title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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A homologous series of [Fe(H₂Bpz₂)₂(L)] spin-crossover complexes with annelated bipyridyl co-ligands. | Four new iron(II) complexes [Fe(H2Bpz2)2(L)] were prepared (pz = pyrazolyl), where L is dipyrido[3,2-f:2',3'-h]quinoxaline (dpq), dipyrido[3,2-a:2'3'-c]phenazine (dppz), dipyrido[3,2-a:2'3'-c]benzo[i]-phenazine (dppn), and dipyrido[3,2-a:2',3'-c](6,7,8,9-tetrahydro)phenazine (dppc). Crystal structures of [Fe(H2Bpz2)2(dpq)], [Fe(H2Bpz2)2(dppz)], and [Fe(H2Bpz2)2(dppn)] all reveal stacks of complex molecules formed through π-π stacking between interdigitated bipyridyl chelate ligands, often with additional intercalated toluene or uncoordinated bipyridyl ligand (dpq). Molecules of [Fe(H2Bpz2)2(dppc)] form a different stacking motif in the crystal, with weaker contacts between individual molecules. Many of the structures also contain channels of disordered solvent, running between the molecular stacks. Despite their different stacking motifs, all these compounds exhibit very gradual thermal spin-crossover (SCO) on cooling, which occur over different temperature ranges but are otherwise quite similar in form. Weak thermal hysteresis in one of these spin equilibria can be attributed to the effects of a change in bipyridyl ligand conformation in the molecular stacks around 150 K, which was observed crystallographically. These results demonstrate that strong mechanical coupling between molecules in a crystal is not sufficient to engineer cooperative SCO switching, if other regions of the lattice are less densely packed. | 25,171,341 | [
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Reappraising roles. | After its August break, Nursing Older People welcomes you back. I hope that you all managed to take a rest from work too and had an enjoyable summer. | 25,171,345 | [
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MPs urged to keep assisted dying high on the agenda. | MPS ARE being urged by a leading nurse to keep the controversial issue of assisted dying 'high on the political agenda' in the run up to the general election. | 25,171,351 | [
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Test and learn: Working towards integrated services. | By 2018 the government expects integrated health and social care to become the norm in England. From next April a £3.8 billion pooled budget called the Better Care Fund will be launched to support service redesign for integrated care. The overall aim of the integration policy is to shift more care into the community to address the challenges of an ageing population by preventing delayed discharges and avoiding emergency hospital admissions. Across England, there are as many different approaches to attaining this holy grail as there are interpretations of the word integration. Nursing Older People visited one pilot site in south east London to explore how integration works in practice and what effect it is having on community nursing services. | 25,171,364 | [
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Thermophoretic manipulation of molecules inside living cells. | The complexity of biology requires that measurements of biomolecular interactions be performed inside living cells. While electrophoresis inside cells is prohibited by the cell membrane, the movement of molecules along a temperature gradient appears feasible. This thermophoresis could be used to quantify binding affinities in vitro at picomolar levels and perform pharmaceutical fragment screens. Here we changed the measurement paradigm to enable measurements inside living cells. The temperature gradient is now applied along the optical axis and measures thermophoretic properties for each pixel of the camera image. We verify the approach for polystyrene beads and DNA of various lengths using finite element modeling. Thermophoresis inside living cells is able to record thermophoretic mobilities and intracellular diffusion coefficients across the whole cytoplasm. Interestingly, we find a 30-fold reduced diffusion coefficient inside the cell, indicating that molecular movement across the cell cytoplasm is slowed down due to molecular crowding. | 25,171,388 | [
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Monkeys rely on recency of stimulus repetition when solving short-term memory tasks. | Seven monkeys performed variants of two short-term memory tasks that others have used to differentiate between selective and nonselective memory mechanisms. The first task was to view a list of sequentially presented images and identify whether a test matched any image from the list, but not a distractor from a preceding list. Performance was best when the test matched the most recently presented image. Response rates depended linearly on recency of repetition whether the test matched a sample from the current list or a distractor from a preceding list, suggesting nonselective memorization of all images viewed instead of just the sample images. The second task was to remember just the first image in a list selectively and ignore subsequent distractors. False alarms occurred frequently when the test matched a distractor presented near the beginning of the sequence. In a pilot experiment, response rates depended linearly on recency of repetition irrespective of whether the test matched the first image or a distractor, again suggesting nonselective memorization of all images instead of just the first image. Modification of the second task improved recognition of the first image, but did not abolish use of recency. Monkeys appear to perform nonspatial visual short-term memory tasks often (or exclusively) using a single, nonselective, memory mechanism that conveys the recency of stimulus repetition. | 25,171,424 | [
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Ovarian germinoma accelerating the presentation of diabetes mellitus. | A 12-year-old girl presented to the Children's Emergency Department with symptoms of diabetes mellitus. Glutamic acid decarboxylase autoantibodies and anti-Islet cell antibodies were absent. She was also found to have ovarian dysgerminoma with markedly elevated serum β-human chorionic gonadotropin (β-HCG). With treatment of her ovarian tumor and normalization of the serum β-HCG her insulin therapy was quickly discontinued and metformin started. The ovarian dysgerminoma appeared to have accelerated the presentation of severe diabetes. We hypothesized that the elevated β-HCG and possibly other placental hormones from the germ cell tumor caused her to develop insulin resistance and inadequate β-cell insulin secretory response. | 25,171,445 | [
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Comparison of three tracheal intubation techniques in thyroid tumor patients with a difficult airway: a randomized controlled trial. | To investigate the effectiveness of the Shikani optical stylet (SOS) and GlideScope video laryngoscope (GVL) for tracheal intubation of thyroid tumor patients with a difficult airway. One hundred and twenty thyroid tumor patients with a difficult airway, who were undergoing elective surgery requiring general anesthesia, were enrolled in the study. They were randomly allocated to 3 groups (n = 40 each) who underwent direct laryngoscopy (DL), SOS or GVL. The outcomes recorded were time to intubation, first-attempt success rate, mean artery pressure (MAP), heart rate (HR) and incidence of complications. The mean time to intubation in the SOS group (group S; 42.4 ± 24.1 s) and the GLV group (group G; 29.8 ± 22.3 s) was significantly less than that in the DL group (group D) (68.8 ± 26.6 s). The first-attempt success rate in group S (90.0%) and group G (97.5%) was significantly higher than that in group D (75.0%; all p < 0.05). The HR and MAP at 1 min after intubation were lowest in group S (76.4 ± 9.2 beats/min and 12.9 ± 1.1 kPa), followed by group G (79.9 ± 9.3 beats/min and 13.0 ± 0.9 kPa) and then group D (90.4 ± 8.1 beats/min and 16.6 ± 1.2 kPa). The difference was statistically significant (all p < 0.05). The incidence of lip or mucosal trauma was lowest in group S, followed by group G and then group D. The SOS and the GLV had advantages over the DL in the management of thyroid tumor patients with a difficult airway in terms of a shorter time to intubation, a higher first-attempt success rate and a reduced incidence of complications. Thus, a rational choice of one of these techniques may be better for the perioperative safety of thyroid tumor patients with a difficult airway. | 25,171,459 | [
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Preparation of carbon-coated iron nanofluid and its application in radiofrequency ablation. | Carbon-coated iron nanoparticles (Fe@C CCINs) were synthesized by carbon arc discharge method and were studied via X-ray diffraction (XRD) and transmission electron microscopy (TEM). The results showed that CCINs have good core-shell structure and are in size of 40-50 nm. Also, carbon-coated iron nanofluid (CCINs-nanofluid) was prepared via two-step method by dispersing as-prepared CCINs and polyvinylpyrrolidone (PVP) into physiological saline. Its dispersion stability and thermal conductivity were detected by gravity sedimentation method and Hotdisk thermal constant analyzer respectively. The results indicated that CCINs-nanofluid possesses good dispersity and stability. Moreover, CCINs-nanofluid showed enhanced thermal conductivity compared with its base fluid physiological saline. The enhancement of thermal conductivity even reaches 41%. Additionally, CCINs-nanofluid injection aided radiofrequency ablation (RFA) was carried out. The relation between tissue temperature and ablation time revealed that by injecting CCINs-nanofluid into pork livers during RFA, target tissue temperatures were less than 100°C. Dissected pork livers showed that there was little or no tissue charring around the ablation probe. Results of ablation area calculation showed that the ablation area of CCINs-nanofluid injection aided RFA was 67% larger than that of saline injection aided RFA, indicating that a larger-volume tumor tissue necrosis at a single session can be achieved by CCINs-nanofluid injection aided RFA. | 25,171,467 | [
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The interleukin-10-1082A>G polymorphism and lymphoma risk: a meta-analysis. | The Interleukin-10 (IL-10) gene polymorphism (-1082 A>G) has been linked to the risk of developing lymphoma, but the available results were inconsistent. To derive a more precise estimation, we performed a meta-analysis. A comprehensive search was conducted to examine all the eligible studies about IL-10-1082A>G polymorphism and lymphoma risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. We included 12 studies, including 5847 cases and 6016 controls. The overall results suggested that the IL-10-1082G allele was associated with a borderline significantly increased risk of lymphoma (G vs. A: OR=1.07, 95% CI=1.01-1.12; GG vs. AA: OR=1.14, 95% CI=1.02-1.26; and AG+GG vs. AA: OR=1.10, 95% CI=1.02-1.19). Stratifying by ethnicity (Caucasian and mixed), tumor type [non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)], sample size (> 1000 and ⩽ 1000 subjects) and Hardy-Weinberg equilibrium (HWE) in controls, similar results were found in mixed subgroup, NHL subgroup, large studies and the subgroup conforming to HWE. In conclusion, the meta-analysis suggests that the IL-10-1082A>G polymorphism is weakly associated with altered susceptibility to lymphoma. Further studies with haplotype analysis and on larger population of mixed ethnicity are warranted for a more definitive conclusion. | 25,171,480 | [
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Association between raf kinase inhibitor protein loss and prognosis in cancers of the digestive system: a meta-analysis. | Loss of Raf kinase inhibitor protein (RKIP) may contribute to metastasis in a variety of human cancers. Many studies have evaluated whether loss of RKIP expression is a prognostic factor for survival in cancers of the digestive system, however, its predictive value remains controversial. Thus, we performed a meta-analysis to obtain a more comprehensive estimate of the prognostic value of RKIP expression in digestive system cancers. Studies were identified by searching multiple electronic databases through December 12, 2013, and by reviewing reference lists of obtained articles. Studies reported hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between RKIP and overall survival (OS) and disease-free survival (DFS) in cancers of the digestive system were eligible, including esophageal cancer, gastric cancer, colorectal cancer and pancreatic cancer. Nineteen studies involving approximately 3700 participants were included in the final analysis. The pooled results suggested that loss of RKIP expression was associated with unfavorable OS (HR 0.55, 95% CI 0.46-0.65) and DFS (HR 0.46, 95% CI 0.30-0.62) among patients with digestive system cancers, whereas the difference was not statistically significant in pancreatic cancer specifically (OS, HR 0.76; 95% CI 0.51-1.01; DFS, HR 0.71; 95% CI 0.28-1.13). Loss of RKIP expression might be an independent indicator of poor prognosis in patients with digestive tract cancers, which includes esophageal cancer, gastric cancer and colorectal cancer. More studies are needed to further clarify the prognostic value of RKIP in pancreatic cancer. Future studies, preferably large prospective studies utilizing formal marker assessment processes, are needed to establish the prognostic value of RKIP before these results can be clinically applied. | 25,171,481 | [
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Development of a method to quantify the DNA content in cationic peptide-DNA nanoparticles. | Gene therapy has the potential to provide safe and targeted therapies for a variety of diseases. A range of intracellular gene delivery vehicles have been proposed for this purpose. Non-viral vectors are a particularly attractive option and among them cationic peptides have emerged as promising candidates. For the pharmaceutical formulation and application to clinical studies it is necessary to quantify the amount of pDNA condensed with the delivery system. There is a severe deficiency in this area, thus far no methods have been reported specifically for pDNA condensed with cationic peptide to form nanoparticles. The current study seeks to address this and describes the evaluation of a range of disruption agents to extract DNA from nanoparticles formed by condensation with cationic fusogenic peptides RALA and KALA. Only proteinase K exhibited efficient and reproducible results and compatibility with the PicoGreen reagent based quantification assay. Thus we report for the first time a simple and reliable method that can quantify the pDNA content in pDNA cationic peptide nanoparticles. | 25,171,486 | [
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Quantum-size-controlled photoelectrochemical fabrication of epitaxial InGaN quantum dots. | We demonstrate a new route to the precision fabrication of epitaxial semiconductor nanostructures in the sub-10 nm size regime: quantum-size-controlled photoelectrochemical (QSC-PEC) etching. We show that quantum dots (QDs) can be QSC-PEC-etched from epitaxial InGaN thin films using narrowband laser photoexcitation, and that the QD sizes (and hence bandgaps and photoluminescence wavelengths) are determined by the photoexcitation wavelength. Low-temperature photoluminescence from ensembles of such QDs have peak wavelengths that can be tunably blue shifted by 35 nm (from 440 to 405 nm) and have line widths that narrow by 3 times (from 19 to 6 nm). | 25,171,507 | [
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Prospect theory based estimation of drivers' risk attitudes in route choice behaviors. | This paper applied prospect theory (PT) to describe drivers' route choice behavior under Variable Message Sign (VMS), which presented visual traffic information to assist them to make route choice decisions. A quite rich empirical data from questionnaire and field spot was used to estimate parameters of PT. In order to make the parameters more realistic with drivers' attitudes, they were classified into different types by significant factors influencing their behaviors. Based on the travel time distribution of alternative routes and route choice results from questionnaire, the parameterized value function of each category was figured out, which represented drivers' risk attitudes and choice characteristics. The empirical verification showed that the estimates were acceptable and effective. The result showed drivers' risk attitudes and route choice characteristics could be captured by PT under real-time information shown on VMS. For practical application, once drivers' route choice characteristics and parameters were identified, their route choice behavior under different road conditions could be predicted accurately, which was the basis of traffic guidance measures formulation and implementation for targeted traffic management. Moreover, the heterogeneous risk attitudes among drivers should be considered when releasing traffic information and regulating traffic flow. | 25,171,520 | [
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Impact of hypertriglyceridemia on the outcome of acute biliary pancreatitis. | Hypertriglyceridemia (HTG) is a well-recognized cause of acute pancreatitis (AP). However, the role of HTG in modulating disease course remains to be cleared. We aimed to explore the impact of HTG on the outcome of acute biliary pancreatitis (ABP). A total of 90 ABP patients with HTG were enrolled in this study and were divided into 3 groups based on ABP severity: mild AP, moderately severe AP (MSAP) and severe AP (SAP), according to the modified Atlanta classification. Besides, patients were divided into type I, II and III HTG groups based on the triglyceride (TG) level, according to the national cholesterol education program (NCEP). Disease severity, Ranson score and complications were recorded and analyzed. Logistic regression analysis was performed to screen predictive risk factors of severe outcomes. There were 23 patients with SAP, 41 with MSAP and 26 with mild AP among the ABP patients with HTG. Significant differences were observed in the obesity, plasma TG level and Ranson score among groups. The risk of developing MSAP in ABP patients with type II and III HTG was increased. Similarly, the risk of developing SAP in ABP patients with type III HTG was also enhanced. The incidence of systemic, especially respiratory failure, and local complications in type III HTG group were significantly higher than normal lipid group. High TG level (≥2.26 mmol/L or 200.11 mg/mL) may be a risk factor for severe ABP and the development of systemic and local complications in ABP. | 25,171,545 | [
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Depression and anxiety symptoms in mothers of newborns hospitalized on the neonatal intensive care unit. | Mothers of infants hospitalized in the neonatal intensive care unit (NICU) are at risk for clinically significant levels of depression and anxiety symptoms; however, the maternal/infant characteristics that predict risk have been difficult to determine. Previous studies have conceptualized depression and anxiety symptoms separately, ignoring their comorbidity. Moreover, risk factors for these symptoms have not been assessed together in one study sample. The primary aim of this study was to determine whether a diagnostic classification approach or a common factor model better explained the pattern of symptoms reported by NICU mothers, including depression, generalized anxiety, panic, and trauma. A secondary aim was to assess risk factors of aversive emotional states in NICU mothers based on the supported conceptual model. In this cross-sectional study, a nonprobability convenience sample of 200 NICU mothers completed questionnaires assessing maternal demographic and infant health characteristics, as well as maternal depression and anxiety symptoms. Structural equation modeling was used to test a diagnostic classification model and a common factor model of aversive emotional states and the risk factors of aversive emotional states in mothers in the NICU. Maximum likelihood estimates indicated that examining symptoms of depression and anxiety disorders as separate diagnostic classifications did not fit the data well, whereas examining the common factor of negative emotionality rendered an adequate fit to the data and identified a history of depression, infant illness, and infant prematurity as significant risk factors. This study supports a multidimensional view of depression and should guide both clinical practice and future research with NICU mothers. | 25,171,558 | [
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Managing heart failure in the long-term care setting: nurses' experiences in Ontario, Canada. | Implementation of heart failure guidelines in long-term care (LTC) settings is challenging. Understanding the conditions of nursing practice can improve management, reduce suffering, and prevent hospital admission of LTC residents living with heart failure. The aim of the study was to understand the experiences of LTC nurses managing care for residents with heart failure. This was a descriptive qualitative study nested in Phase 2 of a three-phase mixed methods project designed to investigate barriers and solutions to implementing the Canadian Cardiovascular Society heart failure guidelines into LTC homes. Five focus groups totaling 33 nurses working in LTC settings in Ontario, Canada, were audiorecorded, then transcribed verbatim, and entered into NVivo9. A complex adaptive systems framework informed this analysis. Thematic content analysis was conducted by the research team. Triangulation, rigorous discussion, and a search for negative cases were conducted. Data were collected between May and July 2010. Nurses characterized their experiences managing heart failure in relation to many influences on their capacity for decision-making in LTC settings: (a) a reactive versus proactive approach to chronic illness; (b) ability to interpret heart failure signs, symptoms, and acuity; (c) compromised information flow; (d) access to resources; and (e) moral distress. Heart failure guideline implementation reflects multiple dynamic influences. Leadership that addresses these factors is required to optimize the conditions of heart failure care and related nursing practice. | 25,171,561 | [
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Timing of cleft lip and palate repair. | The opinions presented below concerning the choice of the timing of the cleft lip and palate repair have been presented on the basis of the literature and own experience. The comments and attempts to make an assessment reflect both direct contacts with representatives of numerous centres conducting interdisciplinary treatment of patients with clefts, as well as 35 years of the first author's experience gained in the course of treating 5,500 cases of primary clefts, besides own patients and numerous post- cleft deformities. | 25,171,626 | [
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Crystallization of methyl ammonium lead halide perovskites: implications for photovoltaic applications. | Hybrid organic/lead halide perovskites are promising materials for solar cell fabrication, resulting in efficiencies up to 18%. The most commonly studied perovskites are CH3NH3PbI3 and CH3NH3PbI3-xClx where x is small. Importantly, in the latter system, the presence of chloride ion source in the starting solutions used for the perovskite deposition results in a strong increase in the overall charge diffusion length. In this work we investigate the crystallization parameters relevant to fabrication of perovskite materials based on CH3NH3PbI3 and CH3NH3PbBr3. We find that the addition of PbCl2 to the solutions used in the perovskite synthesis has a remarkable effect on the end product, because PbCl2 nanocrystals are present during the fabrication process, acting as heterogeneous nucleation sites for the formation of perovskite crystals in solution. We base this conclusion on SEM studies, synthesis of perovskite single crystals, and on cryo-TEM imaging of the frozen mother liquid. Our studies also included the effect of different substrates and substrate temperatures on the perovskite nucleation efficiency. In view of our findings, we optimized the procedures for solar cells based on lead bromide perovskite, resulting in 5.4% efficiency and Voc of 1.24 V, improving the performance in this class of devices. Insights gained from understanding the hybrid perovskite crystallization process can aid in rational design of the polycrystalline absorber films, leading to their enhanced performance. | 25,171,634 | [
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Eating habits of patients with cleft lip and palate terated with fixed appliances. | Health education, built on the basis of various models as a lifelong process, has a considerable impact on eating habits. Correct nutritional patterns are particularly important during the period of intense growth and adolescence. The need to observe dietary recommendations concerns healthy, as well as sick persons, especially those with chronic diseases. To-date the data on the dietary habits of patients with cleft lip and palate during orthodontic treatment have been scarce. The objective of the study was to determine the eating habits of patients with cleft lip and palate before and during orthodontic treatment with a fixed appliance. The study covered 125 patients with cleft lip and palate, aged 14 to 31. The research tool was an own questionnaire assessing the dietary behaviour and oral hygiene habits during the treatment with a fixed orthodontic appliance. In the course of the orthodontic treatment with a fixed appliance, 79 patients (57.6%) did not change their eating patterns and 32 patients (24%) changed them to a moderate degree. The mean of 53 patients (42.7%) changed their hygienic habits considerably. The number of meals remained the same, however in the period when patients suffered pain after orthodontic adjustment appointments, the number of persons having 4-5 meals a day decreased by 32%. It is worth considering that no statistically significant changes were recorded as regards the habit of having sweet snacks and the insufficient consumption of fruit and vegetables. Difficulties with correct oral hygiene were reported after the consumption of e.g. spinach (59.8%), cucumber (57.6%), berries (54.4%), meat (58.2%). Eating habits of a considerable percentage of patients with a cleft defect, before or during the treatment with a fixed appliance, do not comply with healthy nutrition recommendations. The dietary education of patients undergoing orthodontic treatment is necessary to ensure proper oral health and prevent diet-related illnesses. | 25,171,628 | [
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Early and late complications of germinal matrix-intraventricular haemorrhage in the preterm infant: what is new? | Germinal matrix-intraventricular haemorrhage (GMH-IVH) remains a serious problem in the very and extremely preterm infant. This article reviews current methods of diagnosis, treatment and neurodevelopmental outcome in preterm infants with low-grade and severe GMH-IVH. We conclude that there is still no consensus on timing of intervention and treatment of infants with GMH-IVH, whether or not complicated by post-haemorrhagic ventricular dilatation. The discrepancies between the studies underline the need for international collaboration to define the optimal strategy for these infants. | 25,171,657 | [
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Effectiveness of intra-articular injection in wrist joints according to triamcinolone hexacetonide dose in rheumatoid arthritis: a randomized controlled double-blind study. | The aim of this study was to compare the effectiveness in the medium term between low and high doses of triamcinolone hexacetonide used in intra-articular injection in medium-sized joints of rheumatoid arthritis (RA) patients. A randomized double-blind study was carried out in rheumatoid arthritis patients with wrist painful refractory synovitis. Sixty wrists were included and randomized to receive low dose (20 mg) or high dose (40 mg). The outcomes assessed in T0, T1, T4, T8, and T12 weeks were visual analog scale for pain and for swelling, chronic disease activity index, goniometry, simplified Stanford Health Assessment Questionnaire, and side effects. Baseline mean (standard deviation) values were pain visual analog scale of 6.1 (1.6) and 6.3 (1.7), P = 0.562; swelling visual analog scale of 5.9 and 6.4, P = 0.466; chronic disease activity index of 17.8 and 16.8, P = 0.366; and Health Assessment Questionnaire of 0.8 and 0.7, P = 0.238, in the high- and low-dose groups, respectively. Both groups improved pain and swelling assessed by the visual analog scale, P < 0.001, in the intragroup analysis. Chronic disease activity index, goniometry, and Health Assessment Questionnaire also improved equally over time in both groups in the intragroup analysis (P < 0.001, 0.001, and 0.002, respectively). No serious side effects were detected. High and low triamcinolone hexacetonide doses had good effectiveness in wrist-blinded intra-articular injection of rheumatoid arthritis patients, without statistical difference between them. | 25,171,663 | [
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Whole-body strength training using a Huber Motion Lab in coronary heart disease patients: safety, tolerance, fuel selection, and energy expenditure aspects and optimization. | The aim of this study was to investigate safety, tolerance, relative exercise intensity, and muscle substrate oxidation during sessions performed on a Huber Motion Lab in coronary heart disease patients. After an assessment of Vo2 peak, 20 coronary heart disease patients participated in two different exercises performed in random order at 40% and 70% (W40 and W70) of the maximal isometric voluntary contraction. No significant arrhythmia or abnormal blood pressure responses occurred during either session, and no muscle soreness was reported within 48 hrs posttest. The authors found a difference between W40 and W70 sessions for mean (standard deviation) ventilation (25.1% [8%] and 32.1% [9%] of maximal ventilation, respectively; P = 0.04) and a small difference for mean (standard deviation) heart rate (73 [7] and 79 [8] beats/min, respectively; P < 0.01). When compared with the W40, the W70 was associated with higher active energy expenditure (2.4 [0.6] and 3.1 [0.9] Kcal/min, respectively; P < 0.0001) and a similar mean (standard deviation) oxygen uptake (5.5 [1] and 6.6 [1] ml/min per kilogram, respectively; P = 0.07). The qualitative percentages of carbohydrates and lipids oxidized were 71% and 29%, respectively, at W40 and 91% and 9%, respectively, at W70. Both protocols, which consisted of repeating 6-sec phases of contractions with 10 secs of passive recovery on the Huber Motion Lab, seemed to be well tolerated, safe, and feasible in this group of coronary heart disease patients. | 25,171,664 | [
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Symptoms induced by transgenic expression of p23 from Citrus tristeza virus in phloem-associated cells of Mexican lime mimic virus infection without the aberrations accompanying constitutive expression. | Citrus tristeza virus (CTV) is phloem restricted in natural citrus hosts. The 23-kDa protein (p23) encoded by the virus is an RNA silencing suppressor and a pathogenicity determinant. The expression of p23, or its N-terminal 157-amino-acid fragment comprising the zinc finger and flanking basic motifs, driven by the constitutive 35S promoter of cauliflower mosaic virus, induces CTV-like symptoms and other aberrations in transgenic citrus. To better define the role of p23 in CTV pathogenesis, we compared the phenotypes of Mexican lime transformed with p23-derived transgenes from the severe T36 and mild T317 CTV isolates under the control of the phloem-specific promoter from Commelina yellow mottle virus (CoYMV) or the 35S promoter. Expression of the constructs restricted to the phloem induced a phenotype resembling CTV-specific symptoms (vein clearing and necrosis, and stem pitting), but not the non-specific aberrations (such as mature leaf epinasty and yellow pinpoints, growth cessation and apical necrosis) observed when p23 was ectopically expressed. Furthermore, vein necrosis and stem pitting in Mexican lime appeared to be specifically associated with p23 from T36. Phloem-specific accumulation of the p23Δ158-209(T36) fragment was sufficient to induce the same anomalies, indicating that the region comprising the N-terminal 157 amino acids of p23 is responsible (at least in part) for the vein clearing, stem pitting and, possibly, vein corking in this host. | 25,171,669 | [
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Do stress markers and anesthetic technique predict delirium in the elderly? | Postoperative delirium (PD) is a prevalent complication of elderly surgical patients, which predisposes to worsened cognitive recovery and dementia. Risk of PD has been associated with increasing magnitude of the hypothalamic-pituitary-adrenal stress response (serum cortisol, epinephrine and norepinephrine) to surgery. Anesthetics suppress this response; however, some (total intravenous anesthesia, TIVA) more than others (anesthetic gases). Prior comparisons of anesthetics have been equivocal but have not included stress markers. We hypothesized that TIVA would decrease serum stress markers and the incidence of PD. We performed a prospective cohort study of 76 elderly major surgical patients. Patients received TIVA or sevoflurane gas, and blood was drawn for serum markers pre-, intra-, and postoperatively. PD was assessed with the Confusion Assessment Method. We compared stress markers and PD between patients who received TIVA versus sevoflurane, and then modeled PD including stress and anesthetic. The group that received TIVA during surgery demonstrated lower levels of all stress markers compared to the gas group, but no difference in PD. However, across groups, the postoperative norepinephrine level was much higher in patients who developed PD. Other markers and other times had no effect. The development of PD depends more on postoperative stress than intraoperative stress or anesthetic. | 25,171,689 | [
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Fifteen years' experience of a College of American Pathologists program for continuous monitoring and improvement. | The Q-Tracks program, created in 1999, is a quality monitoring subscription service offered by the College of American Pathologists. To establish benchmarks in quality metrics, monitor changes in performance over time, and identify practice characteristics associated with better performance. The Q-Tracks program provides ongoing study of multiple metrics offered in most laboratory disciplines. The design enables measuring the effects of process changes and comparisons with other participating laboratories. Each laboratory Q-Tracks monitor has a primary quality indicator and additional secondary indicators. To date, 19 Q-Tracks monitors have been offered, with 12 currently active monitors. Q-Tracks are primarily conducted in hospital-based laboratories in the United States, Canada, and 21 other countries. Common to most Q-Tracks monitors is a demonstration of performance improvement by subscribers with long-term participation. This finding was seen in preanalytic, turnaround time, and postanalytic measures. Q-Tracks monitors contribute to the overall demonstration and improvement of laboratory and hospital quality because they address core quality measures for the College of American Pathologists Laboratory Accreditation Program and multiple Joint Commission National Patient Safety Goals. The Q-Tracks program has established multiple benchmarks in most disciplines of the laboratory and has demonstrated significant performance improvement in benchmarks and individual laboratories over time. | 25,171,697 | [
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Modulation of α-enolase post-translational modifications by dengue virus: increased secretion of the basic isoforms in infected hepatic cells. | Hepatic cells are major sites of dengue virus (DENV) replication and liver injury constitutes a characteristic of severe forms of dengue. The role of hepatic cells in dengue pathogenesis is not well established, but since hepatocytes are the major source of plasma proteins, changes in protein secretion by these cells during infection might contribute to disease progression. Previously, we showed that DENV infection alters the secretion pattern of hepatic HepG2 cells, with α-enolase appearing as one of the major proteins secreted in higher levels by infected cells. ELISA analysis demonstrated that DENV infection modulates α-enolase secretion in HepG2 cells in a dose-dependent manner, but has no effect on its gene expression and on the intracellular content of the protein as assessed by PCR and western blot analyses, respectively. Two-dimensional western blots showed that both intracellular and secreted forms of α-enolase appear as five spots, revealing α-enolase isoforms with similar molecular weights but distinct isoeletric points. Remarkably, quantification of each spot content revealed that DENV infection shifts the isoform distribution pattern of secreted α-enolase towards the basic isoforms, whereas the intracellular protein remains unaltered, suggesting that post-translational modifications might be involved in α-enolase secretion by infected cells. These findings provide new insights into the mechanisms underlying α-enolase secretion by hepatic cells and its relationship with the role of liver in dengue pathogenesis. In addition, preliminary results obtained with plasma samples from DENV-infected patients suggest an association between plasma levels of α-enolase and disease severity. Since α-enolase binds plasminogen and modulates its activation, it is plausible to speculate the association of the increase in α-enolase secretion by infected hepatic cells with the haemostatic dysfunction observed in dengue patients including the promotion of fibrinolysis and vascular permeability alterations. | 25,171,719 | [
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Exclusive breastfeeding is associated with reduced cow's milk sensitization in early childhood. | Although breastfed infants have consistently been reported as having fewer infections and respiratory morbidity during infancy, none have reached a definitive conclusion as to whether breastfeeding is an effective strategy to prevent allergic diseases. This study aims to investigate the relationship between exclusive breastfeeding and sequential changes of several biomarkers of allergy, such as absolute eosinophil count, total IgE level, and specific IgE level during the first 3 yrs of life. This is an unselected, population-based study that is part of a prospective birth cohort called the PATCH (Prediction of Allergy in Taiwanese Children). Blood analysis was performed at ages 6, 12, 18, 24, and 36 months. Clinical records of breastfeeding and detailed questionnaires regarding to allergic diseases were also obtained. Analysis comparing exclusive breastfeeding ≥4 months with those <4 months and those partially breastfed showed a decreased risk of sensitization toward cow's milk protein up to the age of 2 yr (adjusted OR for cow's milk sensitization at 12 months was 0.2 [95% CI, 0.07-0.5]), at 18 months of age it was 0.2 [95% CI, 0.07-0.5], and at 24 months of age it was 0.2 [95% CI, 0.04-0.7]). In addition, although not significant, children of the exclusive breastfeeding group showed a trend of lower absolute eosinophil counts than their counterparts at all ages, and a lower total IgE level at the age of 3 yr. Results of this study suggest that exclusive breastfeeding is associated with a reduced risk of cow's milk protein sensitization during early childhood. | 25,171,739 | [
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Lack of the NS5B S282T mutation in HCV isolates from liver tissue of treatment-naive patients with HCV genotype-1b infection. | Despite the availability of several direct-acting antivirals (DAAs) specifically inhibiting different HCV proteins, treatment of chronic HCV infection is still a challenge also because of the possible selection of resistant viral variants under DAA therapy. Indeed, only the emergence of viruses resistant to the nucleoside inhibitors of the HCV NS5B polymerase (Pol) has not yet been reported, in spite of the fact that in vitro studies have clearly shown that an S282T amino acid change in the Pol protein may confer resistance to these drugs. On the basis of a previous study showing that viral variants resistant to HCV protease inhibitors are largely present in the liver - but not in the serum - of untreated patients, we investigated the possible natural occurrence of viral populations with the S282T change in the Pol protein, analysing viral isolates from liver and serum of HCV genotype-1b treatment-naive patients. HCV-1b isolates from liver specimens and serum samples of 10 chronic hepatitis C patients were analysed by cloning and sequencing. The S282T mutation was not found in any of the viral isolates from either liver or serum samples of all the cases, although an S282G mutation of unknown virological/clinical relevance was detected in 2/19 liver isolates from one patient. Our study confirms that the natural selection of the S282T mutation is a rare event, thus explaining the lack of emergence and takeover of these variants under drug pressure. | 25,171,743 | [
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Linear-selective hydroarylation of unactivated terminal and internal olefins with trifluoromethyl-substituted arenes. | We report a series of hydroarylations of unactivated olefins with trifluoromethyl-substituted arenes that occur with high selectivity for the linear product without directing groups on the arene. We also show that hydroarylations occur with internal, acyclic olefins to yield linear alkylarene products. Experimental mechanistic data provide evidence for reversible formation of an alkylnickel-aryl intermediate and rate-determining reductive elimination to form the carbon-carbon bond. Labeling studies show that formation of terminal alkylarenes from internal alkenes occurs by initial establishment of an equilibrating mixture of alkene isomers, followed by addition of the arene to the terminal alkene. Computational (DFT) studies imply that the aryl C-H bond transfers to a coordinated alkene without oxidative addition and support the conclusion from experiment that reductive elimination is rate-determining and forms the anti-Markovnikov product. The reactions are inverse order in α-olefin; thus the catalytic reaction occurs, in part, because isomerization creates a low concentration of the reactant α-olefin. | 25,171,744 | [
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The cold-rolling behaviour of AZ31 tubes for fabrication of biodegradable stents. | Mg alloys are receiving considerable attention for biomedical stents due to their combination of good mechanical properties and high biodegradability. Cold rolling is necessary to process Mg alloy tubes before final drawing and fabrication of the magnesium stents. In this paper, cold-rolled tubes were subjected to a cross-sectional reduction rate (ε) of up to 19.7%, and were further processed at various ratios of wall-thickness to diameter reduction (Q) from 0 to 2.24 with a constant ε of 19.7%. The results show that the cold-rolled tubes exhibited a rise in ultimate tensile strength (UTS), yield strength (YS), and a reduction in elongation as ε increased from 5.5% to 19.7%. UTS, YS and elongation decreased when Q was increased from 0 to 2.24. Mechanical twinning was observed and analysed. Extension twins increased with increasing ε and were almost saturated at a ε of 16.5%. Extension twins play an important role in determining the evolution of mechanical behaviour in the case of increasing ε, whilst contraction/double twins and secondary extension twins have a large effect on mechanical behaviour in the case of varying Q. The results indicate that the proportions and types of twins play a major role in determining the mechanical behaviour of the AZ31 tubes. | 25,171,746 | [
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The toolbox of Trichoderma spp. in the biocontrol of Botrytis cinerea disease. | Botrytis cinerea is a necrotrophic fungal pathogen causing disease in many plant species, leading to economically important crop losses. So far, fungicides have been widely used to control this pathogen. However, in addition to their detrimental effects on the environment and potential risks for human health, increasing fungicide resistance has been observed in the B. cinerea population. Biological control, that is the application of microbial organisms to reduce disease, has gained importance as an alternative or complementary approach to fungicides. In this respect, the genus Trichoderma constitutes a promising pool of organisms with potential for B. cinerea control. In the first part of this article, we review the specific mechanisms involved in the direct interaction between the two fungi, including mycoparasitism, the production of antimicrobial compounds and enzymes (collectively called antagonism), and competition for nutrients and space. In addition, biocontrol has also been observed when Trichoderma is physically separated from the pathogen, thus implying an indirect systemic plant defence response. Therefore, in the second part, we describe the consecutive steps leading to induced systemic resistance (ISR), starting with the initial Trichoderma-plant interaction and followed by the activation of downstream signal transduction pathways and, ultimately, the defence response resulting in ISR (ISR-prime phase). Finally, we discuss the ISR-boost phase, representing the effect of ISR priming by Trichoderma spp. on plant responses after additional challenge with B. cinerea. | 25,171,761 | [
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Spatial ecotoxicology: migratory Arctic seabirds are exposed to mercury contamination while overwintering in the northwest Atlantic. | Arctic organisms are exposed to various levels of pollutants, among which mercury (Hg) has raised important environmental concerns. Previous studies examining Hg levels, trends, and effects on Arctic marine top predators have focused on the Arctic region. However, many of these top predators, such as seabirds, migrate to spend a large part of their life cycle far from the Arctic in areas where their exposure to contaminants is largely unknown. By combining biotelemetry and Hg and stable isotope analyses, we studied the seasonal Hg contamination of little auks (Alle alle, the most abundant Arctic seabird) in relation to their distribution and marine foraging habitat, as well as its potential impacts on bird reproduction. We show that little auks were ∼ 3.5 times more contaminated when outside the breeding season, and that Hg that accumulated during this nonbreeding non-Arctic period was related to egg size the following season, with females having more Hg laying smaller eggs. Our results highlight that ecotoxicological studies should be expanded to yield a comprehensive understanding of contamination risks and associated threats to top predators over their entire annual cycle. Furthermore, we show that an important nonbreeding area located in the northwest Atlantic was associated with greater Hg contamination and demonstrate the utility of bird-borne miniaturized technology for evaluating the contamination of marine systems on large spatial scales. | 25,171,766 | [
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Relationship between the shape and density distribution of the femur and its natural frequencies of vibration. | It has been recently suggested that mechanical loads applied at frequencies close to the natural frequencies of bone could enhance bone apposition due to the resonance phenomenon. Other applications of bone modal analysis are also suggested. For the above-mentioned applications, it is important to understand how patient-specific bone shape and density distribution influence the natural frequencies of bones. We used finite element models to study the effects of bone shape and density distribution on the natural frequencies of the femur in free boundary conditions. A statistical shape and appearance model that describes shape and density distribution independently was created, based on a training set of 27 femora. The natural frequencies were then calculated for different shape modes varied around the mean shape while keeping the mean density distribution, for different appearance modes around the mean density distribution while keeping the mean bone shape, and for the 27 training femora. Single shape or appearance modes could cause up to 15% variations in the natural frequencies with certain modes having the greatest impact. For the actual femora, shape and density distribution changed the natural frequencies by up to 38%. First appearance mode that describes the general cortical bone thickness and trabecular bone density had one of the strongest impacts. The first appearance mode could therefore provide a sensitive measure of general bone health and disease progression. Since shape and density could cause large variations in the calculated natural frequencies, patient-specific FE models are needed for accurate estimation of bone natural frequencies. | 25,171,786 | [
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Primary sensory neurons regulate Toll-like receptor-4-dependent activity of glial cells in dorsal root ganglia. | Toll-like receptor-4 (TLR4) has been identified in primary sensory neurons, both in vivo and in vitro, but is reportedly absent from satellite glial cells (SGCs). Herein we reveal that, in rat dorsal root ganglia (DRG), SGCs do express TLR4 but this expression is inhibited by direct contact with neurons. Thus, TLR4 mRNA and protein is strongly up-regulated in isolated DRG glial cells in the absence of neurons. Lipopolysaccharide (LPS) increased cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNFα) mRNA expression with greater efficacy in DRG glial cell cultures than in mixed DRG cell cultures containing TLR4-positive neurons. Using an insert co-culture system, we have shown that neuronal inhibition of glial cell TLR4 is likely to be dependent on cell-cell contact rather than diffusible factors from neurons. LPS stimulated prostaglandin E2 (PGE2) production from DRG glial cells in a TLR4- and COX-2-dependent manner. In addition, exogenous PGE2 potentiated LPS-stimulated COX-2 mRNA while inhibiting TNFα mRNA expression by DRG cells, suggestive of a complex regulatory system to control inflammation within the DRG. In addition to LPS, conditioned medium from heat-shocked DRG neurons also increased COX-2 mRNA expression in DRG glial cells in a partially TLR4-dependent manner. We therefore hypothesize that neuronal suppression of glial TLR4 activity is a protective mechanism to prevent uncontrolled inflammation within the DRG. Under conditions where DRG neuronal viability is compromised, DRG glial cells become responsive to PAMPs (pathogen-associated molecular patterns) and DAMPs (danger-associated molecular patterns) and generate a range of classical inflammatory responses. | 25,171,787 | [
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Can the new McGrath laryngoscope rival the GlideScope Ranger portable video laryngoscope? A randomized manikin study. | We hypothesized that novices would be able to use the McGrath MAC (Aircraft Medical Ltd, Edinburgh, UK) equally as well as the GlideScope Ranger (Verathon, Inc, Bothell, WA) for intubation in regular simulated airways. We performed a prospective, randomized crossover study of 39 medical students using the McGrath MAC, GlideScope Ranger, and Macintosh in a manikin with 2 normal airways. The primary outcome was the intubation time. Secondary outcomes included the success rates and the overall glottic view of the 3 laryngoscopes. The mean intubation times for each attempt with the McGrath MAC were 30.8 ± 16.9 seconds or less and did not differ significantly from those obtained with the GlideScope Ranger or the Macintosh in both airway scenarios (P = .18; P = .49). The mean success rates at each attempt with the McGrath MAC were 82.0% ± 38.8% or more, equal to the Macintosh and the GlideScope Ranger in both scenarios (P = .026; P = .72) except during the first intubation attempt in a normal airway (P = .008). The median grades of the glottic view visible at each intubation attempt with the McGrath Mac were Cormack-Lehane grade 1 (scenario 1: interquartile range, 1-1; scenario 2: interquartile range, 1-2), which was significantly better than the Macintosh laryngoscope in both scenarios. However, the McGrath Mac did not produce a better glottic view than the GlideScope Ranger with either scenario. The intubation performance of novices using the McGrath MAC was equal to their performance using the GlideScope Ranger in regular simulated airways. | 25,171,799 | [
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Relationship between the hemodynamic changes on multi-Td pulsed arterial spin labeling images and the degrees of cerebral artery stenosis. | To explore the relationship between the hemodynamic changes on multi-Td (delay time) pulsed arterial spin labeling (PASL) images and the degrees of cerebral artery stenosis, and to evaluate the value of multi-Td PASL in detecting the signal changes in cerebral arteries with stenosis. 29 patients with less than 50% stenosis (mild stenosis group) and 22 patients with 50%-69% stenosis (moderate stenosis group) in M1 segment of unilateral middle cerebral artery (MCA) were included in this study. The degrees of MCA stenosis were measured using time of flight MR angiography (TOF MRA). Multi-Td PASL imaging was performed to detect the signal changes in bilateral MCA. We selected and hand-drew bilateral symmetric branches of MCA as regions of interest (ROIs) on eight-Td PASL images. The intensities of ROIs were measured, and the time-signal intensity curves were acquired by post-processing on a MR workstation. SPSS19.0 statistical software was used for statistics. The differences in the peak intensities and the times to peak intensities between the normal and narrowed sides of the mild and moderate stenosis groups were respectively examined by paired-samples t test. The differences in the changes of peak intensities and times to peak intensity of the two sides between the mild and moderate stenosis groups were examined by independent samples t test. A p value less than 0.05 was considered statistically significant. There were significant difference in the peak intensities (t=-2.720, p=0.011<0.05) and no significant difference in the times to peak intensities (t=-1.279, p=0.212>0.05) between the normal and narrowed sides of the mild stenosis group. There were both significant differences in the peak intensities (t=-6.076, p=0.000<0.05) and times to peak intensities (t=7.232, p=0.000<0.05) between the normal side and narrowed side of the moderate stenosis group. There were both significant differences in the changes of peak intensities (t=-2.11, p=0.040<0.05) and times to peak intensity (t=-4.23, p=0.000<0.05) between the mild and moderate stenosis groups. The hemodynamic changes on multi-Td PASL images were different with the degrees of cerebral artery stenosis. Moderate stenosis means greater hemodynamic changes in the arteries than mild stenosis. Multi-Td PASL imaging is a promising means to evaluate the hemodynamic changes in cerebral arteries with stenosis. | 25,171,819 | [
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Cultural consonance, constructions of science and co-existence: a review of the integration of traditional, complementary and alternative medicine in low- and middle-income countries. | This review examined the determinants, patterns and imports of official recognition, and incorporation of different traditional, complementary and alternative systems of medicine (TCAM) in the public health establishment of low- and middle-income countries, with a particular focus on India. Public health systems in most countries have tended to establish health facilities centred on allopathy, and then to recognize or derecognize different TCAM based on evidence or judgement, to arrive at health-care configurations that include several systems of medicine with disparate levels of authority, jurisdiction and government support. The rationale for the inclusion of TCAM providers in the public health workforce ranges from the need for personnel to address the disease burden borne by the public health system, to the desirability of providing patients with a choice of therapeutic modalities, and the nurturing of local culture. Integration, mostly described as a juxtaposition of different systems of medical practice, is often implemented as a system of establishing personnel with certification in different medical systems, in predominantly allopathic health-care facilities, to practise allopathic medicine. A hierarchy of systems of medicine, often unacknowledged, is exercised in most societies, with allopathy at the top, certain TCAM systems next and local healing traditions last. The tools employed by TCAM practitioners in diagnosis, research, pharmacy, marketing and education and training, which are seen to increasingly emulate those of allopathy, are sometimes inappropriate for use in therapeutic systems with widely divergent epistemologies, which call for distinct research paradigms. The coexistence of numerous systems of medicine, while offering the population greater choice, and presumably enhancing geographical access to health care as well, is often fraught with tensions related to the coexistence of philosophically disparate, even opposed, disciplines, with distinct and unaligned notions of evidence and efficacy, and ethical and operational challenges of the administration of a plural workforce. | 25,171,821 | [
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[Consensus document for the detection and management of chronic kidney disease]. | Chronic kidney disease (CKD) is an important global health problem, involving to 10% of the Spanish population, promoting high morbidity and mortality for the patient and an elevate consumption of the total health resources for the National Health System. This is a summary of an executive consensus document of ten scientific societies involved in the care of the renal patient, that actualizes the consensus document published in 2007. The central extended document can be consulted in the web page of each society. The aspects included in the document are: Concept, epidemiology and risk factors for CKD. Diagnostic criteria, evaluation and stages of CKD, albuminuria and glomerular filtration rate estimation. Progression factors for renal damage. Patient remission criteria. Follow-up and objectives of each speciality control. Nephrotoxicity prevention. Cardio-vascular damage detection. Diet, life-style and treatment attitudes: hypertension, dyslipidaemia, hyperglycemia, smoking, obesity, hyperuricemia, anemia, mineral and bone disorders. Multidisciplinary management for Primary Care, other specialities and Nephrology. Integrated management of CKD patient in haemodialysis, peritoneal dialysis and renal transplant patients. Management of the uremic patient in palliative care. We hope that this document may be of help for the multidisciplinary management of CKD patients by summarizing the most updated recommendations. | 25,171,835 | [
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The salt content of products from popular fast-food chains in Costa Rica. | Salt is a major determinant of population blood pressure levels. Salt intake in Costa Rica is above levels required for good health. With an increasing number of Costa Ricans visiting fast food restaurants, it is likely that fast-food is contributing to daily salt intake. Salt content data from seven popular fast food chains in Costa Rica were collected in January 2013. Products were classified into 10 categories. Mean salt content was compared between chains and categories. Statistical analysis was performed using Welch ANOVA and Tukey-Kramer HSD tests. Significant differences were found between companies; Subway products had lowest mean salt content (0.97 g/100 g; p < 0.05) while Popeye's and KFC had the highest (1.57 g/100 g; p < 0.05). Significant variations in mean salt content were observed between categories. Salads had a mean salt content of 0.45 g/100 g while sauces had 2.16 g/100 g (p < 0.05). Wide variation in salt content was also seen within food categories. Salt content in sandwiches ranged from 0.5 to 2.1 g/100 g. The high levels and wide variation in salt content of fast food products in Costa Rica suggest that salt reduction is likely to be technically feasible in many cases. With an increasing number of consumers purchasing fast foods, even small improvements in salt levels could produce important health gains. | 25,171,851 | [
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Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxiredoxin 6 (Prdx6) proteins in healthy and pathologic placentas of human and rat. | A relationship has been shown between preeclampsia (PE) and intrauterine growth restriction (IUGR) and oxidative stress (OS). Since such pregnancies experience OS, we aimed to detect the distribution pattern and expression levels of a transcription factor, Nuclear factor erythroid 2-related factor-2 (Nrf2) that has a role in the regulation of antioxidant enzymes, and peroxiredoxin 6 (Prdx6) an antioxidant enzyme, in human healthy, IUGR, PE and in groups of rat healthy and IUGR placentas using immunohistochemistry and Western blotting. Both Nrf2 and Prdx6 immunoreactivities were weaker in human and rat IUGR group placentas compared to human and rat control group placentas, respectively. Nrf2 and Prdx6 were immunostained in labyrinth trophoblasts, decidua, giant, glycogen and fetal vessel endothelial cells in rat control and IUGR group placentas. Nrf2 and Prdx6 immunoreactivities were seen in the decidua, syncytiotrophoblasts, villous stromal cells, and vascular endothelium in human control, IUGR and PE group placentas. Results of Nrf2 and Prdx6 Western blotting applied for rat and human placentas were compatible with the results of Nrf2 and Prdx6 immunohistochemical observations with regard to rat and human placentas. Down-regulation of Nrf2 and Prdx6 proteins in human and rat IUGR group placentas may have led to the formation of OS which may have impaired proliferation and invasion of cytotrophoblasts. | 25,171,874 | [
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Development of a non-blurring, dual-imaging tissue marker for gastrointestinal tumor localization. | Knowing the exact location of gastrointestinal tumors both preoperatively and intraoperatively is essential for planning and performing laparoscopic surgery. Different techniques have been introduced to ascertain tumor locations during surgery, but none of these are fully satisfactory at establishing the minimum margins for organ resection while retaining curability. A new, non-blurring tissue marker, detectable by both X-ray computed tomography (CT) and near-infrared (NIR) fluorescence laparoscopy, has been developed, and we here examine its utility using an animal model. Liposomes, comprised phospholipids and an NIR fluorescent dye (an indocyanine green derivative), and emulsions, consisting of phospholipids and oily radiographic contrast medium, were combined with polyglycerol-polyricinoleate to form giant cluster-like vesicles. This vesicular dispersion (300 μl) was administered into the porcine gastric submucosa using a gastroendoscope, and the detectability of the marker was examined using X-ray CT and NIR fluorescence laparoscopy. One hour after the administration of the vesicular dispersion, X-ray CT identified four individual injection sites, each at a 1-cm radius of a metal hemostasis clip. NIR fluorescence laparoscopy detected individual fluorescent spots 18 hours after the administration of the vesicular dispersion. We anticipate that this newly developed tissue marker will contribute to the preoperative simulation of laparoscopic gastrointestinal cancer surgery and its intraoperative navigation. | 25,171,886 | [
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Imaging frontotemporal lobar degeneration. | The term frontotemporal lobar degeneration (FTLD) refers to a group of neurodegenerative disorders that target the frontal and temporal lobes. It accounts for approximately 10 % of pathologically confirmed dementias but has been demonstrated to be as prevalent as Alzheimer's disease in patients below the age of 65. The 3 major clinical syndromes associated with FTLD include behavioral variant frontotemporal dementia, semantic and nonfluent variants of primary progressive aphasia. The more recently introduced term logopenic variant appears to represent an atypical form of Alzheimer's disease in the majority of cases. The neuropathology underlying these clinical syndromes is very heterogeneous and does not correlate well with the clinical phenotype. This causes great difficulties in early and reliable diagnosis and treatment of FTLD. However, significant advances have been made in recent years via the application of magnetic resonance imaging and positron emission tomography imaging methods as biomarkers. The current review aims to provide a synopsis on the value of magnetic resonance imaging-based and molecular imaging procedures in FTLD. | 25,171,901 | [
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Comparison of adverse obstetric outcomes and maternity hospitalization among heroin-exposed and methadone-treated women in Taiwan. | To identify sociodemographic and clinical factors predicting the overall risk of adverse obstetric outcomes and the length of maternal hospital stay among heroin-exposed and methadone-treated women in Taiwan. Using the retrospective matched cohort study design, 396 births to women on methadone treatment during pregnancy (the methadone-treated group) and 609 to women who started methadone treatment after childbirth (the heroin-exposed group) were identified in the National Methadone Maintenance Program. Adverse pregnancy outcomes were assessed by still birth, low birth weight and preterm delivery. We used multivariate methods and zero-truncated negative binomial regression to evaluate association estimates. Both heroin-exposed and methadone-treated women had 2-4-fold greater risk of adverse pregnancy outcomes. HIV infection increased the overall risk of adverse pregnancy outcome in the methadone-treated group, whereas being unmarried and having treatment history of substance use disorders increased such risk in the heroin-exposed group. Maternal ages at delivery and healthcare facility used had moderate effects on the length of maternal hospital stay; HIV infection significantly increased the length of hospital stay for women in the heroin-exposed group (adjusted relative risk=1.32, 95% CI=1.05-1.68). Our results showed no appreciable differences in the occurrence of adverse obstetric outcomes and the length of maternity hospitalization between the methadone-treated and the heroin-exposed women; the profile of sociodemographic and clinical predictors was similar as well. Coordination of addiction treatment and prenatal care may help reduce unfavorable obstetric outcomes among female heroin addicts seeking substitution treatment. | 25,171,908 | [
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Sexual identity, same-sex partners and risk behaviour among a community-based sample of young people in Australia. | Young people who are same-sex attracted report higher rates of substance use, sexual risk behaviour, and mental health problems. Numerous studies have shown that sexual identity, sexual behaviour and sexual attraction do not always correspond, particularly among young people. We describe sexual identity, sexual partners, and associations between sexual identity and risk in a community-based sample of young people. From 2011 to 2013, young people (16-29 years) were recruited at a music festival in Melbourne, Australia to self-complete a questionnaire. We describe sexual identity and gender of anal/vaginal sex partners in the past year. Secondly, we assess associations between risk behaviours, health outcomes and gay/lesbian/bisexual/queer/questioning (GLBQQ)-identity using multivariable logistic regression. Among 3793 (91%) participants with complete data, 115 (9%) males and 266 (11%) females were GLBQQ-identifying. Among GLBQQ-identifying males, 23% reported only same-sex partners, 34% reported both sex partners, 26% reported only opposite-sex partners, 5% reported no sex partners in the past year, and 12% had never had sex. Among GLBQQ-identifying females, 10% reported only same-sex partners, 22% reported both sex partners, 48% reported only opposite-sex partners, 3% reported no sex partners in the past year, and 17% had never had sex. Controlling for age and sex, significant (p<0.05) associations with GLBQQ-identity included: recent drug use (adjusted odds ratio [AOR] 1.7, 95%CI 1.3-2.2); ever injected drugs (AOR 5.7, 95%CI 3.3-9.7); young age at first sex (AOR 1.8, 95%CI 1.3-2.3); ≥11 lifetime sex partners (AOR 1.5, 95%CI 1.1-2.0); multiple sex partners in the past year (AOR 1.9, 95%CI 1.5-2.5); and rating mental health as fair/poor (AOR 3.0, 95%CI 1.9-4.6). Young people with GLBQQ-identity commonly engage in high risk behaviours and are more at risk relative to their heterosexual-identifying peers. Targeted interventions to promote the health and wellbeing of this group should account for the complexities of identity and behaviour. | 25,171,911 | [
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Lights and shadows of anti-HLA antibodies detected by solid-phase assay. | Recently, management of patients awaiting solid organ transplantation has taken advantages after the development of more sensitive and accurate solid phase assays which have supported the historic complement dependent cytotoxicity. This approach has allowed the detection of antibodies in patients previously considered negative. The use of the single antigen beads resulted in a more accurate anti-human leukocyte antigen (HLA) antibody characterization. The detection of anti-HLA antibodies specific for C, DQ and DP loci that were not so well characterized has been possible through the implementation of the single antigen assay. The assessment of HLA compatibility has been expanded through the introduction of "epitope matching" concept and the definition of the unacceptable antigens for a more adequate evaluation of donor-recipient compatibility. However, the clinical impact of pre-formed and de novo anti-HLA antibodies detected by solid phase assays is still controversial due to the drawback related to result interpretation. Until today, the unresolved issues concern if all antibodies affect the medium and long term clinical outcome. An open debate on the clinical relevance of anti-HLA antibodies detected by single-antigen beads highlights needing to further investigations. Here, we describe the novel applications and the improvements of the solid-phase assay use. | 25,171,913 | [
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Microsatellite-centromere mapping in common carp through half-tetrad analysis in diploid meiogynogenetic families. | Gene-centromere (G-C) mapping provides insights into the understanding of the composition, structure, and evolution of vertebrate genomes. Common carp (Cyprinus carpio) is an important aquaculture fish and has been proposed to undertake tetraploidization. In this study, we selected 214 informative microsatellite markers across 50 linkage groups of a common carp genetic map to perform gene-centromere mapping using half-tetrad analysis. A total of 199 microsatellites were segregated under the Mendelian expectations in at least one of the three gynogenetic families and were used for G-C distance estimation. The G-C recombination frequency (y) ranged from 0 to 0.99 (0.43 on average), corresponding to a fixation index (F) of 0.57 after one generation of gynogenesis. Large y values for some loci together with significant correlation between G-C distances and genetic linkage map distances suggested the presence of high interference in common carp. Under the assumption of complete interference, 50 centromeres were localized onto corresponding linkage groups (LGs) of common carp, with G-C distances of centromere-linked markers per LG ranging from 0 to 10.3 cM (2.9 cM on average). Based on the information for centromere positions, we proposed a chromosome formula of 2n = 100 = 58 m/sm + 42 t/st with 158 chromosome arms for common carp, which was similar to a study observed by cytogenetic method. The examination of crossover distributions along 10 LGs revealed that the proportion of crossover chromatids was overall higher than that of non-crossover chromatids in gynogenetic progenies, indicating high recombination levels across most LGs. Comparative genomics analyses suggested that the chromosomes of common carp have undergone extensive rearrangement after genome duplication. This study would be valuable to elucidate the mechanism of genome evolution and integrate physical and genetic maps in common carp. | 25,171,918 | [
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Automated medical resident rotation and shift scheduling to ensure quality resident education and patient care. | At academic teaching hospitals around the country, the majority of clinical care is provided by resident physicians. During their training, medical residents often rotate through various hospitals and/or medical services to maximize their education. Depending on the size of the training program, manually constructing such a rotation schedule can be cumbersome and time consuming. Further, rules governing allowable duty hours for residents have grown more restrictive in recent years (ACGME 2011), making day-to-day shift scheduling of residents more difficult (Connors et al., J Thorac Cardiovasc Surg 137:710-713, 2009; McCoy et al., May Clin Proc 86(3):192, 2011; Willis et al., J Surg Edu 66(4):216-221, 2009). These rules limit lengths of duty periods, allowable duty hours in a week, and rest periods, to name a few. In this paper, we present two integer programming models (IPs) with the goals of (1) creating feasible assignments of residents to rotations over a one-year period, and (2) constructing night and weekend call-shift schedules for the individual rotations. These models capture various duty-hour rules and constraints, provide the ability to test multiple what-if scenarios, and largely automate the process of schedule generation, solving these scheduling problems more effectively and efficiently compared to manual methods. Applying our models on data from a surgical residency program, we highlight the infeasibilities created by increased duty-hour restrictions placed on residents in conjunction with current scheduling paradigms. | 25,171,938 | [
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Allergy and risk of hematologic malignancies: associations and mechanisms. | Increasing evidence indicates that a dysregulated immune system, as the one found in allergic disorders, can affect survival of tumor cells. A possible association between allergies and risk of hematologic malignancies has been examined in several epidemiological studies; however, results were not always consistent. The aim of this review is to report the preclinical and clinical data, which support a correlation between allergy and hematologic neoplasms. Immune system modulation could represent a powerful tool in the prevention and treatment of hematologic malignancies. | 25,171,954 | [
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Virtual screening strategies: recent advances in the identification and design of anti-cancer agents. | Virtual screening (VS) is a well-established technique, which is now routinely employed in computer aided drug designing process. VS can be broadly classified into two categories, i.e., ligand-based and structure-based approach. In recent years, VS has emerged as a time saving and cost effective technique, capable of screening millions of compounds in a user friendly manner. In the area of cancer drug design, VS methods have been widely used and helped in identifying novel molecules as potential anti-cancer agents. Both ligand-based VS (LBVS) structure-based VS (SBVS) methods have been highly useful in the identification of a number of potential anti-cancer agents exhibiting activities in nanomolar range. In tune with the rapid progress in the enhancement of computational power, VS has witnessed significant change in terms of speed and hit rate and in future it is expected that VS will be a preferential alternative to high throughput screening (HTS). This review, discusses recent trends and contribution of VS in the area of anti-cancer drug discovery. | 25,171,960 | [
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Indocyanine green videoangiography methodological variations: review. | Indocyanine green videoangiography (ICGVA) procedures have become widespread within the spectrum of microsurgical techniques for neurovascular pathologies. We have conducted a review to identify and assess the impact of all of the methodological variations of conventional ICGVA applied in the field of neurovascular pathology that have been published to date in the English literature. A total of 18 studies were included in this review, identifying four primary methodological variants compared to conventional ICGVA: techniques based on the transient occlusion, intra-arterial ICG administration via catheters, use of endoscope system with a filter to collect florescence of ICG, and quantitative fluorescence analysis. These variants offer some possibilities for resolving the limitations of the conventional technique (first, the vascular structure to be analyzed must be exposed and second, vascular filling with ICG follows an additive pattern) and allow qualitatively superior information to be obtained during surgery. Advantages and disadvantages of each procedure are discussed. More case studies with a greater number of patients are needed to compare the different procedures with their gold standard, in order to establish these results consistently. | 25,171,963 | [
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Serum lactate as a potential biomarker of malignancy in primary adult brain tumours. | Lactate, a by-product of glycolysis, is an indicator of poor tissue perfusion and is a useful biomarker with prognostic value in risk-stratifying patients in several diseases. Furthermore, elevated lactate production is observed in tumour glycolysis, also known as the Warburg effect, and is essential in promoting tumour cell invasion, metastasis, and immune system evasion, promoting resistance to cell death. However, there are no studies of elevated serum lactate in brain tumour patients as a potential biomarker, to our knowledge. The aim of this study is to determine possible correlations between the malignancy of tumours and pre- and intraoperative serum lactate elevation in patients undergoing craniotomy for tumour resection. We provide initial evidence that a rise in serum lactate can be used as a non-invasive biomarker that correlates with brain tumour grade. The results from this study and future prospective studies may allow for determination of tumour progression and response to therapy using serum lactate as a biomarker. | 25,172,017 | [
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Revision of primary total hip arthroplasty for peri-prosthetic fracture: A prospective epidemiological study of 249 consecutive cases in France. | Revision total hip arthroplasty (reTHA) for peri-prosthetic fracture (PPF) is increasingly performed but still ranks fourth among reasons for reTHA in registries. In France, no specific registry is available and the frequency of PPF among reasons for THA revision is therefore unknown. Here, our objectives were to determine the relative frequency of PPF as a reason for reTHA, to identify patient-related and primary-THA-related factors associated with reTHA for PPF, to describe reTHA modalities for PPF, and to determine the morbidity and mortality associated with reTHA for PPF. PPF is the second most common reason for reTHA, after loosening. Consecutive reTHA procedures performed in 30 French centres over a 2-year period were collected prospectively. Repeat revisions and revisions of hemi-arthroplasties were excluded. The epidemiological, clinical, and surgical data needed to answer the questions of the study were collected. PPF was the second leading reason for reTHA (249/2107, 11.8%). Vancouver type B2 fractures were the most common (n=127 [51.5%]). Compared to patients who underwent reTHA for reasons other than PPF, those with reTHA for PPF were older at primary THA (67.9 years versus 57.7 years) and more often had intra-operative complications (16.9% versus 11.6%); furthermore, the primary THA was more often cementless (62.7% versus 42.7%) with a dual-mobility cup (20.6% versus 11.1%). At reTHA, the patients with PPF were older (77.6 years versus 69.2 years), had worst medical condition (mean ASA score, 2.4 versus 2.1) and less physically active (mean Devane score, 2.1 versus 2.4). The patients with reTHA for PPF had a shorter time to revision (9.8 years versus 11.4 years), a longer operative time (144 minutes versus 128 minutes), and more frequent use of the posterior approach (77% versus 67%) with a cementless dual-mobility cup (78% versus 60%) and a cementless revision femoral stem (72% versus 50%). Morbidity and mortality rates were high (5.9% operative complication rate and 12% of surgical complications with 4.8% mortality within the first 3 months) however, these results were similar to those in the rest of the cohort. PPF is the second most common reason for reTHA, a result that is at variance with data in national registries. Level IV, prospective observational cohort study. | 25,172,019 | [
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Clinical laboratory data: acquire, analyze, communicate, liberate. | The availability of portable healthcare devices, which can acquire and transmit medical data to remote experts would dramatically affect healthcare in areas with poor infrastructure. Smartphones, which feature touchscreen computer capabilities and sophisticated cameras, have become widely available with over billion units shipped in 2013. In the clinical laboratory, smartphones have recently brought the capabilities of key instruments such as spectrophotometers, fluorescence analyzers and microscopes into the palm of the hand. Several research groups have developed sensitive and low-cost smartphone-based diagnostic assay prototypes for testing cholesterol, albumin, vitamin D, tumor markers, and the detection of infectious agents. This review covers the use of smartphones to acquire, analyze, communicate, and liberate clinical laboratory data. Smartphones promise to dramatically improve the quality and quantity of healthcare offered in resource-limited areas. | 25,172,035 | [
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Correlation of nodal mast cells with clinical outcome in dogs with mast cell tumour and a proposed classification system for the evaluation of node metastasis. | Lymph node metastasis in dogs with mast cell tumour has been reported as a negative prognostic indicator; however, no standardized histological criteria exist to define metastatic disease. The primary aim of this study was to determine whether different histological patterns of node-associated mast cells correlate with clinical outcome in dogs with mast cell tumour. A secondary goal was to propose a criteria-defined classification system for histological evaluation of lymph node metastasis. The Colorado State University Diagnostic Medicine Center database was searched for cases of canine mast cell tumours with reported lymph node metastasis or evidence of node-associated mast cells. Additional cases were obtained from a clinical trial involving sentinel lymph node mapping and node extirpation in dogs with mast cell neoplasia. Forty-one cases were identified for inclusion in the study. Demographic data, treatment and clinical outcome were collected for each case. Lymph nodes were classified according to a novel classification system (HN0-HN3) based on the number of, distribution of, and architectural disruption by, nodal mast cells. The findings of this study indicate that characterization of nodal mast cells as proposed by this novel classification system correlates with, and is prognostic for, clinical outcome in dogs with mast cell tumours. | 25,172,053 | [
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Platelet-derived growth factors and receptors in Canine Lymphoma. | Platelet-derived growth factors (PDGFs) belong to a family of polypeptide growth factors that signal through cell surface tyrosine kinase receptors to stimulate growth, proliferation and differentiation. Platelet-derived growth factor receptors (PDGFRs) are also considered important targets for specific kinase inhibitors in the treatment of several human tumours. The aim of this study was to investigate the role of PDGF-A, PDGF-B, PDGFR-α and PDGFR-β in canine lymphoma by determining gene and protein expression in lymph nodes of dogs with diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), T-lymphoblastic lymphoma (T-LBL) and in healthy control dogs. One lymph node was also studied at the end of therapy in a subset of dogs in remission for DLBCL. In controls, PDGF-A, PDGFR-α and PDGFR-β mRNA levels were significantly higher than in DLBCLs, PTCLs and T-LBLs. However, PDGFR-α and PDGFR-β were minimally expressed by lymphocytes and plasma cells in normal lymph nodes as determined by immunohistochemistry, while neoplastic B and T cells showed the highest score (P <0.05). This discordant result may be compatible with the constitutive expression of these molecules by endothelial cells and fibroblasts in normal lymph nodes, thereby influencing gene expression results. Furthermore, these cells were not included in the immunohistochemical analysis. Similarly, dogs with DLBCL that were in remission at the end of therapy showed significantly higher gene expression of PDGFs and receptors than at the time of diagnosis and with an opposite trend to the protein assay. PDGF-B protein and mRNA were overexpressed in PTCLs and T-LBLs when compared with DLBCLs and controls (P <0.05). Additionally, there was a correlation between protein expression of PDGF-B and both PDGFRs in PTCLs and T-LBLs, suggesting an autocrine or paracrine loop in the aetiology of aggressive canine T-cell lymphomas. These data provide a rationale for the use of PDGFR antagonists in the therapy of aggressive T-cell lymphomas, but not in DLBCLs. | 25,172,054 | [
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Consumption of 2-chlorophenol using anaerobic sludge: physiological and kinetic analysis. | Chlorophenols are toxic and recalcitrant compounds produced by many industrial. Different strategies have been used to improve their biological consumption, but there is insufficient information to understand how the process is carried out. The objective of this study was to evaluate in batch tests the effect of the addition of phenol, acetate, or glucose as electron donors at different concentrations on the efficiencies, yields, and specific rates of 2-chlorophenol (2-CP) consumption. The addition of phenol (177.6 mg C/L), acetate (127.6 mg C/L), or glucose (77.6 mg C/L) increased the 2-CP consumption efficiency up to 54.6, 98.6, and 97.8 %, respectively. With respect to the control assay without electron donor, the specific rate of 2-CP consumption was up to 2.5 times higher with phenol (177.6 mg C/L), 8.4 times higher with acetate (127.6 mg C/L), and 3 times higher with glucose (127.6 mg C/L). The results showed that the type and concentration of electron donor determine the physiological behavior of the anaerobic sludge, modifying efficiency, yield, and specific rate values of the 2-CP consumption process. The addition of readily oxidable cosubstrates seems to be a good alternative and might be used for the biological treatment of industrial wastewater polluted with chlorinated phenols. | 25,172,056 | [
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Nutrition and cardiovascular health. | A multitude of studies have been published on the relationship between cardiovascular disease risk and a variety of nutrients, foods, and dietary patterns. Despite the well-accepted notion that diet has a significant influence on the development and prevention of cardiovascular disease, the foods considered healthy and harmful have varied over the years. This review aims to summarize the current scientific evidence on the cardioprotective effect of those foods and nutrients that have been considered healthy as well as those that have been deemed unhealthy at any given time in history. For this purpose, we reviewed the most recent literature using as keywords foods and nutrients (ie, meat, omega-3) and cardiovascular disease-related terms (ie, cardiovascular diseases, stroke). Emphasis has been placed on meta-analyses and Cochrane reviews. In general, there is a paucity of intervention studies with a high level of evidence supporting the benefits of healthy foods (ie, fruits and vegetables), whereas the evidence supporting the case against those foods considered less healthy (ie, saturated fat) seems to be weakened by most recent evidence. In summary, most of the evidence supporting the benefits and harms of specific foods and nutrients is based on observational epidemiological studies. The outcome of randomized clinical trials reveals a more confusing picture with most studies providing very small effects in one direction or another; the strongest evidence comes from dietary patterns. The current status of the relationship between diet and cardiovascular disease risk calls for more tailored recommendations based on genomic technologies. | 25,172,070 | [
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Imaging techniques in the evaluation of post-infarction function and scar. | Imaging techniques are essential in the clinical evaluation of patients with a myocardial infarction. They are of value for both initial assessment of the ischemic injury and for detection of the subgroup of patients at higher risk of developing cardiovascular events during follow-up. Echocardiography remains the technique of choice for the initial evaluation, owing to its bedside capability to determine strong predictors, such as ventricular volumes, global and regional systolic function, and valvular regurgitation. New techniques for evaluating ventricular mechanics, mainly assessment of ventricular deformation, are revealing important aspects of post-infarction ventricular adaptation. The main alternative to echocardiography is cardiac magnetic resonance imaging. This technique is highly accurate for determining ventricular volumes and ventricular function and has the additional advantage of being able to characterize the myocardium and demonstrate changes associated with the ischemic insult such as necrosis/fibrosis, edema, microvascular obstruction, and intramyocardial hemorrhage. These features not only allow detection and quantification of the infarct size, but also reveal additional characteristics of the scar tissue with prognostic value. | 25,172,072 | [
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Heat stress during the Black Saturday event in Melbourne, Australia. | The Black Saturday bushfire event of February 7, 2009, devastated the state of Victoria, Australia, resulting in 173 deaths. On this day, the maximum temperature in Melbourne (state capital of Victoria, population 4 million people) exceeded 46 °C, there were wind gusts of over 80 km h(-1) and the relative humidity dropped below 5 %. We investigated the severe meteorological conditions of Black Saturday and the risk of heat stress and dehydration for the residents of Melbourne. This was through the analysis of weather station data, air pollution data, the apparent temperature (AT) and the COMfort FormulA human energy budget model. A very strong pressure gradient caused hot and dry air to be advected to Melbourne from the desert interior of Australia creating the extreme weather conditions. The AT showed that on Black Saturday, heat stress conditions were present, though underrepresented due to assumptions in the AT formula. Further investigation into the human energy budget revealed that the conditions required a sweating rate of 1.4 kg h(-1) to prevent heat accumulation into the body. If sweating stopped, hyperthermia could occur in 15 min. Sensitivity tests indicated that the dry air and strong winds on Black Saturday helped to release latent heat, but the required sweating rate was virtually unattainable for an average person and would result in intense dehydration. Air particulates were at dangerous concentrations in Melbourne on Black Saturday, further intensifying the stresses to the human body. In the future, we recommend that the AT is not used as a thermal comfort measure as it underestimates the physical stress people experience. | 25,172,086 | [
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A study of the reliability of the Nociception Coma Scale. | In this study, we investigated the reliability of the Nociception Coma Scale which has recently been developed to assess nociception in non-communicative, severely brain-injured patients. Prospective cross-sequential study. Semi-intensive care unit and long-term brain injury care. Forty-four patients diagnosed as being in a vegetative state (n=26) or in a minimally conscious state (n=18). Patients were assessed by two experts (rater A and rater B) on two consecutive weeks to measure inter-rater agreement and test-retest reliability. Total scores and subscores of the Nociception Coma Scale. We performed a total of 176 assessments. The inter-rater agreement was moderate for the total scores (k = 0.57) and fair to substantial for the subscores (0.33 ≤ k ≤ 0.62) on week 2. The test-retest reliability was substantial for the total scores (k = 0.66) and moderate to almost perfect for the subscores (0.53 ≤ k ≤ 0.96) for rater A. The inter-rater agreement was weaker on week 1, whereas the test-retest reliability was lower for the least experienced rater (rater B). This study provides further evidence of the psychometric qualities of the Nociception Coma Scale. Future studies should assess the impact of practical experience and background on administration and scoring of the scale. | 25,172,088 | [
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Diversified bioactivities of four types of naturally occurring quinochalcones. | Quinochalcones, quinone-containing chalcones, belong to the flavonoid family and have attracted increasing popularity in Western countries in the last decade due to their pharmacological activities. This review describes four types of naturally occurring quinochalcones and summarizes their different pharmacological activities, including anti-cerebral ischemia, anti-tumor, and anti-infection activities. In addition, the pharmacological activities and relevant structure-activity relationships of synthetic quinochalcones are also reviewed. | 25,172,102 | [
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The apparent prevalence of skin lesions suspected to be human-inflicted in Danish finishing pigs at slaughter. | Skin lesions on pigs inflicted by humans compromise animal welfare and are the subject of increased public and political attention in Denmark. Systematic surveillance of such skin lesions was enforced in April 2010 at all Danish pig abattoirs, through the recording of meat inspection Code 904 for the presence of skin lesions suspected to be human inflicted. The objectives of the present study were to (a) estimate the apparent prevalence of Code 904s at the pig and herd owner level; (b) characterise the distribution of deliveries with pigs demonstrating a Code 904; (c) characterise the distribution of herd owners with repeated Code 904 recordings; and (d) determine the developments in Code 904 prevalence over time in Danish finishing pigs in the period from May 1, 2010 to September 30, 2013. Data from the 12 largest finishing pig abattoirs from Denmark were included and recordings were comprised from 65,504,021 pigs from 651,681 deliveries originating from 10,796 herd owners. Overall, 7200 (0.011%) of the pigs were recorded with a Code 904, and 21% of herd owners had a minimum of one Code 904 delivery with at least one pig with skin lesions inflicted by humans. On the pig-level, the apparent prevalence was 0.020% in 2010, which was reduced to 0.008% in 2013. In the first quarter of the study period, 17% of the herd owners had a Code 904 delivery, while 7% had one in the last quarter. Nine per cent of the herds had more than one Code 904 recording, with up to 16 Code 904 deliveries from one herd owner. Most deliveries included one single pig with a Code 904, but up to 102 Code 904 recordings were made in a single delivery. The apparent prevalence at the four smallest and four middle sized abattoirs decreased from the first to the second quarter, while the apparent prevalence decreased more substantially in the largest four abattoirs; with significant decreases from both the first to the second, and from the second to the third quarter. The study showed that recorded skin lesions suspected to be inflicted by humans are prevalent, but the apparent prevalence decreased from 2010 to 2012 and 2013. The development in Code 904 over time could be due to a real decrease or be due to other factors such as changes in the way the lesions were recorded, while both underestimation and overestimation appeared to be present. | 25,172,120 | [
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Development of (18)F-labeled radiotracers for neuroreceptor imaging with positron emission tomography. | Positron emission tomography (PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including genetically-engineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo. | 25,172,118 | [
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Synthesis of α-L-rhamnosyl ceramide and evaluation of its binding with anti-rhamnose antibodies. | An α-L-rhamnosyl ceramide (1, α-L-RhaCer) has been prepared that was recognized by anti-L-rhamnose (anti-Rha) antibodies. During these studies we explored the use of an α-L-rhamnosyl thioglycoside and a trichloroacetimidate as a glycosyl donors. Subsequently, the acceptors desired for glycosylation, 3-O-benzoylazidosphingosine or 3-O-alloxycarbonylsphingosine, were prepared from D-xylose. The thioglycoside donor, 2,3,4-tri-O-acetyl-1-(4-tolyl)thio-α-L-rhamnopyranoside, and the trichloroacetimidate donor, 2,3,4-tri-O-acetyl-1-(2,2,2-trichloroethanimidate)-α-L-rhamnopyranoside, were synthesized in 50% and 78% yield overall, respectively. The synthesis of the glycosylation acceptor employed an addition-fragmentation olefination that was successfully carried out in 53% yield. With the successful synthesis of key intermediates, α-L-RhaCer (1) was prepared without any insurmountable obstacles. Anti-Rha antibodies were prepared in BALB/c mice by immunizing them with rhamnose-ovalbumin (Rha-Ova) with Sigma Adjuvant System (SAS) and the anti-L-Rha antibodies were isolated from the blood sera. Liposomes and EL4 tumor cells were used as model systems to demonstrate the ability of 1 to insert into a lipid bilayer. The interaction of the liposomes or the EL4 cells with α-L-RhaCer (1) and anti-Rha antibodies were investigated by fluorescence microscopy and flow cytometry, respectively, to confirm the ability of glycolipid 1 to be displayed on the tumor cell surface as well as the ability to be recognized by anti-Rha antibodies. | 25,172,148 | [
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Novel chromogenic aminopeptidase substrates for the detection and identification of clinically important microorganisms. | A series of amino acid derivatives 8-10, 42 and 43 have been prepared as chromogenic enzyme substrates in order to detect aminopeptidase activity in clinically important Gram-negative and Gram-positive bacteria. Enzymatic hydrolysis liberates the amino acid moiety and either a 4-aminophenol or a 4-dialkylaminoaniline derivative which undergoes oxidative coupling with 1-naphthol or a substituted 1-naphthol giving an indophenol dye. Substrates and 1-naphthols were incorporated into an agar-based culture medium and this allowed growth of intensely coloured bacterial colonies based on hydrolysis by specific enzymes. Red/pink coloured colonies were produced by the substrates 8-10 and blue coloured colonies were formed by the substrates 42 and 43. The L-alanyl aminopeptidase substrates 8 targeted L-alanyl aminopeptidase activity and gave coloured colonies with a range of Gram-negative bacteria. Substrates 9 targeted β-alanyl aminopeptidase activity and generated coloured colonies with selected Gram-negative species including Pseudomonas aeruginosa. Three substrates for L-pyroglutamyl acid aminopeptidase (10a, 10c and 43) were hydrolysed by enterococci and Streptococcus pyogenes to generate coloured colonies. Two yeasts were also included in the study, but they did not produce coloured colonies with any of the substrates examined. | 25,172,150 | [
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Analyzing cardiac rhythm in the presence of chest compression artifact for automated shock advisory. | Defibrillation is often required to terminate a ventricular fibrillation or fast ventricular tachycardia rhythm and resume a perfusing rhythm in sudden cardiac arrest patients. Automated external defibrillators rely on automatic ECG analysis algorithms to detect the presence of shockable rhythms before advising the rescuer to deliver a shock. For a reliable rhythm analysis, chest compression must be interrupted to prevent corruption of the ECG waveform due to the artifact induced by the mechanical activity of compressions. However, these hands-off intervals adversely affect the success of treatment. To minimize the hands-off intervals and increase the chance of successful resuscitation, we developed a method which asks for interrupting the compressions only if the underlying ECG rhythm cannot be accurately determined during chest compressions. Using this method only a small percentage of cases need compressions interruption, hence a significant reduction in hands-off time is achieved. Our algorithm comprises a novel filtering technique for the ECG and thoracic impedance waveforms, and an innovative method to combine analysis from both filtered and unfiltered data. Requiring compression interruption for only 14% of cases, our algorithm achieved a sensitivity of 92% and specificity of 99%. | 25,172,189 | [
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Long-term clinical and radiological improvement of chronic acquired hepatocerebral degeneration after obliteration of portosystemic shunt: Report of a case. | Neurological manifestations are common in patients with decompensated cirrhosis. The majority of these patients show hepatic encephalopathy or chronic acquired (non-Wilsonian) hepatocerebral degeneration (CAHD). They characteristically present with dysarthria, ataxia, involuntary movements, and altered mental status. Neuroradiological examination in patients with hepatic encephalopathy often shows abnormal signals in multiple regions of the brain, such as the pallidum, putamen, caudate nucleus, hemispheric white matter, and ventral midbrain. The pathogenesis of hepatic encephalopathy and CAHD is poorly understood and the response to conventional therapies is often poor. We report a male patient with cirrhosis of unknown cause, who developed slowly progressive cerebellar truncal and limb ataxia and slurred speech. Magnetic resonance imaging (MRI) showed focal T2 hyperintensity in bilateral dentate nuclei and middle cerebellar peduncles (MCPs). After treatment by obliteration of the portosystemic shunt, clinical manifestations and MRI abnormalities were dramatically improved. He was followed for six years until he died of uncontrollable bleeding due to hepatocellular carcinoma. At the last examination 9 months before death, he showed no apparent aggravation of neurological symptoms, and no abnormal signal intensities in the MCPs and supratentorial compartment. The clinical course and changes of brain MRI findings of this case are extremely rare, suggesting that obliteration of the portosystemic shunt may be effective for CAHD over long term. | 25,172,193 | [
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Mitochondrial complex I gene variations; as a potential genetic risk factor in pathogenesis of multiple sclerosis. | Multiple sclerosis (MS) is an autoimmune-mediated inflammatory and debilitating disease of the central nervous system. Several investigations have suggested that the mitochondrial DNA encoded subunits of complex I gene variations are involved in the progression of MS. In this study, we investigated the possible association between mitochondrial complex I gene variations and MS in a Filipino population. A total of 300 individuals were included in the present study, two-hundred patients with MS clinical symptoms, and one-hundred healthy subjects without MS clinical features. We amplified target genes of mtDNA using polymerase chain reaction technique (PCR), and sequenced these to evaluate mitochondrial complex I gene variations. We found nine variations (Nt 4216 T>C, Nt 5153 A>G, Nt 10142 C>T, Nt 11353 T>C, Nt 11935 T>C, Nt 12062 C>T, Nt 13042 G>A, Nt 13708 G>A and Nt 14179 G>A) in mtDNA-encoded complex I subunit genes. Our results showed that the prevalence of ND1, ND2, ND3, ND4 and ND5 gene variations was significantly higher in patients than in healthy controls (P<0.0001). Whereas, the frequency of Nt 14179 G>A variation in ND6 gene was significantly higher in the control group compared with the patients (P<0.0001). Taken together our data supports a strongly positive association between mitochondrial complex I gene variations and MS pathogenesis in a Filipino population. | 25,172,194 | [
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Mitochondrial bioenergetics and neuronal survival modelled in primary neuronal culture and isolated nerve terminals. | Mitochondria play multiple roles in the maintenance of neuronal function under physiological and pathological conditions. In addition to ATP generation, they can act as major short-term calcium sinks and can both generate, and be damaged by, reactive oxygen species. Two complementary preparations have been extensively employed to investigate in situ neuronal mitochondrial bioenergetics, primary neuronal cultures and acutely isolated nerve terminals, synaptosomes. A major focus of the cell culture preparation has been the investigation of glutamate excitotoxicity. Oxidative phosphorylation, calcium transport and reactive oxygen species play complex interlocking roles in the life and death of the glutamate exposed neuron. Synaptosomes may be isolated from specific brain regions at any developmental stage and therefore provide a valuable ex vivo approach in studying mouse models. Recent advances have allowed synaptosomal bioenergetics to be studied on a microgram scale, and, in combination with approaches to correct for functional and transmitter heterogeneity, have allowed hypotheses concerning presynaptic mitochondrial dysfunction to be tested on a variety of genetic models of neurodegenerative disorders. | 25,172,197 | [
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Decoupling function and anatomy in atlases of functional connectivity patterns: language mapping in tumor patients. | In this paper we construct an atlas that summarizes functional connectivity characteristics of a cognitive process from a population of individuals. The atlas encodes functional connectivity structure in a low-dimensional embedding space that is derived from a diffusion process on a graph that represents correlations of fMRI time courses. The functional atlas is decoupled from the anatomical space, and thus can represent functional networks with variable spatial distribution in a population. In practice the atlas is represented by a common prior distribution for the embedded fMRI signals of all subjects. We derive an algorithm for fitting this generative model to the observed data in a population. Our results in a language fMRI study demonstrate that the method identifies coherent and functionally equivalent regions across subjects. The method also successfully maps functional networks from a healthy population used as a training set to individuals whose language networks are affected by tumors. | 25,172,207 | [
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Small amounts of functional ATP7A protein permit mild phenotype. | Mutations in ATP7A lead to at least three allelic disorders: Menkes disease (MD), Occipital horn syndrome and X-linked distal motor neuropathy. These disorders are mainly seen in male individuals, but a few affected females have been described. More than 400 different mutations have been identified in the ATP7A gene. We have conducted several studies in the hope of uncovering the relationship between genotype and phenotype. We have examined the X-inactivation pattern in affected females, the effect of exon-deletions and--duplications, and splice-site mutations on the composition and amount of ATP7A transcript, and we have examined the structural location of missense mutations. The X-inactivation pattern did not fully explain the manifestation of MD in a small fraction of carriers. Most of the affected females had preferential inactivation of the X-chromosome with the normal ATP7A gene, but a few individuals exhibited preferential inactivation of the X-chromosome with the mutated ATP7A gene. The observed mild phenotype in some patients with mutations that effect the composition of the ATP7A transcript, seems to be explained by the presence of a small amount of normal ATP7A transcript. The location of missense mutations on structural models of the ATP7A protein suggests that affected conserved residues generally lead to a severe phenotype. The ATP7A protein traffics within the cells. At low copper levels, ATP7A locates to the Trans-Golgi Network (TGN) to load cuproenzymes with copper, whereas at higher concentrations, ATP7A shifts to the post-Golgi compartments or to the plasma membrane to export copper out of the cell. Impaired copper-regulation trafficking has been observed for ATP7A mutants, but its impact on the clinical outcome is not clear. The major problem in patients with MD seems to be insufficient amounts of copper in the brain. In fact, prenatal treatment of mottled mice as a model for human MD with a combination of chelator and copper, produces a slight increase in copper levels in the brain which perhaps leads to longer survival and more active behavior. In conclusion, small amounts of copper at the right location seem to relieve the symptoms. | 25,172,213 | [
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Prediction of 3-dimensional pharyngeal airway changes after orthognathic surgery: a preliminary study. | Recent studies have shown some contradictory results when evaluating the consequences of orthodontic-surgical treatments on the pharyngeal airway. Therefore, the purpose of this study was to correlate the amount of jaw displacement with the volume variation and the minimal cross-sectional area of the pharyngeal airway. A comparison was made between the correlations with the percentage and the absolute values of the measurement variations. Forty-two patients were divided into 2 groups according to the kind of orthognathic surgery that they had undergone. Group 1 had 22 subjects who had undergone maxillary advancement associated with mandibular setback, and group 2 had 20 patients who had undergone maxillomandibular advancement. The pharyngeal airway was divided into the upper segment and the lower segment, and the sum of these volumetric measures resulted in the total volume. The maxillary and mandibular displacements were assessed using closest point iteration after a voxel-wise cone-beam computed tomography superimposition. Hence, jaw displacements were correlated, using Pearson's correlation and linear regression analysis, to the volume variations of the pharyngeal airway (first time separately and then both groups together) and to the minimal cross-sectional area variation. The strongest correlation found was between maxillary displacement and the upper segment in group 2 (r = 0.898, R(2) = 0.888; P ≤0.001). With the groups' data combined, the variables mandibular displacement and the lower segment showed a linear correlation (r = 0.921, R(2) = 0.914; P ≤0.001). Maxillary displacement showed a strong positive correlation with the minimal cross-sectional area variation in group 2 (r = 0.710, R(2) = 0.604; P ≤0.01). Correlations with the percentage values were substantially stronger than the correlations with the absolute values. Stronger positive correlations were found between the jaw's displacement and the volume variation of the volume segment that was closer to it in both kinds of surgeries. Only the maxillary displacement is a reliable predictor of the minimal cross-sectional area variation after maxillomandibular advancement. | 25,172,252 | [
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Patterns in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009. | The examination of lung cancer by histology type is important for monitoring population trends that have implications for etiology and prevention, screening and clinical diagnosis, prognosis and treatment. We provide a comprehensive description of recent histologic lung cancer incidence rates and trends in the USA using combined population-based registry data for the entire nation. Histologic lung cancer incidence data was analyzed from CDC's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program. Standardized rates and trends were calculated for men and women by age, race/ethnicity, and U.S. Census region. Rate ratios were examined for differences in rates between men and women, and annual percent change was calculated to quantify changes in incidence rates over time. Trend analysis demonstrate that overall rates have decreased, but incidence has remained stable for women aged 50 or older. Adenocarcinoma and squamous cell carcinoma were the two most common histologic subtypes. Adenocarcinoma rates continued to increase in men and women, and squamous cell rates increased in women only. All histologic subtype rates for white women exceeded rates for black women. Histologic rates for black men exceeded those for white men, except for small cell carcinoma. The incidence rate for Hispanics was nearly half the rate for blacks and whites. The continuing rise in incidence of lung adenocarcinoma, the rise of squamous cell cancer in women, and differences by age, race, ethnicity and region points to the need to better understand factors acting in addition to, or in synergy with, cigarette smoking that may be contributing to observed differences in lung cancer histology. | 25,172,266 | [
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Restrictive symptomatic inclusion criteria create barriers to clinical research in schizophrenia negative symptoms: an analysis of the CATIE dataset. | Persistent negative symptoms are an important area of clinical research. However, there is limited consensus on how to define positive and negative symptom severity thresholds for inclusion in clinical trials. From the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset we evaluated the performance of varying baseline negative and positive symptom thresholds on baseline symptom severity, change from baseline, and negative symptom variance attributable to positive symptom change. In CATIE, we first identified the group of subjects lacking an exacerbation prior to study enrollment. Six subsets with varying baseline positive and negative symptom thresholds were then identified. Baseline characteristics were summarized; negative and positive symptom change from baseline through month 3 was calculated both as crude change and change adjusted for corresponding baseline scores. Sensitivity analyses and correlations were calculated to assess the extent to which negative symptom variance was attributable to positive symptom change. More restrictive baseline symptom severity thresholds yielded a considerably smaller sample size and higher negative and lower positive symptoms at baseline. Unadjusted negative symptom change was greater with more restrictive criteria; when adjusted for baseline severity the magnitude of change was comparable across subsets. The amount of variance in negative symptom change attributed to positive symptom change was also comparable across subsets. The use of restrictive positive and negative symptom thresholds yields a marked decrease in eligible sample size with no clear improvement in adjusted negative symptom change or amount of variance associated with positive symptom change. | 25,172,269 | [
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Brain areas that influence general anesthesia. | This document reviews the literature on local brain manipulation of general anesthesia in animals, focusing on behavioral and electrographic effects related to hypnosis or loss of consciousness. Local inactivation or lesion of wake-active areas, such as locus coeruleus, dorsal raphe, pedunculopontine tegmental nucleus, perifornical area, tuberomammillary nucleus, ventral tegmental area and basal forebrain, enhanced general anesthesia. Anesthesia enhancement was shown as a delayed emergence (recovery of righting reflex) from anesthesia or a decrease in the minimal alveolar concentration that induced loss of righting. Local activation of various wake-active areas, including pontis oralis and centromedial thalamus, promoted behavioral or electrographic arousal during maintained anesthesia and facilitated emergence. Lesion of the sleep-active ventrolateral preoptic area resulted in increased wakefulness and decreased isoflurane sensitivity, but only for 6 days after lesion. Inactivation of any structure within limbic circuits involving the medial septum, hippocampus, nucleus accumbens, ventral pallidum, and ventral tegmental area, amygdala, entorhinal and piriform cortex delayed emergence from anesthesia, and often reduced anesthetic-induced behavioral excitation. In summary, the concept that anesthesia works on the sleep-wake system has received strong support from studies that inactivated/lesioned or activated wake-active areas, and weak support from studies that lesioned sleep-active areas. In addition to the conventional wake-sleep areas, limbic structures such as the medial septum, hippocampus and prefrontal cortex are also involved in the behavioral response to general anesthesia. We suggest that hypnosis during general anesthesia may result from disrupting the wake-active neuronal activities in multiple areas and suppressing an atropine-resistant cortical activation associated with movements. | 25,172,271 | [
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Gene inactivation in Coxiella burnetii. | Coxiella burnetii, the agent of human Q fever, is a zoonotic bacterial pathogen with a worldwide distribution. Owing to an historic lack of methods for genetic manipulation, virulence factors deployed by this bacterium for disease pathogenesis are poorly understood. However, the recent advance of host cell-free (axenic) growth of C. burnetii has coincided with development of several new genetic technologies including site-specific and random transposon systems, shuttle vectors, and an inducible gene expression system. We have recently added two methods for targeted gene inactivation to the expanding C. burnetii genetics toolbox. Here, we describe a "loop in/loop out" gene inactivation system for C. burnetii. This procedure allows for generation of site-directed mutants in approximately 10 weeks and has been used by our laboratory to generate more than 50 individual C. burnetii mutants. The collection of C. burnetii genetic tools now allows for conventional mutation and complementation strategies to define virulence factors. | 25,172,290 | [
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A phase II study of S-1 chemotherapy with concurrent thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer: the Okayama Lung Cancer Study Group Trial 0801. | Although thoracic irradiation (TRT) is a standard treatment for elderly patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treatment outcomes are poor. We previously reported a phase I trial combining S-1, an oral 5-fluorouracil derivative, and thoracic radiation, which yielded safe and effective outcomes. In this phase II trial, 30 patients aged 76 years or older with LA-NSCLC received S-1 (80 mg/m(2) on days 1-14 and 29-42) and TRT (60Gy). The primary end-point was the response rate. The median age and pre-treatment Charlson score were 79 years and 1, respectively. The mean proportions of the actual doses of S-1 and TRT delivered relative to the planned doses were 95% and 98%, respectively. Partial responses were observed in 19 patients (63%; 95% confidence interval: 45-82%), which did not attain the end-point. At a median follow-up time of 23.7 months, the median progression-free survival and median survival times were 13.0 months and 27.9 months, respectively. No difference in efficacy was observed upon stratification by tumour histology. Toxicities were generally mild, except for grade 3 or greater febrile neutropenia and pneumonitis in 7% and 10% of patients, respectively. No patient developed severe oesophagitis. Although the primary end-point was not met, concurrent S-1 chemotherapy and radiotherapy yielded favourable survival data. Also, the combined treatment was well-tolerated in elderly patients with LA-NSCLC. | 25,172,295 | [
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Silver and fullerene nanoparticles' effect on interleukin-2-dependent proliferation of CD4 (+) T cells. | Immunotoxicity studies of nanoparticles on T cells addressed their effects on activation by T antigen receptor, but have neglected the regulation of proliferation by IL-2. In this study, the IL-2-dependent T lymphoblastoid WE17/10 cell line was used to compare silver (Ag-NPs) and fullerene (C60-NPs) nanoparticles' toxicity and evaluate whether these NPs could interfere with IL-2-dependent proliferation. Results have shown that Ag-NPs are more toxic, as they reduced cell viability at the highest concentration tested (100 μg/ml), while C60-NPs have shown good biocompatibility. Characterization of NP suspensions by dynamic light scattering measured large aggregates for C60-NPs, whereas Ag-NPs were relatively stable and well dispersed. This translated into a much larger uptake of Ag-NPs compared to C60-NPs, as measured by flow cytometry. Proliferation measurements by CFSE following 72 h incubation have shown that Ag-NPs decrease cell proliferation and C60-NPs slightly increase proliferation. CD25 expression was unchanged following exposure to C60-NPs, but was significantly increased by Ag-NPs' presence for short and long-term incubations. Analyses of three key signaling proteins activated by IL-2 receptor (Stat5, JNK and ERK1/2) by western immunoblotting have shown no effects from either NPs on Stat5 and JNK phosphorylation. ERK1/2 was slightly activated following a short exposure to Ag-NPs, while C60-NPs had no effect. Our results show that C60-NPs have good biocompatibility and do not interfere with IL-2-dependent proliferation. A deeper investigation would be needed for the case of Ag-NPs, since the mechanism of their action is still unclear. | 25,172,299 | [
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Intermittent whole-body cold immersion induces similar thermal stress but different motor and cognitive responses between males and females. | The main aim of this study was to compare the thermal responses and the responses of cognitive and motor functions to intermittent cold stress between males and females. The intermittent cold stress continued until rectal temperature (TRE) reached 35.5°C or for a maximum of 170 min. Thermal response and motor and cognitive performance were monitored. During intermittent cold stress, body temperature variables decreased in all subjects (P < 0.001) and did not differ between sexes. The presence of fast and slow cooling types for participants with similar effect on physiological variables were observed; thus the different rate coolers were grouped together and were attributed only sex specific responses. Overall, TRE cooling rate and cold strain index did not differ between sexes. Maximal voluntary contraction (MVC) decreased after intermittent cold exposure only in males (P < 0.001), whereas changes in muscle electromyography (EMG) activity did not differ between sexes. The effects of intermittent cold stress on electrically evoked muscle properties, spinal (H-reflex), and supraspinal (V-waves) reflexes did not differ between sexes. Intermittent cold-induced cognitive perturbation of attention and memory task performance was greater in males (P < 0.05). Contrary to our expectations, the results of the present study indicated that males and females experience similar thermal stress induced by intermittent whole-body cold immersion. Although no sex-specific differences were observed in muscle EMG activity, involuntary muscle properties, spinal and supraspinal reflexes, some of the sex differences observed (e.g., lower isometric MVC and greater cognitive perturbation in males) support the view of sex-specific physiological responses to core temperature decrease. | 25,172,303 | [
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Energy expenditure at work in physical education teachers. | The objective of this study was to quantify work energy expenditure (EE) in physical education (PE) teachers. Sixty-four (64) physical educators (49 men, 15 women) had their individualized linear function between heart rate (HR) and oxygen consumption measured by laboratory testing. HR was then recorded on 2 different days at work to estimate EE, correlated with a diary of daily tasks. Average absolute EE was low-to-moderate (2.7 ± 1.4 to 4.6 ± 2.5 kcal·min(-1)) and low when expressed in relative values (15.3 ± 6.1% to 24.8 ± 7.6% of VO2max). However, these physical educators often reached very high intensities (from 7.5 ± 7.9% to 23.8 ± 22.3% of work time at 100 bpm and more). PE teaching requires a light-to-moderate EE with more intense periods of physical activity. The variety of tasks performed (office work, supervision and monitoring, mixed participation and active participation) significantly influenced EE. | 25,172,305 | [
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Frontal theta activity is pronounced during illusory perception. | Object perception is driven by sensory information as well as expectations and prior experiences. The latter influence may increase when the sensory information is poor or inconclusive. Visual illusions, for example induced by ambiguous stimuli, provide a tool to investigate perceptual uncertainty, because ambiguous stimuli elicit switching between at least two perceptual alternatives. Theta oscillations may reflect the impact of visual illusion on perception since they are specifically important to coordinate information in large-scale brain networks, including visual sensory as well as higher-order brain areas. Theta responses elicited by an ambiguous and an unambiguous apparent motion-inducing stimulus were compared, thereby differentiating time periods of perceptual switching and perceptual stability (non-switching). The theta responses were larger at anterior than at posterior sites. This gradient was stronger during the ambiguous task than during the unambiguous task, even though sensory stimulation was comparable for both tasks. A transient increase of the theta response occurred during switching time periods for both the ambiguous and the unambiguous tasks, indicating that the theta response related to the perceptual switch might not be affected by the ambiguity of the stimulus. Irrespective of the percept switching or not, ambiguous stimuli elicited an enduring more prominent activation of higher-order rather than visual sensory brain areas. This indicates an increased reliance on expectations and prior information to ensure coherent object perception in particular when the visual information is degraded or elicits an ongoing conflict between perceptual interpretations. | 25,172,312 | [
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Neural transposition in the Drosophila brain: is it all bad news? | Transposition of mobile genetic elements can radically alter genome structure and sequence. In doing so, they can alter gene expression and cellular function. Perhaps unsurprisingly, this potentially catastrophic process is heavily constrained, especially in the germ line where aberrations lead to sterility or could be passed onto the next generation. However, recent studies in mammals and fruit flies suggest that transposition happens at measurable levels in the brain, and possibly more so in some cell types than in others. This has led to the suggestion that certain cell types may utilize transposable elements to diversify cellular properties. In this review, we discuss these findings and ideas in light of our current understanding of transposons and their control in the fly, and the growing evidence for an involvement of transposition in neurological disease in humans. | 25,172,346 | [
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MicroRNAs in respiratory disease. A clinician's overview. | Since their initial discovery in the early 1990s, microRNAs have now become the focus of a multitude of lines of investigation ranging from basic biology to translational applications in the clinic. Previously believed to be of no biological relevance, microRNAs regulate processes fundamental to human health and disease. In diseases of the lung, microRNAs have been implicated in developmental programming, as drivers of disease, potential therapeutic targets, and clinical biomarkers; however, several obstacles must be overcome for us to fully realize their potential therapeutic use. Here, we provide for the clinician an overview of microRNA biology in selected diseases of the lung with a focus on their potential clinical application. | 25,172,373 | [
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Dietary fatty acids alter left ventricular myocardial gene expression in Wistar rats. | Obesity increases the risk for cardiomyopathy in the absence of comorbidities. Myocardial structure is modified by dietary fatty acids. Left ventricular hypertrophy is associated with Western (WES) diet consumption, whereas intake of n-3 polyunsaturated fatty acids is associated with antihypertrophic effects. We previously observed no attenuation of left ventricular thickening after 3 months of docosahexaenoic acid (DHA) supplementation of a WES diet, compared with WES diet intake alone, in rats that had similar weight, adiposity, and insulin sensitivity to control animals. The objective of this study was to define left ventricular gene expression in these animals to determine whether diet alone was associated with a physiologic or pathologic hypertrophic response. We hypothesized that WES diet consumption would favor a pathologic or maladaptive myocardial gene expression pattern and that DHA supplementation would favor a physiologic or adaptive response. Microarray analysis identified 64 transcripts that were differentially expressed (P ≤ .001) within one or more treatment comparisons. Using quantitative real-time polymerase chain reaction, 29 genes with fold change at least 1.74 were successfully validated; all but 3 had similar directionality to that observed using microarray, and 2 genes, connective tissue growth factor and cathepsin M, were differentially expressed according to diet. WES blot analysis was performed on 4 proteins relevant to myocardial hypertrophy and metabolism. Acyl-CoA thioesterase 1, B-cell translocation gene 2, and carbonic anhydrase III showed directional change consistent with gene expression. Retinol saturase (all-trans-retinol 13,14-reductase), although not consistent with gene expression, was different according to diet, with increased concentrations in WES-fed rats compared with control and DHA-supplemented animals. Diet did not distinguish a transcriptome reflecting physiologic or pathologic myocardial hypertrophy; furthermore, the modest changes observed suggest that obesity and associated comorbidities may play a larger role than mere dietary fatty acid composition in development of cardiomyopathy. | 25,172,377 | [
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Evidence of degraded BMD and geometry at the proximal femora in male patients with alcoholic liver cirrhosis. | We examined the association of alcoholic cirrhosis in 33 patients with areal bone mineral density (BMD) and the assessed bone geometric strength of their proximal femora. Lower areal BMD, cross-sectional area and section modulus, thinner cortex, and higher buckling ratio suggest that the alcoholic liver cirrhosis is associated with lower measures of bone strength. Hepatic bone disease is an important complication of chronic liver disease and is associated with significant morbidity through fractures resulting in pain, deformity, and immobility. In this study, we examined the association of alcoholic cirrhosis and liver insufficiency stage with areal bone mineral density (aBMD) and additionally employed hip structure analysis (HSA) as an advanced method to assess bone geometric strength of the proximal femur in men with alcoholic liver cirrhosis. The study included 33 male patients with alcoholic liver cirrhosis and a control group of 36 healthy patients. Laboratory testing included the following biochemical markers of bone turnover: serum levels of osteocalcin and C-telopeptide of type 1 collagen. Areal BMD was measured by dual x-ray absorptiometry on the proximal femora. Structural parameters were then derived from these scans using hip structure analysis software. After adjusting for age, body height, and weight, we found lower cross-sectional area (p = 0.005) and section modulus (p = 0.005), thinner cortex (p = 0.012), and higher buckling ratio (p = 0.043) in the neck region among patients with cirrhosis. The findings suggest that alcoholic liver cirrhosis is associated with lower measures of bone strength. These findings were consistent with decreased osteocalcin values and increased C-telopeptide of type 1 collagen in patients with cirrhosis, indicating reduction in bone formation and increased bone resorption. Our results emphasize that HSA-derived structural indices of proximal femoral structure may be an important index of greater fragility in patients with alcoholic cirrhosis. | 25,172,381 | [
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Bone density is normal and does not change over 2 years in sarcoidosis. | Small studies have previously suggested that sarcoidosis may be associated with low bone mineral density. In this observational study of 64 patients with sarcoidosis, bone mineral density was within the normal range at baseline, and there was no evidence of accelerated bone loss over 1-2 years. Several small studies have suggested that sarcoidosis may be associated with low bone mineral density (BMD). We undertook a cross-sectional study of BMD in 64 patients with sarcoidosis. Of these, 27 with 25-hydroxyvitamin D<50 nmol/L entered a 1-year intervention study of vitamin D supplements, and 37 entered a 2-year longitudinal study of BMD, with the primary endpoint of the change in lumbar spine BMD. The mean age of participants was 58 years, 68% were female, and 8% were currently using oral glucocorticoids. At baseline, BMD for the entire cohort was greater than the expected values for the population at the lumbar spine (mean Z-score 0.7, P<0.001) and total body (0.5, P<0.001) and similar to expected values at the femoral neck (0.2, P=0.14) and total hip (0.2, P=0.14). BMD did not change at any of these four sites (P>0.19) over 2 years in the longitudinal study. In the intervention study, vitamin D supplements had no effect on BMD, and therefore we pooled the data from all participants. BMD did not change over 1 year at the spine, total hip, or femoral neck (P>0.3), but decreased by 0.7% (95% confidence interval 0.3-1.1) at the total body (P=0.019). BMD was normal at baseline, and there was no consistent evidence of accelerated bone loss over 1-2 years, regardless of baseline vitamin D status. Patients with sarcoidosis not using oral glucocorticoids do not need routine monitoring of BMD. | 25,172,384 | [
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The time course of spoken word recognition in Mandarin Chinese: a unimodal ERP study. | In the present study, two experiments were carried out to investigate the time course of spoken word recognition in Mandarin Chinese using both event-related potentials (ERPs) and behavioral measures. To address the hypothesis that there is an early phonological processing stage independent of semantics during spoken word recognition, a unimodal word-matching paradigm was employed, in which both prime and target words were presented auditorily. Experiment 1 manipulated the phonological relations between disyllabic primes and targets, and found an enhanced P2 (200-270 ms post-target onset) as well as a smaller early N400 to word-initial phonological mismatches over fronto-central scalp sites. Experiment 2 manipulated both phonological and semantic relations between monosyllabic primes and targets, and replicated the phonological mismatch-associated P2, which was not modulated by semantic relations. Overall, these results suggest that P2 is a sensitive electrophysiological index of early phonological processing independent of semantics in Mandarin Chinese spoken word recognition. | 25,172,388 | [
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Reconsideration of the WHO NCTB strategy and test selection. | The World Health Organization-recommended neurobehavioral core test battery (NCTB) became the international standard for identifying adverse human behavioral effects due to neurotoxic chemical exposure when it was first proposed in 1983. Since then the WHO NCTB has been repeatedly cited as the basis for test selection in human neurotoxicology research. A discussion group was held before the International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health to review the NCTB and reconsider its tests. The workshop made three consensus recommendations to the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP):. 1. A 'screening' battery of broadly sensitive tests is needed as guidance to the field of human neurotoxicology 2. The SCNP should convene a panel to reconsider the functions measured and the tests in the WHO NCTB 3. Three disciplines should be represented in the panel recommending a revised NCTB: neuropsychology; experimental psychology; neurology. This recommendation will be pursued at the next meeting of the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP). | 25,172,409 | [
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Assessment of repeatability of hyperpolarized gas MR ventilation functional imaging in cystic fibrosis. | Hyperpolarized (HP) gas magnetic resonance imaging (MRI) is an advanced imaging technique that provides high-resolution regional information on lung function without using ionizing radiation. Before this modality can be considered for assessing clinical or investigational interventions, baseline repeatability needs to be established. We assessed repeatability of lung function measurement using HP helium-3 MRI (HP (3)He MRI) in a small cohort of patients with cystic fibrosis (CF). We examined repeatability of HP (3)He MR images of five patients with CF in four scanning sessions over a 4-week period. We acquired images on a Philips 3.0 Tesla Achieva MRI scanner using a quadrature, flexible, wrap-around, (3)He radiofrequency coil with a fast gradient-echo pulse sequence. We determined ventilation volume and ventilation defect volume using an advanced semiautomatic segmentation algorithm and also quantified ventilation heterogeneity. There were no significant differences in total ventilation volume, ventilation defect volume, ventilation defect percentage, or mean ventilation heterogeneity (repeated-measures analysis of variance, P = .2116, P = .2825, P = .2871, and P = .7265, respectively) in the patients across the four scanning sessions. Our results indicate that total ventilation volume, ventilation defect volume, ventilation defect percentage, and mean ventilation heterogeneity as assessed by HP gas MRI in CF patients with stable health are reproducible over time. This repeatability and the technique's capability to provide noninvasive high-resolution data on regional lung function without ionizing radiation make (3)He MRI a potentially useful outcome measure for CF-related clinical trials. | 25,172,411 | [
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Facile synthesis of SSR180575 and discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[(18)F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, a potent pyridazinoindole ligand for PET imaging of TSPO in cancer. | A novel synthesis of the translocator protein (TSPO) ligand 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (SSR180575, 3) was achieved in four steps from commercially available starting materials. Focused structure-activity relationship development about the pyridazinoindole ring at the N3 position led to the discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (14), a novel ligand of comparable affinity. Radiolabeling with fluorine-18 ((18)F) yielded 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[(18)F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide ([(18)F]-14) in high radiochemical yield and specific activity. In vivo studies of [(18)F]-14 revealed this agent as a promising probe for molecular imaging of glioma. | 25,172,419 | [
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Design, synthesis and molecular modeling of biquinoline-pyridine hybrids as a new class of potential EGFR and HER-2 kinase inhibitors. | A new series of biquinoline-pyridine hybrids were designed and synthesized by a base-catalyzed cyclocondensation through one-pot multicomponent reaction. All compounds were tested for in vitro anticancer activities against two cancer cell lines A549 (adenocarcinomic human alveolar basal epithelial) and Hep G2 (liver cancer). Enzyme inhibitory activities of all compounds were carried out against EGFR and HER-2 kinase. Of the compounds studied, majority of the compounds showed effective anticancer activity against used cancer cell lines. Compound 9i (IC50=0.09 μM) against EGFR and (IC50=0.2 μM) against HER-2 kinase displayed the most potent inhibitory activity as compared to other member of the series. In the molecular modelling study, compound 9i was bound in to the active pocket of EGFR with four hydrogen bonds and two π-cation interactions having minimum binding energy ΔGb=-54.4 kcal/mol. | 25,172,421 | [
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AHNAK: the giant jack of all trades. | The nucleoprotein AHNAK is an unusual and somewhat mysterious scaffolding protein characterised by its large size of approximately 700 kDa. Several aspects of this protein remain uncertain, including its exact molecular function and regulation on both the gene and protein levels. Various studies have attempted to annotate AHNAK and, notably, protein interaction and expression analyses have contributed greatly to our current understanding of the protein. The implicated biological processes are, however, very diverse, ranging from a role in the formation of the blood-brain barrier, cell architecture and migration, to the regulation of cardiac calcium channels and muscle membrane repair. In addition, recent evidence suggests that AHNAK might be yet another accomplice in the development of tumour metastasis. This review will discuss the different functional roles of AHNAK, highlighting recent advancements that have added foundation to the proposed roles while identifying ties between them. Implications for related fields of research are noted and suggestions for future research that will assist in unravelling the function of AHNAK are offered. | 25,172,424 | [
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Comparison of personality beliefs between depressed patients and healthy controls. | According to the cognitive model, the common mechanism underlying all psychological disorders is distorted or dysfunctional thoughts that affect mood and behaviors. Dysfunctional thoughts predispose an individual to depression and are among the processes that form the basis of personality traits. Elucidating the personality beliefs associated with depression and dysfunctional thoughts is important to understanding and treating depression. The aim of the present study is to determine whether depressed patients exhibited pathological personality beliefs compared with healthy controls. Furthermore, we investigated which personality beliefs were more common among such depressed patients. A total of 70 patients who were admitted to the Department of Psychiatry at Ankara Diskapi Yildirim Beyazit Training and Research Hospital (Ankara, Turkey) and diagnosed with major depressive disorder according to The Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnostic criteria were included in the study. Additionally, 70 healthy controls matched for age, marital status, and education were included in the study. The Sociodemographic Data Form and Personality Belief Questionnaire-Short form (PBQ-SF) were administered to the participants. A comparison of the depression group with the healthy controls revealed higher scores in dependent, passive-aggressive, obsessive-compulsive, antisocial, histrionic, paranoid, borderline, and avoidant personality subscales in the depressive group. These results suggest that personality beliefs at the pathological level are more common in depressive patients and that the detection of these beliefs would be useful for predicting the prognosis of the disease and determining appropriate treatment methods. | 25,172,443 | [
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-0.115352,
... |
In silico analysis of L-asparaginase from different source organisms. | L-asparaginases are widely distributed enzymes among plants, fungi and bacteria. This enzyme catalyzes the conversion of l-asparagine to l-aspartate and ammonia and to a lesser extent the formation of l-glutamate from l-glutamine. In the present study, forty-five full-length amino acid sequences of L-asparaginases from bacteria, fungi and plants were collected and subjected to multiple sequence alignment (MSA), domain identification, discovering individual amino acid composition, and phylogenetic tree construction. MSA revealed that two glycine residues were identically found in all analyzed species, two glycine residues were also identically found in all the fungal and bacterial sources and three glycine residues were identically found in all plant and bacterial sources while no residue was identically found in plant and fungal L-asparaginases. Two major sequence clusters were constructed by phylogenetic analysis. One cluster contains eleven species of fungi, twelve species of bacteria, and one species of plant, whereas the other one contains fourteen species of plant, four species of fungi and three species bacteria. The amino acid composition result revealed that the average frequency of amino acid alanine is 10.77 percent that is very high in comparison to other amino acids in all analyzed species. | 25,172,447 | [
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... |
Whole genome phylogeny of Prochlorococcus marinus group of cyanobacteria: genome alignment and overlapping gene approach. | Prochlorococcus is the smallest known oxygenic phototrophic marine cyanobacterium dominating the mid-latitude oceans. Physiologically and genetically distinct P. marinus isolates from many oceans in the world were assigned two different groups, a tightly clustered high-light (HL)-adapted and a divergent low-light (LL-) adapted clade. Phylogenetic analysis of this cyanobacterium on the basis of 16S rRNA and other conserved genes did not show consistency with its phenotypic behavior. We analyzed phylogeny of this genus on the basis of complete genome sequences through genome alignment, overlapping-gene content and gene-order approach. Phylogenetic tree of P. marinus obtained by comparing whole genome sequences in contrast to that based on 16S rRNA gene, corresponded well with the HL/LL ecotypic distinction of twelve strains and showed consistency with phenotypic classification of P. marinus. Evidence for the horizontal descent and acquisition of genes within and across the genus was observed. Many genes involved in metabolic functions were found to be conserved across these genomes and many were continuously gained by different strains as per their needs during the course of their evolution. Consistency in the physiological and genetic phylogeny based on whole genome sequence is established. These observations improve our understanding about the adaptation and diversification of these organisms under evolutionary pressure. | 25,172,453 | [
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... |
Acid-activated biochar increased sulfamethazine retention in soils. | Sulfamethazine (SMZ) is an ionizable and highly mobile antibiotic which is frequently found in soil and water environments. We investigated the sorption of SMZ onto soils amended with biochars (BCs) at varying pH and contact time. Invasive plants were pyrolyzed at 700 °C and were further activated with 30 % sulfuric (SBBC) and oxalic (OBBC) acids. The sorption rate of SMZ onto SBBC and OBBC was pronouncedly pH dependent and was decreased significantly when the values of soil pH increased from 3 to 5. Modeled effective sorption coefficients (K D,eff) values indicated excellent sorption on SBBC-treated loamy sand and sandy loam soils for 229 and 183 L/kg, respectively. On the other hand, the low sorption values were determined for OBBC- and BBC700-treated loamy sand and sandy loam soils. Kinetic modeling demonstrated that the pseudo second order model was the best followed by intra-particle diffusion and the Elovich model, indicating that multiple processes govern SMZ sorption. These findings were also supported by sorption edge experiments based on BC characteristics. Chemisorption onto protonated and ligand containing functional groups of the BC surface, and diffusion in macro-, meso-, and micro-pores of the acid-activated BCs are the proposed mechanisms of SMZ retention in soils. Calculated and experimental q e (amount adsorbed per kg of the adsorbent at equilibrium) values were well fitted to the pseudo second order model, and the predicted maximum equilibrium concentration of SBBC for loamy sand soils was 182 mg/kg. Overall, SBBC represents a suitable soil amendment because of its high sorption rate of SMZ in soils. | 25,172,460 | [
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Thallium and potassium uptake kinetics and competition differ between durum wheat and canola. | Thallium (Tl) is very toxic to mammals but little is known about its accumulation by plants, and it would be useful if prediction of Tl accumulation could be done using potassium (K) accumulation models. The objectives of this study were to compare the uptake kinetics of Tl(+) and K(+), and to determine how readily K(+) can inhibit Tl(+) uptake. Durum wheat (Triticum turgidum L.) and spring canola (Brassica napus L.) were grown hydroponically and exposed to 0-75 μM Tl or 0-250 μM K for up to 150 min (kinetics experiment), or to 0.1 or 10 μM Tl with Tl to K ratios of 1:1 to 1:10,000 for up to 300 min (competition experiment). The rate of uptake of Tl(+) by canola was about three to five times faster than by wheat, while the rate of Tl(+) uptake in wheat was the same as the rate of K(+) uptake by either species. Uptake of Tl(+) was more readily suppressed by K(+) in wheat than in canola. When exposed to 0.1 uM Tl for 300 min with 100 or 1,000 uM K(+), Tl(+) uptake by wheat was reduced by 20 % and 50 %, respectively, while Tl(+) uptake by canola was not reduced. Our results suggest that predicting Tl accumulation using a K accumulation model with a correction factor may be possible for canola, but would be much more difficult for wheat, since uptake of Tl(+) is very sensitive to levels of K(.) | 25,172,467 | [
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Notch signaling at later stages of NK cell development enhances KIR expression and functional maturation. | The Notch signaling pathway plays a substantial role in human NK cell development. However, the role of Notch on killer Ig-like receptor (KIR) upregulation and acquisition of effector function has not been explored. To evaluate how Notch influences terminal differentiation, cord blood-derived NK cells or sorted peripheral blood NK cells were cultured with IL-15 for 7 d with inhibitory or activating Notch signals. Inhibition of Notch signaling significantly decreased KIR expression, whereas activation enhanced it. Overexpression of activated Notch on cord blood-derived NK cells resulted in a 2-fold increase in KIR expression, indicating that Notch signaling plays a direct, cell-intrinsic role in KIR regulation. Moreover, Notch-mediated KIR expression on NK cells is regulated through cis inhibition by delta-like ligand 1. Notch signaling also enhances CD16 upregulation that precedes KIR expression. Concomitant with the upregulation of KIR and CD16, Notch signaling induces increased cytolytic effector capacity and cytokine secretion, even in posttransplant samples in which NK cell function is inherently defective. Given these attributes of Notch signaling, we propose that Notch agonists may enhance NK cell maturation and tumor killing in a posttransplant setting. | 25,172,483 | [
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0.... |
Assembly of telomeric chromatin to create ALTernative endings. | Circumvention of the telomere length-dependent mechanisms that control the upper boundaries of cellular proliferation is necessary for the unlimited growth of cancer. Most cancer cells achieve cellular immortality by up-regulating the expression of telomerase to extend and maintain their telomere length. However, a small but significant number of cancers do so via the exchange of telomeric DNA between chromosomes in a pathway termed alternative lengthening of telomeres, or ALT. Although it remains to be clarified why a cell chooses the ALT pathway and how ALT is initiated, recently identified mutations in factors that shape the chromatin and epigenetic landscape of ALT telomeres are shedding light on these mechanisms. In this review, we examine these recent findings and integrate them into the current models of the ALT mechanism. | 25,172,551 | [
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0.05607802,
0.01567032,
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0.2594202,
0.1582399,
-0.240875... |
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