisolone. Although the oral administration of H1R antagonists is widely used to treat AD, it is not very effective. In contrast, JNJ39758979, a novel H4R antagonist, had marked effects against pruritus in Japanese patients with AD in a phase II clinical trial. Next generation antihistaminic agents possessing H1R and H4R antagonistic actions may be a potent therapeutic drug for AD. | 25,249,063 | [
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Clinical and laboratory characteristics that differentiate hereditary angioedema in 72 patients with angioedema. | Hereditary angioedema (HAE) is a rare but life-threatening condition that results from mutations in C1-inhibitor (C1-INH). Since distinguishing HAE from other causes of angioedema (AE) is a critical problem in emergencies, the objective of the present study was to clarify the differences between HAE and other forms of AE. Seventy-two patients with AE were enrolled in this study. The medical history and laboratory data of patients with HAE at the first visit were compared to those with other types of AE. Subjects included 23 patients with HAE, 33 with mast cell-mediated AE, 5 with drug-induced AE and 11 with idiopathic AE. The average age of HAE onset (19.5 ± 8.0 years old) was significantly lower than in other groups. A family history of AE was noted in 82.6% of HAE patients, which was significantly higher than other groups. Swelling affecting the extremities and gastrointestinal (GI) tract was observed in the majority (60 to 80%) of HAE patients. Life threatening laryngeal edema was observed in 30.4% of HAE patients. In 95.6% of HAE patients serum levels of C4 were less than the lower limit of the normal range. In our subjects, the sensitivity and specificity of low C4 for HAE were 95.6% and 93.8%, respectively. Early onset of AE, positive family history, recurrent AE in the extremities and GI tract, and suffocation are distinctive characteristics of HAE. A low serum level of C4 is a useful marker for making a differential diagnosis of HAE. | 25,249,065 | [
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Quality of life assessment after peroral endoscopic myotomy. | Peroral Endoscopic Myotomy (POEM) is a promising treatment option for motor disorders of the esophagus. The purpose of this study was to assess quality of life (QOL) postoperatively. All patients who presented to our institution for surgical treatment of achalasia after 2011 were asked to complete QOL (SF-36), dysphagia, reflux severity index, and GERD questionnaires in clinic preoperatively and postoperatively at approximately 3 weeks, 6 months, and 1 year. Those patients who underwent a POEM procedure (n = 37) demonstrated a significant improvement in dysphagia scores, reflux severity scores, and GERD scores (p < 0.05) at each time point. SF-36 questionnaires specifically demonstrated a significant improvement in several concepts. At 3 weeks, emotional well-being scores were significantly higher (p = 0.006). At 6 months, the following concepts were significantly higher: emotional well-being (p = 0.039), social functioning (p = 0.038), and general health (p = 0.029). At 1 year, the following concepts were significantly higher: role limitations due to physical health (p = 0.001) and social functioning (p = 0.002). There is a significant improvement in several measures of QOL after POEM, which is comparable to that seen after laparoscopic Heller myotomy. | 25,249,144 | [
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[Investigation of the use of triclosan in patients with indwelling catheters: a randomized, double blind, multicenter, placebo-controlled clinical study]. | This article presents the first randomized, double blind, multicenter, placebo-controlled, non-interventional trial with a medical product after approval by the ethical committee of the medical council of North-Rhine. The study investigated the use of the antimicrobial agent triclosan (Farco-fill® Protect) as a liquid for inflation of catheter balloons in patients with chronic indwelling catheters. In this study 84 patients were investigated (43 in the treatment group and 41 in the placebo group) all with a suprapubic catheter and a positive history of catheter incrustation. The catheters were changed after 6 weeks and endpoints were the quantitative analysis of the incrustation, weight of the catheter, pain during catheter change and the number of urinary tract infections. The maintenance of the catheter was a secondary endpoint. The primary endpoint could not be reached because the study, which was initially planned with 70 patients in each arm, had to be terminated due to logistical and technical problems with the catheter weighing. The maintenance of the catheter as the most important clinical parameter showed statistically significant differences with a longer indwelling time in the triclosan group. Adverse events with respect to the product were not recorded. Using the antimicrobial solution triclosan as a fluid for inflation of catheter balloons led to a statistically significant extension in the catheter indwelling time. The reduction of pain during changing the catheter and the reduction of incrustation, although not statistically significant, led to an improvement in the quality of life of these patients. | 25,249,158 | [
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Comparative community-level associations of helminth infections and microparasite shedding in wild long-tailed macaques in Bali, Indonesia. | Helminthes have the capacity to modulate host immunity, leading to positive interactions with coinfecting microparasites. This phenomenon has been primarily studied during coinfections with a narrow range of geo-helminthes and intracellular microparasites in human populations or under laboratory conditions. Far less is known regarding differences in coinfection dynamics between helminth types, the range of microparasites that might be affected or the overall community-level effects of helminth infections on microparasites in wild systems. Here, we analysed the presence/absence and abundance patterns of enteric parasites in long-tailed macaques (Macaca fascicularis) on the island of Bali, Indonesia, to assess whether naturally occurring helminth infections were associated with increased shedding of the most common intracellular (Cryptosporidium spp., Isospora spp.) and extracellular (Entamoeba spp., Giardia spp.) microparasites. We also comparatively assessed the statistical correlations of different helminth taxa with microparasite shedding to determine if there were consistent relationships between the specific helminth taxa and microparasites. Helminth infections were associated with increased shedding of both intracellular and extracellular microparasites. Platyhelminthes repeatedly displayed strong positive correlations with several microparasites; while nematodes did not. Our results indicate that helminthes can influence microparasite community shedding dynamics under wild conditions, but that trends may be driven by a narrow range of helminthes. | 25,249,163 | [
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Cognitive consequences of overweight and obesity in the ninth decade of life? | the association between late-life obesity and late-life cognitive abilities is poorly understood. We studied the association between body mass index (BMI) and cognitive change in longitudinal population-based study spanning over the ninth decade of life. in total, 475 participants free of dementia at baseline from the Lothian Birth Cohort 1921 (mean age: 79.1 years, SD: 0.6) were included. Height and weight were assessed at baseline. BMI was calculated as kg/m(2). Cognitive abilities were assessed at age ∼11 years and at age ∼79, ∼83, ∼87 and ∼90 years. latent growth models showed that men being overweight and obese had a 0.65 (SD: 0.3) and 1.10 (SD: 0.5) points less steep decline in general cognitive ability (as measured by the Moray House Test) for each year than people of normal weight. These associations were to some extent confounded by childhood intelligence. No other association between BMI and cognition was significant, either for men or women. People who were obese in old age had significantly lower childhood intelligence (m = 43.6, SD: 1.3) than people who were normal in weight (m = 47.0, SD: 0.8) and persons being overweight (m = 47.5, SD: 0.8), F (472, 3) = 3.2, P = 0.043. the current study shows weak or no evidence for an association between BMI in old age and cognitive function, especially not when childhood intelligence is controlled for. Lower intelligence at the age of 11 years predicted obesity at the age of 79 years. | 25,249,169 | [
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Equilibrium spin current in graphene with Rashba spin-orbit coupling. | The existence of a background spin current under thermodynamic equilibrium is an interesting phenomenon in the two-dimensional electron gas with Rashba spin-orbit coupling (RSOC). Here we study the equilibrium spin current (ESC) in graphene with RSOC. For an infinite graphene with uniform RSOC, we found that the ESC is proportional to λ(2) with λ the Rashba strength and mainly comes from the energy window [-λ, λ] near Dirac points. In the regime of energy far away from Dirac points, the λ(3) dependence as that in a normal two-dimensional electron gas is recovered. In a system with a normal graphene strip inserted between two Rashba graphene sheets, we found that the ESC can penetrate through the normal graphene layer (perpendicular to the interface). This unique effect can be understood by considering the spin-filtered scattering from the normal region to the RSOC region. The finding of the ESC through the normal region without RSOC advances the understanding of ESC and provides a new way to generate a pure spin current in graphene. For an experimentally accessible strength of Rashba spin-orbit coupling, the ESC remains over room temperature. | 25,249,215 | [
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Caecum lipoma: a rare cause of lower gastrointestinal bleeding. | Gastrointestinal bleeding caused by benign tumours of the colon is rare. A 70-year-old woman with a significant medical history of diabetes, hypertension and ischaemic heart disease was presented in consultation with marked anaemia secondary to lower gastrointestinal bleeding with a right colonic tumour found by CT. The patient underwent a right colectomy without complications. Histopathological examination revealed a 4 cm transmural caecum lipoma with mucosal ulceration. The patient is asymptomatic without anaemia at 6 months follow-up. | 25,249,223 | [
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Systematic review and meta-analysis of effects of foot orthoses on pain and disability in rheumatoid arthritis patients. | This meta-analysis examined the effects of foot orthoses (FO) on pain and disability in rheumatoid arthritis (RA) patients. MEDLINE, Cochrane Controlled Trials Register, EMBASE, SPORT Scielo, and CINAHL were searched through July 2014 for randomized controlled trials (RCTs) examining the effects of orthoses on pain and disability in RA patients. Two reviewers selected studies independently. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I(2) test. Three studies, involving 110 patients who received FO and 108 control patients, met the study criteria. Relative to controls, FO had a positive impact on pain (WMD 0.40; 95% CI 0.04-0.57). Between group differences in disability were not statistically significant. FO may improve pain in RA patients, but their impact on disability remains undetermined. Additional large RCTs are needed to investigate the effects of these devices in RA patients. Implications for Rehabilitation The use of foot orthoses (FO) often part of the conservative treatment of patients with rheumatoid arthritis (RA). However, the indication of these devices is usually empiric. Thus, the results of this meta-analysis can provide guidance to rehabilitation professionals to undertake these devices to therapeutic programs. There is no consensus among rehabilitation professionals regarding the efficacy of FO improved pain and disability in patients with RA. The results of this meta-analysis suggest that the use of the FO improves pain but has no impact on disability. Thus, rehabilitation professionals, from reading this article will make clear to their patients that benefit of the FO is exclusively in pain improvement. Healthcare professionals and organizations should take into account the costs of production of FO during the definition of the therapeutic program. In case of low cost, the effect on improvement of pain in the feet can justify the indication of these devices to a patient with RA. | 25,249,238 | [
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Effect of iron oxide loading on magnetoferritin structure in solution as revealed by SAXS and SANS. | Synthetic biological macromolecule of magnetoferritin containing an iron oxide core inside a protein shell (apoferritin) is prepared with different content of iron. Its structure in aqueous solution is analysed by small-angle synchrotron X-ray (SAXS) and neutron (SANS) scattering. The loading factor (LF) defined as the average number of iron atoms per protein is varied up to LF=800. With an increase of the LF, the scattering curves exhibit a relative increase in the total scattered intensity, a partial smearing and a shift of the match point in the SANS contrast variation data. The analysis shows an increase in the polydispersity of the proteins and a corresponding effective increase in the relative content of magnetic material against the protein moiety of the shell with the LF growth. At LFs above ∼150, the apoferritin shell undergoes structural changes, which is strongly indicative of the fact that the shell stability is affected by iron oxide presence. | 25,249,246 | [
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Description of robotically assisted single-site transabdominal preperitoneal (RASS-TAPP) inguinal hernia repair and presentation of clinical outcomes. | The aim of our study is to report our initial clinical experience with robotically assisted single-site transabdominal preperitoneal (RASS-TAPP) hernia repair, to verify the safety and efficacy of the procedure and to describe the surgical procedure. We retrospectively reviewed all patients undergoing RASS-TAPP at our institution from March 2013 through December 2013. Data regarding patient demographics, type and location of hernia, operative time and clinical outcomes were collected and analyzed. Fourty five hernias were repaired in 34 patients (30M, 4F) by a single surgeon. The mean age was 49.3 years and mean BMI was 26.5. 31 lateral defects, 13 medial defects and 1 femoral defect were repaired. Three patients presented with recurrent hernias and nine had bilateral defects. The mean operative time for all cases was 80.5 min and for all unilateral hernias 69 min. Considering just the unilateral hernias without any additional procedures, operative time was 63 min. The mean follow-up time was 5.5 months. There has been one superficial surgical site infection, but no observed clinical recurrence or neuralgia to date. Robotically assisted single-site transabdominal preperitoneal hernia repair is safe and effective. The absence of clinical evidence of recurrence or neuralgia is encouraging and should promote further study. | 25,249,251 | [
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Synthesis and influenza virus inhibitory activities of carbosilane dendrimers peripherally functionalized with hemagglutinin-binding Peptide. | A series of carbosilane dendrimers uniformly functionalized with hemagglutinin (HA) binding peptide (sialic acid-mimic peptide, Ala-Arg-Leu-Pro-Arg) was systematically synthesized, and their anti-influenza virus activity was evaluated. The carbosilane-based peptide dendrimers, unlike sialylated dendrimers, cannot be digested by virus neuraminidases. The peptide dendrimers exhibited intriguing biological activities depending on the form of their core frame, with a dumbbell-type peptide dendrimer showing particularly strong inhibitory activities against two human influenza viruses, A/PR/8/34 (H1N1) and A/Aichi/2/68 (H3N2). The IC50 values of the dumbbell-type peptide dendrimer for both strains were 0.60 μM, the highest activity among the HA-binding peptide derivatives. The results suggest that a dumbbell-shaped carbosilane dendrimer is the most suitable core scaffold for HA-binding peptide dendrimers. | 25,249,262 | [
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Cyclodextrin-functionalized chromatographic materials tailored for reversible adsorption. | Novel dendronized silica substrates were synthesized. First- and second- generation polyaryl ether dendrons were appended to silica surfaces. Using Cu(I) mediated cycloaddition "click" chemistry, β-cyclodextrin was tethered to the dendronized surfaces and to a nondendronized surface for comparison purposes. This synthesis strategy affords a modular, versatile method for surface functionalization in which the density of functional groups can be readily varied by changing the generation of dendron used. The surfaces, which are capable of adsorbing target analytes, have been characterized and studied using X-ray photoelectron spectroscopy (XPS) and vibrational sum frequency spectroscopy (VSFS). Fluorescence spectroscopy was used to study the surfaces' ability to retain coumarin 152 (C152). These studies indicated that the β-cyclodextrin functionalized surfaces not only adsorbed C152 but also retained it through multiple aqueous washes. Furthermore, these observations were quantified and show that substrates functionalized with first-generation dendrons have a more than 6 times greater capacity to adsorb C152 than slides functionalized with monomeric β-cyclodextrin. The first-generation dendrons also have 2 times greater the capacity than the larger generation dendrons. This result is explained by describing a dendron that has an increased number of β-cyclodextrin monomers but, when covalently bound to silica, has a footprint too large to optimize the number of accessible monomers. Overall, both dendronized surfaces demonstrated an increased capacity to adsorb targeted analytes over the slides functionalized with monomeric β-cyclodextrin. The studies reported provide a methodology for characterizing and evaluating the properties of novel, highly functional surfaces. | 25,249,268 | [
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Modeling the implementation of universal coverage for HIV treatment as prevention and its impact on the HIV epidemic. | The Joint United Nations Programme on HIV/AIDS (UNAIDS) recently updated its global targets for antiretroviral therapy (ART) coverage for HIV-positive persons under which 90 % of HIV-positive people are tested, 90 % of those are on ART, and 90 % of those achieve viral suppression. Treatment policy is moving toward treating all HIV-infected persons regardless of CD4 cell count-otherwise known as treatment as prevention-in order to realize the full therapeutic and preventive benefits of ART. Mathematical models have played an important role in guiding the development of these policies by projecting long-term health impacts and cost-effectiveness. To guide future policy, new mathematical models must consider the barriers patients face in receiving and taking ART. Here, we describe the HIV care cascade and ART delivery supply chain to examine how mathematical modeling can provide insight into cost-effective strategies for scaling-up ART coverage in sub-Saharan Africa and help achieve universal ART coverage. | 25,249,293 | [
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Survival analysis of postoperative nausea and vomiting in patients receiving patient-controlled epidural analgesia. | Postoperative nausea and vomiting as well as postoperative pain are two major concerns when patients undergo surgery and receive anesthetics. Various models and predictive methods have been developed to investigate the risk factors of postoperative nausea and vomiting, and different types of preventive managements have subsequently been developed. However, there continues to be a wide variation in the previously reported incidence rates of postoperative nausea and vomiting. This may have occurred because patients were assessed at different time points, coupled with the overall limitation of the statistical methods used. However, using survival analysis with Cox regression, and thus factoring in these time effects, may solve this statistical limitation and reveal risk factors related to the occurrence of postoperative nausea and vomiting in the following period. In this retrospective, observational, uni-institutional study, we analyzed the results of 229 patients who received patient-controlled epidural analgesia following surgery from June 2007 to December 2007. We investigated the risk factors for the occurrence of postoperative nausea and vomiting, and also assessed the effect of evaluating patients at different time points using the Cox proportional hazards model. Furthermore, the results of this inquiry were compared with those results using logistic regression. The overall incidence of postoperative nausea and vomiting in our study was 35.4%. Using logistic regression, we found that only sex, but not the total doses and the average dose of opioids, had significant effects on the occurrence of postoperative nausea and vomiting at some time points. Cox regression showed that, when patients consumed a higher average dose of opioids, this correlated with a higher incidence of postoperative nausea and vomiting with a hazard ratio of 1.286. Survival analysis using Cox regression showed that the average consumption of opioids played an important role in postoperative nausea and vomiting, a result not found by logistic regression. Therefore, the incidence of postoperative nausea and vomiting in patients cannot be reliably determined on the basis of a single visit at one point in time. | 25,249,302 | [
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Effect of milrinone therapy on splanchnic perfusion after heart transplantation. | Milrinone is a selective inhibitor of the cAMP-specific phosphodiesterase III isoenzyme in myocardium and vascular smooth muscle. Milrinone administration following heart transplantation is routine practice. The purpose of this study was to evaluate the influence of milrinone therapy on splanchnic perfusion following heart transplantation. There were 12 patients (10 males and 2 females) with a mean age of 42 ± 12 who underwent heart transplantation. Milrinone parenteral following surgery was started after surgery and continued for the next 67 ± 4 h. Repeated Swann-Ganz measurements and control transthoracic echocardiography were performed. Blood samples were taken to estimate level of lactic acid (LA), liver transaminases, serum amylase, and GFR ratio. The mean time of milrinone administration was 67 ± 4 h. The serum LA increase following milrinone discontinuation was 1.7 ± 0.7 mmol/dm(3) vs. 3.8 ± 0.9 mmol/dm(3), (p<0.0001). The serum AST increase following milrinone discontinuation was 79 ± 30 IU/L vs. 135 ± 55 IU/L, p<0.04). We found a significant increase of blood ALT (29 ± 9 IU/L vs. 60 ± 23 IU/L) (p<0.0002) after milrinone withdrawn. There was a progressive increase in serum amylase levels after milrinone was withdrawn (80.6 ± 29 IU/L vs. 134 ± 45 IU/L, p<0.05). Milrinone withdrawal during the postoperative period was associated with deterioration of splanchnic perfusion, as shown by a transient increase in lactic acid and serum increase of aminotransferases (ALT/ASP) concentration and amylase activity. The study results show the extracardiac effects of milrinone therapy. | 25,249,304 | [
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Surgical removal of intra-abdominal intrauterine devices at one center in a 20-year period. | To review 20 years of experience of the removal of intra-abdominal intrauterine devices (IUDs) and to compare the surgical methods used. In a retrospective study, charts dating from between September 1, 1992, and August 31, 2012, were reviewed. Patients were eligible for inclusion when they had an IUD surgically removed by minilaparotomy or laparoscopy at a tertiary referral center in Izmir, Turkey. Among the 36 eligible women, 18 (50%) had undergone laparoscopy and 18 (50%) had undergone minilaparotomy. Mean operation length was 55.3±6.3 minutes in the laparoscopy group and 29.1±4.2 minutes in the minilaparotomy group (P=0.008). Conversion to full laparotomy was necessary in 4 (22%) women in the laparoscopy group and 1 (6%) in the minilaparotomy group (P=0.02). Perioperative complications were observed in 5 (14%) women, with no difference in frequency between groups (P=0.09). Total cost of medical/surgical procedures was US$436.4±35.4 for the laparoscopy group and $323.4±21.3 for the minilaparotomy group (P=0.04). Minilaparotomy seems to be an important alternative to laparoscopy for the removal of intra-abdominal IUDs. This procedure should be an integral part of gynecologic surgical training. | 25,249,316 | [
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Benign breast tissue composition in breast cancer patients: association with risk factors, clinical variables, and gene expression. | Breast tissue composition (epithelium, non-fatty stroma, and adipose) changes qualitatively and quantitatively throughout the lifespan, and may mediate relationships between risk factors and breast cancer initiation. We sought to identify relationships between tissue composition, risk factors, tumor characteristics, and gene expression. Participants were 146 patients from the Polish Breast Cancer Study, with data on risk factor and clinicopathological characteristics. Benign breast tissue composition was evaluated using digital image analysis of histologic sections. Whole-genome microarrays were performed on the same tissue blocks. Mean epithelial, non-fatty stromal, and adipose proportions were 8.4% (SD = 4.9%), 27.7% (SD = 24.0%), and 64.0% (SD = 24.0%), respectively. Among women <50 years old, stroma proportion decreased and adipose proportion increased with age, with approximately 2% difference per year (P < 0.01). The variation in epithelial proportion with age was modest (0.1% per year). Higher epithelial proportion was associated with obesity (7.6% in nonobese vs. 10.1% in obese; P = 0.02) and with poorly differentiated tumors (7.8% in well/moderate vs. 9.9% in poor; P = 0.05). Gene expression signatures associated with epithelial and stromal proportion were identified and validated. Stroma-associated genes were in metabolism and stem cell maintenance pathways, whereas epithelial genes were enriched for cytokine and immune response pathways. Breast tissue composition was associated with age, body mass index, and tumor grade, with consequences for breast gene expression. Breast tissue morphologic factors may influence breast cancer etiology. Composition and gene expression may act as biomarkers of breast cancer risk and progression. | 25,249,325 | [
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Stone disease in pregnancy: imaging-guided therapy. | Renal colic is the most frequent nonobstetric cause for abdominal pain and subsequent hospitalization during pregnancy. The physio-anatomical changes in the urinary tract and the presence of the fetus may complicate the clinical presentation and management of nephrolithiasis. Ultrasound (US) is the primary radiological investigation of choice. Magnetic resonance urography (MRU) and low-dose computed tomography (CT) have to be considered as a second- and third-line test, respectively. If a study that uses ionizing radiation has to be performed, the radiation dose to the fetus should be as low as possible. The initial management of symptomatic ureteric stones is conservative during pregnancy. Intervention will be necessary in patients who do not respond to conservative measures. Therefore, it is crucial to obtain a prompt and accurate diagnosis to optimize the management of these patients. Teaching Points • In pregnancy, renal colic is the most frequent nonobstetric cause for abdominal pain and hospitalization. • Magnetic resonance urography should be considered when ultrasound is nondiagnostic. • Low-dose CT should be considered as a last-line test during pregnancy. | 25,249,333 | [
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Cellular and subcellular localization of cholecystokinin (CCK)-1 receptors in the pancreas, gallbladder, and stomach of mice. | Information concerning the cellular localization of cholecystokinin (CCK)-1 receptors has been discrepant and remained scanty at ultrastructural levels. The present immunohistochemical study at light and electron microscopic levels revealed the distinct localization of CCK1 receptors in visceral organs. Immunohistochemistry by use of a purified antibody against mouse CCK1 receptor was applied to fixed tissue sections of the pancreas, gallbladder, stomach, and intestine of mice. A silver-intensified immunogold method revealed the subcellular localization under electron microscope. The immunoreactivity for CCK1 receptors was selectively found in the basolateral membrane of pancreatic acinar cells and gastric chief cells but was absent in pancreatic islets and gastric D cells. Another intense expression in the gut was seen in the myenteric nerve plexus of the antro-duodenal region and some populations of c-Kit-expressing pacemaker cells in the duodenal musculature. The gallbladder contained smooth muscle fibers with an intense immunoreactivity of CCK1 receptors on cell surfaces. The restricted localization of CCK1 receptors on the basolateral membrane of pancreatic acinar cells and gastric chief cells, along with their absence in the islets of Langerhans and gastric D cells, provides definitive information concerning the regulatory mechanism by circulating CCK. Especially, the subcellular localization in the acinar cells completes the investigation for the detection of circulating CCK by the basolateral membrane. | 25,249,350 | [
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Cytokine gene variations associated with trait and state anxiety in oncology patients and their family caregivers. | Anxiety is common among cancer patients and their family caregivers (FCs) and is associated with poorer outcomes. Recently, associations between inflammation and anxiety were identified. However, the relationship between variations in cytokine genes and anxiety warrants investigation. Therefore, phenotypic and genotypic characteristics associated with trait and state anxiety were evaluated in a sample of 167 oncology patients with breast, prostate, lung, or brain cancer and 85 of their FCs. Using multiple regression analyses, the associations between participants' demographic and clinical characteristics as well as variations in cytokine genes and trait and state anxiety were evaluated. In the bivariate analyses, a number of phenotypic characteristics were associated with both trait and state anxiety (e.g., age, functional status). However, some associations were specific only to trait anxiety (e.g., number of comorbid conditions) or state anxiety (e.g., participation with a FC). Variations in three cytokine genes (i.e., interleukin (IL) 1 beta, IL1 receptor 2 (IL1R2), nuclear factor kappa beta 2 (NFKB2)) were associated with trait anxiety, and variations in two genes (i.e., IL1R2, tumor necrosis factor alpha (TNFA)) were associated with state anxiety. These findings suggest that both trait and state anxiety need to be assessed in oncology patients and their FCs. Furthermore, variations in cytokine genes may contribute to higher levels of anxiety in oncology patients and their FCs. | 25,249,351 | [
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Successful catheter ablation of a left anterior accessory pathway from the non-coronary cusp of the aortic valve. | Left anterior accessory pathways are considered to be rare findings. Catheter ablation of accessory pathways in this location remains a challenging target, and few reports about successful ablation of these accessory pathways are available. We describe our experience regarding a case of a manifest left anterior accessory pathway ablation using radiofrequency energy at the junction of the left coronary cusp with the non-coronary cusp. | 25,249,369 | [
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The potential application of personalized preventive research. | With increases in life expectancy, the focus has shifted to living a healthier, longer life. By concentrating on preventing diseases before occurrence, researchers aim to diminish the increasing gap in medical costs and health inequalities prevalent across many nations. Although we have entered an era of post-genomics, we are still in infancy in terms of personalized preventive research. Personalized preventive research has and will continue to improve with advancements in the use of biomarkers and risk assessment. More evidence based on well-designed epidemiologic studies is required to provide comprehensive preventive medical care based on genetic and non-genetic profile data. The realization of personalized preventive research requires building of evidence through appropriate methodology, verification of results through translational studies as well as development and application of prediction models. | 25,249,379 | [
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A functional comparison of conventional knee-ankle-foot orthoses and a microprocessor-controlled leg orthosis system based on biomechanical parameters. | The microprocessor-controlled leg orthosis C-Brace enables patients with paretic or paralysed lower limb muscles to use dampened knee flexion under weight-bearing and speed-adapted control of the swing phase. The objective of the present study was to investigate the new technical functions of the C-Brace orthosis, based on biomechanical parameters. The study enrolled six patients. The C-Brace orthosis is compared with conventional leg orthoses (four stance control orthoses, two locked knee-ankle-foot orthoses) using biomechanical parameters of level walking, descending ramps and descending stairs. Ground reaction forces, joint moments and kinematic parameters were measured for level walking as well as ascending and descending ramps and stairs. With the C-Brace, a nearly natural stance phase knee flexion was measured during level walking (mean value 11° ± 5.6°). The maximum swing phase knee flexion angle of the C-Brace approached the normal value of 65° more closely than the stance control orthoses (66° ± 8.5° vs 74° ± 6.4°). No significant differences in the joint moments were found between the C-Brace and stance control orthosis conditions. In contrast to the conventional orthoses, all patients were able to ambulate ramps and stairs using a step-over-step technique with C-Brace (flexion angle 64.6° ± 8.2° and 70.5° ± 12.4°). The results show that the functions of the C-Brace for situation-dependent knee flexion under weight bearing have been used by patients with a high level of confidence. The functional benefits of the C-Brace in comparison with the conventional orthotic mechanisms could be demonstrated most clearly for descending ramps and stairs. The C-Brace orthosis is able to combine improved orthotic function with sustained orthotic safety. | 25,249,381 | [
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Motor skill learning enhances the expression of activity-regulated cytoskeleton-associated protein in the rat cerebellum. | Motor skill learning is essential for environmental adaptations during everyday life. It has been shown that the cerebellum plays an important role in both the adaptation of eye movements and the motor skill learning. However, the neuronal substrates responsible for consolidation of complex motor skills rather than simple reflexes are still uncertain. Because the induction of immediate-early genes activity-regulated cytoskeleton-associated protein (Arc) and zinc finger binding protein clone 268 (Zif268) has been regarded as a marker for recent neuronal activity, therefore, in the present study, a rat paradigm of motor skill learning was used to investigate the protein expression of Arc and zif268 in the cerebellum after motor skill learning. Rats were trained to traverse the runway apparatus for 5 days. Protein samples were collected from the cerebellar cortices 1 hour after the training on days 1, 3, and 5, and analyzed by western blotting. The results showed that the expression of Arc, but not zif268, was significantly increased in the cerebellum following motor skill learning. These findings suggest that motor skill learning induces Arc expression in the cerebellum, which may play a role in acquiring complex motor skills. | 25,249,385 | [
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Syndemic vulnerability, sexual and injection risk behaviors, and HIV continuum of care outcomes in HIV-positive injection drug users. | Limited investigations have been conducted on syndemics and HIV continuum of care outcomes. Using baseline data from a multi-site, randomized controlled study of HIV-positive injection drug users (n = 1,052), we examined whether psychosocial factors co-occurred, and whether these factors were additively associated with behavioral and HIV continuum of care outcomes. Experiencing one type of psychosocial problem was significantly (p < 0.05) associated with an increased odds of experiencing another type of problem. Persons with 3 or more psychosocial problems were significantly more likely to report sexual and injection risk behaviors and were less likely to be adherent to HIV medications. Persons with 4 or more problems were less likely to be virally suppressed. Reporting any problems was associated with not currently taking HIV medications. Our findings highlight the association of syndemics not only with risk behaviors, but also with outcomes related to the continuum of care for HIV-positive persons. | 25,249,392 | [
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OrthoClust: an orthology-based network framework for clustering data across multiple species. | Increasingly, high-dimensional genomics data are becoming available for many organisms.Here, we develop OrthoClust for simultaneously clustering data across multiple species. OrthoClust is a computational framework that integrates the co-association networks of individual species by utilizing the orthology relationships of genes between species. It outputs optimized modules that are fundamentally cross-species, which can either be conserved or species-specific. We demonstrate the application of OrthoClust using the RNA-Seq expression profiles of Caenorhabditis elegans and Drosophila melanogaster from the modENCODE consortium. A potential application of cross-species modules is to infer putative analogous functions of uncharacterized elements like non-coding RNAs based on guilt-by-association. | 25,249,401 | [
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Neuroanatomy of Individual Differences in Language in Adult Males with Autism. | One potential source of heterogeneity within autism spectrum conditions (ASC) is language development and ability. In 80 high-functioning male adults with ASC, we tested if variations in developmental and current structural language are associated with current neuroanatomy. Groups with and without language delay differed behaviorally in early social reciprocity, current language, but not current autistic features. Language delay was associated with larger total gray matter (GM) volume, smaller relative volume at bilateral insula, ventral basal ganglia, and right superior, middle, and polar temporal structures, and larger relative volume at pons and medulla oblongata in adulthood. Despite this heterogeneity, those with and without language delay showed significant commonality in morphometric features when contrasted with matched neurotypical individuals (n = 57). In ASC, better current language was associated with increased GM volume in bilateral temporal pole, superior temporal regions, dorsolateral fronto-parietal and cerebellar structures, and increased white matter volume in distributed frontal and insular regions. Furthermore, current language-neuroanatomy correlation patterns were similar across subgroups with or without language delay. High-functioning adult males with ASC show neuroanatomical variations associated with both developmental and current language characteristics. This underscores the importance of including both developmental and current language as specifiers for ASC, to help clarify heterogeneity. | 25,249,409 | [
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Lingual traction to facilitate fiber-optic intubation of difficult airways: a single-anesthesiologist randomized trial. | Flexible fiber-optic bronchoscope-guided orotracheal intubation is a valuable technique with demonstrated benefits in the management of difficult airways. Despite its popularity with anesthesia providers, the technique is not fail-safe and airway-related complications secondary to failed intubation attempts remain an important problem. We sought to determine the effect of incorporating lingual traction on the success rate of fiber-optic bronchoscope-guided intubation in patients with anticipated difficult airways. In this prospective, randomized, cohort study, we enrolled 91 adult patients with anticipated difficult airways scheduled for elective surgery to undergo fiber-optic bronchoscope-guided orotracheal intubation alone or with lingual traction by an individual anesthesiologist after induction of general anesthesia and neuromuscular blockade. A total of 78 patients were randomized: 39 patients to the fiber-optic bronchoscope-guided intubation with lingual traction group and 39 patients to the fiber-optic bronchoscope-guided intubation alone group. The primary endpoint was the rate of successful first attempt intubations. The secondary outcome was sore throat grade on post-operative day 1. Fiber-optic intubation with lingual traction compared to fiber-optic intubation alone resulted in a higher success rate (92.3 vs. 74.4 %, χ (2) = 4.523, p = 0.033) and greater odds for successful first attempt intubation (OR 4.138, 95 % CI 1.041-16.444, p = 0.044). Sore throat severity on post-operative day 1 was not significantly different but trended towards worsening grades with lingual traction. In this study, lingual traction was shown to be a valuable maneuver for facilitating fiber-optic bronchoscope-guided intubation in the management of patients with anticipated difficult airways. | 25,249,430 | [
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Classification of subpopulations of cells within human primary brain tumors by single cell gene expression profiling. | Brain tumors are heterogeneous with respect to genetic and histological properties of cells within the tumor tissue. To study subpopulations of cells, we developed a protocol for obtaining viable single cells from freshly isolated human brain tissue for single cell gene expression profiling. We evaluated this technique for characterization of cell populations within brain tumor and tumor penumbra. Fresh tumor tissue was obtained from one astrocytoma grade IV and one oligodendroglioma grade III tumor as well as the tumor penumbra of the latter tumor. The tissue was dissociated into individual cells and the expression of 36 genes was assessed by reverse transcription quantitative PCR followed by data analysis. We show that tumor cells from both the astrocytoma grade IV and oligodendroglioma grade III tumor constituted cell subpopulations defined by their gene expression profiles. Some cells from the oligodendroglioma grade III tumor proper shared molecular characteristics with the cells from the penumbra of the same tumor suggesting that a subpopulation of cells within the oligodendroglioma grade III tumor consisted of normal brain cells. We conclude that subpopulations of tumor cells can be identified by using single cell gene expression profiling. | 25,249,434 | [
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Transcriptomic analysis of mouse limb tendon cells during development. | The molecular signals driving tendon development are not fully identified. We have undertaken a transcriptome analysis of mouse limb tendon cells that were isolated at different stages of development based on scleraxis (Scx) expression. Microarray comparisons allowed us to establish a list of genes regulated in tendon cells during mouse limb development. Bioinformatics analysis of the tendon transcriptome showed that the two most strongly modified signalling pathways were TGF-β and MAPK. TGF-β/SMAD2/3 gain- and loss-of-function experiments in mouse limb explants and mesenchymal stem cells showed that TGF-β signalling was sufficient and required via SMAD2/3 to drive mouse mesodermal stem cells towards the tendon lineage ex vivo and in vitro. TGF-β was also sufficient for tendon gene expression in late limb explants during tendon differentiation. FGF does not have a tenogenic effect and the inhibition of the ERK MAPK signalling pathway was sufficient to activate Scx in mouse limb mesodermal progenitors and mesenchymal stem cells. | 25,249,460 | [
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Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord. | Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord. | 25,249,462 | [
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The number of locking screws predicts the risk of nonunion and reintervention in periprosthetic total knee arthroplasty fractures treated with a nail. | Periprosthetic knee fractures following total knee arthroplasty are increasing proportionally to the number of primary procedures done. We performed a retrospective review of Rorabeck type II fractures treated with a retrograde nail, trying to find the relationship between failure and the number of distal locking screws used. Twenty-six patients were included. The number of distal interlocking screws (patients with one or two distal interlocking screws and patients with three screws) correlated with nonunion (p < 0.1), did not correlate with the malunion rate (p > 0.1) and correlated with the reintervention rate (p < 0.1). | 25,249,480 | [
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Effects of far-infrared radiation on heart rate variability and central manifestations in healthy subjects: a resting-fMRI study. | The aim of this study was to investigate the autonomic responses and central manifestations by peripheral FIR stimulation. Ten subjects (mean ± SD age 26.2 ± 3.52 years) received FIR stimulation at left median nerve territory for 40 min. Electrocardiograph was continuously recorded and heart rate variability (HRV) were analyzed. By using a 3 T-MRI scanner, three sessions of resting-state functional magnetic resonance images (fMRI) were acquired, namely, before (baseline-FIR), immediately after (IA-FIR) and 15 min after FIR was turned off (Post-FIR). The fractional amplitude of low-frequency (0.01-0.08 Hz) fluctuation (fALFF) of each session to evaluate the intensity of resting-brain activity in each session was analyzed. Our results showed that FIR stimulation induced significant HRV responses such as an increasing trend of nLF and LF/HF ratio, while FIR increased fALFF in right superior front gyrus, middle frontal gyrus and decreased the resting brain activity at fusiform gyrus, extrastriae cortex, inferior temporal gyrus and middle temporal gyrus, especially 15 min after FIR was turned off. We conclude that the central manifestation and the autonomic responses are prominent during and after FIR stimulation, which provide important mechanistic explanation on human disorder treated by such energy medicine. | 25,249,495 | [
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The current state of stem cell therapeutics: Canadian approaches in the international context. | After ischemic injury, the endogenous repair mechanisms of the human heart are insufficient for meaningful tissue regeneration, so muscle lost is replaced by noncontractile scar tissue. Current treatments for ischemic cardiomyopathy improve quality of life and increase life expectancy, but cannot cure the underlying disease of cardiomyocyte loss. Cellular transplantation is emerging as a valuable therapeutic approach to heal the ischemic heart. Adult bone marrow stem cells are capable of differentiation, regeneration of infarcted myocardium, and induction of myogenesis and angiogenesis, ultimately leading to improved contractility. Positive results from animal studies have prompted several clinical trials to ascertain the safety and feasibility of cell therapy. However, despite all the excitement in stem cell research resulting from initial experimental data and preliminary clinical trials, the mixed results observed have raised many unanswered questions. A major obstacle to the identification of the optimal cell therapy is that the fate of the implanted cells and the nature of their beneficial effects are ill-defined. A better understanding is fundamental for the development of new therapeutic agents, and to optimize stem cell applications. Well-designed and powered double-blinded randomized studies are clearly needed to confirm promising findings from early studies. With several ongoing randomized trials directed toward evaluation of stem cell therapies in patients with acute or chronic ischemic cardiomyopathy, the Canadian initiative represents a milestone. | 25,249,498 | [
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Maternal insulin resistance and transient hyperglycemia impact the metabolic and endocrine phenotypes of offspring. | Studies in both humans and rodents suggest that maternal diabetes leads to a higher risk of the fetus developing impaired glucose tolerance and obesity during adulthood. However, the impact of hyperinsulinemia in the mother on glucose homeostasis in the offspring has not been fully explored. We aimed to determine the consequences of maternal insulin resistance on offspring metabolism and endocrine pancreas development using the LIRKO mouse model, which exhibits sustained hyperinsulinemia and transient increase in blood glucose concentrations during pregnancy. We examined control offspring born to either LIRKO or control mothers on embryonic days 13.5, 15.5, and 17.5 and postpartum days 0, 4, and 10. Control offspring born to LIRKO mothers displayed low birth weights and subsequently rapidly gained weight, and their blood glucose and plasma insulin concentrations were higher than offspring born to control mothers in early postnatal life. In addition, concentrations of plasma leptin, glucagon, and active GLP-1 were higher in control pups from LIRKO mothers. Analyses of the endocrine pancreas revealed significantly reduced β-cell area in control offspring of LIRKO mothers shortly after birth. β-Cell proliferation and total islet number were also lower in control offspring of LIRKO mothers during early postnatal days. Together, these data indicate that maternal hyperinsulinemia and the transient hyperglycemia impair endocrine pancreas development in the control offspring and induce multiple metabolic alterations in early postnatal life. The relatively smaller β-cell mass/area and β-cell proliferation in these control offspring suggest cell-autonomous epigenetic mechanisms in the regulation of islet growth and development. | 25,249,504 | [
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Blood volumes in cardiac surgery with cardiopulmonary bypass. | Total blood volume (TBV) estimation potentially impacts various aspects of cardiac surgical care, including pharmacological and transfusion interventions, hemodynamic and volume management and perfusion equipment selection. TBV is commonly computed during cardiopulmonary bypass (CPB), using standardized formulae. We hypothesized that these equations fail to accurately predict individual blood volume variability. The aim of this study was to determine TBV with a dilution technique and compare the results to commonly utilized TBV calculations. After institutional review board approval, data was prospectively collected and analyzed for 101 patients undergoing open-heart surgery. Hematocrits (Hct) just prior to and immediately after the initiation of CPB were used to calculate the TBV. Results were compared to (1) the Allen formula and (2) weight-based standards (70 ml/kg for males (SM); 65 ml/kg for females (SF)). The average dilution TBV (male: 4684 ± 1641 ml; female: 3027 ± 1067 ml; total: 4175 ± 1617 ml) was significantly smaller (p<0.05) than TBV estimated by Allen's formula (male: 6328 ± 973 ml; female: 4167 ± 643 ml; total: 5665 ± 1134 ml) and weight-based standards (male: 6278 ± 1256 ml; female: 4924 ± 1064 ml; total: 5862 ± 1350 ml). Allen's formula and the weight-based standards correlated strongly (R(2) = 0.821, p<0.001), suggesting similar estimates of TBV when using these methods. In contrast, hemodilution correlated poorly with the estimates by Allen (R(2) = 0.221, p<0.001) and weight-based formulae (R(2) = 0.122, p<0.001), suggesting different TBV computation. The dilution method during CPB for TBV estimation is applicable and reproducible in the cardiac surgical arena and can be utilized to calculate TBV. Our results suggest that traditional TBV assessment in cardiac surgical patients by Allen's and weight-based formulae lacks the desired accuracy in estimating true TBV. | 25,249,518 | [
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Tissue perfusion in neonates undergoing open-heart surgery using autologous umbilical cord blood or donor blood components. | This study evaluates the hemoglobin-oxygen relationship and tissue perfusion during cardiopulmonary bypass (CPB) in neonates undergoing open-heart surgery using autologous umbilical cord blood or donor blood components. We compared perioperative hematocrit (Hct), fetal hemoglobin (HbF), p(50)O(2), pH, pCO(2), serum lactate, duration of mechanical ventilation and intensive care unit (ICU) length of stay in neonates undergoing open-heart surgery using autologous umbilical cord blood (Group I, N=45) or donor blood components (Group II, N=65). The groups were similar with respect to diagnosis, weight, type of procedure, duration of CPB and duration of myocardial ischemia. Mean p(50)O(2) was significantly lower in Group I during CPB (19.7 vs. 22.3 mmHg, p=0.004) and at the end of CPB (20.1 vs. 22.8 mmHg, p=0.003). Median peak lactate during CPB was higher in Group I (4.8 vs. 2.2 mmol/l, p<0.001). Carbon dioxide tension was identified as an independent predictor of higher p(50)O(2) during CPB in Group I (β=0.88, p=0.002), but not Group II. Bodyweight, Hct, duration of CPB, pre-CPB lactate level and pCO(2) affected peak lactate level during CPB. Although mean duration of ventilation was longer in Group II (mean 51 vs. 43, p=0.004), the groups experienced similar duration of ICU stay (5.8 vs. 5.9 days, p=0.280). Despite the fact that the oxyhemoglobin dissociation curve is shifted leftward in patients who receive autologous umbilical cord blood, tissue oxygen delivery appears to be preserved in neonates who undergo open-heart surgery using autologous umbilical cord blood. | 25,249,520 | [
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[Microbial synthesis of deuterium labelled L-phenylalanine with different levels of isotopic enrichment by facultative methylotrophic bacterium Brevibacterium methylicum with RMP assimilation of carbon]. | The preparative microbial synthesis of amino acids labelled with stable isotopes, including deuterium ( 2 H), suitable for biomedical applications by methylotrophic bacteria was studied using L-phenylalanine as example. This amino acid is secreted by Gram-negative aerobic facultative methylotrophic bacteria Brevibacterium methylicum, assimilating methanol via ribulose-5-monophosphate (RMP) cycle of assimilation of carbon, The data on adaptation of L-phenylalanine secreted by methylotrophic bacterium В. methylicum to the maximal concentration of deuterium in the growth medium with 98% 2 Н 2 O and 2% [ 2 Н]methanol, and biosynthesis of deuterium labelled L-phenylalanine With different levels of enrichment are presented. The strain was adapted by means of plating initial cells on firm (2% agarose) minimal growth media with an increasing gradient of 2 Н 2 O concentration from 0; 24.5; 49.0; 73.5 up to 98% 2 Н 2 O followed by subsequent selection of separate colonies stable to the action of 2 Н 2 O. These colonies were capable to produce L-phenylalanine. L-phenylalanine was extracted from growth medium by extraction with isopropanol with the subsequent crystallization in ethanol (output 0.65 g/l). The developed method of microbial synthesis allows to obtain deuterium labelled L-phenylalanine with different levels of isotopic enrichment, depending on concentration of 2 Н 2 O in growth media, from 17% (on growth medium with 24,5% 2 Н 2 O) up to 75% (on growth medium with 98% 2 Н 2 O) of deuterium in the molecule that is confirmed with the data of the electron impact (EI) mass- spectrometry analysis of methyl ethers of N-dimethylamino(naphthalene)-5-sulfochloride (dansyl) phenylalanine in these experimental conditions. | 25,249,528 | [
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An antimesothelin-monomethyl auristatin e conjugate with potent antitumor activity in ovarian, pancreatic, and mesothelioma models. | Mesothelin (MSLN) is an attractive target for antibody-drug conjugate therapy because it is highly expressed in various epithelial cancers, with normal expression limited to nondividing mesothelia. We generated novel antimesothelin antibodies and conjugated an internalizing one (7D9) to the microtubule-disrupting drugs monomethyl auristatin E (MMAE) and MMAF, finding the most effective to be MMAE with a lysosomal protease-cleavable valine-citrulline linker. The humanized (h7D9.v3) version, αMSLN-MMAE, specifically targeted mesothelin-expressing cells and inhibited their proliferation with an IC50 of 0.3 nmol/L. Because the antitumor activity of an antimesothelin immunotoxin (SS1P) in transfected mesothelin models did not translate to the clinic, we carefully selected in vivo efficacy models endogenously expressing clinically relevant levels of mesothelin, after scoring mesothelin levels in ovarian, pancreatic, and mesothelioma tumors by immunohistochemistry. We found that endogenous mesothelin in cancer cells is upregulated in vivo and identified two suitable xenograft models for each of these three indications. A single dose of αMSLN-MMAE profoundly inhibited or regressed tumor growth in a dose-dependent manner in all six models, including two patient-derived tumor xenografts. The robust and durable efficacy of αMSLN-MMAE in preclinical models of ovarian, mesothelioma, and pancreatic cancers justifies the ongoing phase I clinical trial. | 25,249,555 | [
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Nocardioides daecheongensis sp. nov., isolated from soil. | Strain KIS2-16(T) was isolated from a soil sample collected from Daecheong Island of Incheon region, South Korea. KIS2-16(T) was Gram-staining-positive, aerobic, non-spore-forming, non-motile, catalase-positive, oxidase-negative and mesophilic. On the basis of 16S rRNA gene sequence analysis, strain KIS2-16(T) represented a member of the genus Nocardioides, being most closely related to the type strains of species of the genus Nocardioides, Nocardioides maradonensis RP-B30(T) (97.8 % sequence similarity) and Nocardioides ultimimeridianus RP-B26(T) (97.0 %). The fatty acid profile of KIS2-16(T) was dominated by C18 : 1ω9c, C17 : 1ω8c, C16 : 0, C18 : 0 10-methyl (TBSA), C16 : 0 2-OH and C17 : 0 2-OH. The major isoprenoid quinone was MK-8(H4), and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. The peptidoglycan structure was A3γ-type with ll-diaminopimelic acid. The genomic DNA G+C content of KIS2-16(T) was 64.9 mol%. Strain KIS2-16(T) showed DNA-DNA hybridization values of less than 70 % with the closely related species of the genus Nocardioides. Based on phenotypic, genotypic and phylogenetic data, the isolate represents a novel species of the genus Nocardioides, for which the name Nocardioides daecheongensis sp. nov. (type strain KIS2-16(T) = DSM 27136(T) = KACC 17297(T) = NBRC 109597(T)) is proposed. | 25,249,564 | [
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What Do We Really Need? Visions of an Ideal Human-Machine Interface for NOTES Mechatronic Support Systems From the View of Surgeons, Gastroenterologists, and Medical Engineers. | To investigate why natural orifice translumenal endoscopic surgery (NOTES) has not yet become widely accepted and to prove whether the main reason is still the lack of appropriate platforms due to the deficiency of applicable interfaces. To assess expectations of a suitable interface design, we performed a survey on human-machine interfaces for NOTES mechatronic support systems among surgeons, gastroenterologists, and medical engineers. Of 120 distributed questionnaires, each consisting of 14 distinct questions, 100 (83%) were eligible for analysis. A mechatronic platform for NOTES was considered "important" by 71% of surgeons, 83% of gastroenterologist,s and 56% of medical engineers. "Intuitivity" and "simple to use" were the most favored aspects (33% to 51%). Haptic feedback was considered "important" by 70% of participants. In all, 53% of surgeons, 50% of gastroenterologists, and 33% of medical engineers already had experience with NOTES platforms or other surgical robots; however, current interfaces only met expectations in just more than 50%. Whereas surgeons did not favor a certain working posture, gastroenterologists and medical engineers preferred a sitting position. Three-dimensional visualization was generally considered "nice to have" (67% to 72%); however, for 26% of surgeons, 17% of gastroenterologists, and 7% of medical engineers it did not matter (P = 0.018). Requests and expectations of human-machine interfaces for NOTES seem to be generally similar for surgeons, gastroenterologist, and medical engineers. Consensus exists on the importance of developing interfaces that should be both intuitive and simple to use, are similar to preexisting familiar instruments, and exceed current available systems. | 25,249,584 | [
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Fluorescence lifetime imaging of the ocular fundus in mice. | Fundus autofluorescence (AF) is characterized not only by its intensity or excitation and emission spectra but also by the lifetimes of the fluorophores. Fluorescence lifetime is influenced by the fluorophore's microenvironment and may provide information about the metabolic tissue state. We report quantitative and qualitative autofluorescence lifetime imaging of the ocular fundus in mice. A fluorescence lifetime imaging ophthalmoscope (FLIO) was used to measure fluorescence lifetimes of endogenous fluorophores in the murine retina. FLIO imaging was performed in 1-month-old C57BL/6, BALB/c, and C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. Measurements were repeated at monthly intervals over the course of 6 months. For correlation with structural changes, an optical coherence tomogram was acquired. Fundus autofluorescence lifetime images were readily obtained in all mice. In the short spectral channel (498-560 nm), mean ± SEM AF lifetimes were 956 ± 15 picoseconds (ps) in C57BL/6; 801 ± 35 ps in BALB/c mice; and 882 ± 37 ps in C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. In the long spectral channel (560-720 nm), mean ± SEM AF lifetimes were 298 ± 14 ps in C57BL/6 mice, 241 ± 10 ps in BALB/c mice, and 288 ± 8 ps in C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. There was a general decrease in mean AF lifetimes with age. Although fluorescence lifetime values differ among mouse strains, we found little variance within the groups. Fundus autofluorescence lifetime imaging in mice may provide additional information for understanding retinal disease processes and may facilitate monitoring of therapeutic effects in preclinical studies. | 25,249,601 | [
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The relationship between retinal nerve fiber layer thickness and optic nerve head neuroretinal rim tissue in glaucoma. | The purpose of this study was to determine the relationship between optical coherence tomography (OCT) measures of retinal nerve fiber layer (RNFL) and neuroretinal rim (NRR) in a nonhuman primate experimental glaucoma model, and in a population of clinical patients. For nonhuman primates, normative data were collected from 44 healthy monkeys, and nine animals with unilateral experimental glaucoma that were followed longitudinally. Cross-sectional human subjects data were collected from 89 healthy, 74 glaucoma suspects, and 104 glaucoma patients. Individualized transverse scaling for OCT scans was calculated using a schematic eye that incorporated optical ocular biometry. Custom algorithms were used to quantify RNFL thickness with and without vessels removed, scaled minimum rim width (sMRW), and neural rim volume (NRV). For the experimental glaucoma group, NRR parameters showed the first changes with increased cumulative IOP. The data for both NRR and RNFL measures were best fit by an exponential rise model (NRV, R2=0.79, P<0.01, sMRW, R2=0.74, P<0.01). The major retinal vascular thickness contribution to the RNFL decreased (0.03 μm/μm, P<0.01) with RNFL loss, but the percent vascular contribution increased (-0.1%/μm, P<0.01) with disease progression. Overall, the findings for the cross-sectional human data were similar to those of the experimental model. The findings illustrate a nonlinear relationship between NRR and RNFL measures and provide support for the use of multiple OCT scaled morphological measures for the diagnosis and management of primary open angle glaucoma in humans. | 25,249,610 | [
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Simultaneous binding to the tracking strand, displaced strand and the duplex of a DNA fork enhances unwinding by Dda helicase. | Interactions between helicases and the tracking strand of a DNA substrate are well-characterized; however, the role of the displaced strand is a less understood characteristic of DNA unwinding. Dda helicase exhibited greater processivity when unwinding a DNA fork compared to a ss/ds DNA junction substrate. The lag phase in the unwinding progress curve was reduced for the forked DNA compared to the ss/ds junction. Fewer kinetic steps were required to unwind the fork compared to the ss/ds junction, suggesting that binding to the fork leads to disruption of the duplex. DNA footprinting confirmed that interaction of Dda with a fork leads to two base pairs being disrupted whereas no disruption of base pairing was observed with the ss/ds junction. Neutralization of the phosphodiester backbone resulted in a DNA-footprinting pattern similar to that observed with the ss/ds junction, consistent with disruption of the interaction between Dda and the displaced strand. Several basic residues in the 1A domain which were previously proposed to bind to the incoming duplex DNA were replaced with alanines, resulting in apparent loss of interaction with the duplex. Taken together, these results suggest that Dda interaction with the tracking strand, displaced strand and duplex coordinates DNA unwinding. | 25,249,618 | [
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SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression. | Polycomb group (PcG) complexes regulate cellular identity through epigenetic programming of chromatin. Here, we show that SSX2, a germline-specific protein ectopically expressed in melanoma and other types of human cancers, is a chromatin-associated protein that antagonizes BMI1 and EZH2 PcG body formation and derepresses PcG target genes. SSX2 further negatively regulates the level of the PcG-associated histone mark H3K27me3 in melanoma cells, and there is a clear inverse correlation between SSX2/3 expression and H3K27me3 in spermatogenesis. However, SSX2 does not affect the overall composition and stability of PcG complexes, and there is no direct concordance between SSX2 and BMI1/H3K27me3 presence at regulated genes. This suggests that SSX2 antagonizes PcG function through an indirect mechanism, such as modulation of chromatin structure. SSX2 binds double-stranded DNA in a sequence non-specific manner in agreement with the observed widespread association with chromatin. Our results implicate SSX2 in regulation of chromatin structure and function. | 25,249,625 | [
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Insyght: navigating amongst abundant homologues, syntenies and gene functional annotations in bacteria, it's that symbol! | High-throughput techniques have considerably increased the potential of comparative genomics whilst simultaneously posing many new challenges. One of those challenges involves efficiently mining the large amount of data produced and exploring the landscape of both conserved and idiosyncratic genomic regions across multiple genomes. Domains of application of these analyses are diverse: identification of evolutionary events, inference of gene functions, detection of niche-specific genes or phylogenetic profiling. Insyght is a comparative genomic visualization tool that combines three complementary displays: (i) a table for thoroughly browsing amongst homologues, (ii) a comparator of orthologue functional annotations and (iii) a genomic organization view designed to improve the legibility of rearrangements and distinctive loci. The latter display combines symbolic and proportional graphical paradigms. Synchronized navigation across multiple species and interoperability between the views are core features of Insyght. A gene filter mechanism is provided that helps the user to build a biologically relevant gene set according to multiple criteria such as presence/absence of homologues and/or various annotations. We illustrate the use of Insyght with scenarios. Currently, only Bacteria and Archaea are supported. A public instance is available at http://genome.jouy.inra.fr/Insyght. The tool is freely downloadable for private data set analysis. | 25,249,626 | [
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Relation of exercise capacity with lung volumes before and after 6-minute walk test in subjects with COPD. | There is growing evidence that exercise-induced variation in lung volumes is an important source of ventilatory limitation and is linked to exercise intolerance in COPD. The aim of this study was to compare the correlations of walk distance and lung volumes measured before and after a 6-min walk test (6MWT) in subjects with COPD. Forty-five subjects with stable COPD (mean pre-bronchodilator FEV1: 47 ± 18% predicted) underwent a 6MWT. Body plethysmography was performed immediately pre- and post-6MWT. Correlations were generally stronger between 6-min walk distance and post-6MWT lung volumes than between 6-min walk distance and pre-6MWT lung volumes, except for FEV1. These differences in Pearson correlation coefficients were significant for residual volume expressed as percent of total lung capacity (-0.67 vs -0.58, P = .043), percent of predicted residual volume expressed as percent of total lung capacity (-0.68 vs -0.59, P = .026), inspiratory vital capacity (0.65 vs 0.54, P = .019), percent of predicted inspiratory vital capacity (0.49 vs 0.38, P = .037), and percent of predicted functional residual capacity (-0.62 vs -0.47, P = .023). In subjects with stable COPD, lung volumes measured immediately after 6MWT are more closely related to exercise limitation than baseline lung volumes measured before 6MWT, except for FEV1. Therefore, pulmonary function testing immediately after exercise should be included in future studies on COPD for the assessment of exercise-induced ventilatory constraints to physical performance that cannot be adequately assessed from baseline pulmonary function testing at rest. | 25,249,649 | [
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Liraglutide and the preservation of pancreatic β-cell function in early type 2 diabetes: the LIBRA trial. | Clinical studies evaluating the effects of medications on β-cell function in type 2 diabetes (T2DM) are compromised by an inability to determine the actual baseline degree of β-cell dysfunction independent of the reversible dysfunction induced by hyperglycemia (glucotoxicity). Short-term intensive insulin therapy (IIT) is a strategy for eliminating glucotoxicity before randomization. This study determined whether liraglutide can preserve β-cell function over 48 weeks in early T2DM following initial elimination of glucotoxicity with IIT. In this double-blind, randomized, placebo-controlled trial, 51 patients with T2DM of 2.6 ± 1.9 years' duration and an A1C of 6.8 ± 0.8% (51 ± 8.7 mmol/mol) completed 4 weeks of IIT before randomization to daily subcutaneous liraglutide or placebo injection, with serial assessment of β-cell function by Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test performed every 12 weeks. The primary outcome of baseline-adjusted ISSI-2 at 48 weeks was higher in the liraglutide group than in the placebo group (339.8 ± 27.8 vs. 229.3 ± 28.4, P = 0.008). Baseline-adjusted HbA1c at 48 weeks was lower in the liraglutide group (6.2 ± 0.1% vs. 6.6 ± 0.1%, P = 0.055) (44 ± 1.1 vs. 49 ± 1.1 mmol/mol). At each quarterly assessment, >50% of participants on liraglutide had an HbA1c ≤6.0% (42 mmol/mol) and glucose tolerance in the nondiabetic range. Despite this level of glycemic control, no difference was found in the incidence of hypoglycemia between the liraglutide and placebo groups (P = 0.61). Two weeks after stopping treatment, however, the beneficial effect on ISSI-2 of liraglutide versus placebo was entirely lost (191.9 ± 24.7 vs. 238.1 ± 25.2, P = 0.20). Liraglutide provides robust enhancement of β-cell function that is sustained over 48 weeks in early T2DM but lost upon cessation of therapy. | 25,249,651 | [
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Extracardiac Fontan in apicocaval juxtaposition. | Extracardiac total cavopulmonary connection between the inferior vena cava and right pulmonary artery has become the most popular Fontan modification nowadays, yielding good results. However, certain situs anomalies along with systemic venous drainage variations give rise to an issue about the best way for extracardiac conduit routing. Three cases of apicocaval juxtaposition are described. The situs was inversus with the apex and inferior vena cava on the same side (left), whereas the superior vena cava (Glenn) was located on the right in all cases. The literature is revisited and technical options are discussed. Surgery was carried out with excellent short- and midterm results. | 25,249,659 | [
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The effects of dipeptidyl peptidase-4 inhibition on microvascular diabetes complications. | We performed a review of the literature to determine whether the dipeptidyl peptidase-4 inhibitors (DPP4-I) may have the capability to directly and positively influence diabetic microvascular complications. The literature was scanned to identify experimental and clinical evidence that DPP4-I can ameliorate diabetic microangiopathy. We retrieved articles published between 1 January 1980 and 1 March 2014 in English-language peer-reviewed journals using the following terms: ("diabetes" OR "diabetic") AND ("retinopathy" OR "retinal" OR "nephropathy" OR "renal" OR "albuminuria" OR "microalbuminuria" OR "neuropathy" OR "ulcer" OR "wound" OR "bone marrow"); ("dipeptidyl peptidase-4" OR "dipeptidyl peptidase-IV" OR "DPP-4" OR "DPP-IV"); and ("inhibition" OR "inhibitor"). Experimentally, DPP4-I appears to improve inflammation, endothelial function, blood pressure, lipid metabolism, and bone marrow function. Several experimental studies report direct potential beneficial effects of DPP4-I on all microvascular diabetes-related complications. These drugs have the ability to act either directly or indirectly via improved glucose control, GLP-1 bioavailability, and modifying nonincretin substrates. Although preliminary clinical data support that DPP4-I therapy can protect from microangiopathy, insufficient evidence is available to conclude that this class of drugs directly prevents or decreases microangiopathy in humans independently from improved glucose control. Experimental findings and preliminary clinical data suggest that DPP4-I, in addition to improving metabolic control, have the potential to interfere with the onset and progression of diabetic microangiopathy. Further evidence is needed to confirm these effects in patients with diabetes. | 25,249,673 | [
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Functional Genomics and a New Era in Radiation Biology and Oncology. | Ionizing radiation is a ubiquitous stress to which all life is continuously exposed, and thus complex mechanisms have evolved to regulate cellular responses to radiation, including cell cycle arrest, DNA repair, and programmed cell death. Changes in gene expression shape part of the response to radiation, and have historically provided insight into the underlying mechanisms of that response. However, the advent of microarrays, which can measure expression of all the genes in a cell simultaneously, has transformed the study of gene expression, and is beginning to have an impact on both basic mechanistic and clinical studies. This article provides an overview of concepts in gene expression and microarray technology, and highlights their impacts on the study of radiation biology. | 25,249,699 | [
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Feature Screening via Distance Correlation Learning. | This paper is concerned with screening features in ultrahigh dimensional data analysis, which has become increasingly important in diverse scientific fields. We develop a sure independence screening procedure based on the distance correlation (DC-SIS, for short). The DC-SIS can be implemented as easily as the sure independence screening procedure based on the Pearson correlation (SIS, for short) proposed by Fan and Lv (2008). However, the DC-SIS can significantly improve the SIS. Fan and Lv (2008) established the sure screening property for the SIS based on linear models, but the sure screening property is valid for the DC-SIS under more general settings including linear models. Furthermore, the implementation of the DC-SIS does not require model specification (e.g., linear model or generalized linear model) for responses or predictors. This is a very appealing property in ultrahigh dimensional data analysis. Moreover, the DC-SIS can be used directly to screen grouped predictor variables and for multivariate response variables. We establish the sure screening property for the DC-SIS, and conduct simulations to examine its finite sample performance. Numerical comparison indicates that the DC-SIS performs much better than the SIS in various models. We also illustrate the DC-SIS through a real data example. | 25,249,709 | [
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Prevention of bacterial foodborne disease using nanobiotechnology. | Foodborne disease is an important source of expense, morbidity, and mortality for society. Detection and control constitute significant components of the overall management of foodborne bacterial pathogens, and this review focuses on the use of nanosized biological entities and molecules to achieve these goals. There is an emphasis on the use of organisms called bacteriophages (phages: viruses that infect bacteria), which are increasingly being used in pathogen detection and biocontrol applications. Detection of pathogens in foods by conventional techniques is time-consuming and expensive, although it can also be sensitive and accurate. Nanobiotechnology is being used to decrease detection times and cost through the development of biosensors, exploiting specific cell-recognition properties of antibodies and phage proteins. Although sensitivity per test can be excellent (eg, the detection of one cell), the very small volumes tested mean that sensitivity per sample is less compelling. An ideal detection method needs to be inexpensive, sensitive, and accurate, but no approach yet achieves all three. For nanobiotechnology to displace existing methods (culture-based, antibody-based rapid methods, or those that detect amplified nucleic acid) it will need to focus on improving sensitivity. Although manufactured nonbiological nanoparticles have been used to kill bacterial cells, nanosized organisms called phages are increasingly finding favor in food safety applications. Phages are amenable to protein and nucleic acid labeling, and can be very specific, and the typical large "burst size" resulting from phage amplification can be harnessed to produce a rapid increase in signal to facilitate detection. There are now several commercially available phages for pathogen control, and many reports in the literature demonstrate efficacy against a number of foodborne pathogens on diverse foods. As a method for control of pathogens, nanobiotechnology is therefore flourishing. | 25,249,756 | [
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Molecular cloning and mRNA expression of the peptidoglycan recognition protein gene HcPGRP1 and its isoform HcPGRP1a from the freshwater mussel Hyriopsis cumingi. | Peptidoglycan recognition proteins (PGRPs) are innate immune molecules that have been structurally conserved throughout evolution in invertebrates and vertebrates. In this study, peptidoglycan recognition protein HcPGRP1 and its isoform HcPGRP1a were identified in the freshwater mussel Hyriopsis cumingii. The full-length cDNAs of HcPGRP1 (973 bp) and HcPGRP1a (537 bp) encoded polypeptides with 218 and 151 amino acids, respectively. Sequence analysis showed that HcPGRP1 had one C-terminal PGRP domain that was conserved throughout evolution. Phylogenetic analysis showed that HcPGRP1 clustered closely with EsPGRP4 of Euprymna scolopes. Real-time PCR showed that the mRNA transcripts of HcPGRP1 and HcPGRP1a were constitutively expressed in various tissues, with the highest level in hepatopancreas. Stimulation with lipopolysaccharide (LPS) and peptidoglycan (PGN) significantly up-regulated HcPGRP1 mRNA expression in hepatopancreas and foot, but not in gill, whereas HcPGRP1a expression was significantly up-regulated in all three tissues. Our results indicate that HcPGRP1 is both a constitutive and inducible protein that may be involved in immune responses (recognition and defense) against invaders. | 25,249,773 | [
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Genetic variation in cultivated Rheum tanguticum populations. | To examine whether cultivation reduced genetic variation in the important Chinese medicinal plant Rheum tanguticum, the levels and distribution of genetic variation were investigated using ISSR markers. Fifty-eight R. tanguticum individuals from five cultivated populations were studied. Thirteen primers were used and a total of 320 DNA bands were scored. High levels of genetic diversity were detected in cultivated R. tanguticum (PPB = 82.19, H = 0.2498, HB = 0.3231, I = 0.3812) and could be explained by the outcrossing system, as well as long-lived and human-mediated seed exchanges. Analysis of molecular variance (AMOVA) showed that more genetic variation was found within populations (76.1%) than among them (23.9%). This was supported by the coefficient of gene differentiation (Gst = 0.2742) and Bayesian analysis (θ B = 0.1963). The Mantel test revealed no significant correlation between genetic and geographic distances among populations (r = 0.1176, p = 0.3686). UPGMA showed that the five cultivated populations were separated into three clusters, which was in good accordance with the results provided by the Bayesian software STRUCTURE (K = 3). A short domestication history and no artificial selection may be an effective way of maintaining and conserving the gene pools of wild R. tanguticum. | 25,249,777 | [
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Propofol infusion syndrome or not? A case report. | Propofol is commonly used and well tolerated for induction of general anesthesia and is also used as a sedative in the intensive care unit. However, in rare cases, the agent may cause a fatal condition known as propofol infusion syndrome (PRIS). We present a case of PRIS that could have been fatal in a previously healthy male patient with multiple gunshot wounds. Because patients typically exhibit other potentially fatal comorbidities, PRIS is always a diagnosis of exclusion. The true incidence of PRIS remains unknown, and more objective criteria for its diagnosis need to be established. | 25,249,811 | [
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Peduncular hallucinosis: a case report. | Peduncular hallucinosis is a rare form of visual hallucination often described as vivid, colorful visions of people and animals. The exact pathophysiology is unknown; however, most cases have been described in relation to lesions in the thalamus or midbrain. We present the case of a 59-year-old female with peduncular hallucinosis associated with infarction in the right basal ganglia with the background of malignant hypertension. The patient's visual hallucinations decreased without pharmaceutical treatment by the time of discharge and on further follow-up had resolved completely. We believe ours is one of few reported cases of peduncular hallucinosis in a patient with an infarct isolated to the basal ganglia (striatum and globus pallidus). | 25,249,815 | [
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Temporomandibular condylar alterations in juvenile idiopathic arthritis most common in longitudinally severe disease despite medical treatment. | Juvenile idiopathic arthritis (JIA) is an autoimmune, heterogeneous disease and the temporomandibular joint (TMJ) can be affected, with consequences for mandibular growth and function. The aim of this study was to evaluate the importance of longitudinal medical treatment and the burden of disease activity on the development of temporomandibular condylar alterations as judged on panoramic radiographs. The study was a retrospective evaluation of dental and medical records in consecutive JIA patients referred to three specialist dental clinics in Sweden during an eight-year period. Data on the total pharmacological treatment and disease activity were evaluated longitudinally from disease onset to the time of the panoramic examination, during a median observation period of 2.5 years. The radiographs were analysed in terms of structural and shape alterations in the condyles and judged dichotomously. Panoramic examinations were analysed in 158 patients from 266 referrals diagnosed with JIA. Condylar alterations (shape or structural) were seen in 68 patients (43%). Patients with condylar alterations were more extensively treated over time compared with those without condylar alterations. Powerful disease activity and/or potent medication at any time during the course of the disease implied an increased risk of alterations. Patients with JIA who require more intensive medication over time run the greatest risk of condylar alterations. As yet, current medical programmes have not been specified for the TMJ and more knowledge in this area is needed. | 25,249,821 | [
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Burn wound healing with injection of adipose-derived stem cells: a mouse model study. | Stem cells have shown promise with regard to the healing process of burn wounds. However, donor sites for these cells are still under investigation. The aim of this study is to review the efficacy of adipose tissue-derived stem cells (ADSCs) in accelerating wound healing of third degree burns in a mouse model. To this end, forty healthy male inbred Balb/c mice were selected and set up as an experimental model for third degree burn wounds. They were randomly divided into 3 equally sized groups: the ADSCs group, the mechanically prepared adipose tissue group, and the control group. The wounds were examined daily until the mice were sacrificed for tissue sampling in the 3(rd) week. Our results showed that wound surface area and eschar thickness were smaller in the ADSCs group throughout the study period, although there was no significant difference between the groups for decreasing values of wound area characteristics. In terms of wound healing parameters, lymphocyte and macrophage cell counts were larger in the ADSCs group compared to the other groups. Fibroplasia, collagen synthesis and remodeling were more aberrant in this group. However, there was no statistically significant difference in either of these observed differences (p>0.05). Although enzymatically prepared ADSCs seem a potential treatment in wound healing, our study of a mouse model burn wound revealed no significant improvement in using this option. | 25,249,847 | [
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Crystal structure of bis-[3-meth-oxy-17β-estra-1,3,5(10)-trien-17-yl] oxalate. | In the title compound, C40H50O6, a symmetrical steroid oxalate diester, the dihedral angle between the CO2 planes of the oxalate linker is 61.5 (5)° and the C-C bond length is 1.513 (6) Å. The steroid B, C and D rings adopt half-chair, chair and envelope conformations, respectively, in both halves of the mol-ecule, which adopts an overall shallow V-shaped conformation. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions, forming a three-dimensional network. | 25,249,855 | [
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Crystal structures of potassium tri-fluorido-(4-meth-oxy-phen-yl)borate and potassium tri-fluorido(4-fluoro-phen-yl)borate. | The title compounds, K(+)·C7H7BF3O(-), (I), and K(+)·C6H4BF4 (-), (II), are mol-ecular salts containing para-substituted phenyl-tri-fluorido-borate anions. In each compound, the B atom adopts a distorted tetra-hedral BCF3 geometry. Despite their different compositions and space groups, the irregular KF8 coordination polyhedra of the potassium cations in the structures are almost identical. These polyhedra share faces and edges, generating infinite (010) layers in (I) and infinite (001) layers in (II). In (I), adjacent layers are stacked in an AAA… fashion, whereas in (II), they are stacked in an ABAB… sequence. | 25,249,857 | [
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Crystal structure of bis-[1-(naphthalen-1-ylmeth-yl)pyridinium] bis-(2,2-di-cyano-ethene-1,1-di-thiol-ato-κ(2) S,S')nickelate(II). | A new ion-pair complex, (C16H14N)2[Ni(C4N2S2)2] or (1-NaMePy)2[Ni(imnt)2], where 1-NaMePy is 1-(4-naphthyl-methyl-ene)pyridinium and imnt is 2,2-di-cyano-ethene-1,1-di-thiol-ate, was obtained by the direct reaction of NiCl2, K2imnt and (1-NaMePy)(+)Br(-) in H2O. The asymmetric unit contains a [1-NaMePy](+) cation and one half of an Ni(imnt)2 (2-) anion. The Ni(II) ion lies on an inversion centre and adopts a square-planar configuration with Ni-S bond lengths of 2.200 (1) and 2.216 (1) Å. In the [1-NaMePy](+) cation, the naphthyl ringsystem and the pyridinium ring make a dihedral angle of 90.0 (2)°. In the crystal, C-H⋯N and C-H⋯Ni hydrogen bonds, as well as π-π inter-actions between the chelate ring and the pyridinium ring [centroid-centroid distance = 3.675 (2) Å] link the ions into a three-dimensional network. | 25,249,870 | [
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Diterbium hepta-nickel: a crystal structure redetermination. | The crystal structure of the title compound, Tb2Ni7, was redetermined from single-crystal X-ray diffraction data. In comparison with previous studies based on powder X-ray diffraction data [Lemaire et al. (1967). C. R. Acad. Sci. Ser. B, 265, 1280-1282; Lemaire & Paccard (1969). Bull. Soc. Fr. Mineral. Cristallogr. 92, 9-16; Buschow & van der Goot (1970). J. Less-Common Met. 22, 419-428], the present redetermination affords refined coordinates and anisotropic displacement parameters for all atoms. A partial occupation for one Tb atom results in the non-stoichiometric composition Tb1.962 (4)Ni7. The title compound adopts the Ce2Ni7 structure type and can also be derived from the CaCu5 structure type as an inter-growth structure. The asymmetric unit contains two Tb sites (both site symmetries 3m.) and five Ni sites (.m., mm2, 3m., 3m., -3m.). The two different coordination polyhedra of Tb are a Frank-Kasper polyhedron formed by four Tb and 12 Ni atoms and a pseudo Frank-Kasper polyhedron formed by two Tb and 18 Ni atoms. The four different coordination polyhedra of Ni are Frank-Kasper icosa-hedra formed by five Tb and seven Ni atoms, four Tb and eight Ni atoms, three Tb and nine Ni atoms, and six Tb and six Ni atoms, respectively. | 25,249,871 | [
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Poly[[tri-μ-aqua-do-deca-aqua-tris-(μ3-1-hy-droxy-ethyl-idene-1,1-di-phospho-nato)tricalcium(II)tripalladium(II)] penta-hydrate]. | The asymmetric unit of the title compound, {[CaPd{CH3OHC(PO3)2}(H2O)5]·5/3H2O} n , consists of one half of the complex [Pd{CH3OHC(PO3)2}](2-) anion (point group symmetry m..), one Ca(2+) cation [site symmetry (.2.)] that is surrounded by three water mol-ecules (one of which is on the same rotation axis) and by three disordered lattice water mol-ecules. The anions form a trinuclear metallocycle around a crystallographic threefold rotation axis. The cations are related by a twofold rotation axis to form a [Ca2(H2O)10](2+) dimer. The slightly distorted square-planar coordination environment of the Pd(II) atoms in the complex anions is formed by O atoms of the bidentate chelating phospho-nate groups of the 1-hy-droxy-ethyl-idene-1,1-di-phospho-nate ligands. In the crystal, cations are bound to anions through -Ca-O-P-O- bonds, as well as through O-H⋯O hydrogen bonds, resulting in a three-dimensional polymer. The structure is completed by five disordered solvent mol-ecules localized in cavities within the framework. | 25,249,877 | [
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Bis(2-amino-4-phenyl-1,3-thia-zol-3-ium) tetra-chlorido-palladate(II). | The title compound, (C9H9N2S)2[PdCl4], consists of two monoprotonated 2-amino-4-phenyl-1,3-thia-zole molecules and one tetra-chlorido-palladate anion. The organic molecules exhibit a dihedral angle between the main rings planes of 31.82 (9)°. In the anion, the Pd(II) atom is located on a crystallographic centre of symmetry with a square-planar geometry. In the crystal, the anions and cations are connected through bifurcated N-H⋯Cl hydrogen bonds, and these inter-actions lead to hydrogen-bonded tapes of cations and anions along [100]. | 25,249,879 | [
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-... |
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