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pubmed_1063_24087
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Attention is not constant, but fluctuates from moment-to-moment. Multiple neurocognitive factors contribute to these fluctuations, acting to help us get 'in the zone' as well as pulling us away from this optimal and fleeting state. Models of arousal, mind wandering, cognitive resource allocation, and effort have consequences for this fundamental process. Integrating these models with an understanding of how attentional fluctuations impact information processing-from stimulus to motor representations-will help to reveal the causes and consequences of these fluctuations. This integrated perspective has implications for a range of clinical populations and cognitive processes that rely on attention.
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10.1016/j.copsyc.2019.03.005
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pubmed_425_9674
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The original version of the article was published with few errors in Tables 2 and 4. The correct version of the tables are presented along in this erratum.
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10.1007/s10964-019-01036-9
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pubmed_367_12030
|
OBJECTIVE
To evaluate the usefulness of computed tomographic (CT) predictors on portal venous phase images and a new CT predictor on unenhanced images in differentiating focal eosinophilic necrosis (FEN) from hepatic metastases.
MATERIALS AND METHODS
Computed tomographic findings were analyzed in 20 patients with FEN (n = 84) and 23 patients with hepatic metastases (n = 81). Computed tomographic features were compared using univariate and multivariate analyses to determine significant findings.
RESULTS
An irregular shape, a subtle low attenuation, a fuzzy margin, and absences of a contour bulging and a rimlike enhancement on the portal venous phase images and absence of a discernable low attenuation on the unenhanced images were significant variables favoring FEN in univariate analysis. In multivariate analysis, no discernable low attenuation on the unenhanced images and an irregular shape and a subtle low attenuation on the portal venous phase images were the variables independently favoring FEN.
CONCLUSIONS
Not only portal phase images but also unenhanced images can be helpful to differentiate FEN from hepatic metastases.
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10.1097/RCT.0b013e3181949b3b
|
pubmed_512_24904
|
Older people are often prescribed multiple medicines and have a high prevalence of polypharmacy. Polypharmacy is associated with an increased risk of inappropriate use of medicines and drug-related problems. As experts in pharmacotherapy, pharmacists are well placed to review complex medication regimens and identify causes of drug-related problems and recommend solutions to prevent or resolve them. Involvement in medication review services represents a major philosophical shift and paradigm change in the way pharmacists practice, in that the focus is shifted away from the dispensing of prescription medicines to the provision of a professional service for a patient, in collaboration with their general practitioner (GP). In Australia, there are two established medication review programs: Home Medicines Review (HMR) and Residential Medication Management Review (RMMR). The objectives of this article were to describe the process of government-funded medication review services in Australia and to evaluate the contribution of pharmacists to HMR and RMMR, using evidence-based measures, such as the Drug Burden Index (DBI) and the Medication Appropriateness Index (MAI). This review found that there is good evidence to support the role of pharmacists in delivering medication review services across different settings. Although the positive impact of such services has been demonstrated using a variety of validated measures (DBI, MAI), there remains a need to also evaluate actual clinical outcomes and/or patient-reported outcomes.
|
10.1007/s40266-016-0357-2
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pubmed_530_10659
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This study aimed to assess the prevalence, severity, and etiology of neutropenia in infants and children admitted to a children's hospital in Egypt. A total of 200 patients with neutropenia were recruited from April 1, 2010 to September 30, 2010. Patients with a known hematological or immunological disease were excluded. Patients were followed till recovery or an underlying cause was uncovered. Viral serological analysis was done for patients with moderate/severe neutropenia, including cytomegalovirus (CMV); Epstein-Barr virus (EBV); hepatitis A, B, and C viruses; and HIV. Antineutrophil cytoplasmic antibody (ANCA) tested by enzyme immunoassay and bone marrow aspirate were done for prolonged neutropenia. The results revealed that neutropenia was mild in 90 (45%), moderate in 56 (28%), and severe in 54 (27%). Clinical diagnosis at admission was bronchopneumonia (38%), pyrexia of undetermined etiology (17%), bronchiolitis (13%), urinary tract infection (9%), acute gastroenteritis (8%), hepatitis (6.5%), and septicemia (5%). Patients with mild neutropenia recovered within 1 week. Among 110 patients with moderate/severe neutropenia, 80 (73%) recovered in <3 weeks. Predictors of prolonged neutropenia were age younger than 18 months (P < .01), absolute neutrophils count (ANC) < 500/mm(3) (P < .05), hemoglobin < 10 gm/dL (P < .05), and positive CMV serology (P < .01). CMV and EBV serology were positive in 34.5% and 7.3% of patients, respectively. ANCA was positive in 42.8% of patients with prolonged severe neutropenia. In conclusion, neutropenia is a frequent finding in Egyptian infants and children, usually mild and transient, and mainly associated with infection. CMV and EBV are associated with prolonged neutropenia. Immune neutropenia is a common cause of moderate/severe neutropenia in the first two years of life.
|
10.3109/08880018.2012.743199
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pubmed_125_124
|
How chief executive officers (CEOs) use their leisure to help respond to the demands of their job is important for themselves, their employees, and their organizations. This study shines light on this hardly explored subject by focusing on CEOs of major US companies and their "serious leisure," the goal-oriented pursuit of a non-work passion. Serious leisure is increasingly practiced by the population at large as well as by top leaders. This study is based on 16 interviews with "serious leisurite" CEOs of Fortune 500, S&P 500, or comparable organizations. Novel insights are brought into the ways in which CEOs believe their passionate non-work pursuit supports not only coping with the strain of the top job but also optimal functioning in it, as well as into how they perceive the demands of the CEO role. This work contributes to research on leader personal resources and leader effectiveness, executive job demands, as well as to the leisure-based recovery literature.
|
10.3389/fpsyg.2020.01453
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pubmed_95_13321
|
Alphavirus vectors have become widely used in basic research to study the structure and function of proteins and for protein production purposes. Development of a variety of vectors has made it possible to deliver foreign sequences as naked RNA or DNA, or as suicide virus particles produced using helper vector strategies. Preliminary reports also suggest that these vectors may be useful for in vivo applications where transient, high-level protein expression is desired, such as recombinant vaccines. The initial studies have already shown that alphavirus vaccines can induce strong humoral and cellular immune responses with good immunological memory and protective effects.
|
10.1016/s0378-1119(96)00679-8
|
pubmed_405_18710
|
It is estimated that Haiti has the highest incidence of cervical cancer in the Western Hemisphere. There are currently no sustainable and affordable cervical cancer screening programs in Haiti. The current status of screening services and knowledge of health care professionals was assessed through a Knowledge, Attitudes, and Practices survey on cervical cancer screening and prevention. It was distributed to Project Medishare for Haiti health care workers (n = 27) in the Central Plateau. The majority (22/27) of participants stated pre-cancerous cells could be detected through screening, however, only four had ever performed a pap smear. All of the participants felt a screening program should be started in their area. Our data establishes that knowledge is fairly lacking among healthcare workers and there is an opportunity to train them in simple, cost effective "screen-and-treat" programs that could have a great impact on the overall health of the population.
|
10.3390/ijerph111111541
|
pubmed_403_10859
|
Using the available data on deeply virtual Compton scattering (DVCS) off protons and utilizing neural networks enhanced by the dispersion relation constraint, we determine six out of eight leading Compton form factors in the valence quark kinematic region. Furthermore, adding recent data on DVCS off neutrons, we separate contributions of up and down quarks to the dominant form factor, thus paving the way towards a three-dimensional picture of the nucleon.
|
10.1103/PhysRevLett.125.232005
|
pubmed_410_15334
|
The efficacy and safety of early renal replacement therapy (eRRT) for critically ill patients with acute kidney injury (AKI) remain controversial. Therefore, the purpose of our study was to perform an up-to-date meta-analysis with the trial sequential analysis (TSA) of randomized controlled trials (RCTs) to evaluate the therapeutic effect of eRRT on patients in an intensive care unit (ICU). We extensively searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov, Gray Literature Report, and Bielefeld Academic Search Engine (BASE), and conducted an updated search on December 27, 2021. The included studies were RCTs, which compared the efficacy and safety of eRRT and delayed renal replacement therapy (dRRT) on critically ill patients with AKI. We adopted TSA and sensitivity analysis to strengthen the robustness of the results. About 12 RCTs with a total of 5,423 participants were included. Patients receiving eRRT and dRRT had the similar rate of all-cause mortality at day 28 (38.7% vs. 38.9%) [risk ratio (RR), 1.00; 95%CI, 0.93-1.07, p = 0.93, I 2 = 0%, p = 0.93]. A sensitivity and subgroup analysis produced similar results for the primary outcome. TSA showed that the required information size was 5,034, and the cumulative Z-curve crossed trial sequential monitoring boundaries for futility. Patients receiving eRRT had a higher rate of renal replacement therapy (RRT) (RR, 1.50, 95% CI: 1.28-1.76, p < 0.00001, I 2 = 96%), and experienced more adverse events comparing to those receiving dRRT (RR: 1.41, 95% CI: 1.22-1.63, p < 0.0001, heterogeneity not applied). The most remarkable and important experimental finding is that, to our knowledge, the current meta-analysis included the largest sample size from the RCTs, which were published in the past 10 years to date, show that eRRT had no significant survival benefit for ill patients with AKI compared with dRRT and TSA indicating that no more studies were needed to confirm it.
Trial Registration
INPLASY, INPLASY2020120030. Registered 04 December 2020.
|
10.3389/fmed.2022.820624
|
pubmed_1073_3219
|
Drug-induced phospholipidosis indicates an accumulation of phospholipids within lysosomes, which can occur during therapeutic treatment. Whether or not phospholipidosis represents a toxicological phenomenon is still under investigation, and in the last decade the Food and Drug Administration has been raising concerns about the possible consequences of this adverse event. Cationic amphiphilic drugs represent the majority of phospholipidosis inducers, followed by aminoglycoside and macrolide antibiotics. Although the mechanism of phospholipidosis induction is still uncertain, the interaction of drugs with phospholipids in the lysosomal membrane represents a key step. Therefore, the study of the drug/lipid complex formation will provide valuable insight into the causation of phospholipidosis at the molecular level and to identify the potential phospholipidosis risk associated with drug. In this study, we investigated the insertion profile of eleven drugs with known phospholipidosis effect into preformed Langmuir monolayers of various lipid compositions, to evaluate for the first time the drug/lipid interaction for phospholipidosis inducers and non-inducers in a dynamic approach. We found that the addition of dipalmitoylphosphatidylserine (DPPS) to dipalmitoylphosphatidylcholine (DPPC) to form the lipid monolayer allowed a clear identification of the phospholipidosis effect of the selected drugs based on the variation of the surface pressure, not only for cationic amphiphilic drugs but also for the aminoglycoside and the macrolide antiobiotics tested. Compared to a standard PAMPA assay, the new method appears to be more effective for the study of poorly soluble drugs.
|
pubmed_1073_3219
|
pubmed_465_7965
|
We compared the bovine melanotic and amelanotic retinal pigment epithelial (RPE) cells cultivated in vitro using a number of parameters. Both cell types could be readily harvested from the eye by dissection or by enzyme treatment of the RPE. Both types of cells grew equally well in the primary culture, and in serial subcultures for over 600 days, and also after being stored frozen for over two months. The two types of cells were similar in their growth patterns, morphology, chromosome characteristics and phagocytic activity but they differed in their tyrosinase activity. Although in long-term cultures cells showed chromosome loss, a high proportion of the cells retained their normal diploid chromosome number (2n = 60) with apparently normal karyotype.
|
10.1016/0014-4835(83)90105-7
|
pubmed_189_1838
|
This study involved evaluating the effects of rotational impeller speed agitation (N) and specific air flow rate (Фair) on bikaverin production and on the growth of Fusarium oxysporum employing 11 bench-scale bioreactor assays. The results showed that the maximum bikaverin production (close to 300 mg L-1) was achieved after 48 h of fermentation in rice medium (20 g L-1 milled rice in water) at 28 °C with a volumetric oxygen transfer coefficient (KLa) and shear stress values of approximately 20 h-1 and 17 N m-2, respectively. We reached this combination of parameters using an N of 340 rpm and Фair of 0.935 vvm. These KLa and shear stress values can be used as references when upscaling this process. Thus, this study was important to demonstrate how the main parameters in bioreactors affect bikaverin production and it presented important indications for upscaling this bioprocess.
|
10.1007/s00449-022-02693-0
|
pubmed_439_12176
|
From 2009 to 2019 there were 77 youth and 1046 adults injured in tree stand-related emergency department visits. There was no statistically significant different in sex or gender. Injury types were similar among groups and were categorized by body part. Despite the above-mentioned insignificant differences between the groups, we did identify several statistically significant findings. Adults that were not Caucasian or African-American were more likely to sustain injuries related to tree stands when compared to their youth counterparts (P-value 0.029). Adult patients were also more likely to sustain trauma to their torso (P-value 0.017). Lastly, adult patients were found to be more likely to require hospitalization in comparison to the youth population (P-value 0.018). Improved education and safety guidelines in the use of tree stands, particularly in individuals in ages 18 and up, would likely lessen the discrepancies between age groups identified in this study.
|
10.1177/00031348211065106
|
pubmed_311_3564
|
Proinsulin was first identified as the primary translation product of the insulin gene in Donald Steiner's laboratory in 1967, and was the first prohormone to be isolated and sequenced. While its role as an insulin precursor has been extensively studied in the field of endocrinology, the bioactivity of the proinsulin molecule itself has received much less attention. Insulin binds to isoforms A and B of the insulin receptor (IR) with high affinity. Proinsulin, in contrast, binds with high affinity only to IR-A, which is present in the nervous system, among other tissues and elicits antiapoptotic and neuroprotective effects in the developing and postnatal nervous system. Proinsulin specifically exerts neuroprotection in the degenerating retina in mouse and rat models of retinitis pigmentosa (RP), delaying photoreceptor and vision loss after local administration in the eye or systemic (intramuscular) administration of an adeno-associated viral (AAV) vector that induces constitutive proinsulin release. AAV-mediated proinsulin expression also decreases the expression of neuroinflammation markers in the hippocampus and sustains cognitive performance in a mouse model of precocious brain senescence. We have therefore proposed that proinsulin should be considered a functionally distinct member of the insulin superfamily. Here, we briefly review the legacy of Steiner's research, the neural expression of proinsulin, and the tissue expression patterns and functional characteristics of IR-A. We discuss the neuroprotective activity of proinsulin and its potential as a therapeutic tool in neurodegenerative conditions of the central nervous system, particularly in retinal dystrophies.
|
10.3389/fnmol.2018.00426
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pubmed_693_7809
|
The effects of a maternal injection of trypan blue on primitive streak mouse embryos were studied with electron microscopy. Commercial trypan blue was purified by descending paper chromatography, and pregnant females received an intraperitoneal injection of the collected blue fraction on the evening of the 7th day of gestation. Ultrastructurally, the changes in the visceral endoderm were apparent 10 min after the injection and included an increase in the number of fuzzy-coated vesicles in the apical cytoplasm. By 20 min the apical cytoplasm of the extraembryonic visceral endodermal cells was filled with many fuzzy-coated vesicles and numerous vacuoles of various size and electron density. 30 min after the injection, the extraembryonic visceral endodermal cells were relatively smooth lacking a microvillous border and evidence of endocytic activity was rare. Many embryonic visceral endodermal cells were observed in various stages of degeneration although the underlying embryonic ectoderm appeared unaffected. Morphologically, it appears that trypan blue exerts its first effect by altering the endocytic activity of the visceral endoderm.
|
10.1159/000145129
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pubmed_647_6910
|
Because corticospinal excitability, as assessed with transcranial magnetic stimulation, has been repeatedly shown to increase during motor imagery, we used this approach to determine whether appreciating object-hand interactions involves motor imagery. Corticospinal excitability was measured in nine healthy participants who were asked to decide whether a hand presented in a given posture was compatible with the use of an object. The control task consisted in deciding whether two hands were in the same posture; a dimming task was used to determine the baseline. We found a significant increase in corticospinal excitability while judging object-hand interactions in comparison with the two other tasks. This finding suggests that predicting the consequences of an action involves implicit motor imagery.
|
10.1097/00001756-200508010-00012
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pubmed_508_14319
|
Prader-Willi syndrome is a complex multisystem disorder characterized by neonatal hypotonia, developmental delay, short stature, obesity, behaviour problems, hypothalamic hypogonadism and characteristic appearance. A number of sex chromosome abnormalities have been reported in children with Prader-Willi syndrome. We report on an infant with a 47, XXY karyotype and Prader-Willi syndrome diagnosed at 2 months of age. He is possibly the youngest to be reported with both Prader-Willi syndrome and Klinefelter syndrome. We have shown that the extra X chromosome causing Klinefelter syndrome is paternal in origin and Prader-Willi syndrome is due to maternal heterodisomy indicating that these two events occurred coincidentally.
|
10.1097/MCD.0b013e32801472cf
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pubmed_687_18736
|
In this study, the influence of supra-nutritional organic selenium (Se) supplement on hematology and plasma biochemicals, including antioxidant parameters and plasma reproductive hormones, as well as blood flow characteristics in the supratesticular and common carotid arteries (STA and CCA, respectively) were investigated. For this purpose, 15 male goats were used and classified into three equal groups according to the supplementation of the basal diet (BD): negative control (NC), probiotic (Pro), and Se-probiotic (Se-Pro) groups. Blood perfusion in the STA and CCA was assessed by Doppler ultrasonography at three different time intervals: at the experimental onset (T0), 3 weeks of dietary supplement (T3), and after 6 weeks of observation (T6). Concomitantly, blood samples were withdrawn for hematobiochemical and hormonal changes. Results revealed no evidence of clinical abnormality, with some enhanced hematological parameters and antioxidant (SOD and GPX) levels in goats of the Se-Pro and Pro groups. High concentrations of FSH were found in the Se-Pro at T6 compared to its values in other groups. Similarly, testosterone levels were elevated in the Pro and Se-Pro groups at T3 compared to other time points. There were significant increases in levels of IGF-1 in the Pro and Se-Pro groups compared to the NC group. Significant (P < 0.05) increases in the values of the blood volume within the CCA and the STA were noted in the Se-Pro group, and the highest values were observed at T6 (CCA, 427.4 ± 33 ml/min; STA, 49.9 ± 5.0 ml/min). In conclusion, supra-nutritional organic selenium improves some hematobiochemical parameters, reproductive hormones, and the blood perfusion within the CCA and STA in goats.
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10.1007/s11356-020-08294-2
|
pubmed_41_18339
|
PURPOSE
To characterize and quantify early foveal development in preterm infants and to compare this development between eyes treated with intravitreal bevacizumab or laser photocoagulation (LPC) and untreated eyes.
DESIGN
Observational case series.
PARTICIPANTS
One hundred thirty-one preterm infants undergoing retinopathy of prematurity (ROP) screenings.
METHODS
Handheld OCT imaging was performed longitudinally on all patients. Thickness measurements of the inner and outer retinal layers were obtained at the foveal center and the nasal and temporal foveal rims. Comparisons between treated and untreated eyes were adjusted for age and other confounding variables.
MAIN OUTCOME MEASURES
Weekly change in inner and outer retinal thickness and presence of inner retinal layers, ellipsoid zone (EZ), and cystoid macular changes (CMCs).
RESULTS
Outer retinal thickness at the foveal center increased by 3.1 μm/week in untreated eyes and 7.2 μm/week in bevacizumab-treated eyes (P = 0.038). Eyes treated with LPC had a lower probability of having all inner retinal layers present at the foveal center (odds ratio, 0.04; P = 0.001) and a lower probability of having the EZ present at the foveal center (odds ratio, 0.07; P = 0.024) compared with untreated eyes. Cystoid macular changes were found in 53% of patients and 22% of imaging sessions. The age-adjusted incidence of CMCs was not correlated with bevacizumab or LPC treatment.
CONCLUSIONS
Intravitreal bevacizumab therapy for ROP is associated with more rapid outer retinal thickening at the foveal center, whereas LPC is associated with earlier extrusion of the inner retinal layers and delayed development of the EZ at the foveal center. Long-term follow-up is needed to determine the visual significance of these findings.
|
10.1016/j.ophtha.2017.09.020
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pubmed_744_16846
|
Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non-infectious febrile episodes (n = 10). On first day of fever, mean (+/- SD) PCT level was 0.3 ng/ml (0.2) in neutropenic fever of unknown origin, 0.5 ng/ml (0.7) in microbiologically confirmed infections, 0.2 ng/ml (0.2) in clinically documented infections and 1.7 (4.2) in non-infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10.1 ng/ml (6.7)] than all remaining groups (P = 0.027; Kruskal-Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values > or = 3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.
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10.1111/j.1365-2141.2004.05053.x
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pubmed_348_7516
|
PURPOSE
Single-center experiences have shown that myocardial meta-iodobenzylguanidine (mIBG) uptake has prognostic value in heart failure (HF) patients. To verify these observations using a rigorous clinical trial methodology, a retrospective review and prospective quantitative reanalysis was performed on a series of cardiac (123)I-mIBG scans acquired during a 10-year period at six centers in Europe.
METHODS
(123)I-mIBG scans obtained on 290 HF patients [(262 with left ventricular ejection fraction (LVEF) < 50%)] from 1993 to 2002 were reanalyzed using a standardized methodology to determine the heart-to-mediastinum ratio (H/M) on delayed planar images. All image results were verified by three independent reviewers. Major cardiac events [MCEs; cardiac death, cardiac transplant, potentially fatal arrhythmia (including implantable cardioverter-defibrillator discharge)] during 24-month follow-up were confirmed by an adjudication committee.
RESULTS
MCEs occurred in 67 patients (26%): mean H/M ratio was 1.51 +/- 0.30 for the MCE group and 1.97 +/- 0.54 for the non-MCE group (p < 0.001). Two-year event-free survival using an optimum H/M ratio threshold of 1.75 was 62% for H/M ratio less than 1.75, 95% for H/M ratio greater than or equal to 1.75 (p < 0.0001). Logistic regression showed H/M ratio and LVEF as the only significant predictors of MCE. Using the lower and upper H/M quartiles of 1.45 and 2.17 as high- and very low-risk thresholds, 2-year event-free survival rates were 52% and 98%, respectively. Among patients with LVEF < or = 35% and H/M > or = 1.75 (n = 73), there were nine MCEs because of progressive HF and only one because of an arrhythmia.
CONCLUSION
Application of a clinical trial methodology via the retrospective reanalysis of (123)I-mIBG images confirms the previously reported prognostic value of this method in HF patients, including potential identification of a quantitative threshold for low risk for cardiac mortality and potentially fatal ventricular arrhythmias.
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10.1007/s00259-007-0639-3
|
pubmed_432_7398
|
Hydrochlorothiazide was administered at two doses to Long-Evans rats for 7-10 days. Both doses resulted in an initial natriuresis and diuresis. After 1 day of treatment the natriuresis abated, but the diuresis persisted. The mechanisms responsible for these chronic effects were investigated by performing clearance and micropuncture studies on all animals; collections were made from late proximal tubules and from early and late regions of distal tubules. Values for total glomerular filtration rate and single-nephron filtration rate in thiazide-treated rats were not significantly different from those in control animals. The delivery of sodium to the end of the proximal convoluted tubule was considerably reduced in each group of thiazide-treated rats. Although sodium delivery to the early distal tubule was also significantly lower than in control animals, the difference had disappeared by the late distal tubule. It is concluded that the return of sodium excretion to control levels during chronic hydrochlorothiazide administration is a consequence of increased fractional reabsorption by the proximal tubules, secondary to a thiazide-induced sodium depletion. This results in less sodium being delivered to the nephron site at which thiazides exert their major inhibitory effect. Fluid delivery to the end of the proximal convoluted tubule and to the early distal tubule was significantly reduced in thiazide-treated rats; in animals given the higher dose of diuretic it was also significantly reduced at the end of the distal tubule. Nevertheless, in both thiazide-treated groups urine flow rate was elevated, suggesting that reabsorption of water from the collecting ducts is reduced during chronic thiazide administration.
|
10.1042/cs0700379
|
pubmed_150_22429
|
Tuning chemical structure and molecular layering of ionic liquids (IL) at solid interfaces offers leverage to tailor performance of ILs in applications such as super-capacitors, catalysis or lubrication. Recent experimental interpretations suggest that ILs containing cations with long hydrophobic tails form well-ordered bilayers at interfaces. Here we demonstrate that interfacial bilayer formation is not an intrinsic quality of hydrophobic ILs. In contrast, bilayer formation is triggered by boundary conditions including confinement, surface charging and humidity present in the IL. Therefore, we performed force versus distance profiles using atomic force microscopy and the surface forces apparatus. Our results support models of disperse low-density bilayer formation in confined situations, at high surface charging and/or in the presence of water. Conversely, interfacial structuring of long-chain ILs in dry environments and at low surface charging is disordered and dominated by bulk structuring. Our results demonstrate that boundary conditions such as charging, confinement and doping by impurities have decisive influence on structure formation of ILs at interfaces. As such, these results have important implications for understanding the behavior of solid/IL interfaces as they significantly extend previous interpretations.
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10.1038/srep30058
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pubmed_750_3992
|
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential. Improving the turnaround time and decreasing sample volume is critical for incorporating this liquid biopsy tool into routine practice. The objective of the current study was to validate the clinical feasibility of a self-assembled cell array (SACA) chip, a CTC counting platform with less than 4 h turnaround time, in patients with newly diagnosed colorectal cancers. In total, 179 patients with newly diagnosed colorectal cancers from a single institute were enrolled. Epithelial cell adhesion molecule positive (EpCAM(+)), cluster of differentiation 45 negative (CD45(-)) cells were isolated and enumerated from 2 mL of peripheral vein blood (PB) and inferior mesenteric vein blood (IMV) samples obtained during surgery. We found that the CTC count in PB but not IMV correlates with disease stages. Neoadjuvant chemotherapy did not lead to decreased CTC count in both types of blood samples. With cutoffs of four CTCs per 2 mL of blood, and serum carcinoembryonic antigen (CEA) level of 5 ng/mL, patients with non-metastatic disease were more likely to experience recurrence if they had high PB CTC count and high serum CEA concentration (odds ratio, 8.9). Our study demonstrates the feasibility of enumerating CTCs with a SACA chip in patients with colorectal cancer.
|
10.3390/cancers11010056
|
pubmed_345_8348
|
The light emission properties of the complex formed from deoxyribonucleic acid (DNA)-cetyltrimethylammonium chloride (CTMA) surfactant doped with different concentrations of Rhodamine 610 (Rh610) dye and dissolved in butanol are investigated and discussed. The results are compared to those obtained when only the Rh610 dye is dissolved in butanol, at the same concentrations. The light emission is excited in the investigated samples by the nanosecond pulses of a frequency-doubled Nd:YAG laser, at a wavelength of 532 nm. We have demonstrated the lasing effect in the investigated complex and we have studied its efficiency and coherence properties. The lasing properties of the Rh610 dye are favourably influenced by the presence of the DNA-CTMA complex in the investigated compound. It leads to an increase in the lasing efficiency and in the slope efficiency. Also the temporal coherence of the emitted light is larger and the emission can be tuned to shorter wavelengths.
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10.1039/c5cp01727k
|
pubmed_730_14045
|
Genetics, cell biology, and whole-genome sequencing of pathogens have changed dramatically the opportunities to investigate the epidemiology, pathogenesis, diagnosis, and control of microbial diseases. For example, recombinant DNA and PCR are powerful tools used to isolate genes whose role in pathogenicity can be investigated in biologically relevant virulence assays. Vaccines that target one or more of these genes can then be developed. Complete genome sequences of microbes provide an inventory of the genes encoding every virulence factor and potential immunogen. Candidate vaccines can be selected and developed using various approaches, including the recent innovation of immunisation with nucleic acids. Although many successful vaccines have been and will continue to be developed through empirical approaches, molecular microbiology provides a rational basis for discovery, development, and implementation of safer, more effective and, potentially cheaper vaccines.
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10.1016/S0140-6736(97)03259-5
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pubmed_371_1163
|
Six monoclonal antibodies identify a 210 kDa polypeptide which shows a cell cycle specific redistribution from the nucleus to the mitotic spindle. In interphase cells this polypeptide was localized in the nucleus and behaved during differential cell extraction as a component of the nuclear matrix. It accumulated in the centrosome region at prophase, in the pole regions of the mitotic spindle at metaphase and in crescents at the poles in anaphase, and reassociated with the nuclei as they reformed in telophase. Due to its staining pattern we call the protein the Spindle Pole-Nucleus (SPN) antigen. The localization of SPN antigen during mitosis was dependent on the integrity of the spindle since treatment of cells with nocodazole resulted in the dispersal of SPN antigen into many small foci which acted as microtubule organizing centres when the drug was removed. The SPN antigen was present in nuclei and mitotic spindles of all human and mammalian cell lines and tissues so far tested. When microinjected into the cytoplasm or nuclei of HeLa cells, one antibody caused a block in mitosis. Total cell number remained constant or decreased slightly after 24 h. At this time, about half the cells were arrested in a prometaphase-like state and revealed aberrant spindles. Many other cells were multinucleate. These results show that the SPN antigen is a protein associated with mitotic spindle microtubules which has to function correctly for the cell to complete mitosis.
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10.1002/j.1460-2075.1991.tb04899.x
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pubmed_133_13911
|
OBJECTIVE
We sought to determine whether indomethacin tocolysis immediately before delivery is associated with any increased complications in neonates delivered between 24 and 32 weeks' gestation.
STUDY DESIGN
We performed a case-control analysis of neonates delivered between 24 and 32 weeks' gestation after maternal indomethacin treatment for preterm labor. All infants were delivered within 48 hours of indomethacin exposure. Seventy-five patients were matched with 150 control subjects in a patient/control ratio of 1:2. Matching variables in order of priority included gestational age at delivery, fetal number, betamethasone exposure >24 hours before delivery, magnesium sulfate use, mode of delivery, infant sex, and race. Data were analyzed by using the Student t test, chi(2) analysis, and the Fisher exact test and Yates' correction.
RESULTS
The gestational age at delivery (mean +/- SD) was 28.7 +/- 2.3 weeks in the indomethacin group and 28.3 +/- 2.1 weeks for the control subjects. Birth weights (mean +/- SD) were 1121 +/- 243 and 1141 +/- 287 g, respectively. All mothers received both magnesium sulfate and betamethasone before delivery. The median cumulative dose of indomethacin was 225 mg. The median interval from last dose of indomethacin until delivery was 12 hours. There were no significant differences between the groups in the incidence of necrotizing enterocolitis (odds ratio, 1.12; 95% confidence interval, 0.31-3.84), grade III/IV intraventricular hemorrhage (odds ratio, 0.37; 95% confidence interval, 0.10-1.19), patent ductus arteriosus (odds ratio, 0.85; 95% confidence interval, 0.44-1.64), bronchopulmonary dysplasia (odds ratio, 0.97; 95% confidence interval, 0.49-1.91), pulmonary hypertension (odds ratio, 0.49; 95% confidence interval, 0. 02-4.80), anuria (odds ration, 1.21; 95% confidence interval, 0.22-6. 01), thrombocytopenia (odds ratio, 1.14; 95% confidence interval, 0. 53-2.42), sepsis (odds ratio, 1.21; 95% confidence interval, 0.22-6. 01), or neonatal death (odds ratio, 1.34; 95% confidence interval, 0. 55-3.25).
CONCLUSION
Maternal indomethacin exposure immediately before delivery was not associated with increased neonatal complications for infants delivered between 24 and 32 weeks' gestation.
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10.1016/s0002-9378(99)70085-2
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pubmed_155_935
|
Isolation of normal human glandular epithelia and their growth and maintenance in vitro have been major problems. The primary objective of studies presented here was to isolate postpubertal, normal human, viable prostatic epithelium for in vitro cultivation. The long-term objective of these investigations was to develop an in vitro human cell model system for studies on prostatic carcinogenesis. A method for isolation of viable, normal and benign human prostatic epithelium, using collagenase for tissue dissociation, is described. Intact acini were isolated, which, on plating gave rise to vigorously growing monolayer cultures of epithelial cells. The purity of epithelial cultures partly depended upon the source of tissue. Specimens of normal prostate and those of benign tissue derived from open prostatectomies provided primarily pure epithelial cultures with occasional fibroblast colonies in some cultures, which could be removed. Cultures from some specimens of transurethral resection of the prostate (TURP) contained many fibroblast colonies due to incomplete separation of acini from the stroma. This resulted from incomplete digestion of denatured tissue caused by electrocauterization during surgery. Cultures established in this manner are being used to study the effects of hormones, vitamins and other growth regulators in order to establish growth requirements of these cells in vitro, which would facilitate their long-term maintenance.
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10.1007/BF02619156
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pubmed_796_18042
|
Phencyclidine, 1-(1-phenylcyclohexyl)piperidine, was found in this study to be a mechanism-based inactivating agent for cytochrome P-450 form 2, the major phenobarbital-inducible cytochrome of rabbit liver microsomes. This process is highly selective for P-450 form 2, both in microsomes and in the reconstituted enzyme system, in that forms 3a, 3b, 4, and 6 are not affected. However, phencyclidine iminium ion, an oxidative metabolite, inactivates both P-450 form 2 and form 3b in a metabolism-dependent manner. Both phencyclidine and its iminium ion give biphasic kinetics of inactivation with similar rate constants, which supports the hypothesis that the iminium ion is an intermediate in the inactivation of P-450 form 2 by the parent compound. The absorption of the oxidized cytochrome and of the ferrous-carbonyl complex in the visible spectrum are both decreased upon inactivation by phencyclidine, indicating modification of the heme moiety. Several modified hemes produced by the action of phencyclidine were isolated by HPLC.
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pubmed_796_18042
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pubmed_292_3010
|
Type 2 diabetes (T2D) is a well-established risk factor for patients with coronary artery disease (CAD). Patients with CAD and comorbid T2D also have a higher risk of cardiovascular complications, such as silent ischemia and stable angina. In treating the symptoms of stable angina in patients with CAD and comorbid T2D, it is vital to utilize therapies that reduce symptoms and improve outcomes. At the same time, there is significant concern about the preservation of glycometabolic parameters, such as glycosylated hemoglobin (HbA1c), particularly because some antianginal therapies, such as β-blockers and calcium channel blockers-although effective at improving the symptoms of stable angina and reducing ischemia-may also worsen glycemic control by increasing HbA1c levels. Available trial data on the efficacy of antianginal agents in patients with stable angina and comorbid T2D are limited. Therefore, in patients with stable angina and T2D, a tailored approach to treatment of stable angina by selecting therapies with a neutral or positive glycometabolic profile may improve outcomes and increase treatment compliance. Additionally, patients with a dual diagnosis may benefit from therapies that have beneficial effects on both stable angina and T2D, thereby reducing polypharmacy. Prospective studies in patients with stable angina and T2D are needed to guide therapy decisions.
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10.3909/ricm0742
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pubmed_896_9433
|
Although the healing effect of music has been recognized since time immemorial, there has been a renewed interest in its use in modern medicine. This can be attributed to the increasing focus on holistic healing and on the subjective and objective aspects of well-being. In ophthalmology, this has ranged from using music for patients undergoing diagnostic procedures and surgery, as well as for doctors and the operation theatre staff during surgical procedures. Music has proven to be a potent nonpharmacological sedative and anxiolytic, allaying both the pain and stress of surgery. This review aims to explore the available evidence about the role of music as an adjunct for diagnostic and surgical procedures in current ophthalmic practices.
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10.1177/25158414211040890
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pubmed_688_17858
|
The case of a patient who underwent left pneumonectomy at 23 years of age is described. When he was 54 years old, he required resection of the right upper and middle lobes. He survived and lived an active life for more than three years with the right lower lobe as his only lung tissue.
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10.1016/s0003-4975(10)60364-5
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pubmed_935_5396
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Hepatobiliary functional scintigraphy (HBFS) using 99m Tc-labeled Diethyl-IDA was tested in 84 patients suffering from various hepatic and bile duct disorders. The investigated pathologies were: gall bladder dysfunction, parital bile duct obstruction, total obstruction, hepatocellular disease, cirrhosis and drug induced cholostastis. The diagnosis accuracy of the method was found to be 95 %, and the method proved to be useful for guiding the clinician in selecting those additional investigation techniques most apt to define the etiology of the pathological condition accurately. In conclusion, the non-invasive character of the technique, its usefulness even in the presence of elevated bilirubin levels and the information yielded by HBFS make it a method of choice to be placed in the beginning of the test series liver or duct patients are submitted to.
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pubmed_935_5396
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pubmed_448_5221
|
CD11d/CD18 is the most recently discovered and least understood β2 integrin. Known CD11d adhesive mechanisms contribute to both extravasation and mesenchymal migration - two key aspects for localizing peripheral leukocytes to sites of inflammation. Differential expression of CD11d induces differences in monocyte/macrophage mesenchymal migration including impacts on macrophage sub-set migration. The participation of CD11d/CD18 in leukocyte localization during atherosclerosis and following neurotrauma has sparked interest in the development of CD11d-targeted therapeutic agents. Whereas the adhesive properties of CD11d have undergone investigation, the signalling pathways induced by ligand binding remain largely undefined. Underlining each adhesive and signalling function, CD11d is under unique transcriptional control and expressed on a sub-set of predominately tissue-differentiated innate leukocytes. The following review is the first to capture the nearly three decades of CD11d research and discusses the emerging role of CD11d in leukocyte migration and retention during the progression of a staged immune response.
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10.3389/fimmu.2021.775447
|
pubmed_997_816
|
Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders that are challenging with regard to diagnosis and clinical management. To study the similarities and differences of these disorders we undertook a multi-center international study of one of the largest case series (CNL, n=24; aCML, n=37 cases, respectively), focusing on the clinical and mutational profiles (n=53 with molecular data) of these diseases. We found no differences in clinical presentation or outcomes between both entities. As previously described, both CNL and aCML share a complex mutational profile with mutations in genes involved in epigenetic regulation, splicing and signaling pathways. Apart from CSF3R, only EZH2 and TET2 were differentially mutated between them. The molecular profiles support the notion of CNL and aCML being a continuum of the same disease that may fit best within the myelodysplastic/myeloproliferative neoplasms (MDS/MPN). We identified four high-risk mutated genes, specifically CEBPA (β=2.26, HR=9.54, p=0.003), EZH2 (β=1.12, HR=3.062, p=0.009), NRAS (β=1.29, HR=3.63, p=0.048) and U2AF1 (β=1.75, HR=5.74, p=0.013) by multivariate analysis. Our findings underscore the relevance of molecular-risk classification in CNL/aCML as well as the importance of CSF3R mutations in these diseases.
|
10.1182/bloodadvances.2022008204
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pubmed_448_13128
|
This paper presents a unifying theory for autism by applying the framework of a pathogenetic triad to the scientific literature. It proposes a deconstruction of autism into three contributing features (an autistic personality dimension, cognitive compensation, and neuropathological risk factors), and delineates how they interact to cause a maladaptive behavioral phenotype that may require a clinical diagnosis. The autistic personality represents a common core condition, which induces a set of behavioral issues when pronounced. These issues are compensated for by cognitive mechanisms, allowing the individual to remain adaptive and functional. Risk factors, both exogenous and endogenous ones, show pathophysiological convergence through their negative effects on neurodevelopment. This secondarily affects cognitive compensation, which disinhibits a maladaptive behavioral phenotype. The triad is operationalized and methods for quantification are presented. With respect to the breadth of findings in the literature that it can incorporate, it is the most comprehensive model yet for autism. Its main implications are that (1) it presents the broader autism phenotype as a non-pathological core personality domain, which is shared across the population and uncoupled from associated features such as low cognitive ability and immune dysfunction, (2) it proposes that common genetic variants underly the personality domain, and that rare variants act as risk factors through negative effects on neurodevelopment, (3) it outlines a common pathophysiological mechanism, through inhibition of neurodevelopment and cognitive dysfunction, by which a wide range of endogenous and exogenous risk factors lead to autism, and (4) it suggests that contributing risk factors, and findings of immune and autonomic dysfunction are clinically ascertained rather than part of the core autism construct.
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10.3389/fpsyt.2021.767075
|
pubmed_462_4571
|
Transcutaneous oxygen pressure (tcPO2) on the dorsum of the foot and Doppler ankle/arm pressure ratio (AAR) were measured in nine patients with peripheral arterial occlusive disease (PAOD)-stage IIb-III during treadmill exercise before and after (two days and one month) atherectomy. These parameters were compared with nine normal controls and nine PAOD I-IIa patients without atherectomy. All patients with atherectomy showed an increase in their pain free walking distance, and, both two days and one month after the intervention, a significant (p less than 0.05) increase in their exercise/rest tcPO2 ratio (pre-atherectomy: 25% (12-81), two days after: 78% (49-92), one month after: 85% (81-92). AAR displays a significant increase only between pre- and two days after atherectomy, without further significant improvement after one month. We conclude that tcPO2 measurement is an adequate measurement for follow-up studies in patients with PAOD after invasive therapeutic interventions. Furthermore, these data suggest that, while the maximum improvement for the macrocirculation (AAR) occurs shortly after atherectomy, improvement of the microcirculation (tcPO2) is delayed for a prolonged period after revascularization of major arteries, possibly due to reperfusion injury.
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pubmed_462_4571
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pubmed_899_1683
|
Congenital (hypo)dysfibrinogenemia patients may have obstetric complications during their pregnancies. This study aimed to evaluate thromboelastography (TEG) as a potential tool for assessing the tendency for obstetric complications in those patients in a non-pregnant state. A total of 22 female subjects with congenital (hypo)dysfibrinogenemia were recruited. Nine subjects had histories of obstetric complications and the other 13 subjects had at least one uneventful pregnancy without obstetric complications as yet. Detailed clinical investigation and phenotype/genotype detection were carried out, and both kaolin-activated TEG and functional fibrinogen TEG (FF-TEG) were applied in all subjects. Significant differences were identified in all TEG parameters except for R and angle between these two groups (P < 0.05) by covariance analysis. Receiver operating characteristic (ROC) analysis of discrimination between these two groups of patients was performed for TEG parameters. Significantly high odds ratio (OR) of obstetric complications occurrence were demonstrated in K ≥ 3.8 min, maximum amplitude (MA) ≤ 54.2 mm, comprehensive index (CI) ≤ -3 (11.67, 95% CI 1.527-89.121, P < 0.05 in all), and MA-CFF ≤ 12.1 mm (20.00, 95% confidence interval (95% CI) 1.967-203.322, P = 0.002). Moreover, MA-CFF had better prognostic performance, with a corresponding area under the receiver operating curve of 0.923 (range 0.815-1.031, P = 0.001). This study suggests that (hypo)dysfibrinogenemia patients with values outside of the cut-off values of TEG assays under non-pregnant state may have a higher risk of obstetric complications occurring when they are pregnant. No parameters under non-pregnant state in clinical laboratory have ever been reported to be risk factors for obstetric complication occurrence in (hypo)dysfibrinogenemia patients. This study explored such parameters in TEG assays and found that parameters of TEG assays under non-pregnant status might predict the occurrence of obstetric complications, which could provide physicians with important information about whether fibrinogen replacement therapy is required, so as to prevent the occurrence of obstetric complications, especially for patients who are asymptomatic in daily life.
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10.1111/1440-1681.12509
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pubmed_313_18824
|
Immunization with DNA vaccines as a novel alternative to conventional vaccination strategy requires adjuvant for improving vaccine efficacy. The conserved immunogenic HA2 subunit, which harbors neutralizing epitopes is a promising vaccine candidate against influenza viruses. In this study, for the first time we explore the idea of using host interferon inducible Mx protein to increase the immunogenicity of HA2 H9N2 influenza DNA vaccine. The potency and safety of the Mx adjuvanted-HA2 vaccine was evaluated in BALB/c mice by different prime-boost strategies. To assess the effect of the vaccination on the virus clearance rate, mice were challenged with homologous influenza virus. Administration of the adjuvanted vaccine and boosting with the same regimen could effectively enhance both humoral and cellular immune responses in treated mice. These data demonstrated that Mx as host defense peptide can be potentiated for improving influenza vaccine efficacy.
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10.1016/j.biologicals.2016.11.004
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pubmed_69_9210
|
AIMS
In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype-genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation.
METHODS
We measured TPMT (activity, as units ml(-1) packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 10(8) RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97.
RESULTS
Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P < 0.0001). At diagnosis genotype-phenotype was discordant. During chemotherapy the overall concordance was 92%, but this fell to 55% in the intermediate activity cohort (45% had wild-type genotypes). For both thiopurines TGN concentrations differed by TPMT status. For mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P < 0.0001), whilst median MeMPNs, products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients.
CONCLUSIONS
In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy.
|
10.1111/bcp.12066
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pubmed_218_9471
|
The current study investigated whether there were age-related differences in episodic feeling-of-knowing (FOK) accuracy and whether accuracy was influenced by when the FOK judgements were made. Younger and older participants were randomly assigned to one of four conditions that manipulated the timing of the FOK in relation to cued recall and associative recognition. Age-related differences in FOK accuracy were not reliable either when the FOK was immediate or when it was delayed. Moreover, FOK accuracy was above chance for both age groups. Remember/Know (RK) judgements correlated reliably with FOKs for unrecalled words for both age groups and did not vary by FOK timing. The invariance in FOK accuracy occurred despite robust age differences in associative cued recall and associative recognition, as well as age differences in recollection as measured by RK judgements. The findings are inconsistent with the argument that there is a general age deficit in episodic FOK accuracy. Possible reasons for discrepant findings in the literature are discussed.
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10.1080/09658210903374537
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pubmed_786_15942
|
The identification of agents with antiproliferative activity against endothelial cells has significant value for the treatment of many angiogenesis-dependent pathologies. Herein, we describe the discovery of a series of thalidomide analogues possessing inhibitory effects against both endothelial and prostate cancer cells. More specifically, several analogues exhibited low micromolar to mid-nanomolar potency in the inhibition of human microvascular endothelial cell (HMEC) proliferation, both in the presence and absence of vascular endothelial growth factor (VEGF), with the tetrafluorophthalimido class of compounds demonstrating the greatest potency. Additionally, all the compounds were screened against two different androgen independent prostate cancer cell lines (PC-3 and DU-145). Again, the tetrafluorophthalimido analogues exhibited the greatest effect with GI(50) values in the low micromolar range. Thalidomide was found to demonstrate selective inhibition of androgen receptor positive LNCaP prostate cancer cells. Furthermore, we showed that, as an example, tetrafluorophthalimido analogue 19 was able to completely inhibit the prostate specific antigen (PSA) secretion by the LNCaP cell line, while thalidomide demonstrated a 70% inhibition. We have also demonstrated that a correlation exists between HMEC and prostate cancer cell proliferation for this structural class. Altogether, our study suggests that these analogues may serve as promising leads for the development of agents that target both androgen dependent and independent prostate cancer and blood vessel growth.
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10.1016/j.bmc.2003.11.007
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pubmed_559_15651
|
Shigella boydii, Shigella flexneri, Shigella dysenteriae and Shigella sonnei were identified using gas chromatography instead of the traditional techniques. Their acid methyl esters profiles were determined using a gas chromatograph Hewlett Packard 5890A and a RSL-150 heliflex capillary column. A total of 192 samples were analyzed both reference strains (ATCC 8700, INDRE B2188, B2194 and B2199) and environmental isolates. 12 fatty acids were included in the profiles from which 3-hydroxytetradecanoic acid (peak 12), trans 9-octadecanoic acid (peak 22), heptadecanoic acid (peak 18) and octadecanoic acid (peak 23), were the most important for the differentiation of the species analyzed.
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pubmed_559_15651
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pubmed_381_2321
|
2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO) has been extensively utilized as a radical scavenger or an oxidation catalyst. In contrast, TEMPO as a hydrogen atom transfer (HAT) catalyst has rarely been studied. Here, we report that TEMPO, as the HAT catalyst, homolytically cleaves benzylic or allylic C-H bonds to give the corresponding alkyl radicals. Benefiting from the dual roles played by TEMPO as the HAT catalyst and the radical scavenger, the highly challenging aerobic dehydrogenation of activated alkanes to alkenes is successfully developed.
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10.1021/acs.joc.2c01302
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pubmed_13_889
|
Background
Based on its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Therefore, identification of tumor types with increased HRD is important for the optimal use of this class of therapeutic agents. HRD levels can be estimated using various mutational signatures from next generation sequencing data and we used this approach to determine whether breast cancer brain metastases show altered levels of HRD scores relative to their corresponding primary tumor.
Patients and methods
We used a previously published next generation sequencing dataset of 21 matched primary breast cancer/brain metastasis pairs to derive the various mutational signatures/HRD scores strongly associated with HRD. We also carried out the myChoice HRD analysis on an independent cohort of 17 breast cancer patients with matched primary/brain metastasis pairs.
Results
All of the mutational signatures indicative of HRD showed a significant increase in the brain metastases relative to their matched primary tumor in the previously published whole exome sequencing dataset. In the independent validation cohort, the myChoice HRD assay showed an increased level in 87.5% of the brain metastases relative to the primary tumor, with 56% of brain metastases being HRD positive according to the myChoice criteria.
Conclusions
The consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment. This observation warrants further investigation to assess whether this increase is common to other metastatic sites as well, and whether clinical trials should adjust their strategy in the application of HRD measures for the prioritization of patients for PARP inhibitor therapy.
|
10.1093/annonc/mdy216
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pubmed_412_11639
|
Health related quality of life was evaluated in 40 schizophrenics from day hospital at admission, during the treatment and after 8 weeks. In contrast to the psychopathology which significantly decreased after 4 weeks already, the improvement of quality of life was found to be significant only at the discharge from day hospital. The quality of life did not correlate with the severity of schizophrenic symptoms. The older and more frequently hospitalized patients were, the less favorably they evaluated the quality of life. Patients professionally disabled were also less pleased with their quality of life. All quality of life domains improved after treatment with the exception of physical functioning and reported health transition. Physical functioning, role-physical, general health and mental health correlated inversely with severity of schizophrenia after treatment. There was no correlation between clinical improvement after treatment and quality of life domains. The higher was the patients' educational level the better they evaluated their vitality, social functioning and reported health transition.
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pubmed_412_11639
|
pubmed_80_14342
|
Zirconium pentatelluride was recently reported to be a 3D Dirac semimetal, with a single conical band, located at the center of the Brillouin zone. The cone's lack of protection by the lattice symmetry immediately sparked vast discussions about the size and topological or trivial nature of a possible gap opening. Here, we report on a combined optical and transport study of ZrTe_{5}, which reveals an alternative view of electronic bands in this material. We conclude that the dispersion is approximately linear only in the a-c plane, while remaining relatively flat and parabolic in the third direction (along the b axis). Therefore, the electronic states in ZrTe_{5} cannot be described using the model of 3D Dirac massless electrons, even when staying at energies well above the band gap 2Δ=6 meV found in our experiments at low temperatures.
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10.1103/PhysRevLett.122.217402
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pubmed_403_12545
|
As guest editors, we are pleased to present this Special Issue on endogenous retroviruses (ERVs) and their impact on mammalian development and disease [...].
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10.3390/v12121446
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pubmed_1047_10720
|
It has been shown that alterations in QT/RR relationship may be associated arrhythmogenesis in several clinical settings. In the present study the QT/RR relationship was studied in 20 patients with idiopathic ventricular tachycardia (12 men and 8 women, aged 41 +/- 14 years) compared to 20 normal subjects (9 men and 11 women, aged 39 +/- 13 years). All the patients were off any antiarrhythmic drugs and had no evidence of intraventricular conduction defects. The QT intervals and their preceding RR intervals were measured on electrocardiogram strips from 24-hour Holter tapes at hourly intervals. The differences in the maximum, minimum, and mean of either the QT interval or its corrected values between patients with idiopathic ventricular tachycardia and normal subjects were not statistically significant. There was a significant correlation between the QT and RR intervals in normal subjects (gamma = 0.73 +/- 0.12, P < 0.05) and in patients with idiopathic ventricular tachycardia (gamma = 0.80 +/- 0.10, P < 0.05). However, the linear regression line of the QT interval against the RR interval were significantly (P < 0.001) altered in patients with idiopathic ventricular tachycardia (QT = 0.24 +/- 0.18 RR) compared to normal subjects (QT = 0.27 +/- 0.12 RR). We conclude that although there is no significant change in the QT interval and its corrected values, the QT/RR relationship is significantly altered in patients with idiopathic ventricular tachycardia as compared to normal subjects. This may be of importance in the pathogenesis of idiopathic ventricular tachycardia in these patients.
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10.1111/j.1540-8159.1994.tb01372.x
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pubmed_407_21470
|
Many cationic antimicrobial peptides (AMPs) target the unique lipid composition of the prokaryotic cell membrane. However, the micromolar activities common for these peptides are considered weak in comparison to nisin, which follows a targeted, pore-forming mode of action. Here we show that AMPs can be modified with a high-affinity targeting module, which enables membrane permeabilization at low concentration. Magainin 2 and a truncated peptide analog were conjugated to vancomycin using click chemistry, and could be directed towards specific membrane embedded receptors both in model membrane systems and whole cells. Compared with untargeted vesicles, a gain in permeabilization efficacy of two orders of magnitude was reached with large unilamellar vesicles that included lipid II, the target of vancomycin. The truncated vancomycin-peptide conjugate showed an increased activity against vancomycin resistant Enterococci, whereas the full-length conjugate was more active against a targeted eukaryotic cell model: lipid II containing erythrocytes. This study highlights that AMPs can be made more selective and more potent against biological membranes that contain structures that can be targeted.
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10.1371/journal.pone.0039768
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pubmed_263_10942
|
AIMS
Increases to radiotherapy dose are constrained by normal tissue effects. The relationship between bowel dose volume data and late bowel toxicity in patients with muscle-invasive bladder cancer treated with radical radiotherapy was assessed.
MATERIALS AND METHODS
The bowel was contoured retrospectively on radiotherapy plans of 47 patients recruited to the BC2001 trial (CRUK/01/004). The relationship between bowel volume at various dose levels and prospectively collected late bowel toxicity was explored.
RESULTS
Fifteen per cent and 6% of patients experienced grade 1 and grade 2 or more late bowel toxicity, respectively. The mean bowel volume was significantly less at doses ≥50 Gy in those treated with reduced high dose volume radiotherapy compared with standard radiotherapy. The probability of late bowel toxicity increased as bowel volume increased (P ≤ 0.05 for dose levels 30-50 Gy). No grade 2 or more late bowel toxicity was observed in patients with bowel volumes under the thresholds given in the model that predict for 25% probability of late bowel toxicity.
CONCLUSIONS
There is a dose volume effect for late bowel toxicity in radical bladder radiotherapy. We have modelled the probability of late bowel toxicity from absolute bowel volumes to guide clinicians in assessing radical bladder radiotherapy plans. Thresholds predicting for a 25% probability of late bowel toxicity are proposed as dose volume constraints.
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pubmed_263_10942
|
pubmed_310_23038
|
The catabolism of rat chylomicrons, labeled in their triacylglycerol (TG) component, was investigated using perfused working mouse hearts. Perfusion of mouse hearts with heparin increased lipoprotein lipase (LPL) activity in the perfusate. This heparin-releasable LPL pool remained constant over a variety of experimental conditions, including workload and fatty acid concentrations, making the mouse heart a suitable model to study chylomicron catabolism. Endothelium-bound LPL hydrolyzed radiolabeled (3)H-labeled chylomicrons (0.4 mM TG); the fate of LPL-derived (3)H-labeled fatty acids was split evenly between oxidation (production of (3)H(2)O) and esterification (incorporation into tissue lipids, mainly TG). In comparison, the oxidation of 0.4 mM [(3)H]palmitate complexed to albumin was fourfold greater than esterification into tissue lipids. Surprisingly, the addition of unlabeled palmitate (0.4 or 1.2 mM) to perfusions with (3)H-chylomicrons did not affect the fate (either oxidation or esterification) of LPL-derived (3)H-fatty acids. These results suggest that fatty acids produced from lipoprotein hydrolysis by the action of LPL and fatty acids from a fatty acid-albumin complex do not enter a common metabolic pool in the heart.
|
10.1152/ajpendo.2001.281.2.E357
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pubmed_949_18195
|
Ciliary neurotrophic factor, along with other neuropoietic cytokines, signals through the shared receptor subunit gp130 [1-3], leading to the tyrosine phosphorylation of a number of substrates [4,5], including the transcription factors STAT1 and STAT3 and the protein tyrosine phosphatase SHP-2 [6,7] [8]. SHP-2 (also known as PTP1D, SHPTP2, Syp and PTP2C) is a positive regulatory molecule required for the activation of the mitogen-activated protein kinase pathway and the stimulation of gene expression in response to epidermal growth factor, insulin and platelet-derived growth factor stimulation [9-11]. We have previously shown that cytokines that signal via the gp130 receptor subunit activate transcription of the vasoactive intestinal peptide (VIP) gene through a 180 bp cytokine response element (CyRE) [12,13]. To characterize the role of SHP-2 in the regulation of gp130-stimulated gene expression, we examined the regulation of the VIP CyRE in two systems that prevented ligand-dependent SHP-2 phosphorylation. Inhibition of SHP-2, either by mutating the tyrosine residue in gp130 that mediates the SHP-2 interaction, or by expression of dominant-negative SHP-2, resulted in dramatic increases in gp130-dependent gene expression, through the VIP CyRE and more specifically through multimerized STAT-binding sites. These data suggest that SHP-2 has a negative role in gp130 signaling by modulating STAT-mediated transcriptional activation.
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10.1016/s0960-9822(06)00298-3
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pubmed_569_12805
|
OBJECTIVE
To evaluate the performance of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in the differential diagnosis of Angiomyolipoma (AML), clear cell renal cell carcinoma (clear cell RCC) and non-clear cell renal cell carcinoma (non-clear cell RCC).
METHOD
Forty-five patients were enrolled and classified into three groups according to the surgical pathology results. There were even amount of subjects (15) in each group of AML group, clear cell RCC group and non-clear cell RCC group (including 6 Papillary RCC and 9 Chromophobe RCC). ALL the patients underwent respiratory-triggered DWI on 3.0T MR system using multi b-values of 0, 20, 50, 100, 150, 200, 400, 600, 800 sec/mm2. Pure molecular-based (D), perfusion-related (D*) and vascular fraction (f) were calculated using a bi-exponential model. Comparisons of derived parameters derived by IVIM-DWI among three groups were performed using One-way ANOVA.
RESULTS
D in clear cell RCC (1.8±1.5)×10(-3) mm2/s was significantly higher than that in AML (0.7±0.3)×10(-3) mm2/s or non-clear cell RCC (0.9±0.3)×10(-3) mm2/s (P<0.05), while no statistical difference was observed between AML and non-clear cell RCC (P=0.807). D* demonstrated significant difference between AML (33.3±18.2)×10(-3) mm2/s and non-clear cell RCC (17.8±17.3)×10(-3) mm2/s, (P<0.05). No observed significant difference in f was revealed between any two groups.
CONCLUSION
Pure water molecules (true diffusion) and capillary microcirculation (pseudo-diffusion) may result in the observed difference of parameters in these three types of renal tumors. D value can contribute to differentiate the clear cell RCC from AML, and between clear cell and non-clear cell RCC as well. D* value may be applied to differentiate AML from non-clear cell RCC.
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pubmed_569_12805
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pubmed_559_5080
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Older people constitute one of the highest risk groups for suicide. Existing research in this area has been largely dominated by a risk factor approach. This is of limited usefulness since only a minority of those at risk go on to make an attempt. Therefore, prediction, prevention and the management of risk remain challenging. The present study aimed to capture the subjective experience of older people who had recently made a suicide attempt through exploring their understanding of the pathway to and from this attempt, within the context of ageing. Fifteen participants were interviewed. Transcripts were analysed using Interpretative Phenomenological Analysis. Three broad themes emerged--Struggle (experiencing life as a struggle before and after the attempt, and in relation to growing older), Control (trying to maintain control over life before the attempt, and following it either failing or succeeding to regain control) and Visibility (feeling invisible or disconnected from others and trying to fight against this before the attempt and either becoming more or less connected afterwards). Risk factors identified in the literature were often absent or construed by participants as not relevant to their attempt. Individual accounts highlight the diversity and complexity of experience of older people who attempt suicide.
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10.1080/13607860600640905
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pubmed_819_14599
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Olfactory hallucinations, although relatively rare, are reportedly indicative of serious psychopathology and poor prognosis in psychotic patients. This article describes the development of a rating scale for assessing olfactory experiences of psychotic and psychoticlike deviancy. The scale is modeled after Chapman and Chapman's rating scales for other psychoticlike experiences, which have been found to predict psychosis and psychosis-proneness. In a longitudinal study, college students who reported deviant olfactory experiences at their initial assessment (n = 31) exceeded the remaining subjects (n = 477) on DSM-III-R psychosis and on measures of psychosis proneness at a 10-year followup. Furthermore, hypothetically psychosis-prone subjects identified by the Perceptual Aberration and Magical Ideation scales exceeded control subjects on ratings of olfactory experiences at both initial and followup assessments.
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10.1093/schbul/22.2.371
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pubmed_974_22564
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Factor VII (FVII) activating protease (FSAP) is a circulating protease with a putative function in blood coagulation and fibrinolysis. Genetic epidemiological studies have implied a role for FSAP in carotid stenosis, stroke and thrombosis. To date, no in vivo evidence is available to support these claims. We have, for the first time, used FSAP-/- mice to define its role in thrombosis and haemostasis in vivo and to characterise the molecular mechanisms involved. FeCl3-induced arterial thrombosis in carotid and mesenteric artery revealed that the occlusion time was significantly increased in FSAP-/- mice (p< 0.01) and that some FSAP-/- mice did not occlude at all. FSAP-/- mice were protected from lethal pulmonary thromboembolism induced by collagen/ epinephrine infusion (p< 0.01). Although no spontaneous bleeding was evident, in the tail bleeding assay a re-bleeding pattern was observed in FSAP-/- mice. To explain these observations at a mechanistic level we then determined how haemostasis factors and putative FSAP substrates were altered in FSAP-/- mice. Tissue factor pathway inhibitor (TFPI) levels were higher in FSAP-/- mice compared to WT mice whereas FVIIa levels were unchanged. Other coagulation factors as well as markers of platelet activation and function revealed no significant differences between WT and FSAP-/- mice. This phenotype of FSAP-/- mice could be reversed by application of exogenous FSAP. In conclusion, a lack of endogenous FSAP impaired the formation of stable, occlusive thrombi in mice. The underlying in vivo effect of FSAP is more likely to be related to the modulation of TFPI rather than FVIIa.
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10.1160/TH14-06-0519
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pubmed_433_3917
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Emerging technologies have the potential to transform our approach to medical education. A goal in this chapter is to inspire researchers, educators and scholars in the bio-medical visualisation field who can benefit from integrating wearable Augmented Reality (AR) technologies, like the HoloLens into their existing teaching and learning environments. We draw from case studies, existing research and the educational technology literature, to propose the design of purposeful learner-centered experiences that might benefit from wearable AR technologies in the classroom.
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10.1007/978-3-030-24281-7_2
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pubmed_921_16068
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Concentric multilamellar microvesicles, named spherulites(TM), were evaluated as an oligonucleotide carrier. Up to 80% oligonucleotide was encapsulated in these vesicles. The study was carried out on two different spherulite(TM) formulations. The spherulite(TM) size and stability characteristics are presented. Delivery of encapsulated oligonucleotide was performed on a rat hepatocarcinoma and on a lymphoblastoid T cell line, both expressing the luciferase gene. We showed that spherulites(TM) were able to transfect both adherent and suspension cell lines and deliver the oligonucleotide to the nucleus. Moreover, 48-62% luciferase inhibition was obtained in the rat hepatocarcinoma cell line when the antisense oligonucleotide targeted to the luciferase coding region was encapsulated at 500 nM concentration in spherulites(TM) of different compositions.
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10.1093/nar/28.16.3134
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pubmed_915_587
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Long noncoding RNAs (lncRNAs) are an important class of pervasive noncoding RNA involved in a variety of biological functions. Numerous studies have demonstrated their important regulatory role in human disease, especially cancer. However, the mechanism underlying the transcription of lncRNAs is not fully elucidated. Here, a comparison of local chromatin structure of the ROR lncRNA locus revealed a cohesin-complex-mediated intrachromosomal loop that is juxtaposed with an upstream enhancer to the ROR promoter, enabling activation of endogenous ROR lncRNA in tumor cells. This chromosomal interaction was not observed in normal control cells. Knockdown of SMC1 by RNAi or deletion of the enhancer DNA by CRISPR/Cas9 abolished the intrachromosomal interaction, resulting in ROR lncRNA silencing and inhibition of the tumor progression in animals carrying tumor xenografts. Our results reveal a novel mechanism by which the cohesin-orchestrated intrachromosomal looping may serve as a critical epigenetic driver to activate transcription of ROR lncRNA, subsequently inducing tumorigenesis. Our data represent a novel chromosomal folding pattern of lncRNA regulation, thereby providing a novel alternative concept of chromosomal interaction in lncRNA-triggered tumorigenesis.
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10.1016/j.ymthe.2019.07.020
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pubmed_355_10321
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The aim of this study is to estimate the prevalence of obesity and factors associated with it in Bahraini secondary school students. A cross-sectional study involving a sample of 825 students (417 boys and 408 girls) aged 15 to 21 years was obtained from secondary schools. Obesity was determined using body mass index (BMI = Wt/Ht2). The findings revealed that 15.6% of boys and 17.4% of girls were either overweight or obese (BMI > or = 25). Family size, parents education, and family history of obesity were significantly associated with obesity among boys, while family history was the only socio-economic factors statistically associated with obesity among girls. Meal patterns such as eating between meals, number of meals per day, and method of eating were not associated with obesity in students. Boys who ate alone were 3 times more likely to be obese than those who ate with family members (odd ratio = 3.4). Measures to prevent and control obesity among children are suggested.
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10.1177/026010609300900103
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pubmed_476_4144
|
Sulfate reducing bacteria (SRB) have the capability of bioreducing hexavalent chromium [Cr(VI)] to trivalent chromium [Cr(III)] under sulfate-reducing conditions for toxicity reduction. However, a high amount of sulfate addition would cause elevated sulfide production, which could inhibit the growth of SRB and result in reduced Cr(VI) bioreduction efficiency. A slow release reagent, viscous carbon and sulfate-releasing colloidal substrates (VCSRCS), was prepared for a long-lasting carbon and sulfate supplement. In the column study, VCSRCS was injected into the column system to form a VCSRCS biobarrier for Cr(VI) containment and bioreduction. A complete Cr(VI) removal was observed via the adsorption and bioreduction mechanisms in the column with VCSRCS addition. Results from X-ray diffractometer analyses indicate that Cr(OH)3(s) and Cr2O3(s) were detected in precipitates, indicating the occurrence of Cr(VI) reduction followed by Cr(III) precipitation. Results from the Fourier-transform infrared spectroscopy analyses show that cell deposits carried functional groups, which could adsorb Cr. Addition of VCSRCS caused increased populations of total bacteria and dsrA, which also enhanced Cr(VI) reduction. Microbial diversity results indicate that VCSRCS addition resulted in the growth of Cr(VI)-reducing bacteria including Exiguobacterium, Citrobacter, Aerococcus, and SRB. Results of this study will be helpful in developing an effective and green VCSRCS biobarrier for the bioremediation of Cr(VI)-polluted groundwater.
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10.1016/j.chemosphere.2022.133877
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pubmed_262_5550
|
UNLABELLED
Attempts to engage the scientific community to annotate biological data (such as protein/gene function) stored in databases have not been overly successful. There are several hypotheses on why this has not been successful but it is not clear which of these hypotheses are correct. In this study we have surveyed 50 biologists (who have recently published a paper characterizing a gene or protein) to better understand what would make them interested in providing input/contributions to biological databases. Based on our survey two things become clear: a) database managers need to proactively contact biologists to solicit contributions; and b) potential contributors need to be provided with an easy-to-use interface and clear instructions on what to annotate. Other factors such as 'reward' and 'employer/funding agency recognition' previously perceived as motivators was found to be less important. Based on this study we propose community annotation projects should devote resources to direct solicitation for input and streamlining of the processes or interfaces used to collect this input.
REVIEWERS
This article was reviewed by I. King Jordan, Daniel Haft and Yuriy Gusev.
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10.1186/1745-6150-5-12
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pubmed_639_6895
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The rice water weevil, Lissorhoptrus oryzophilus Kuschel, is the most important economic pest of rice in the United States with the ability to substantially reduce rice yields. Stem borers, including the Mexican rice borer, Eoreuma loftini (Dyar), are emerging as more consistent pests in Louisiana and Texas, but the relationship between blanked panicles (whiteheads) caused by stem borer feeding and yield loss is not well understood. A series of field trials was conducted in Louisiana from 2019 to 2020 to determine the relative yield loss by manipulating infestations of both pests with selective insecticides. Results indicate losses from L. oryzophilus infestations are greater than those for E. loftini in early planted rice. In contrast, relative yield losses were approximately equal in later planted rice in 2019, in which E. loftini infestations were high. Additive impacts of the root-feeding L. oryzophilus and the stem-feeding E. loftini were not observed in our study. Linear regression revealed that each increase of one whitehead per square meter is associated with a 1.7% loss in yield. Results from ratoon rice suggest that protection from L. oryzophilus in the main crop also improves yield in the second crop. Collectively, results demonstrate the continued need for effective L. oryzophilus management programs to prevent economic losses. Conversely, findings suggest that benefits of E. loftini control may be minimal in many instances. Control of E. loftini is most likely to be economical under conditions where high populations are anticipated such as in late-planted fields or regions that previously had high infestations.
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10.1093/jee/toab046
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pubmed_621_14129
|
Just as Newtonian law governs classical physics, the Schrödinger equation (SE) and the relativistic Dirac equation (DE) rule the world of chemistry. So, if we can solve these equations accurately, we can use computation to predict chemistry precisely. However, for approximately 80 years after the discovery of these equations, chemists believed that they could not solve SE and DE for atoms and molecules that included many electrons. This Account reviews ideas developed over the past decade to further the goal of predictive quantum chemistry. Between 2000 and 2005, I discovered a general method of solving the SE and DE accurately. As a first inspiration, I formulated the structure of the exact wave function of the SE in a compact mathematical form. The explicit inclusion of the exact wave function's structure within the variational space allows for the calculation of the exact wave function as a solution of the variational method. Although this process sounds almost impossible, it is indeed possible, and I have published several formulations and applied them to solve the full configuration interaction (CI) with a very small number of variables. However, when I examined analytical solutions for atoms and molecules, the Hamiltonian integrals in their secular equations diverged. This singularity problem occurred in all atoms and molecules because it originates from the singularity of the Coulomb potential in their Hamiltonians. To overcome this problem, I first introduced the inverse SE and then the scaled SE. The latter simpler idea led to immediate and surprisingly accurate solution for the SEs of the hydrogen atom, helium atom, and hydrogen molecule. The free complement (FC) method, also called the free iterative CI (free ICI) method, was efficient for solving the SEs. In the FC method, the basis functions that span the exact wave function are produced by the Hamiltonian of the system and the zeroth-order wave function. These basis functions are called complement functions because they are the elements of the complete functions for the system under consideration. We extended this idea to solve the relativistic DE and applied it to the hydrogen and helium atoms, without observing any problems such as variational collapse. Thereafter, we obtained very accurate solutions of the SE for the ground and excited states of the Born-Oppenheimer (BO) and non-BO states of very small systems like He, H(2)(+), H(2), and their analogues. For larger systems, however, the overlap and Hamiltonian integrals over the complement functions are not always known mathematically (integration difficulty); therefore we formulated the local SE (LSE) method as an integral-free method. Without any integration, the LSE method gave fairly accurate energies and wave functions for small atoms and molecules. We also calculated continuous potential curves of the ground and excited states of small diatomic molecules by introducing the transferable local sampling method. Although the FC-LSE method is simple, the achievement of chemical accuracy in the absolute energy of larger systems remains time-consuming. The development of more efficient methods for the calculations of ordinary molecules would allow researchers to make these calculations more easily.
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10.1021/ar200340j
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pubmed_1036_12856
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A solution-gate field effect transistor (SGFET) has been fabricated on few-layer graphene (FLG). The ideally polarizable graphene/aqueous electrolyte interface allows the capacitive charging of the surface by hydroxyl (OH-) and hydroxonium ions (H3O+). The conductivity versus gate potential curve exhibits "V" shaped ambipolar transfer characteristics of graphene, with hole and electron mobilities of 3600 cm2/Vs and 2100 cm2/Vs, respectively. The shift of the negative gate potential with pH shows a supra-Nernstian response of 99 meV/pH. Our work points to the potential application of graphene in ultrafast and ultralow noise chemical or biological sensors.
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10.1021/ja805090z
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pubmed_665_1349
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The 5-HT(3) receptor is a member of the Cys-loop family of ligand-gated ion channels. The extracellular domains of these proteins contain six amino acid loops (A-F) that converge to form the ligand binding site. In this study we have mutated 21 residues in or close to the 5-HT(3) receptor F-loop (Ile(192) to Gly(212)) to Ala or to a residue with similar chemical properties. Mutant receptors were expressed in HEK293 cells, and binding affinity was measured using [(3)H]granisetron. Two regions displayed decreases in binding affinity when mutated to Ala (Ile(192)-Arg(196) and Asp(204)-Ser(206)), but only one region was sensitive when mutated to chemically similar residues (Ile(192)-Val(201)). Homology modeling using acetylcholine-binding protein crystal structures with a variety of different bound ligands suggests there may be distinct movements of Trp(195) and Asp(204) upon ligand binding, indicating that these residues and their immediate neighbors have the ability to interact differently with different ligands. The models suggest predominantly lateral movement around Asp(204) and rotational movement around Trp(195), indicating the former is in a more flexible region. Overall our results are consistent with a flexible 5-HT(3) receptor F-loop with two regions that have specific but distinct roles in ligand binding.
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10.1074/jbc.M601265200
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pubmed_1008_13431
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Anti-mu, anti-gamma, and anti-delta antibodies induce proliferation of splenic B lymphocytes from young Lewis rats, measured by 3H-TdR uptake. In contrast, splenic B cells of aged Lewis rats respond poorly or not at all to these reagents. T lymphocytes or interleukin 2 (IL-2) of young or aged rats augment the uptake of 3H-TdR in cultures of "young" B cells responding to anti-Ig reagents or LPS and DxS, but have no significant effect on the responses of "old" B cells. Analysis of spleen cells of young and aged rats in a fluorescence-activated cell sorter indicates the density of mu, gamma, and delta isotypes is reduced in "old" B cells, and that B cells of aged rats are significantly larger than those of young rats. These results delineate anatomic and structural changes in B lymphocytes of aged rats.
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pubmed_1008_13431
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pubmed_133_9148
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Isometric tension responses to rapid temperature jumps (T-jumps) of 2-6 degrees C were examined in skinned muscle fibre bundles isolated from papillary muscles of the rat heart. T-jumps were induced by an infra-red laser pulse (wave length 1.32 microm, pulse duration 0.2 ms) obtained from a Nd-YAG laser, which heated the fibres and bathing buffer solution in a 50 microl trough; the increased temperature by laser pulse was clamped at the high temperature by a Peltier system (see Ranatunga, 1996). In maximally Ca2+ -activated (pCa ca. 4.5) fibres, the relationship between tension and temperature was non-linear, the increase of active tension with temperature being more pronounced at lower temperatures (below ca. 20 degrees C). A T-jump at any temperature (range 3-35 degrees C) induced an initial step decrease of tension of variable amplitude (Phase 1), probably due to thermal expansion, and it was followed by a tension transient which resulted in a net rise of tension above the pre-T-jump level. The rate of net rise of tension (Phase 2b or endothermic force generation) was 7-10/s at ca. 12 degrees C and its Q10 was 6.3 (below 25 degrees C). In cases where the step decrease of tension in Phase 1 was prominent, an initial quick tension recovery phase (Phase 2a, 70-100/s at 12 degrees C) that did not contribute to a rise of tension above the pre-T-jump level, was also seen. This phase (Phase 2a) appeared to be similar to the quick tension recovery induced by a small length release and its rate increased with temperature with a Q10 of 1.8. In some cases where Phase 2a was present, a slower tension rise (Phase 3) was seen; its rate (ca. 5/s) was temperature-insensitive. The results show that the rate of endothermic force generation in cardiac fibres is clearly different from that of either fast-twitch or slow-twitch mammalian skeletal muscle fibres; implication of such fibre type-specific differences is discussed in relation to the difficulty in identifying the biochemical step underlying endothermic cross-bridge force generation.
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10.1023/a:1005509731881
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pubmed_927_460
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Soluble pyrophosphate was measured in the plasma and synovial fluid of various groups of patients and in the plasma of two control groups. The two control groups consisted of 13 healthy subjects and 19 patients suffering from benign lumbar back pain. The other group of patients had rheumatoid arthritis (RA) (14 plasma and 19 synovial fluid examinations), osteoarthrosis (OA) (19 plasma and 26 synovial fluids) and articular chondrocalcinosis (ACC) (27 plasma and 43 synovial fluids). The level of soluble pyrophosphate in the plasma was 3.5 mumol/l in healthy subjects, 4.0 mumol/l in patients with lumbar back pain, 4.1 mumol/l in individuals having OA and 3.5 mumol/l in the group suffering from RA as well as for those with ACC. The differences between these values are not significant statistically. In the synovial fluid the values were 4.6 mumol/l for the group with RA, 12.7 mumol/l for those with OA and 34.2 mumol/l in the group having ACC. If a normal distribution of these values is assumed and the average values and standard deviations recalculated for each group after elimination of cases more than 3 standard deviations above the mean, then we obtain 9.8 mumol/l for the group with OA and 23.8 mumol/l for those with ACC. The difference between the group with RA and that with OA is highly significant (p greater than 0.0001). Even more significant is the difference between the group with RA and ACC (p less than 0.0005). The difference between the OA and the ACC is also highly significant (p less than 0.001). On the basis of these observations various mechanisms leading to the pyrophosphage crystal deposition disease are discussed.
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10.3109/03009748109095305
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pubmed_839_15887
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Randomized controlled trials (RCTs) are the gold standard for evaluating treatment efficacy. Therefore, it is important that RCTs are conducted with methodological rigor to prevent biased results and report results in a manner that allows the reader to evaluate internal and external validity. Most human health journals now require manuscripts to meet the Consolidated Standards of Reporting Trials (CONSORT) criteria for reporting of RCTs. Our objective was to evaluate preharvest food safety trials using a modification of the CONSORT criteria to assess methodological quality and completeness of reporting, and to investigate associations between reporting and treatment effects. One hundred randomly selected trials were evaluated using a modified CONSORT statement. The majority of the selected trials (84%) used a deliberate disease challenge, with the remainder representing natural pathogen exposure. There were widespread deficiencies in the reporting of many trial features. Randomization, double blinding, and the number of subjects lost to follow-up were reported in only 46%, 0%, and 43% of trials, respectively. The inclusion criteria for study subjects were only described in 16% of trials, and the number of animals housed together was only stated in 52% of the trials. Although 91 trials had more than one outcome, no trials specified the primary outcome of interest. There were significant bivariable associations between the proportion of positive treatment effects and failure to report the number of subjects lost to follow-up, the number of animals housed together in a group, the level of treatment allocation, and possible study limitations. The results suggest that there are substantive deficiencies in reporting of preharvest food safety trials, and that these deficiencies may be associated with biased treatment effects. The creation and adoption of standards for reporting in preharvest food safety trials will help to ensure the inclusion of important trial details in all publications.
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10.1089/fpd.2009.0321
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pubmed_984_8931
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The Saccharomyces cerevisiae protein Tfs1p is known as a dual protein. On the one hand, it inhibits the carboxypeptidase Y protease, and on the other, it inhibits Ira2p, a GTPase-activating protein of Ras. We managed to dissect precise areas of Tfs1p specifically involved in only one of those functions. Based on these data, specific Tfs1p point mutants affected in only one of these two functions were constructed. In order to obtain insights on the physiological role of these functions, systematic phenotypic tests were performed on strains expressing these specific Tfs1p mutants. The results obtained demonstrate that the inhibition of Ira2p by Tfs1p is the predominant function under the conditions tested.
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10.1111/j.1567-1364.2009.00535.x
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pubmed_641_11268
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Bone marrow transplantation (BMT) is the last chance of recovery for some children suffering from malignant hemopathy or congenital blood disease. BMT with related donor radically alters previous family relationships: each member of the nuclear family becomes actively involved. Parents and siblings all undergo HLA typing. Only 30% of those who would benefit from bone marrow transplantation are lucky enough to have an HLA matched related donor, brother or sister. Our retrospective study concerned related donors and their parents. This paper reports the parents study. It was carried out at Strasbourg University Hospital. Parents were invited to speak about the child's illness, the graft reasons and their own position to regarding the choice of donor. Semi-structured interviews were used and their content analysed. The results highlight the expression by the parents of the need to maintain some control over the action which will save their child and establish an other gift system to keep their parental status.
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pubmed_641_11268
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pubmed_1092_24787
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OBJECTIVE
The treatment of venous insufficiency using endovenous laser ablation or radiofrequency ablation may result in endothermal heat-induced thrombosis (EHIT), a form of deep venous thrombosis. This study sought to assess whether increasing the ablation distance peripheral to the deep venous junction would result in a reduction in the incidence of EHIT II.
METHODS
This study was a retrospective review of a prospectively maintained database from April 2007 to December 2011. Consecutive patients undergoing great saphenous vein (GSV) or small saphenous vein (SSV) ablation were evaluated. Previous to February 2011, all venous ablations were performed 2 cm peripheral to the saphenofemoral or saphenopopliteal junction (group I). Subsequent to February 2011, ablations were performed greater than or equal to 2.5 cm peripheral to the respective deep system junction (group II). The primary outcome was the development of EHIT II or greater (ie, thrombus protruding into the deep venous system but comprising less than 50% of the deep vein lumen). Secondary outcomes included procedure-site complications such as thrombophlebitis and hematomas. χ(2) tests were performed for all discrete variables, and unpaired Student's t-tests were performed for all continuous variables. P < .05 was considered statistically significant.
RESULTS
A total of 4223 procedures were performed among group I (n = 3239) and group II (n = 984). Patient demographics were similar between the two groups; however, the CEAP classification was higher by a small margin in group II, and the result was significant (group I: 2.6% ± 0.9% vs group II: 2.8% ± 1.0%; P = .006). The incidence of EHIT II was 76 in group I and 13 in group II. This represented a trend toward diminished frequency in group II as compared with group I (group I: 2.3% vs group II: 1.3%; P = .066). There were no reported cases of EHIT III or IV in this patient cohort. Patients who developed an EHIT II in group I were treated using anticoagulation 54% of the time, and patients who developed an EHIT II in group II were treated using anticoagulation 100% of the time.
CONCLUSIONS
This study suggests that changing the treatment distance from 2 cm to greater than or equal to 2.5 cm peripheral to the deep venous junction may result in a diminished incidence of EHIT II. Ongoing evaluation is required to validate these results and to affirm the long-term durability of this technique.
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pubmed_1092_24787
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pubmed_334_9545
|
The alkali-extractable and water-soluble fungal polysaccharide F1SS isolated from the cell wall of Acrospermum compressum has been studied by methylation analyses, reductive cleavage and 1D- and 2D-NMR spectroscopy. The polysaccharide consists of a regular disaccharide repeating unit with the structure: [structure: see text]. The mannan core was obtained by mild hydrolysis of the polysaccharide F1SS and its structure was deduced to be composed of a skeleton of alpha-(1-->6)-mannopyranan, with around 1 out of 11 residues substituted at position 2 by short chains (one to six units) of 2-substituted mannopyranoses. DOSY experiments provided molecular sizes of 60 kDa and 2.5 kDa for the polysaccharide F1SS and the Mannan core, respectively. This is the first report of a fungal mannofuranose-containing cell wall polysaccharide.
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10.1007/s10719-007-9032-5
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pubmed_707_22310
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Electric double layer transistors (EDLTs) based on C60 single crystals and ionic liquid gates display pronounced peaks in sheet conductance versus gate-induced charge. Sheet conductance is maximized at electron densities near 0.5 e/C60 and is suppressed near 1 e/C60. The conductance suppression depends markedly on the choice of ionic liquid cation, with small cations favoring activated transport and essentially a complete shutdown of conductance at ∼1 e/C60 and larger cations favoring band-like transport, higher overall conductances at all charge densities up to 1.7 e/C60, and weaker suppression at 1 e/C60. Displacement current measurements on C60 EDLTs with small cations show clear evidence of sub-band filling at 1 e/C60, which correlates very well with the minimum in the C60 sheet conductance. Overall, the data suggest a significant Mott-Hubbard-like energy gap opens up in the surface density of states for C60 crystals gated with small cations. The causes of this energy gap may include both electron-electron repulsion and electron-cation attraction at the crystal/ionic liquid interface. The energy gap suppresses the insulator-to-metal transition in C60 EDLTs, but it can be manipulated by choice of electrolyte.
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10.1021/acsnano.2c00222
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pubmed_72_12916
|
INTRODUCTION
Peripheral nerve disruptions, frequently occurring during limb injuries, give rise to serious complications of patients recovery resulting from limitations in neural tissue regeneration capabilities. To overcome this problem bridging techniques utilizing guidance channels gain their importance. Biodegradable polymeric tubes seem to be more prospective then non-degradable materials - no necessity of implant removal and possibilities of release of incorporated drugs or biologically active agents that may support nerve regeneration process are the main advantages.
MATERIAL AND METHODS
Polymer blend of commercial poly(L-lactic acid) (PLLA) and in-house synthesized poly(trimethylene carbonate) (PTMC) were processed in an organic solvent - phase inversion process on a supporting rod - to form a guidance porous tube of 1.1 mm inner diameter. In vivo experiments on rat's cut femoral nerve by using either the tubes or end-to-end suturing (control group) involved 22 and 19 rats, respectively. Motor recovery of operated limbs, neuroma occurrence and histopathology of explanted nerves were evaluated after 30, 60 and 90 days of implantation.
RESULTS
Motor recovery of the limbs was of similar rate for the two animal groups. The neuroma formation was evident in over 90% control specimens, while for the bridging group it was less than 40% of all evaluable samples (p = 0.0022). Biocompatibility of applied materials was affirmed by moderate tissue response.
CONCLUSIONS
Application of the biodegradable PLLA/PTMC polymeric tubes effectively supports regeneration of discontinued nerves. The applied material prevents neuroma formation, by reducing the scar tissue formation time and, thus, accelerating the process of neural tissue restoration.
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10.5114/aoms.2013.34732
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pubmed_195_977
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To compare the accuracy of linear and angular measurements between cephalometric and anatomic landmarks on surface models derived from 3D cone beam computed tomography (CBCT) with two different segmentation protocols was the aim of this study. CBCT scans were made of cadaver heads and 3D surface models were created of the mandible using two different segmentation protocols. A high-resolution laser surface scanner was used to make a 3D model of the macerated mandibles. Twenty linear measurements at 15 anatomic and cephalometric landmarks between the laser surface scan and the 3D models generated from the two segmentation protocols (commercial segmentation (CS) and doctor's segmentation (DS) groups) were measured. The interobserver agreement for all the measurements of the all three techniques was excellent (intraclass correlation coefficient 0.97-1.00). The results are for both groups very accurate, but only for the measurements on the condyle and lingual part of the mandible, the measurements in the CS group is slightly more accurate than the DS group. 3D surface models produced by CBCT are very accurate but slightly inferior to reality when threshold-based methods are used. Differences in the segmentation process resulted in significant clinical differences between the measurements. Care has to be taken when drawing conclusions from measurements and comparisons made from different segmentations, especially at the condylar region and the lingual side of the mandible.
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10.1007/s00784-012-0881-3
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pubmed_156_15094
|
Influenza and its related illnesses remain a major cause of preventable morbidity and mortality in the elderly worldwide. The current influenza vaccine campaign in the UK is only a partial success despite annual costly publicity campaigns. The aim of this study was to explore the influences on decision making by elderly people for influenza vaccine uptake. Twenty patients age 75 years and over were purposively selected from those eligible for influenza vaccination in an inner city general practice in England. In-depth qualitative interviews were conducted with 10 patients who accepted and 10 who refused the vaccine. Those interviewed were concerned about maintaining their health, and had a good understanding of influenza, its transmission and prevention. The decision whether to accept or refuse the influenza vaccination was influenced by trust or mistrust of modern medicine, prior experience of vaccination and perceived risk from influenza. Newly acquired lay experience and personal perceived risk from influenza seemed to be more important catalysts for the change in vaccination uptake than professional recommendation or advertising by official government health agencies. In order to improve uptake rates, the official message promoting vaccine uptake needs to take more account of lay knowledge and the subjective assessment of risk.
|
10.1093/her/cyf059
|
pubmed_69_7987
|
Background. Bisphenol A (BPA) is detected in the urine of >95% of US adults. Recent evidence from population-based studies suggests that BPA is associated with individual components for metabolic syndrome (MetS). However, no previous study has examined the direct association between BPA and MetS. Methods. We examined 2,104 participants from the National Health and Nutrition Examination Survey 2003-2008. The main outcome was the presence of MetS (n = 741). Results. Increasing levels of urinary BPA were positively associated with MetS, independent of confounders such as age, gender, race/ethnicity, smoking, alcohol intake, physical activity, and urinary creatinine. Compared to tertile 1 (referent), the multivariable adjusted odds ratio (95% confidence interval) of MetS in tertile 3 was 1.51 (1.07-2.12); P-trend was 0.02. Conclusions. Urinary BPA levels are positively associated with MetS, in a representative sample of US adults and independent of traditional risk factors for MetS. Future, prospective studies are needed to confirm our findings.
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10.1155/2012/598180
|
pubmed_1138_14197
|
Lipopolysaccharide (LPS) is a potent bone resorbing factor. We investigated the effect of LPS on osteoclast formation in three types of cultures. LPS inhibited osteoclast formation induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], in a dose-dependent manner, in cultures of whole bone marrow cells without dexamethasone. LPS increased the amount of granulocyte-macrophage colony stimulating factor (GM-CSF) in the culture supernatant, and anti-GM-CSF antiserum almost abolished the inhibition of osteoclast formation by LPS, thereby indicating that GM-CSF generated by treatment with LPS may be responsible for the inhibition of osteoclast formation. In cultures with dexamethasone, the amount of GM-CSF was decreased to one-third of that with 1,25(OH)2D3 alone and was not changed by treatment with LPS. In this culture system, LPS enhanced osteoclast formation. In the coculture system of nonadherent bone marrow cells and a stromal cell line in the presence of 1,25(OH)2D3 and dexamethasone, where no detectable GM-CSF was present in the supernatant, LPS markedly enhanced osteoclast formation, whereas exogenously added GM-CSF (100 pg/ml) almost completely inhibited osteoclast formation. LPS stimulated pit formation on dentin slices by the osteoclast-like cells formed by in vitro culture system.
|
10.1210/endo.134.2.8299579
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pubmed_422_350
|
The process of autophagy, or bulk degradation of cellular proteins through an autophagosomic-lysosomal pathway, is important in normal growth control and may be defective in tumour cells. However, little is known about the genetic mediators of autophagy in mammalian cells or their role in tumour development. The mammalian gene encoding Beclin 1, a novel Bcl-2-interacting, coiled-coil protein, has structural similarity to the yeast autophagy gene, apg6/vps30, and is mono-allelically deleted in 40-75% of sporadic human breast cancers and ovarian cancers. Here we show, using gene-transfer techniques, that beclin 1 promotes autophagy in autophagy-defective yeast with a targeted disruption of agp6/vps30, and in human MCF7 breast carcinoma cells. The autophagy-promoting activity of beclin 1 in MCF7 cells is associated with inhibition of MCF7 cellular proliferation, in vitro clonigenicity and tumorigenesis in nude mice. Furthermore, endogenous Beclin 1 protein expression is frequently low in human breast epithelial carcinoma cell lines and tissue, but is expressed ubiquitously at high levels in normal breast epithelia. Thus, beclin 1 is a mammalian autophagy gene that can inhibit tumorigenesis and is expressed at decreased levels in human breast carcinoma. These findings suggest that decreased expression of autophagy proteins may contribute to the development or progression of breast and other human malignancies.
|
10.1038/45257
|
pubmed_370_9970
|
Groups of guinea pigs received four injections intramuscularly of lipopolysaccharide vaccine derived from Pseudomonas aeruginosa, cross-protective core glycolipid vaccine derived from the J-5 mutant of Escherichia coli O111, or saline during a two-week period. Titers of passive hemagglutinating antibody to vaccine antigens in serum routinely increased fourfold or more. Experimental hemorrhagic pseudomonas pneumonia was then induced, from which the rates of survival were 15% among animals receiving saline, 81% among animals receiving pseudomonas vaccine (P less than 0.001), and 42% among animals receiving J-5 vaccine. Thus, only weak cross-protection against pseudomonas pneumonia was detected in the recipients of J-5 vaccine. Further studies revealed no protection against pneumonia due to either E. coli or Klebsiella in animals receiving J-5 vaccine. From these data, species-specific vaccination appears to be superior to vaccination with cross-protective antigen against experimental pseudomonas pneumonia.
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10.1093/infdis/144.6.599
|
pubmed_57_22110
|
Excited-state deactivation mechanisms of uracil are investigated using spin-flip time-dependent density functional theory. Two important minimum-energy crossing points are located, for both gas-phase and hydrated uracil, and optimized relaxation pathways connecting the most important critical points on the (1)nπ* and (1)ππ* potential energy surfaces are determined. An ultrafast decay time constant, measured via femtosecond spectroscopy, is assigned to direct (1)ππ* → S0 deactivation, while a slower decay component is assigned to indirect (1)ππ* → (1)nπ* → S0 deactivation. The shorter lifetime of the dark (1)nπ* state in aqueous solution is attributed to a decrease in the energy barrier along the pathway connecting the (1)nπ* minimum to a (1)ππ*/S0 conical intersection. This barrier arises due to hydrogen bonding between uracil and water, leading to a blue-shift in the S0 → (1)nπ* excitation energy and considerable modification of energy barriers on the (1)nπ* potential surface. These results illustrate how hydrogen bonding to the chromophore can significantly impact excited-state dynamics and also highlight that relaxation pathways can be elucidated using low-cost methods based on density functional theory.
|
10.1021/jp412092f
|
pubmed_153_18986
|
OBJECTIVE
We aimed to study the relationships between left anterior hemiblock (LAHB) and the patient characteristics, management, and clinical outcomes in the setting of acute coronary syndromes (ACS).
METHODS
Admission ECGs of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) ECG substudy, and the Canadian ACS Registry I, were analysed independently at a blinded core laboratory. Multivariable logistic regression analysis was performed to assess the independent associations between LAHB on the admission ECG and in-hospital and 6-month mortality.
RESULTS
Of the 11 820 eligible ACS patients, 692 (5.9%) patients had LAHB. The presence of LAHB on admission was associated with older age, male sex, prior myocardial infarction, prior heart failure, worse Killip class, higher creatinine level, and higher GRACE risk score (all p<0.01). Patients with LAHB less frequently underwent cardiac catheterisation, coronary revascularisation or reperfusion therapy (all p<0.05). The LAHB group had higher in-hospital (6.9% vs 3.9%, p<0.001) and 6-month mortality (12.5% vs 7.7%, p<0.001). However, after adjusting for the known predictors of mortality in the GRACE risk models, LAHB was not independently associated with in-hospital death (OR 1.07, 95% CI 0.76 to 1.52, p=0.70), or death at 6 months (OR 1.00, 95% CI 0.75 to 1.34, p=0.99).
CONCLUSIONS
Across the broad spectrum of ACS, LAHB was associated with significant comorbidities, high-risk clinical features on presentation, and worse unadjusted outcomes. However, LAHB was not an independent predictor of in-hospital and 6-month mortality and did not carry incremental prognostic value beyond the known prognosticators in the GRACE risk models.
|
10.1136/heartjnl-2014-305708
|
pubmed_176_17670
|
Articular adipose tissue is a ubiquitous component of human joints, and adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and involved in energy homeostasis. The adiponectin is significantly higher in synovial fluid of patients with osteoarthritis and rheumatoid arthritis. Matrix metalloproteinases (MMP)-3 may contribute to the breakdown of articular cartilage during arthritis. We investigated the signaling pathway involved in MMP-3 caused by adiponectin in human chondrocytes. Adiponectin increased the secretion of MMP-3 in cultured human chondrocytes, as shown by qPCR, Western blot, and ELISA analysis. Adiponectin-mediated MMP-3 expression was attenuated by AdipoR1 but not AdipoR2 siRNA. Pretreatment with 5'-AMP-activated protein kinase (AMPK) inhibitor (araA and compound C), p38 inhibitor (SB203580), and NF-κB inhibitor (PDTC and TPCK) also inhibited the potentiating action of adiponectin. Activations of p38, AMPK, and NF-κB pathways after adiponectin treatment were demonstrated. Taken together, our results provide evidence that adiponectin acts through AdipoR1 to activate p38 and AMPK, resulting in the activations of NF-κB on the MMP-3 promoter and contribute cartilage destruction during arthritis.
|
10.1002/jcb.23059
|
pubmed_363_18109
|
Human plasmacytoid dendritic cells (pDCs), also called type 2 dendritic cell precursors or natural interferon (IFN)-producing cells, represent a cell type with distinctive phenotypic and functional features. They are present in the thymus and probably share a common precursor with T and natural killer (NK) cells. In an effort to identify genes that control pDC development we searched for genes of which the expression is restricted to human pDC using a cDNA subtraction technique with activated monocyte-derived DCs (Mo-DCs) as competitor. We identified the transcription factor Spi-B to be expressed in pDCs but not in Mo-DCs. Spi-B expression in pDCs was maintained on in vitro maturation of pDCs. Spi-B was expressed in early CD34(+)CD38(-) hematopoietic progenitors and in CD34(+)CD1a(-) thymic precursors. Spi-B expression is down-regulated when uncommitted CD34(+)CD1a(-) thymic precursors differentiate into committed CD34(+)CD1a(+) pre-T cells. Overexpression of Spi-B in hematopoietic progenitor cells resulted in inhibition of development of T cells both in vitro and in vivo. In addition, development of progenitor cells into B and NK cells in vitro was also inhibited by Spi-B overexpression. Our results indicate that Spi-B is involved in the control of pDC development by limiting the capacity of progenitor cells to develop into other lymphoid lineages.
|
10.1182/blood-2002-02-0438
|
pubmed_861_14107
|
A substantial fraction of the human transcriptome is composed of the so-called long noncoding RNAs (lncRNAs), yet the available catalogs of known lncRNAs are far from complete. Moreover, functional studies of these RNAs are challenged by several factors, such as their tissue-specific expression and functional heterogeneity, resulting in only ca. 1% of them being well characterized. Here, we describe a set of 41,400 novel lncRNAs discovered with RNA-Seq data from 1463 samples encompassing diverse tissues and cell lines. We utilized publicly available transcriptomic and genomic data to provide their characteristics, such as tissue specificity, cellular abundance, polyA status, cellular localization, evolutionary conservation and transcript stability, which allowed us to speculate on their possible biological roles. We also pinpointed 24 novel lncRNAs as candidates for breast cancer biomarkers. The results bring us closer to a comprehensive annotation of human lncRNAs, though vast amounts of further work are needed to validate the predictions and fully decipher their biology. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen.
|
10.1016/j.bbagrm.2019.05.003
|
pubmed_933_13409
|
This reply attempts to cast some more light on the problematic similarities and differences between gyrotropic and chiral materials.
|
10.1364/ol.19.001664
|
pubmed_159_10573
|
B cells are important pathogenic players in multiple sclerosis (MS), but their exact role is not known. We have previously demonstrated that B cells from cerebrospinal fluid (CSF) of MS patients can activate T cells that specifically recognize antigenic determinants (idiotopes) from their B cell receptors (BCRs). The aim of this study was to evaluate whether in silico prediction models could identify antigenic idiotopes of immunoglobulin heavy-chain variable (IGHV) transcriptomes in MS patients. We utilized a previously assembled dataset of CSF IGHV repertoires from MS patients. To guide selection of potential antigenic idiotopes, we used in silico predicted HLA-DR affinity, endosomal processing, as well as transcript frequency from nine MS patients. Idiotopes with predicted low affinity and low likelihood of cathepsins cleavage were inert controls. Peripheral blood mononuclear cells from these patients were stimulated with the selected idiotope peptides in presence of anti-CD40 for 12 h. T cells were then labeled for activation status with anti-CD154 antibodies and CD3+CD4+ T cells phenotyped as memory (CD45RO+) or naïve (CD45RO-), with potential for brain migration (CXCR3 and/or CCR6 expression). Anti-CD14 and -CD8 were utilized to exclude monocytes and CD8+ T cells. Unstimulated cells or insulin peptides were negative controls, and EBNA-1 peptides or CD3/CD28 beads were positive controls. The mean proportion of responding memory CD4+ T cells from all nine MS patients was significantly higher for idiotope peptides with predicted high HLA-DR affinity and high likelihood of cathepsin cleavage, than toward predicted inert peptides. Responses were mainly observed toward peptides affiliated with the CDR3 region. Activated memory CD4+ T cells expressed the chemokine receptor CCR6, affiliated with a Th17 phenotype and allowing passage into the central nervous system (CNS). This in vitro study suggests that that antigenic properties of BCR idiotopes can be identified in silico using HLA affinity and endosomal processing predictions. It further indicates that MS patients have a memory T cell repertoire capable of recognizing frequent BCR idiotopes found in endogenous CSF, and that these T cells express chemokine receptors allowing them to reach the CSF B cells expressing these idiotopes.
|
10.3389/fimmu.2020.00598
|
pubmed_1006_17965
|
The sulfhydryl-gated 106-kDa Ca(2+)-release channel (SG-106) was purified by biotin-avidin chromatography from skeletal sarcoplasmic reticulum (SR) vesicles and used as an antigen to raise polyclonal antibodies. Western blots showed that the antisera crossreacted with the antigenic SG-106 and not with SR Ca2+, Mg(2+)-ATPase or with junctional foot proteins (JFPs) (Zaidi et al., 1989, J. Biol. Chem. 264(36), 21, 725-21, 736; 21, 737-21, 747). Polyclonal antibody-affinity columns were used to selectively purify SG-106-kDa proteins which, upon incorporation in planar bilayers, revealed the presence of a cationic channels with properties similar to "native" Ca(2+)-release channels obtained through the fusion of SR vesicles with planar bilayers. In agreement with measurements of Ca2+ release from SR vesicles, sulfhydryl oxidizing and reducing agents (i.e., 2,2'-dithiodipyridine and dithiothreitol) respectively increased and decreased the open-time probability of 106-kDa Ca(2+)-release channels. In contrast with reports on JFPs, ryanodine at 0.5-1 nM increased the open-time probability and at 2-10 nM locked 106-kDa Ca(2+)-release channels in a closed state rather than an open subconductance state. The SG-106 was activated by millimolar ATP, inhibited by millimolar Mg2+, and blocked by micromolar ruthenium red. Adriamycin (2-10 microM) caused a transient activation of SG-106 Ca(2+)-release channels, followed by closure in about 5 min, and intermittent activation to a subconductance state. Polyclonal antibodies used to purify the SG-106 also activated the channel when added to the cis side but not the trans side of the bilayer. Thus, SG-106 channels possess features that are similar to "native" SR Ca(2+)-release channels, are immunologically distinct from JFPs, and interact in seconds with nanomolar ryanodine in planar bilayers.
|
10.1016/0003-9861(92)90043-v
|
pubmed_98_25534
|
The molecular mechanisms of pathogenesis of atrial myopathy associated with hypertrophic (HCM) and dilated (DCM) mutations of sarcomeric proteins are still poorly understood. For this, one needs to investigate the effects of the mutations on actin-myosin interaction in the atria separately from ventricles. We compared the impact of the HCM and DCM mutations of tropomyosin (Tpm) on the calcium regulation of the thin filament interaction with atrial and ventricular myosin using an in vitro motility assay. We found that the mutations differently affect the calcium regulation of actin-myosin interaction in the atria and ventricles. The DCM E40K Tpm mutation significantly reduced the maximum sliding velocity of thin filaments with ventricular myosin and its Ca2+-sensitivity. With atrial myosin, its effects were less pronounced. The HCM I172T mutation reduced the Ca2+-sensitivity of the sliding velocity of filaments with ventricular myosin but increased it with the atrial one. The HCM L185R mutation did not affect actin-myosin interaction in the atria. The results indicate that the difference in the effects of Tpm mutations on the actin-myosin interaction in the atria and ventricles may be responsible for the difference in pathological changes in the atrial and ventricular myocardium.
|
10.1016/j.bbrc.2021.12.051
|
pubmed_337_5622
|
There is controversy over the genotoxic effects of volatile anesthetics. The available literature on the genotoxicity of desflurane, one of the newest volatile halogenated agents used for general anesthesia maintenance, is scarce. This study aimed to evaluate the genotoxic potential of desflurane in 15 patients without comorbidities, of both sexes, who underwent minor surgeries lasting at least 90 min. Patients enrolled in the study received desflurane anesthesia (6%); blood samples were collected before anesthesia induction (T0), 90 min after the beginning of anesthesia (T1), and on the day following surgery (T2). DNA damage was evaluated in lymphocytes using the alkaline comet assay. We found statistically significant increases in DNA damage in T2 samples compared to T0. The findings suggest that desflurane anesthesia induces DNA strand breaks/alkali-labile sites on the day after minimally invasive surgery in healthy patients.
|
10.1002/em.22012
|
pubmed_491_14653
|
A significant gap remains in our understanding of the conditions under which parents' racial socialization has consequences for adolescents' functioning. The present study used longitudinal data to examine whether the frequency of communication between African American parents and adolescents (N = 504; 49 % female) moderates the association between parent reports of racial socialization (i.e., cultural socialization and preparation for bias) at 8th grade and adolescent reports of racial identity (perceived structural discrimination, negative public regard, success-oriented centrality) at 11th grade, and in turn, academic attitudes and perceptions. Parents' racial socialization practices were significant predictors of multiple aspects of adolescents' racial identity in families with high levels of communication, but they did not predict any aspects of adolescents' racial identity in families with low levels of communication. Results highlight the importance of including family processes when examining the relations between parents' racial socialization and adolescents' racial identity and academic attitudes and perceptions.
|
10.1007/s10964-015-0351-8
|
pubmed_1084_17699
|
Copper-catalyzed halide exchange reactions under very mild reaction conditions are described for the first time using a family of model aryl halide substrates. All combinations of halide exchange (I, Br, Cl, F) are observed using catalytic amounts of Cu(I). Strikingly, quantitative fluorination of aryl-X substrates is also achieved catalytically at room temperature, using common F(-) sources, via the intermediacy of aryl-Cu(III)-X species. Experimental and computational data support a redox Cu(I)/Cu(III) catalytic cycle involving aryl-X oxidative addition at the Cu(I) center, followed by halide exchange and reductive elimination steps. Additionally, defluorination of the aryl-F model system can be also achieved with Cu(I) at room temperature operating under a Cu(I)/Cu(III) redox pair.
|
10.1021/ja2058567
|
pubmed_336_17191
|
This study analyses the effect of environmental enrichment on the welfare, productive traits and meat quality of lambs housed in feedlots. Sixty lambs were placed in enriched (EE) or conventional (CO) pens (3 pens for each treatment, 10 lambs/pen) where EE had a wooden platform with ramps that provided access to a concentrate hopper, cereal straw as bedding and forage, and one play ramp. The CO pen was barren, similar to commercial feedlots. The physiological adaptation response of EE lambs was more efficient than CO, since the latter mobilised more body reserves (i.e., increased NEFA, P<0.05), and had lower levels of immunity (i.e., increased N/L, P<0.05), which indicate chronic stress, probably associated with the barren environment. The EE lambs had a higher (P<0.05) average daily gain, with heavier carcasses and higher fattening scores, as well as lower pHult, higher L and b values, and lower values of texture (P<0.05).
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pubmed_336_17191
|
pubmed_859_13204
|
BACKGROUND
Textbook outcome (TO) is a multidimensional measure reflecting the ideal outcome after surgery. As a benchmarking tool, it provides an objective overview of quality of care. Uniform definitions of TO in hepato-pancreato-biliary (HPB) surgery are missing. This study aimed to provide a definition of TO in HPB surgery and identify obstacles and predictors for achieving it.
METHODS
A systematic literature search was conducted using PubMed, Embase, and Cochrane Database according to PRISMA guidelines. Studies published between 1993 and 2021 were retrieved. After selection, two independent reviewers extracted descriptive statistics and derived summary estimates of the occurrence of TO criteria and obstacles for achieving TO using co-occurrence maps.
RESULTS
Overall, 30 studies were included. TO rates ranged between 16-69 per cent. Commonly chosen co-occurring criteria to define TO included 'no prolonged length of stay (LOS)', 'no complications', 'no readmission', and 'no deaths'. Major obstacles for achieving TO in HPB surgery were prolonged LOS, complications, and readmission. On multivariable analysis, TO predicted better overall and disease-free survival in patients with cancer. Achievement of TO was more likely in dedicated centres and associated with procedural and structural indicators, including high case-mix index and surgical volume.
CONCLUSION
TO is a useful quality measure to benchmark surgical outcome. Future definitions of TO in HPB surgery should include 'no prolonged LOS', 'no complications', 'no readmission', and 'no deaths'.
|
10.1093/bjsopen/zrac149
|
pubmed_1044_9554
|
Acute cardiac manifestions of COVID-19 have been well described, while chronic cardiac sequelae remain less clear. Various studies have shown conflicting data on the prevalence of new or worsening cardiovascular disease, myocarditis or cardiac dysrhythmias among patients recovered from COVID-19. Data are emerging that show that patients recovering from COVID-19 have an increased incidence of myocarditis and arrhythmias after recovery from COVID-19 compared with the control groups without COVID-19. The incidence of myocarditis after COVID-19 infection is low but is still significantly greater than the incidence of myocarditis from a COVID-19 vaccine. There have been several studies of athletes who underwent a variety of screening protocols prior to being cleared to return to exercise and competition. The data show possible, probable or definite myocarditis or cardiac injury among 0.4-3.0% of the athletes studied. Recent consensus statements suggest that athletes with full recovery and absence of cardiopulmonary symptoms may return to exercise and competition without cardiovascular testing. In conclusion, patients with COVID-19 may be expected to have an increased risk of cardiovascular disease, myocarditis or arrhythmias during the convalescent phase. Fortunately, the majority of patients, including athletes may return to their normal activity after recovery from COVID 19, in the absence of persisting cardiovascular symptoms.
|
10.1016/j.tcm.2022.06.003
|
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