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Retriever2700
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Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes.
BACKGROUND
Hot flashes are often a troublesome symptom in breast carcinoma survivors and men with prostate carcinoma who have undergone androgen deprivation therapy. A previous clinical study demonstrated that, on a short term basis, low dose megestrol acetate markedly reduced hot flashes and was well tolerated. Little information has been available regarding the long term use of low dose megestrol acetate for hot flashes.
METHODS
Patients previously enrolled on a randomized placebo-controlled trial that evaluated the short term use of megestrol acetate for hot flashes were contacted and interviewed by telephone.
RESULTS
A total of 132 persons were contacted. Nine percent of the patients discontinued megestrol acetate after resolution of their hot flashes. Forty-five percent of the patients contacted were continuing to utilize megestrol acetate approximately 3 years beyond the conclusion of the 1992 study. Three-quarters of these patients were utilizing < or =20 mg of megestrol acetate per day. Potential toxicities attributed to megestrol acetate included episodes of chills, appetite stimulation/weight gain, vaginal bleeding, and carpal tunnel syndrome symptoms.
CONCLUSIONS
A substantial proportion of patients continue to use megestrol acetate for periods of up to 3 years or longer with continued control of hot flashes. This treatment appears to be relatively well tolerated.
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No pos
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No neg
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Retriever2701
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Incidence of cancer of the lung, stomach, breast, and cervix in the USSR: pattern and trends.
The most frequent fatal malignant tumors in the Soviet Union are cancers of the lung, stomach, breast, and cervix uteri. From incidence statistics and population estimates provided by the Department of Statistics of the Ministry of Health, age-adjusted incidence rates for the period 1971-87, using the World standard population, have been computed for the USSR as a whole and for each of the 15 Soviet republics. For six republics believed to have the highest quality of data and relatively homogeneous populations, time-trends are examined over the period. There is important geographical variation in the incidence of malignant tumors in the Soviet Union. The differences between high and low incidence areas are four-fold for cancer of the lung and stomach, three-fold for cancer of the breast and two-fold for cancer of the cervix. Overall in the six republics for which time-trends are examined, cancers of the lung and breast have increased, cancers of the stomach and cervix have decreased. There are some variations in specific age groups in some republics.
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No pos
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No neg
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Retriever2702
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Adolescents with intellectual disability and suicidal behavior.
It has been assumed that impaired intellectual capacity could act as a buffer to suicidality in the population of children and adolescents with intellectual disability. The few studies that have been conducted contest this assumption and in fact the findings showed that the characteristics of suicidality in the population of children and adolescents with intellectual disability are very similar to other adolescents without intellectual disability. This paper reviews the few studies conducted and describe the symptomatology in this population.
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No pos
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No neg
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Retriever2703
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[Animal analogs of human embryonal prealbumin-2].
Immunochemical analogs of human embryonal prealbumin-2 (EPA-2) were found in blood sera and amniotic fluid of the cow, sheep and pig fetuses. Meanwhile they were not detected in blood sera of adult animals. Analogs of animal EPA-2 produced the reaction of complete immunochemical identity with human EPA-2. Moreover, they have similar physicochemical properties and electrophoretic mobility of prealbumins. The indirect immunofluorescence technique was used to locate EPA-2 in collagenic fibres of fetuses and in adult animals' connective tissue. It is suggested that EPA-2 might be the protein contained by procollagen or by non-collagenic components of collagenic fibres.
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No pos
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No neg
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Retriever2704
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[Analysis of the mechanisms of the anti-arrhythmic action of marcaine and lidocaine].
It has been demonstrated in experiments on anesthetized cats with heart rhythm abnormalities induced by the creation of an "ectopic focus" by high-frequency electric stimulation of the ventricles that lidocaine in a dose of 5.8 mg/kg is inferior to marcaine in a dose of 1.3 mg/kg as regards the ability to inhibit the sympathetic tone. Lidocaine and marcaine have been discovered to produce different effects: lidocaine produced a dose-dependent selective inhibition of C-components of reflex discharges, whereas marcaine a more prolonged and uniform suppression of both A- and C-components of evoked responses, inhibiting both excitatory and inhibitory components of reflex responses.
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No pos
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No neg
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Retriever2705
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A transcranial magnetic stimulation study of information processing in the motor cortex: relationship between the silent period and the reaction time delay.
The present study was aimed at deciphering whether the delay in choice reaction time (RT) and the silent period (SP) caused by transcranial magnetic stimulation (TMS) of the motor cortex in the ongoing electromyogram are due to the same physiological mechanism. To this end, the effect of TMS was studied in 6 healthy volunteers performing a between-hand choice RT task. Specific predictions were derived from a logic inspired from the "postponed stages" hypothesis (Pashler & Johnson, 1989). This logic predicts a correlation between SP duration and RT when the stimulated cortex is involved in the response, and a stronger correlation when the stimulation is delivered later during the RT interval. The effect of TMS on RT was twofold: At early stimulation times, the stimulation shortened the RT and this effect was independent of the involvement of the stimulated motor cortex in the subsequent response. At later stimulation times, TMS had a disruptive effect, provided that the stimulated cortex was involved in the response. When the stimulated cortex was involved in the response, there was a correlation between SP and RT; this correlation was stronger when the stimulation occurred later. In contrast, there was no correlation between these two variables when the stimulated cortex was not involved.
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No pos
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No neg
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Retriever2706
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A single-molecule with multiple investigations: Synthesis, characterization, computational methods, inhibitory activity against Alzheimer's disease, toxicity, and ADME studies.
This study reports a newly synthesized crystalline molecule with azomethine structure, (E)-1-(5-nitro-2-(piperidin-1-yl)phenyl)-N-(p-tolyl)methanimine, and its structural, spectral, topological, and electronic properties calculated by combined experimental and computational techniques. The study also presents the computational approaches to drug-like nature of the molecule. The main objective of this study is to determine the drug-like properties of the title compound and to demonstrate its acetylcholinesterase inhibitory activity for the cholinergic hypothesis of Alzheimer's disease. In this work, we synthesized the title molecule by the condensation reaction between an aromatic amine and an aldehyde and verified its molecular structure by spectroscopic techniques (X-ray, FTIR, and UV-Vis). The computational results of the title compound (MEP, FTIR, UV-Vis, FMOs, Mulliken charges, HOMO-LUMO analysis, structure optimization) were obtained at the DFT/B3LYP level using the Gaussian package program. In silico biological studies such as target identification, ADMET prediction, BBB permeation, gastrointestinal absorption, and molecular docking studies were performed using web tools or software: BindingDB, SwissTargetPrediction, admetSAR, ADMETlab, SwissADME, ProTox- II, BOILED -Egg method, and AutoDock. The ADME profile of the title compound is at the desired level and within the range of applicability. The compound was evaluated as mutagenic and carcinogenic in toxicity analyzes. The title compound can pass the BBB and be absorbed by the human gastrointestinal tract. The calculated docking score of the title compound is not better than the AChE inhibitors known as galantamine and donepezil (positive control group). The binding energies of the complexes, title compound-AChE, donepezil-AChE, and galantamine-AChE, were calculated to be -7.80, -10.41, and -8.16 kcal/mol, respectively.
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No pos
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No neg
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Retriever2707
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Dental fluorosis in permanent incisor teeth in relation to water fluoridation, social deprivation and toothpaste use in infancy.
OBJECTIVES
To determine the prevalence and severity of fluorosis in permanent incisor teeth in young children in a fluoridated and a fluoride-deficient community and to establish what relationship, if any, there was between the occurrence of dental fluorosis and the reported use of fluoride toothpaste in childhood.
DESIGN
A prevalence study of children aged 8-9 years who had been continuous residents in fluoridated Newcastle or fluoride-deficient Northumberland.
METHOD
The permanent maxillary central incisor teeth were examined clinically and photographically by one examiner using the Thylstrup-Fejerskov index; the photographs were read blind to child identity and clinical score. A closed-response questionnaire enquired into the child's early experiences of toothbrushing and use of fluoride toothpastes. Social deprivation was measured by a Jarman score. The study took place in 1998.
OUTCOME MEASURE
Prevalence of dental fluorosis measured by the Thylstrup-Fejerskov index.
RESULTS
Complete data were available for 78% (n = 409) and 79% (n = 403) of eligible sampled children in the two areas, respectively. Clinical and photographic results agreed closely and had high reproducibility. The prevalence of fluorosis was 54% in the fluoridated area and 23% in the fluoride-deficient area when all grades (> 0) of fluorosis were included; percentage prevalence of mild to moderate fluorosis (> or = 3) was 3% and 0.5% in the two areas, respectively. Multivariate analysis indicated that area of residence (odds ratio = 4.5), Jarman score (odds ratio = 0.99 per Jarman unit) and type of toothpaste (odds ratio = 1.6) were statistically significantly related to presence or absence of fluorosis: the risk factors were--fluoridated area, affluence, and use of adult toothpaste.
CONCLUSIONS AND RECOMMENDATIONS
The prevalence of aesthetically important dental fluorosis was low, although higher in the fluoridated area. Use of a child's toothpaste (with lower fluoride concentration) could decrease risk in a fluoridated area. Adherence to the guidelines published by the British Society of Paediatric Dentistry is recommended.
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No pos
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No neg
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Retriever2708
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Clinically relevant safety issues associated with St. John's wort product labels.
BACKGROUND
St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA.
METHODS
Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings.
RESULTS
Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of a priori safety issues included on a product label was 1.91 (range 0-8) for 23.9% completeness.
CONCLUSION
The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.
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No pos
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No neg
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Retriever2709
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Insights into elastin fiber fragmentation: Mechanisms and treatment of aortic aneurysm in Marfan syndrome.
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by fibrillin 1 (FBN1) gene mutations that results in defects in the skeletal, ocular, and cardiovascular systems. Aortic aneurysm is the leading cause of premature mortality in untreated MFS patients. Elastin fiber fragmentation in the aortic vessel wall is a hallmark of MFS-associated aortic aneurysms. FBN1 mutations result in FBN1 fragments that also contribute to elastin fiber fragmentation. Although recent research has advanced our understanding of MFS, the contribution of elastin fiber fragmentation to the pathogenesis of aneurysm formation remains poorly understood. This review provides a comprehensive overview of the molecular mechanisms of elastin fiber fragmentation and its role in the pathogenesis of aortic aneurysm progression. Increased comprehension of elastin fragmentation has significant clinical implications for developing targeted interventions to block aneurysm progression, which would benefit not only individuals with Marfan syndrome but also other patients with aneurysms. Moreover, this review highlights an overlooked connection between inhibiting aneurysm and the restoration of elastin fibers in the vessel wall with various aneurysm inhibitors, including drugs and chemicals. Investigating the underlying molecular mechanisms could uncover innovative therapeutic strategies to inhibit elastin fragmentation and prevent the progression of aneurysms.
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No pos
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No neg
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Retriever2710
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A breathing wormlike chain model on DNA denaturation and bubble: effects of stacking interactions.
DNA stably exists as a double-stranded structure due to hydrogen-bonding and stacking interactions between bases. The stacking interactions are strengthened when DNA is paired, which results in great enhancement of bending rigidity. We study the effects of this stacking-induced stiffness difference on DNA denaturation and bubble formations. To this end, we model double-stranded DNA as a duplex of two semiflexible chains whose persistence length varies depending on the base-pair distance. Using this model, we perform the Langevin dynamics simulation to examine the characteristics of the denaturation transition and the statistics of the bubbles. We find that the inclusion of the stacking interactions causes the denaturation transition to be much sharper than otherwise. At physiological temperature, the stacking interactions prohibit the initiation of bubble formation but promote bubbles, once grown, to retain the large size.
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No pos
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No neg
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Retriever2711
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Light tunneling inhibition in longitudinally modulated Bragg-guiding arrays.
We consider a waveguide array in which defect channels with reduced refractive index are spaced periodically and the light guiding is achieved because of Bragg reflection. We show that tunneling between defects can be inhibited using out-of-phase longitudinal modulation of refractive index exclusively in defect channels. Tunneling inhibition is almost perfect for strongly localized modes with propagation constants close to the gap center.
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No pos
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No neg
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Retriever2712
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Nucleocapsid protein gene sequence analysis reveals close genomic relationship between turkey coronavirus and avian infectious bronchitis virus.
Antibodies to infectious bronchitis virus (IBV) cross-react with turkey coronavirus (TCV) in immunofluorescence assay (IFA) indicating that IBV and TCV may share an amino acid sequence similarity. To determine its extent, the gene encoding the nucleocapsid (N) protein of TCV was amplified by reverse transcription-PCR (RT-PCR) from RNA purified from intestines of embryos of turkeys infected with various TCV isolates and from allantoic fluid of chicken embryos infected with IBV M41 strain, the obtained N genes were cloned, sequenced and compared with known sequences of N genes of five IBV strains. The primers for amplification were designed from the genome of IBV PCR products were obtained only from two of eight TCV isolates tested. It was found that the two TCV isolates were identical with five IBV strains by 90.1-94.1% at the N gene level. It was also observed that the N gene of eight TCV isolates originating from various regions of the USA could not be amplified by the primers designed from the N gene of bovine coronavirus (BCV).
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No pos
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No neg
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Retriever2713
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Insulin-like growth factor I (IGF-1) supplementation prevents diabetes-induced alterations in coenzymes Q9 and Q10.
Diabetes, which causes enhanced oxidative stress, is a multifactorial disease that leads to deleterious effects in many organ systems within the body. Ubiquinones (coenzyme Q(9) and Q(10)) are amphipathic molecular components of the electron transport chain that function also as endogenous antioxidants and attenuate the diabetes-induced decreases in antioxidant defense mechanisms. Insulin-like growth factor 1 (IGF-1) is considered to be an "essential surviving factor", the level and function of which are compromised in diabetes. This study investigated the impact of IGF-1 supplementation on ubiquinone levels in a rat model of type I diabetes. Adult male Sprague-Dawley rats were divided into four groups: control, control plus IGF-1, diabetic and diabetic plus IGF-1. Diabetic animals received a single intravenous injection of streptozotocin (STZ, 55 mg/kg). IGF-1 supplementation groups received a daily intraperitoneal dose of 3 mg IGF-1 per kilogram body weight for 7 weeks. Coenzyme Q(9) and Q(10) levels were assessed by ultraviolet detection on high pressure liquid chromatography. STZ caused a significant reduction in body weight and an elevation in blood glucose level, which were not prevented by IGF-1 supplementation. In addition Q(9) and Q(10) levels in diabetic liver were significantly elevated. IGF-1 supplementation prevented liver alterations in Q(10) but not Q(9) levels. Q(9) and Q(10) levels in diabetic kidney were significantly depressed, and these deleterious effects were abolished by IGF-1 treatment. These data suggest that IGF-1 antagonizes the diabetes-induced alterations in endogenous antioxidants including coenzyme Q(10), and hence may have a therapeutic role in diabetes.
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No pos
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No neg
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Retriever2714
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Combining magnetic resonance imaging with readout and/or perturbation of neural activity in animal models: Advantages and pitfalls.
One of the main challenges in brain research is to link all aspects of brain function: on a cellular, systemic, and functional level. Multimodal neuroimaging methodology provides a continuously evolving platform. Being able to combine calcium imaging, optogenetics, electrophysiology, chemogenetics, and functional magnetic resonance imaging (fMRI) as part of the numerous efforts on brain functional mapping, we have a unique opportunity to better understand brain function. This review will focus on the developments in application of these tools within fMRI studies and highlight the challenges and choices neurosciences face when designing multimodal experiments.
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No pos
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No neg
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Retriever2715
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Anti-CCL25 antibody prolongs skin allograft survival by blocking CCR9 expression and impairing splenic T-cell function.
Chemokines, by virtue of their ability to recruit immune cells into allografts, play critical roles in acute transplantation rejection. CCR9 and its ligand, CCL25, is one of the key regulators of thymocyte migration and maturation in normal and inflammatory conditions. Moreover, several studies have revealed that high expression of CCR9 and CCL25 participated in many kinds of diseases. However, the role of CCR9 in allograft rejection is still unclear. In this study, we established a murine skin transplantation model of acute rejection. Our findings showed that the proportion of CCR9-expressing T cells was significantly increased in the spleen of allotransplanted mice compared with syngeneic transplantation. Furthermore, expression of CCL25 in allograft was similarly increased. Neutralization of CCL25 by intravenous injection of anti-CCL25 monoclonal antibody significantly prolonged skin allograft survival, decreased the number of infiltrating cells, and simultaneously suppressed the chemotactic ability and the proliferation of the splenic T cells in response to allogeneic antigens. Finally, blockade of CCL25 also diminished the secretion of IFN-γ by splenic T cells. These studies indicated that CCR9/CCL25 was involved in acute transplantation rejection and anti-CCL25 strategies might be useful in preventing acute rejection.
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No pos
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No neg
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Retriever2716
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In situ study of single-walled carbon nanotube growth in an environmental scanning electron microscope.
Monitoring individual single-walled carbon nanotubes (SWCNTs) during their growth is a highly sought-after goal in view of understanding the processes involved in the nucleation, elongation and termination which ultimately control the diameter and chiral selectivity. Here, we report on the first truly in situ observations of SWCNT growth in an environmental scanning electron microscope (ESEM). The CNT growth from lithographically patterned catalysts was investigated as a function of the catalyst type (Fe, Co or Ni), temperature, type of precursor (ethanol or acetylene), gas phase composition and pressure, and pretreatment conditions, and we report on the most appropriate conditions for SWCNT growth in ESEM conditions. We show that this approach allows the observation at the submicron scale of the different steps of the nanotube synthesis including the catalyst reduction, the growth and percolation of the nanotube network, and the deposition of individual nanotubes grown in the gas phase on the substrate. Despite these obvious advantages, we identified a few limitations which will need to be tackled for fully taking advantage of the approach, for instance for monitoring the growth of individual SWCNTs by ESEM, including the short lifetime of the catalyst nanoparticles, the preference for kite growth (by opposition to surface growth) and the influence of the electron beam on the nanotube growth.
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No pos
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No neg
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Retriever2717
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Effect of low- and high-level groundwater arsenic on peripheral blood and lung function of exposed rural women.
The World Health Organization (WHO) recommended maximum contaminant level (MCL) of arsenic (As) in drinking water at 10 μg/L. Many Asian countries still have their MCL for As at 50 μg/L. The current cross sectional study was conducted on asymptomatic females (without As related skin lesions) selected from rural areas of West Bengal, Baruipur and Dhamakhali [low As 11-50 μg/L; N,93]; Kamardanga & Sibhati [high As>50 μg/L; N,70] and Boria [Control; As<10 μg/L N,118] of West Bengal, India. The study was designed to compare the status of peripheral blood and lung function due to prolonged As exposure. The lung function parameters were considered according to Miller's prediction quadrant - FVC less than 80% indicated restrictive lung, FEV1/FVC less than 70% showed obstructive lung and both FVC and FEV1/FVC less than predicted percentage exhibited combined lung function decrement. The study showed that groundwater As concentration [22.5 ± 19.2 (low), 67.8 ± 26.9 (high) and 1.02 ± 2.3 μg/L (control)] was correlated with nail As content of the enrolled women. Linear regression depicted that nail As content influenced reduction of haemoglobin (β: 0.43; 95%CI: 0.02 to -0.006; p = 0.0001) and CD56+ NK cells (β: 0.53; 95%CI: 0.07 to -0.03; p = 0.0001) per 1 μg/g increase in As in nails. Multivariate logistic regression exhibited that nail As content was associated with reduction of lung function parameters [FEV1 (Exp B:1.04; 95%CI: 1.022 to 1.055; p = 0.0001) and FVC (Exp B:1.05; 95%CI: 1.03 to 1.07; p = 0.0001) per 1 μg/g increase in As in nails. Hence the study may be indicative of the fact that even in asymptomatic women, increase in chronic As exposure may weaken immune surveillance and provoke respiratory ailments.
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No pos
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No neg
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Retriever2718
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Deeply learned broadband encoding stochastic hyperspectral imaging.
Many applications requiring both spectral and spatial information at high resolution benefit from spectral imaging. Although different technical methods have been developed and commercially available, computational spectral cameras represent a compact, lightweight, and inexpensive solution. However, the tradeoff between spatial and spectral resolutions, dominated by the limited data volume and environmental noise, limits the potential of these cameras. In this study, we developed a deeply learned broadband encoding stochastic hyperspectral camera. In particular, using advanced artificial intelligence in filter design and spectrum reconstruction, we achieved 7000-11,000 times faster signal processing and ~10 times improvement regarding noise tolerance. These improvements enabled us to precisely and dynamically reconstruct the spectra of the entire field of view, previously unreachable with compact computational spectral cameras.
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No pos
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No neg
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Retriever2719
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Efficacy of moxidectin long-acting injectable formulation (1 mg/kg bodyweight) against first instar larvae of Oestrus ovis in naturally infected sheep.
The objective of the current study was to evaluate the efficacy of a single treatment with a long-acting injectable formulation of moxidectin (MOX) at 1.0 mg/kg bodyweight (b.w.) against natural infection by nasal bots (Oestrus ovis) in sheep with special attention to first instar larvae (L1). Firstly, a local farm with clinical history of oestrosis was chosen to conduct the assay. A total of 49 sheep were pre-selected at the end of the summer according to the presence of evident clinical signs of infection and confirmed later by means of an indirect ELISA against excretory-secretory products from L1 to detect IgG antibodies. After that, 24 sheep were chosen to carry out the study on the basis of positive serology and age since the oldest ones were selected. The day 0 of the assay, the treatment group was administered with the MOX formulation by subcutaneous injection at the base of the left ear and the control group was administered with a saline solution in the same way. All sheep were slaughtered on day 28 post-treatment (pt). At the necropsy, the head of all sheep were cut off and split into two sagital sections and all larvae from nasal passages, septum, middle meatus, conchae and sinuses were recovered. After the necropsy, a significant number of L1 was only found in the control group and therefore the efficacy of the MOX formulation was only calculated against this stage. As a result, the formulation was 90.2% effective against L1 for sheep slaughtered at day 28 pt.
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No pos
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No neg
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Retriever2720
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Electrostatic interactions in soft particle systems: mesoscale simulations of ionic liquids.
Computer simulations provide a unique insight into the microscopic details, molecular interactions and dynamic behavior responsible for many distinct physicochemical properties of ionic liquids. Due to the sluggish and heterogeneous dynamics and the long-ranged nanostructured nature of ionic liquids, coarse-grained meso-scale simulations provide an indispensable complement to detailed first-principles calculations and atomistic simulations allowing studies over extended length and time scales with a modest computational cost. Here, we present extensive coarse-grained simulations on a series of ionic liquids of the 1-alkyl-3-methylimidazolium (alkyl = butyl, heptyl-, and decyl-) family with Cl, [BF4], and [PF6] counterions. Liquid densities, microstructures, translational diffusion coefficients, and re-orientational motion of these model ionic liquid systems have been systematically studied over a wide temperature range. The addition of neutral beads in cationic models leads to a transition of liquid morphologies from dispersed apolar beads in a polar framework to that characterized by bi-continuous sponge-like interpenetrating networks in liquid matrices. Translational diffusion coefficients of both cations and anions decrease upon lengthening of the neutral chains in the cationic models and by enlarging molecular sizes of the anionic groups. Similar features are observed in re-orientational motion and time scales of different cationic models within the studied temperature range. The comparison of the liquid properties of the ionic systems with their neutral counterparts indicates that the distinctive microstructures and dynamical quantities of the model ionic liquid systems are intrinsically related to Coulombic interactions. Finally, we compared the computational efficiencies of three linearly scaling O(N log N) Ewald summation methods, the particle-particle particle-mesh method, the particle-mesh Ewald summation method, and the Ewald summation method based on a non-uniform fast Fourier transform technique, to calculate electrostatic interactions. Coarse-grained simulations were performed using the GALAMOST and the GROMACS packages and hardware efficiently utilizing graphics processing units on a set of extended [1-decyl-3-methylimidazolium][BF4] ionic liquid systems of up to 131 072 ion pairs.
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No pos
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No neg
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Retriever2721
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Identification of circRNA-associated ceRNA networks using longissimus thoracis of pigs of different breeds and growth stages.
BACKGROUND
Long-term artificial selection for growth rate and lean meat rate has eventually led to meat quality deterioration. Muscle fiber type is a key factor that markedly affects meat quality. circRNAs have been reported to participate in diverse biological activities, including myofiber growth and development; thus, we herein compared porcine circRNA transcriptome between oxidative and glycolytic muscle tissues.
RESULTS
Longissimus thoracis muscle tissues were obtained from Lantang and Landrace pigs at birth (LT1D and LW1D, respectively) and 90 postnatal days (LT90D and LW90D, respectively). Hematoxylin and eosin staining and quantitative real-time PCR revealed that all structural traits of the muscle showed large variations between different breeds and growth stages. In total, 329 known miRNAs and 42,081 transcript candidates were identified; 6,962 differentially expressed transcripts were found to play a key role in myogenesis by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. In addition, 3,352 circRNAs were identified using five predicting algorithms, and 104 circRNA candidates were differentially expressed. Integrated analysis of differentially expressed miRNAs, mRNAs, and circRNAs led to the identification of 777, 855, and 22 convincing ceRNA interactions in LT1D vs. LT90D, LW1D vs. LW90D, and LT90D vs. LW90D, respectively. Finally, we identified a circRNA candidate circKANSL1L, which showed high homology between mice and pigs, and it was found to inhibit the proliferation of C2C12 cells but promote their differentiation.
CONCLUSIONS
We identified genome-wide circRNAs in 0- and 90-day-old Lantang and Landrace pigs by RNA-seq and found that circRNAs were abundant, differentially expressed, and associated with myogenesis. Our results should serve as a reference for future studies on pork quality.
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No pos
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No neg
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Retriever2722
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The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring.
OBJECTIVE
The objective of this study was to test the hypothesis whether a maternal dietary pattern is associated with the risk of spina bifida (SB) in the offspring.
DESIGN
Case-control study.
SETTING
Eight clinic sites in the Netherlands, 1999-2001.
SAMPLE
A total of 50 mothers of children with SB and 81 control mothers.
METHODS
Maternal food intakes were obtained by food frequency questionnaires at the standardised study moment of 14 months after the birth of the index child. Principal component factor analysis (PCA) and reduced rank regression (RRR) were used to identify dietary patterns.
MAIN OUTCOME MEASURES
Maternal biomarkers were used as response measures in the RRR analysis and composed of serum and red blood cell (RBC) folate, serum vitamin B12 and total plasma homocysteine. The strength of the use of the dietary pattern in association with SB risk was estimated by odds ratios and 95% CI with the highest quartiles of the dietary pattern as reference.
RESULTS
A predominantly Mediterranean dietary pattern was identified by both PCA and RRR. Those dietary patterns were highly correlated (r = 0.51, P < 0.001) and characterised by joint intakes of fruit, vegetables, vegetable oil, alcohol, fish, legumes and cereals and low intakes of potatoes and sweets. We observed a significantly increased risk of SB offspring in mothers with a weak use of the Mediterranean dietary pattern, OR 2.7 (95% CI 1.2-6.1) and OR 3.5 (95% CI 1.5-7.9). The Mediterranean dietary pattern was correlated with higher levels of serum and RBC folate, serum vitamin B12 and lower plasma homocysteine.
CONCLUSION
The Mediterranean dietary pattern seems to be associated with reduction in the risk of offspring being affected by SB.
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No pos
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No neg
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Retriever2723
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[The relationship between triglyceride glucose index and risk of cardiovascular disease among Kazakh and Uygur population in Xinjiang: a retrospective cohort analysis].
Objective: To analyze whether triglyceride-glucose (TyG) index is associated with increased risk of cardiovascular diseases (CVD) and the value of TyG index in predicting CVD risk among Kazakh and Uighur population of Xinjiang. Methods: In this study, 5 375 Kazakh and Uygur people of Xinyuan county and Jiashi county were selected as the research objects. Subjects were divided into four groups based on the quartile of the TyG index level. Cox regression model was used to analyze the association between TyG index with the risk of CVD. The dose-response relationship between TyG index and CVD risk was described by restricted cubic splines. The area under the receiver operating characteristic curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to estimate the value of TyG index for predicting CVD. Mediating effect analysis was conducted to analyze the mediating effect of TyG index in the association between body mass index and CVD. Results: The age of subjects was 41.06（30.11，53.00）years old, with 46.30%（2 489/5 375）was male. After multivariate adjustment, there was an increasing trend between the risk of CVD and the higher TyG index Ptrend<0.001, compared with subjects of TyG index in Q1, the HR (95%CI) of Q2, Q3, and Q4 groups was 1.53, 1.23 and 1.73, respectively. Restricted cubic splines showed that TyG index was the linearly associated with the risk of CVD. TyG index could improve the prediction ability of Framingham model for the risk of CVD (NRI=0.106,P=0.010; IDI=0.003,P=0.030). The mediating effect analysis showed that in the relationship between body mass index and CVD, the TyG index had a mediating effect (P<0.001), and the ratio of mediating effect was 12.69%. Conclusion: TyG index is an independent predictor of CVD risk among kazakh and Uygur population in Xinjiang and has a good predictive value for the risk of CVD.
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No pos
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No neg
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Retriever2724
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Assimilation and physiological effects of ferrocyanide on weeping willows.
Uptake, assimilation, and toxicity of exogenous iron cyanide complexes in plants were investigated. Pre-rooted young weeping willows (Salix babylonica L.) were exposed to hydroponic solutions spiked with potassium ferrocyanide at 24.0 ± 1°C for 192 h. Transpiration rates, chlorophyll contents, soluble protein, and activities of superoxide dismutases (SOD), catalase (CAT), and peroxidase (POD) of the plants were monitored to determine toxicity to the cuttings. Of all selected parameters, POD activity in leaves was the most sensitive bioindicator to the increase of ferrocyanide concentrations. Between 11% and 19% of applied ferrocyanide in the solutions was removed by willows at the end of the incubation period. Only small amounts of ferrocyanide were recovered in different parts of the plant materials. Mass balance analysis showed that more than 90% of the ferrocyanide taken up from the hydroponic solutions was assimilated by plants. The assimilation of ferrocyanide by plants showed a dose-dependent manner. These findings suggest that phytoremediation of ferrocyanide-contaminating wastewater and soils can be possible for the environmental cleaning up.
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No pos
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No neg
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Retriever2725
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Magnetization Signatures of Light-Induced Quantum Hall Edge States.
Circularly polarized light opens a gap in the Dirac spectrum of graphene and topological insulator (TI) surfaces, thereby inducing a quantum Hall-like phase. We propose to detect the accompanying edge states and their current by the magnetic field they produce. The topological nature of the edge states is reflected in the mean orbital magnetization of the sample, which shows a universal linear dependence as a function of a generalized chemical potential-independent of the driving details and the properties of the material. The proposed protocol overcomes several typically encountered problems in the realization and measurement of Floquet phases, including the destructive effects of phonons and coupled electron baths and provides a way to occupy the induced edge states selectively. We estimate practical experimental parameters and conclude that the magnetization signature of the Floquet topological phase may be detectable with current techniques.
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No pos
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No neg
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Retriever2726
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Biomass, carbon and nitrogen in single tree components of grey poplar (Populus × canescens) in an uncultivated habitat in Van, Turkey.
The biomass, carbon and nitrogen storage in the single tree components (foliage, branch, crown, bark, stem and total aboveground) of the grey poplar (Populus × canescens) in its distribution in Eastern Anatolia (Van, Turkey) were determined and modelled. The biomass, carbon and nitrogen storages were not estimated at a stand level but were based on single trees. Regression models based on the tree diameter at breast height (DBH) and total tree height (H) were developed to estimate the biomass, carbon (C) storage and nitrogen (N) storage of the different tree components of a total of 28 grey poplar trees. The two main regression models in the power function were developed based only on the DBH (Model 1) and the combination of the DBH and height (D2H) (Model 2). All regression models, except for those of the foliage components, developed to estimate the biomass and C and N storages of the tree components were found to be statistically significant (p < 0.001). The partitioning of the total aboveground biomass in the bark, foliage, branches and stems was 0.7, 9, 17 and 73%, respectively. The average C concentrations of the tree components ranged from 48 (foliage) to 50% (bark, branch and stem), while the N concentrations ranged from 0.35 (stem) to 1.32% (foliage). Higher biomass and lower nitrogen concentrations of foliage compared with cultivated poplars were likely related to the natural site conditions, low soil nitrogen and/or characteristics of single tree growth.
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No pos
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No neg
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Retriever2727
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Not just a marker: CD34 on human hematopoietic stem/progenitor cells dominates vascular selectin binding along with CD44.
CD34 is routinely used to identify and isolate human hematopoietic stem/progenitor cells (HSPCs) for use clinically in bone marrow transplantation, but its function on these cells remains elusive. Glycoprotein ligands on HSPCs help guide their migration to specialized microvascular beds in the bone marrow that express vascular selectins (E- and P-selectin). Here, we show that HSPC-enriched fractions from human hematopoietic tissue expressing CD34 (CD34pos) bound selectins, whereas those lacking CD34 (CD34neg) did not. An unbiased proteomics screen identified potential glycoprotein ligands on CD34pos cells revealing CD34 itself as a major vascular selectin ligand. Biochemical and CD34 knockdown analyses highlight a key role for CD34 in the first prerequisite step of cell migration, suggesting that it is not just a marker on these cells. Our results also entice future potential strategies to investigate the glycoforms of CD34 that discriminate normal HSPCs from leukemic cells and to manipulate CD34neg HSPC-enriched bone marrow or cord blood populations as a source of stem cells for clinical use.
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No pos
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No neg
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Retriever2728
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Dynamic Structure of Yeast Septin by Fast Fluctuation-Enhanced Structured Illumination Microscopy.
When Saccharomyces cerevisiae divides, a structure composed of different septin proteins arranged according to a certain rule is formed at the cell division site. The structure undergoes multiple remodeling stages during the cell cycle, thus guiding the yeast cells to complete the entire division process. Although the higher-order structure of septins can be determined using electron microscopy, the septin's dynamic processes are poorly understood because of limitations in living cell super-resolution imaging technology. Herein, we describe a high lateral resolution and temporal resolution technique, known as fast fluctuation-enhanced structured illumination microscopy (fFE-SIM), which more than doubles the SIM resolution at a frame rate of 38 Hz in living cells. This allows a highly dynamic and sparse septin structure to be observed in Saccharomyces cerevisiae.
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No pos
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No neg
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Retriever2729
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Paying for Early Interventions in Psychoses: A Three-Part Model.
Widespread dissemination of early interventions for psychosis, such as the intervention offered in the RAISE study (Recovery After an Initial Schizophrenia Episode), requires a funding mechanism that is both compatible with approaches already used by payers and generates incentives for providers that promote the desired behaviors. The authors propose a funding model with three components: a prospective per-case payment made conditional on patient engagement in treatment, a per-service component to cover the costs of clinical services, and an outcome-based component conditional on achieving measurable outcome milestones. The authors describe the components and how such a payment mechanism might be implemented.
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No pos
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No neg
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Retriever2730
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Application of Cardiac Gating to Improve the Reproducibility of Intravoxel Incoherent Motion Measurements in the Head and Neck.
PURPOSE
To prospectively evaluate whether cardiac gating can improve the reproducibility of intravoxel incoherent motion (IVIM) parameters in the head and neck, we performed IVIM diffusion-weighted imaging (DWI) using 4 b values (4b), 4 b values with cardiac gating (4b gating) and 17 b values (17b).
METHODS
We performed IVIM DWI twice per person on nine healthy volunteers using 4b, 4b gating and 17b and five patients with head and neck masses using 4b gating and 17b. The ADC, perfusion fraction (f), diffusion coefficient (D) and perfusion-related diffusion coefficient (D*) were calculated in the brain, masticator muscle, parotid gland, submandibular gland, tonsil and masses. Intraclass coefficient (ICC), Bland-Altman analysis (BAA) and coefficient of variation (CV) were used to assess short-term test-retest reproducibility. Kruskal-Wallis test and Mann-Whitney test were used to investigate whether 4b, 4b gating or 17b had significant influences on the parameters.
RESULTS
For normal tissues and masses, ICC was excellent for all maps except the D* map. All parameters showed the lowest CV in the 4b gating. BAA also revealed the narrowest 95% limits of agreement using 4b gating for all parameters. In the subgroup analysis, almost all parameters in brain, muscle, parotid gland and submandibular gland showed the best reproducibility using 4b gating. In the muscle, parotid gland and submandibular gland, the values of ADC, f and D were not significantly different between among the three methods.
CONCLUSION
4b gating was more reproducible with respect to measurements of IVIM parameters in comparison with 4b or 17b.
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No pos
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No neg
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Retriever2731
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[Urapidil in intraoperative continuous infusion].
The author reports the results of a clinical experiment with Urapidil administered in continue infusion to induce controlled hypotension during hemilaminectomies. The reduction of pressure values is obtained after 15-20 minutes since the beginning of drug infusion (35-40% compared with the starting basis values); moreover, because of the double action mechanism of the drug (central and peripheral), "reflex tachycardia", a common symptom in hypotensive drugs used in the past, disappears. In addition, the author states that the absence of potentially toxic degrading metabolites and the lack of "rebound" hypertensive phenomena or tachyphylaxia assure very good administration and pharmacological security of the drug.
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No pos
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No neg
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Retriever2732
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Vascular and Neural Complications in Type 2 Diabetic Rats: Improvement by Sacubitril/Valsartan Greater Than Valsartan Alone.
Previously, we had shown that a vasopeptidase inhibitor drug containing ACE and neprilysin inhibitors was an effective treatment for diabetic vascular and neural complications. However, side effects prevented further development. This led to the development of sacubitril/valsartan, a drug containing angiotensin II receptor blocker and neprilysin inhibitor that we hypothesized would be an effective treatment for diabetic peripheral neuropathy. Using early and late intervention protocols (4 and 12 weeks posthyperglycemia, respectively), type 2 diabetic rats were treated with valsartan or sacubitril/valsartan for 12 weeks followed by an extensive evaluation of vascular and neural end points. The results demonstrated efficacy of sacubitril/valsartan in improving vascular and neural function was superior to valsartan alone. In the early intervention protocol, sacubitril/valsartan treatment was found to slow progression of these deficits and, with late intervention treatment, was found to stimulate restoration of vascular reactivity, motor and sensory nerve conduction velocities, and sensitivity/regeneration of sensory nerves of the skin and cornea in a rat model of type 2 diabetes. These preclinical studies suggest that sacubitril/valsartan may be an effective treatment for diabetic peripheral neuropathy, but additional studies will be needed to investigate these effects further.
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No pos
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No neg
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Retriever2733
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Consumption of plant sterols reduces plasma and hepatic triglycerides and modulates the expression of lipid regulatory genes and de novo lipogenesis in C57BL/6J mice.
To investigate emerging clinical data suggesting a triglyceride (TAG)-lowering response to plant sterol (PS) therapy, we characterized changes in TAG metabolism in 16 C57BL/6J mice fed a basal control diet (CON) or the CON diet supplemented with 2% PS for 6 wk. PS consumption reduced (p<0.05) plasma (-28%) and hepatic (-30%) TAG concentrations compared with CON mice. PS consumption increased (p<0.05) hepatic lipogenic gene expression (sterol-regulatory-element-binding protein 1c, 2.4-fold of CON; fatty acid synthase, 6.5-fold of CON) and de novo lipogenesis (4.51+/-0.72 versus 2.82+/-0.61%/day) compared with CON. PS consumption increased (p<0.05) fecal palmitate and stearate excretion and reduced body weight gain compared with CON mice. Although no change in the transcription of intestinal fatty acid absorptive genes was observed, peroxisome proliferator-activated receptor alpha mRNA was reduced (p<0.05, 2.0-fold of CON) in the PS-fed mice. In conclusion, PS-fed C57BL/6J mice showed pronounced reductions in plasma and hepatic TAG concentrations despite increases in hepatic lipogenic gene expression and de novo lipogenesis. Interference with intestinal fatty acid/TAG metabolism as suggested by increased fecal fatty acid loss and reduced weight gain may be associated with the TAG-lowering response to PS consumption.
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No pos
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No neg
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Retriever2734
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Stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B) from D-xylose.
The first naturally occurring anhydrophytosphingosine, pachastrissamine (jaspine B), a marine compound cytotoxic toward P388, A549, HT29, and MEL28 cell lines at IC(50) = 0.01 microg/mL level, has been stereoselectively synthesized from D-xylose in 10 linear steps with 25.7% overall yield.
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No pos
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No neg
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Retriever2735
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Discovery of Two Brominated Oxindole Alkaloids as Staphylococcal DNA Gyrase and Pyruvate Kinase Inhibitors via Inverse Virtual Screening.
In the present study, a small marine-derived natural products library was assessed for antibacterial potential. Among 36 isolated compounds, a number of bis-indole derivatives exhibited growth-inhibitory activity towards Gram-positive strains (Bacillus subtilis and multidrug-resistant Staphylococcus aureus). 5- and 6-trisindoline (5-Tris and 6-Tris) were the most active derivatives (minimum inhibitory concentration, MIC, 4-8 µM) that were subsequently selected for anti-biofilm activity evaluation. Only 5-Tris was able to inhibit the staphylococcal biofilm formation starting at a 5 µM concentration. In order to investigate their possible molecular targets, both natural products were subjected to in silico inverse virtual screening. Among 20 target proteins, DNA gyrase and pyruvate kinase were the most likely to be involved in the observed antibacterial and anti-biofilm activities of both selected natural products. The in vitro validation and in silico binding mode studies revealed that 5-Tris could act as a dual enzyme inhibitor (IC50 11.4 ± 0.03 and 6.6 ± 0.05 µM, respectively), while 6-Tris was a low micromolar gyrase-B inhibitor (IC50 2.1 ± 0.08 µM), indicating that the bromine position plays a crucial role in the determination of the antibacterial lead compound inhibitory activity.
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No pos
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No neg
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Retriever2736
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Collision tumor of thyroid: metastatic lung adenocarcinoma plus papillary thyroid carcinoma.
Collision tumors are rare entities wherein 2 separate, distinct histologic malignant neoplasms occur in adjacent anatomic proximity. The 2 malignancies may originate from the same organ or occur as metastases from other sites. We present a case of a collision tumor of metastatic lung adenocarcinoma and papillary thyroid carcinoma occurring in the thyroid gland of a 63-year-old woman who presented with a multinodular central neck mass. After excision and histopathologic examination, this tumor was identified as a collision tumor. This is the first report of this unique combination of tumors occurring in the thyroid gland. This case report emphasizes the role of detailed histopathologic analysis and the use of immunohistochemistry in better identifying rare thyroid neoplasms.
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No pos
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No neg
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Retriever2737
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Quantum chemical simulations of solvent influence on UV-vis spectra and orbital shapes of azoderivatives of diphenylpropane-1,3-dione.
The DFT modeling of novel synthesized azoderivatives of β-diketones - 2-(2-(2-hydroxyphenyl)hydrazono)-1,3-diphenylpropane-1,3-dione (1), 2-(2-(2-hydroxy-4-nitrophenyl)hydrazono)-1,3-diphenylpropane-1,3-dione (2), 3-(2-(1,3-dioxo-1,3-diphenylpropan-2-ylidene)hydrazinyl)-2-hydroxy-5-nitrobenzene sulfonic acid (3), 2-(2-(1,3-dioxo-1,3-diphenylpropan-2-ylidene)hydrazinyl)benzenesulfonic acid (4), 2-(2-(1,3-dioxo-1,3-diphenylpropan -2-ylidene)hydrazinyl)benzoic acid (5), 2-(2-(2-hydroxy-4-nitrophenyl)hydrazono)-1-phenylbutane-1,3-dione (6) were performed. The collected information confirms that 1-5 exist in hydrazo form, being stabilized by the intramolecular hydrogen bonds in DMSO solution and solid phase, while 6 exists in mixed enol-azo and hydrazo tautomeric forms, the latter dominating in more polar solvents. The relative stability of various tautomeric and izomeric forms of the symmetric 1-5 and unsymmetric 6 azoderivatives of β-diketones is calculated based on the density functional theory (DFT). Polarizable Continuum Model was used to simulate solvatochromic effects. Solvents of different polarities were used to collect experimental spectra, and the same solvents were chosen for the PCM calculations. The optical properties of 1-6 have been investigated by density functional theory and its electronic absorption bands have been assigned by time-dependent density functional theory (TD-DFT).
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No pos
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No neg
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Retriever2738
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The use of telehealth-supported stewardship activities in acute-care and long-term care settings: An implementation effectiveness trial.
BACKGROUND
We assessed the implementation of telehealth-supported stewardship activities in acute-care units and long-term care (LTC) units in Veterans' Administration medical centers (VAMCs).
DESIGN
Before-and-after, quasi-experimental implementation effectiveness study with a baseline period (2019-2020) and an intervention period (2021).
SETTING
The study was conducted in 3 VAMCs without onsite infectious disease (ID) support.
PARTICIPANTS
The study included inpatient providers at participating sites who prescribe antibiotics.
INTERVENTION
During 2021, an ID physician met virtually 3 times per week with the stewardship pharmacist at each participating VAMC to review patients on antibiotics in acute-care units and LTC units. Real-time feedback on prescribing antibiotics was given to providers. Additional implementation strategies included stakeholder engagement, education, and quality monitoring.
METHODS
The reach-effectiveness-adoption-implementation-maintenance (RE-AIM) framework was used for program evaluation. The primary outcome of effectiveness was antibiotic days of therapy (DOT) per 1,000 days present aggregated across all 3 sites. An interrupted time-series analysis was performed to compare this rate during the intervention and baseline periods. Electronic surveys, periodic reflections, and semistructured interviews were used to assess other RE-AIM outcomes.
RESULTS
The telehealth program reviewed 502 unique patients and made 681 recommendations to 24 providers; 77% of recommendations were accepted. After program initiation, antibiotic DOT immediately decreased in the LTC units (-30%; P < .01) without a significant immediate change in the acute-care units (+16%; P = .22); thereafter DOT remained stable in both settings. Providers generally appreciated feedback and collaborative discussions.
CONCLUSIONS
The implementation of our telehealth program was associated with reductions in antibiotic use in the LTC units but not in the smaller acute-care units. Overall, providers perceived the intervention as acceptable. Wider implementation of telehealth-supported stewardship activities may achieve reductions in antibiotic use.
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No pos
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No neg
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Retriever2739
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Development and psychometric testing of the Canine Owner-Reported Quality of Life questionnaire, an instrument designed to measure quality of life in dogs with cancer.
OBJECTIVE To describe development and initial psychometric testing of an owner-reported questionnaire designed to standardize measurement of general quality of life (QOL) in dogs with cancer. DESIGN Key-informant interviews, questionnaire development, and field trial. SAMPLE Owners of 25 dogs with cancer for item development and pretesting and owners of 90 dogs with cancer for reliability and validity testing. PROCEDURES Standard methods for development and testing of questionnaire instruments intended to measure subjective states were used. Items were generated, selected, scaled, and pretested for content, meaning, and readability. Response items were evaluated with exploratory factor analysis and by assessing internal consistency (Cronbach α) and convergence with global QOL as determined with a visual analog scale. Preliminary tests of stability and responsiveness were performed. RESULTS The final questionnaire-which was named the Canine Owner-Reported Quality of Life (CORQ) questionnaire-contained 17 items related to observable behaviors commonly used by owners to evaluate QOL in their dogs. Several items pertaining to physical symptoms performed poorly and were omitted. The 17 items were assigned to 4 factors-vitality, companionship, pain, and mobility-on the basis of the items they contained. The CORQ questionnaire and its factors had high internal consistency (Cronbach α = 0.68 to 0.90) and moderate to strong correlations (r = 0.49 to 0.71) with global QOL as measured on a visual analog scale. Preliminary testing indicated good test-retest reliability and responsiveness to improvements in overall QOL. CONCLUSIONS AND CLINICAL RELEVANCE The CORQ questionnaire was a valid, reliable owner-reported questionnaire that measured general QOL in dogs with cancer and showed promise as a clinical trial outcome measure for quantifying changes in individual dog QOL occurring in response to cancer treatment and progression.
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No pos
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No neg
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Retriever2740
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[An oligopeptide improves solubility of paclitaxel by non-covalent interaction].
Based on the principle of non-covalent interactions between oligopeptides and paclitaxel for improving the solubility of paclitaxel, an oligopeptide, N terminal-W(L)-FFGREKD-C terminal (W8), was designed and the solubilization effect of W8 on paclitaxel was detected through experiments. The binding efficiency and the possible optimal conformation were optimized by molecular docking program. The solubilization effect of W8 on paclitaxel was determined by RP-HPLC. And the solubilization mechanism of oligopeptide to paclitaxel was proposed at molecular level. It was indicated from the docking result that there existed pi-pi interactions and several hydrogen-bond interactions between the oligopeptide and paclitaxel. After being solubilized by the oligopeptide, the aqueous solubility of paclitaxel was increased to 28 times. This study provided basis for further research of the solubilization of paclitaxel by oligopeptide and confirmed a novel approach for the design of safe oligopeptide solubilizing excipient.
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No pos
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No neg
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Retriever2741
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Vascularized osteochondral graft from the medial femoral trochlea: anatomical study and clinical perspectives.
PURPOSE
Few donor sites for vascularized reconstruction of convex joint surfaces have been described. We studied the feasibility of a convex vascularized osteochondral graft harvested from the medial femoral condyle and trochlea, on an anatomical and practical point of view.
METHODS
An injection-corrosion technique was used on 16 fresh cadaver specimens, and completed by a modified Spalteholz clearing. The extra- and intraosseous vascularization of the medial femoral condyle was systematized and the luminal diameter of the arteries was microscopically measured. Radii of curvature of the medial trochlea and of the carpal bones were measured on arthro-CT-scanner reconstructed images.
RESULTS
The periosteal vessels of the medial condyle are responsible for the whole peripheral intraosseous vascularization, without any watershed region. They are fed by the articular branch of the descending genicular artery and/or the superomedial genicular artery. Several constant vascular axes can be found, and may serve as a pedicle for a vascularized osteochondral graft from the medial femoral trochlea. The radii of curvature of this graft do fit those of the proximal carpal row. A simple surgical approach is suggested.
CONCLUSIONS
A vascularized graft harvested on the medial femoral trochlea is a technically feasible procedure that could represent a new reconstructive tool for convex joint surfaces. Osteonecrosis of the proximal pole of the scaphoid or Kienböck's disease are among several situations where such a graft could be beneficial.
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No pos
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No neg
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Retriever2742
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Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV: A cross-sectional study.
We aimed to analyze the efficacy and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV (PLWH). A total of 143 PLWH and 50 healthy individuals were included in this study. A commercially available magnetic chemiluminescence enzyme immunoassay kit was used to detect serum IgG and IgM antibodies against SARS-CoV-2. Serum levels of SARS-CoV-2-specific IgG were significantly higher in the control group than in the PLWH group (p = 0.001). Overall, 76% of individuals in the control group were detected with seropositivity IgG against SARS-CoV-2 compared to 58% in the PLWH group (p = 0.024). In PLWH with IgG seropositivity, CD4+ T-cell counts before antiretroviral therapy (ART) was higher (p = 0.015). Multivariable analysis indicated that CD4+ T cells at IgG detection (odds ratio [OR] = 1.004, p = 0.006) and time after vaccination (OR = 0.977, p = 0.014) were independently associated with seropositivity IgG against SARS-CoV-2 in PLWH. Neutralizing antibody (nAb) titers in PLWH against wild-type SARS-CoV-2 were similar to those in the control group (p = 0.160). The proportion of seropositive nAbs against wild-type SARS-CoV-2 was also similar (95% in the control group vs. 97% in the PLWH group, p = 0.665). Similar results were obtained when nAb was detected against the delta variants with similar titers (p = 0.355) and a similar proportion of seropositive nAbs were observed (p = 0.588). All the side effects observed in our study were mild and self-limiting. The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in Chinese PLWH.
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No pos
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No neg
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Retriever2743
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Non allergic rhinitis: demography of eosinophils in nasal smear, blood total eosinophil counts and IgE levels.
Seventy-eight consecutive patients with non allergic rhinitis (negative allergy skin tests) were evaluated and classified as to possible causes using strict criteria. Sixty-one percent had vasomotor rhinitis (VMR), 33% had non allergic rhinitis with eosinophilia syndrome (NARES), 16% had sinusitis, 12% had a possible hidden allergy (elevated IgE), 4% had blood eosinophilic non allergic rhinitis (BENAR) and 2% had hypothyroidism. Some overlapping of diagnosis was present. Five per cent or greater eosinophils in the nasal smear appeared to be enough to consider the diagnosis of NARES. Sinusitis tended to be more significant in the NARES group compared to VMR. BENARS may be a new syndrome. It differs from NARES in that BENARS has markedly elevated blood eosinophilia and possibly no associated sinusitis. It is similar to NARES in that it has negative allergy skin test, normal serum IgE, and eosinophils in nasal secretions. Other causes of eosinophilia were excluded in our NARES and BENARS groups.
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No pos
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No neg
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Retriever2744
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Immunogenicity of Sm32 synthetic peptides derived from the Schistosoma mansoni adult worm.
The previously called "hemoglobinase" Sm32 molecule of the adult worm of Schistosoma mansoni was chemically synthesized in 22 polymeric peptides based on the t-boc strategy. Their immunogenicity was evaluated in rabbits to which a mixture of five to six peptides of 20 amino acids long were given in three doses with Freund's adjuvant. Seventeen peptides were found to be immunogenic, and sera from immunized rabbits corresponding to the molecule from the first 335 amino acids, recognized the 32 kDa native protein from the adult worm antigen by western blot. Of those, the relevant peptides responsible of the recognition of the original molecule corresponded to amino acids 101-120, 121-140 and 244-268, based on inhibition competitive assays. Because Sm32 is one of the excretory and secretory molecules released with the vomitus of the adult worm, it is one of the target antigens for detection in plasma of infected individuals. The production of these polyclonal monospecific antibodies against the synthetic peptides could be of value in the immunodiagnosis of this parasitosis.
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No pos
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No neg
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Retriever2745
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Rapid fabrication of TiO2@carboxymethyl cellulose coatings capable of shielding UV, antifog and delaying support aging.
Agricultural plastic films capable of shielding UV, filtering visible light and antifog are important to prolong their life and protect safeties of agriculturists and crops. In this work, high stable and small size TiO2@polymer nanoparticles (NPs) were prepared by an efficient one-pot microwave synthesis using titanic sulfate as Ti resource, carboxymethyl cellulose sodium (CMC) as complexing agent and stabilizer. The TiO2@CMC NPs obtained were then utilized to fabricate poly(ethylene imine) (PEI)/TiO2@CMC coatings on the surface of polypropylene films by a layer-by-layer assembly technique. The TiO2@CMC NPs show rapid deposition rate because small, spherical and anion-rich TiO2@CMC NPs possess large specific surface area and fast diffusion rate. More importantly, property experiments confirm that (PEI/TiO2@CMC)*15 coatings can not only effectively shield UV rays, filter visible light and prevent fogging but also delay the aging of their supports.
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No pos
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No neg
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Retriever2746
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Individualized education focusing on self-management improved the knowledge and self-management behaviour of elderly people with atrial fibrillation: A randomized controlled trial.
AIM
This study examined the effect of an individualized educational intervention on the knowledge, attitudes and self-management ability after 12 weeks for outpatients with atrial fibrillation.
METHODS
A randomized control-group pretest-post-test experimental design was used. Elderly outpatients with atrial fibrillation aged over 65 years were recruited from a university hospital in Korea. The experimental group received a 50-min individualized education on self-management, one telephone counselling after 8 weeks and maintenance of a self-management diary for 12 weeks. Data were collected from November 2017 to April 2018 and analysed using SPSS 22.0 for descriptive statistics and hypothesis testing.
RESULTS
The participants' mean age was 71.9 (4.6) years. Compared to the control group (n = 29), the experimental group (n = 31) showed a significantly greater improvement in knowledge regarding atrial fibrillation and stroke prevention (t = -2.27, p = .027) and self-management behaviours (t = -8.02, p < .001). There were no significant group differences in attitudes towards atrial fibrillation.
CONCLUSION
The findings suggest that education for elderly people with atrial fibrillation should be individualized, focusing on self-management in daily life to prevent cardiovascular complications. Future research is needed to confirm the long-term effects of such education programmes.
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No pos
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No neg
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Retriever2747
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Public Health Ethics and Liberalism.
This paper defends a distinctly liberal approach to public health ethics and replies to possible objections. In particular, I look at a set of recent proposals aiming to revise and expand liberalism in light of public health's rationale and epidemiological findings. I argue that they fail to provide a sociologically informed version of liberalism. Instead, they rest on an implicit normative premise about the value of health, which I show to be invalid. I then make explicit the unobvious, republican background of these proposals. Finally, I expand on the liberal understanding of freedom as non-interference and show its advantages over the republican alternative of freedom as non-domination within the context of public health. The views of freedom I discuss in the paper do not overlap with the classical distinction between negative and positive freedom. In addition, my account differentiates the concepts of freedom and autonomy and does not rule out substantive accounts of the latter. Nor does it confine political liberalism to an essentially procedural form.
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No pos
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No neg
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Retriever2748
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Pyriplatin-Boron-Dipyrromethene Conjugates for Imaging and Mitochondria-Targeted Photodynamic Therapy.
Monofunctional pyriplatin analogues cis-[Pt(NH3)2(L)Cl](NO3) (1-3) having boron-dipyrromethene (BODIPY) pendants (L) with 1,3,5,7-tetramethyl-8-(4-pyridyl)-4,4'-difluoroboradiazaindacene moieties were designed and synthesized, and their photocytotoxic properties were studied. The Pt-BODIPY conjugates displayed an absorption band within 505-550 nm and a green emissive band near 535 nm in 1% DMSO/DMEM (Dulbecco's modified Eagle's medium) buffer. Complex cis-[Pt(NH3)2(4-Me-py)Cl](NO3) (4) was used as a control for determining the structural aspects by X-ray crystallography. The mono- and diiodinated BODIPY complexes 2 and 3 showed generation of singlet oxygen on light activation as evidenced from the 1,3-diphenylisobenzofuran (DPBF) titration experiments. The cytotoxicity of the BODIPY complexes was tested against A549 (human lung cancer), MCF-7 (human breast cancer), and HaCaT (human skin keratinocyte) cells in dark and visible light (400-700 nm, 10 J cm-2). While complexes 2 and 3 showed excellent photocytotoxicity (IC50 ≈ 0.05 μM), they remained essentially nontoxic in the dark (IC50 > 100 μM). The emissive bands of 1 and 2 were used for cellular imaging by confocal microscopy study, which showed their mitochondrial localization. This was further supported by platinum estimation from isolated mitochondria and mitochondrial depolarization through a JC-1 assay. The photomediated apoptotic cell death was evidenced from flow cytometric assays, annexin-V/FITC-PI (fluorescein isothiocyanate-propidium iodide) and cell cycle arrest in sub-G1 and G2/M phases. The complexes bind to 9-ethylguanine as a model nucleobase to form monoadducts. A mechanistic study on DNA photocleavage activity using pUC19 DNA showed singlet oxygen as the reactive oxygen species (ROS). The combination of photodynamic therapy with DNA cross-linking property enhanced the anticancer potential of the monofunctional BODIPY-conjugates of pyriplatins.
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No pos
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No neg
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Retriever2749
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Lower urinary tract dysfunction in children - a practical approach.
More than 10 % of schoolchildren suffer from lower urinary tract dysfunction, often leading to contact with the healthcare system. The problem is socially limiting as well as mentally and physically demanding for children and their parents, and it is important to offer treatment. This article describes a structured approach that can form the basis for correct diagnosis and treatment.
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No pos
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No neg
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Retriever2750
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Low- Versus High-dose Cyclophosphamide in Class III/IV Lupus Nephritis: A Retrospective Study from South Asia.
Introduction
The comparative efficacy of low-dose cyclophosphamide (LD-CYC) and high-dose cyclophosphamide (HD-CYC) for treatment of lupus in South Asians is not well established. We aimed to compare treatment outcomes in South Asian patients with class III and IV lupus nephritis treated with either regimen.
Method
This was a single-center, retrospective study conducted in Sri Lanka. Patients with biopsy-proven class III or IV lupus nephritis were recruited. The HD-CYC group was defined as having received ≥6 doses of 0.5-1 g/m2 cyclophosphamide (CYC) followed by quarterly doses. The LD-CYC group was defined as having received six doses of 500 mg CYC at two-weekly intervals. The primary outcome was treatment failure defined as persistent nephrotic range proteinuria or renal impairment at 6 months.
Results
Sixty-seven patients were recruited (HD-CYC 34, LD-CYC 33), all South Asian ethnicity. The HD-CYC group had received treatment between 2000 and 2013, and the LD-CYC group from 2013 onward. The HD-CYC and LD-CYC groups had 30/33 (90.9%) and 31/34 (91.2%) females, respectively. Nephrotic syndrome and nephrotic range proteinuria on presentation were seen in 22/33 (67%) and 20/32 (62%) in the HD-CYC and LD-CYC groups, respectively, and renal impairment was seen in 5/33 (15%) of the HD-CYC group and 7/32 (22%) of the LD-CYC group (P > 0.05). Treatment failure and complete or partial remission occurred in 7/34 (21%) and 28/34 (82%), respectively, of HD-CYC and 10/33 (30%) and 24/33 (73%), respectively, of LD-CYC (P > 0.05). Adverse events rates were similar.
Conclusion
This study suggests that LD-CYC and HD-CYC induction is comparable in South Asian patients with class III and IV lupus nephritis.
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Retriever2751
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How does the onset of physical disability or dementia in older adults affect economic wellbeing and co-payments for health care? the impact of gender.
BACKGROUND
Existing studies have illustrated how the onset of physical disability or dementia negatively impacts economic wellbeing and increases out of pocket costs. However, little is known about this relationship in older individuals. Consequently, this study aimed to identify how the onset of physical disability or dementia in older adults affects economic wellbeing and out of pocket costs, and to explore the impact of gender in the context of Australia.
METHODS
The data was collected from a large, randomized clinical study, ASPirin in Reducing Events in the Elderly (ASPREE). Two generalized linear models (with and without interaction effects) of total out of pocket costs for those who did and did not develop physical disability or dementia were generated, with adjustment for sociodemographic characteristics at baseline.
RESULTS
We included 8,568 older Australian individuals with a mean age of 74.8 years and 53.2% being females. After adjustment for the baseline sociodemographic characteristics, the onset of physical disability did statistically significantly raise out of pocket costs (cost ratio = 1.25) and costs among females were 13.1% higher than males.
CONCLUSIONS
This study highlights that classifying different types of health conditions to identify the drivers of out of pocket costs and to explore the gender differences in a long-term follow-up is of importance to examine the financial impact on the older population. These negative financial impacts and gender disparities of physical disability and dementia must be considered by policymakers.
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Retriever2752
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Development of dome epithelium in gut-associated lymphoid tissues: association of IgA with M cells.
The dome epithelium (DE), which covers gut-associated lymphoid tissues (GALT) and provides both a protective barrier over lymphoid follicles and a route for antigen uptake from the gut, develops in rabbit appendix (caecum) during the first week of neonatal life. To determine if secretory immunoglobulins from maternal milk interact with this developing tissue, their interrelationships in neonatal rabbit appendix were examined by use of immunocytochemical techniques. The glycoprotein, secretory component, was not produced by neonatal rabbits less than 15 days old, since neither the membranous nor the free, secreted forms of maternal secretory component were associated with villi or DE of neonates. Immunoglobulin A (IgA), but neither IgG nor IgM, were noted on DE by light microscopy, even though IgG was abundant in the villus lamina propria and vascular spaces. The epithelial IgA was distributed, in a patchy pattern, across the upper dome surface of some two-day-old, and all five-and ten-day old nursing animals, but IgA was not on DE of rabbits prevented from nursing. Immuno-electron microscopy of appendix from nursed rabbits revealed IgA directly over the apical surface of M cells, where it formed a continuous, thick coating without binding to adjacent immature absorptive cells; it was also within apical vacuoles of M cell cytoplasm. The distribution of IgA on the DE of rabbit appendices indicated that in differentiating GALT, maternal IgA reacted preferentially with M cells or pre-M cells, leading to speculation concerning a role for IgA in the development of GALT and in establishment of mucosal immune responses in neonates.
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Retriever2753
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The Feasibility and Efficacy of a Brief Integrative Treatment for Adults With Depression and/or Anxiety: A Randomized Controlled Trial.
The aim of this study was to investigate the efficacy and suitability of a brief integrative intervention, Personalized Integrative Therapy (PI Therapy), for the treatment of adult depression and/or anxiety. In this 6-week, 3-arm, parallel-group, randomized trial, PI Therapy delivered alone or with nutritional supplements (PI Therapy + Supps) was compared to cognitive behavior therapy (CBT) in 48 adults with depression and/or anxiety. All treatments were delivered as a 1-day workshop plus 6 weeks of reminder phone text messages to reinforce topics and skills covered in the workshop. Affective symptoms decreased significantly and to the same extent in all 3 conditions. At the end of treatment, 33% to 58% of participants reported levels of depressive symptoms in the normal range, and 50% to 58% reported nonclinical levels of anxiety. Compared to CBT and PI Therapy, PI Therapy + Supps was associated with significantly greater improvements in sleep quality. These findings suggest that a brief integrative intervention with or without supplements was comparable to CBT in reducing affective symptoms in adults with depression and/or anxiety. However, sleep quality improved only in the PI Therapy + Supps condition. These findings will require replication with a larger cohort.
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Retriever2754
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Newer antipsychotics and glucose metabolism: a comparison between olanzapine and risperidone.
In order to estimate the degree of glucose tolerance impairment, oral glucose tolerance test was conducted in the group of 15 schizophrenic patients taking olanzapine, the group of 15 schizophrenic patients taking risperidone and in the group of 14 healthy volunteers. In the olanzapine group the tolerance was impaired in 33% of the patients, contrary to the risperidone group in which impairment amounted to 20% of the patients. The authors discuss possible mechanisms responsible for impaired glucose tolerance in patients taking newer antipsychotic drugs.
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Retriever2755
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Interstitial lung disease in clinically amyopathic dermatomyositis (CADM) patients: a retrospective study of 41 Chinese Han patients.
To study the clinical features and associated risk factors of interstitial lung disease (ILD) in clinically amyopathic dermatomyositis (CADM) in Chinese patients. Forty-one Chinese Han patients with a diagnosis of CADM in West China Hospital from August 2008 to 2011 were retrospectively analyzed. The prevalence of ILD in CADM patients is 60.98 %, in which 26.83 % for acute/subacute interstitial pneumonia (A/SIP) and 34.15 % for chronic interstitial pneumonia (CIP). Mortality of A/SIP is 63.64 %, with a 6-month survival rate of 54.50 %. Levels of erythrocyte sedimentation rate, serum ferritin, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, hydroxybutyric dehydrogenase, and immunoglobulin A (IgA) are higher in CADM-ILD patients than CADM patients without ILD. Levels of serum ALB and lymphocyte count in peripheral blood are significant lower in A/SIP than in CIP group. Sign of ground glass opacities in high-resolution computed tomography (HRCT) images is more common in A/SIP group, and diffusion function is worse in these patients compared with CIP group. The prevalence of ILD in Chinese CADM patients is strikingly high, and A/SIP is a major cause of death in CADM patients. Laboratory findings combined with HRCT examination and pulmonary function tests can provide valuable predictive information of ILD or A/SIP in CADM patients.
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Retriever2756
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Direct phase determination by entropy maximization and likelihood ranking: status report and perspectives.
A new multisolution phasing method based on entropy maximization and likelihood ranking, proposed for the specific purpose of extending probabilistic direct methods to the field of macromolecules, has been implemented in two different computer programs and applied to a wide variety of problems. The latter comprise the determination of small crystal structures from X-ray diffraction data obtained from single crystals or from powders, and from electron diffraction data partially phased by image processing of electron micrographs, the ab initio generation and ranking of phase sets for small proteins; and the improvement of poor quality phases for a larger protein at medium resolution under constraint of solvent flatness. These applications show that the primary goal of this new method - namely increasing the accuracy and sensitivity of probabilistic phase indications compared with conventional direct methods - has been achieved. The main components of the method are (1) a tree-directed search through a space of trial phase sets; (2) the saddle-point method for calculating joint probabilities of structure factors, using entropy maximization; (3) likelihood-based scores to rank trial phase sets and prune the search tree; (4) efficient schemes, based on error-correcting codes, for sampling trial phase sets; (5) a statistical analysis of the scores for automatically selecting reliable phase indications. They have been implemented to varying degrees of completeness in a computer program (BUSTER) and tested on two small structures as well as on the small protein crambin. The main obstructions to successful ab initio phasing in the latter case seem to reside in the accumulation of phase sampling errors and in the lack of a properly defined molecular envelope, both of which can be remedied within the methods proposed. A review of the Bayesian statistical theory encompassing all phasing procedures, proposed earlier as an extension of the initial theory, shows that the techniques now available in BUSTER bring closer a number of major enhancements of standard macromolecular phasing techniques, namely isomorphous replacement, molecular replacement, solvent flattening and non-crystallographic symmetry averaging. The gradual implementation of the successive stages of this 'Bayesian programme' should lead to an increasingly integrated, effective and dependable phasing procedure for macromolecular structure determination.
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Retriever2757
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Evaluation of compartmental and spectral analysis models of [18F]FDG kinetics for heart and brain studies with PET.
Various models have been proposed to quantitate from [18F]-Fluoro-Deoxy-Glucose ([18F]FDG) positron emission tomography (PET) data glucose regional metabolic rate. We evaluate here four models, a three-rate constants (3K) model, a four-rate constants (4K) model, an heterogeneous model (TH) and a spectral analysis (SA) model. The data base consists of [18F]FDG dynamic data obtained in the myocardium and brain gray and white matter. All models were identified by nonlinear weighted least squares with weights chosen optimally. We show that: 1) 3K and 4K models are indistinguishable in terms of parsimony criteria and choice should be made on parameter precision and physiological plausibility; in the gray matter a more complex model than the 3K one is resolvable; 2) the TH model is resolvable in the gray but not in the white matter; 3) the classic SA approach has some unnecessary hypotheses built in and can be in principle misleading; we propose here a new SA model which is more theoretically sound; 4) this new SA approach supports the use of a 3K model in the heart with a 60 min experimental period; it also indicates that heterogeneity in the brain is modest in the white matter; 5) [18F]FDG fractional uptake estimates of the four models are very close in the heart, but not in the brain; 6) a higher than 60 min experimental time is preferable for brain studies.
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Retriever2758
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Long-term exposure to dietary sources of genistein induces estrogen-independence in the human breast cancer (MCF-7) xenograft model.
SCOPE
The long-term effect of exposure to relevant dietary levels of genistein (GEN) on estrogen receptor-positive (ER+) human breast cancer (MCF-7) progression after GEN withdrawal in athymic mice xenograft model was studied.
MATERIALS AND METHODS
Feeding studies were conducted to determine the estrogenic effect of diets on MCF-7 tumor growth: (1) implantation (19 weeks) and withdrawal (6 weeks) of 17β-estradiol (E2 ); (2) dietary GEN 500 and 750 ppm during treatment/withdrawal for 23/10 and 15/9 weeks, respectively; and, (3) dietary soy protein isolate (SPI) containing GEN 180 ppm for 31/9 weeks of treatment/withdrawal. MCF-7 tumors grew fast in the presence of E2 implantation and abruptly regressed completely after E2 withdrawal. At different rates, dietary GEN alone (500 and 750 ppm) and GEN (180 ppm)-containing SPI stimulated MCF-7 tumor growth. After removal of the stimulus diet, tumors induced by 750 ppm GEN, but not 500 ppm GEN or SPI, regressed completely. The protein expression of epidermal growth factor receptor 2 (HER2) was higher in the GEN- and SPI-induced nonregressing (GINR) tumors compared to MCF-7 and E2 controls.
CONCLUSION
Long-term consumption of low GEN doses (≤500 ppm) promotes MCF-7 tumor growth and results in GINR tumors with more aggressive and advanced growth phenotypes.
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Retriever2759
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[Mohs micrographic surgery: concept, technic and indications].
Mohs Micrographic Surgery is a technic to treat severe cutaneous carcinoma. By performing a microscopic and topographic analysis of the whole tissue excised, both a reduction of the surgical margin and margins in normal tissue is obtained. The major indications of micrographic surgery are recurrent basalcell carcinoma after surgery or radiotherapy, not fully excised or localized on the nose and the mediofacial region, some spinouscell carcinoma and dermatofibrosarcoma protuberans.
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Retriever2760
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Microsatellites and 16S sequences corroborate phenotypic evidence of trans-Andean variation in the parasitoid Microctonus hyperodae (Hymenoptera: Braconidae).
Eight South American geographical populations of the parasitoid Microctonus hyperodae Loan were collected in South America (Argentina, Brazil, Chile and Uruguay) and released in New Zealand for biological control of the weevil Listronotus bonariensis (Kuschel), a pest of pasture grasses and cereals. DNA sequencing (16S, COI, 28S, ITS1, beta-tubulin), RAPD, AFLP, microsatellite, SSCP and RFLP analyses were used to seek markers for discriminating between the South American populations. All of the South American populations were more homogeneous than expected. However, variation in microsatellites and 16S gene sequences corroborated morphological, allozyme and other phenotypic evidence of trans-Andes variation between the populations. The Chilean populations were the most genetically variable, while the variation present on the eastern side of the Andes mountains was a subset of that observed in Chile.
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Retriever2761
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Effect of Capecitabine Maintenance Therapy Plus Best Supportive Care vs Best Supportive Care Alone on Progression-Free Survival Among Patients With Newly Diagnosed Metastatic Nasopharyngeal Carcinoma Who Had Received Induction Chemotherapy: A Phase 3 Randomized Clinical Trial.
IMPORTANCE
Capecitabine maintenance therapy improves survival outcomes in various cancer types, but data are limited on the efficacy and safety of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC).
OBJECTIVE
To investigate the efficacy and safety of capecitabine maintenance therapy in metastatic NPC.
DESIGN, SETTING, AND PARTICIPANTS
This randomized phase 3 clinical trial was conducted at Sun Yat-sen University Cancer Center from May 16, 2015, to January 9, 2020, among 104 patients with newly diagnosed metastatic NPC who had achieved disease control after 4 to 6 cycles of induction chemotherapy with paclitaxel, cisplatin, and capecitabine. The final follow-up date was May 30, 2021. All efficacy analyses were conducted in the intention-to-treat population.
INTERVENTIONS
Eligible patients were randomly assigned (1:1) to receive either capecitabine maintenance therapy (1000 mg/m2 orally twice daily on days 1-14) every 3 weeks plus best supportive care (BSC) (capecitabine maintenance group) or BSC alone after 4 to 6 cycles of induction chemotherapy.
MAIN OUTCOMES AND MEASURES
Progression-free survival (PFS). Secondary end points were objective response rate, duration of response, overall survival, and safety.
RESULTS
This study included 104 patients (84 men [80.8%]; median age, 47 years [IQR, 38-54 years]), with 52 assigned to the capecitabine maintenance group and 52 assigned to the BSC group. After a median follow-up of 33.8 months (IQR, 22.9-50.7 months), there were 23 events (44.2%) of progression or death in the capecitabine maintenance group and 37 events (71.2%) of progression or death in the BSC group. Median PFS survival was significantly higher in the capecitabine maintenance group (35.9 months [95% CI, 20.5 months-not reached]) than in the BSC group (8.2 months [95% CI, 6.4-10.0 months]), with a hazard ratio of 0.44 (95% CI, 0.26-0.74; P = .002). Higher objective response rates and longer median duration of response were observed in the capecitabine maintenance group (25.0%; 40.0 months) compared with the BSC group (objective response rate, 25.0% [n = 13] vs 11.5% [n = 6]; and median duration of response, 40.0 months [95% CI, not reached-not reached] vs 13.2 months [95% CI, 9.9-16.5 months]). The most common grade 3 or 4 adverse events during maintenance therapy were anemia (6 of 50 [12.0%]), hand-foot syndrome (5 of 50 [10.0%]), nausea and vomiting (3 of 50 [6.0%]), fatigue (2 of 50 [4.0%]), and mucositis (2 of 50 [4.0%]). No deaths in the maintenance group were deemed treatment-related.
CONCLUSIONS AND RELEVANCE
In this phase 3 randomized clinical trial, capecitabine maintenance therapy significantly improved PFS for patients with newly diagnosed metastatic NPC who achieved disease control after capecitabine-containing induction chemotherapy. Capecitabine exhibited manageable toxic effects.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02460419.
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Retriever2762
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Bilateral ureteral obstruction and renal failure due to a perforated appendix.
Bilateral ureteral obstruction secondary to appendicitis is rare. We here report a case in which the obstruction caused anuria and renal failure.
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Retriever2763
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Portable sampler for microorganisms in incinerator stack emissions.
To obtain reliable information on viable microbial cells in incinerator stack emissions, a new sampling device has been developed that will concentrate microorganisms from large quantities of stack emissions into a small quantity of 0.067 m phosphate buffer. The simple, portable sampler provides a method for qualitative, nonisokinetic sampling, adjustable to isokinetic conditions that will yield quantitative results.
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Retriever2764
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Morphological variations within the ontogeny of Deinonychus antirrhopus (Theropoda, Dromaeosauridae).
This research resulted from the determination that MCZ 8791 is a specimen of Deinonychus antirrhopus between one and two years of age and that the morphological variations within particular growth stages of this taxon have yet to be described. The primary goal of the research is to identify ontogenetic variations in this taxon. Histological analyses determined that the Deinonychus specimens AMNH 3015 and MOR 1178 were adults. Comparisons are made between MCZ 8791 and these adult specimens. The holotype, YPM 5205, and the other associated specimens of this taxon within the YPM collection are similar in size and morphology to AMNH 3015. Further comparisons were made with the three partial specimens OMNH 50268, MCZ 4371, and MOR 1182. Although these specimens represent only a partial ontogenetic series, a number of morphological variations can be described. One secondary goal of this research is to compare the known pattern of variable, informative, ontogenetic characters in MCZ 8791 to a similar pattern of morphological characters in the sub-adult dromaeosaurid specimen Bambiraptor feinbergorum, AMNH FR: 30556. If the characters that have been determined to represent variable juvenile morphology in the ontogeny of Deinonychus are exhibited in Bambiraptor, this study will begin the process of determining whether a similar, conservative, ontogenetic pattern exists throughout the rest of Dromaeosauridae. If defensible, it may reduce the number of sympatric taxa within this clade. The other secondary goal relates to the forelimb function. The approximate body size, forelimb length, wrist development, and the presence of a more prominent olecranon on the ulna of MCZ 8791 support the hypothesis that juveniles of this taxon possessed some form of flight capability.
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Retriever2765
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Purification, properties, and regulation of glutamic dehydrogenase of Bacillus licheniformis.
Cell-free extracts of Bacillus licheniformis and B. cereus were found to contain high specific activities of nicotinamide adenine dinucleotide phosphate (NADP)-dependent-l-glutamate dehydrogenase [EC 1.4.1.4; l-glutamate: NADP oxidoreductase (deaminating)]. Maximum specific activities were found in extracts of cells during the late exponential phase of growth when ammonium ion served as the sole source of nitrogen. Extremely low specific activities were detected throughout the growth cycle when l-glutamate or Casamino Acids served as the source of carbon and nitrogen. The enzyme was purified 55-fold from crude extracts of B. licheniformis, and apparent kinetic constants were determined. Sigmoidal saturation kinetics were not observed, and various adenylates had no effect on the enzyme. Repression of enzyme synthesis during growth on l-glutamate or Casamino Acids was partially overcome by additions of glucose or pyruvate, and this apparent derepression was totally abolished by inhibitors of ribonucleic acid and protein synthesis. Similarly, additions of l-glutamate or Casamino Acids to cells growing on glucose-ammonium ion resulted in strong repression of enzyme synthesis. It is suggested that the enzyme serves an anabolic role in metabolism. Nicotinamide adenine dinucleotide-dependent glutamate dehydrogenase activity was not detected in five species of Bacillus, irrespective of nutritional conditions or of the physiological age of cells.
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Retriever2766
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[Determining surgical policy in combined atherosclerotic lesion of carotid arteries in patients with uncomplicated aortic aneurysm].
Presented herein are the outcomes of managing a total of twenty-six patients suffering from an uncomplicated abdominal aorta aneurysm with a concomitant atherosclerotic lesion of the coronary arteries, referred to our Clinic over the period form 2003 to 2006. Of these, nineteen (70%) patients were diagnosed with the first (symptom-free) stage of cerebral ischaemic disease, and six presented with the second stage [to have endured a transient ischaemic attack (TIA) within the terms from 16 to 3 months prior to admission]. Two patients had residual events of the previously sustained acute cerebral ischaemia (ACI) (stage 4). The current stage ofischaemic cerebral disease was determined according to the classification of A. V. Pokrovskii (1979). The haemodynamically significant stenoses of carotid arteries (over 70%) were revealed in five patients, an aneurysm of the internal carotid artery - in one patient, and eighteen patients were presenting with the degree of carotid arteries stenosis varying from 30 to 60% (of these, in two subjects after previously endured TIA, the plaque was heterogeneous and defined as embolism-threatening). No atherosclerotic lesions of the carotid artery were revealed in two patients, though these patients had previously sustained an AIA with the preserved neurological deficit by the moment of examination. Eight patients underwent reconstruction of the internal carotid arteries. The average age amounted to 64.5 years. Al of the eight operated on patients with a combination of ischaemic cerebral disease and an aneurysm of the abdominal aorta were found to have had no neurological complications either after the first, or after the second operations. The devised algorithm of examination and surgical management for patients presenting with an abdominal aorta aneurysm and a combined lesion of the brachiocephalic arteries made it possible to reduce the rate of neurological complication from 4.3% to 1.3%.
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Retriever2767
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High-performance liquid chromotography analysis of 8-methoxypsoralen monoadducts and crosslinks in lymphocytes and keratinocytes.
Human lymphocytes and murine keratinocytes were treated with clinically relevant doses of 8-methoxypsoralen and long-wavelength ultraviolet radiation. The extent of 8-MOP photoadduct formation was determined by liquid scintillation analysis. The distribution of photoadducts was determined by HPLC analysis of enzymatically hydrolyzed DNA from these cells. Analysis of photoadduct formation in lymphocytes and keratinocytes showed that 4',5'-monoadducts were the predominant photoadducts (42% and 41%, respectively). Monoadduct and crosslink yields were dependent on cell type as well as irradiating wavelength. The photochemical conversion of 400 nm-induced 4',5'-monoadducts to crosslinks, as well as 3,4-monoadducts in poly(dA-dT), was measured.
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Retriever2768
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Differential modulation of protein kinase C isoforms in erythroleukemia during induced differentiation.
Induction of erythroid differentiation of murine erythroleukemia cells (MELC) by exposure to hexamethylene bisacetamide (HMBA) involves the modulation of protein kinase C (PKC) activity. Using immuno- and Northern blot techniques, we have demonstrated that MELC express a pattern of PKC isoforms which includes PKC alpha, PKC delta, PKC epsilon, PKC zeta, and PKC eta. We show that MELC resistant to induction by HMBA express significantly less of the nPKC isoform, PKC delta, and slightly less PKC epsilon. Recovery of HMBA sensitivity is associated with reexpression of PKC delta protein. Upon exposure to HMBA, there is a fall in cytosolic PKC delta and PKC epsilon accompanied by a transient increase in membrane-associated forms of these PKC isoforms. HMBA-resistant MELC fail to display this isoform-specific translocation of PKC. Induction of differentiation is accompanied, over the next 24 h of exposure to HMBA, by a progressive fall in cellular PKC activity, associated with a progressive fall in the cellular content of PKC delta, PKC epsilon, and PKC zeta. These studies suggest that PKC delta, and possibly PKC epsilon and PKC zeta as well, play a role in the pathway of HMBA-mediated terminal cell differentiation of MELC.
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Retriever2769
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Cholesterol oxides in plasma and lipoproteins of magnesium-deficient rabbits and effects of their lipoproteins on endothelial barrier function.
The cholesterol oxide (ChO) levels in the plasma and low density lipoproteins (LDL and VLDL) in four groups of rabbits fed for seven weeks either normal (NC) or high cholesterol (HC) with low or normal magnesium (Mg) diets were determined and compared with the NC group fed a standard rabbit diet. The plasma from the NC group contained low levels of different cholesterol oxides. These cholesterol oxides were significantly elevated in the plasma of rabbits fed a HC-normal magnesium or a HC-low magnesium diet. In the NC-low Mg group, 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol and 7-ketocholesterol were elevated while the other cholesterol oxides remained within the normal range of the NC group. When the cholesterol oxides were assayed in the LDL and VLDL fractions as micrograms/mg protein, the fractions obtained from the groups fed NC-low Mg, HC-normal Mg or HC-low Mg diets showed higher levels of cholesterol oxides than the fractions obtained from the NC group. When LDL and VLDL fractions from the different groups were incubated at equal protein concentration with confluent endothelial cell monolayers, transendothelial albumin transfer was significantly increased by the lipoproteins from the experimental groups as compared to the control group. These results suggest that elevation of cholesterol oxides in magnesium deficiency or hypercholesterolaemia may be related to their atherogenic effects through decreasing the endothelial barrier function which could enhance the deposition of cholesterol rich lipoproteins into the arterial wall.
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Retriever2770
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Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation.
BACKGROUND
Tumour-derived extracellular vesicles (EVs) play a role in tumour progression; however, the spectrum of molecular mechanisms regulating EV secretion and cargo selection remain to be fully elucidated. We have reported that cavin-1 expression in prostate cancer PC3 cells reduced the abundance of a subset of EV proteins, concomitant with reduced xenograft tumour growth and metastasis.
METHODS
We examined the functional outcomes and mechanisms of cavin-1 expression on PC3-derived EVs (PC3-EVs).
RESULTS
PC3-EVs were internalized by osteoclast precursor RAW264.7 cells and primary human osteoblasts (hOBs) in vitro, stimulating osteoclastogenesis 37-fold and hOB proliferation 1.5-fold, respectively. Strikin gly, EVs derived from cavin-1-expressing PC3 cells (cavin-1-PC3-EVs) failed to induce multinucleate osteoblasts or hOB proliferation. Cavin-1 was not detected in EVs, indicating an indirect mechanism of action. EV morphology, size and quantity were also not affected by cavin-1 expression, suggesting that cavin-1 modulated EV cargo recruitment rather than release. While cavin-1-EVs had no osteoclastogenic function, they were internalized by RAW264.7 cells but at a reduced efficiency compared to control EVs. EV surface proteins are required for internalization of PC3-EVs by RAW264.7 cells, as proteinase K treatment abolished uptake of both control and cavin-1-PC3-EVs. Removal of sialic acid modifications by neuraminidase treatment increased the amount of control PC3-EVs internalized by RAW264.7 cells, without affecting cavin-1-PC3-EVs. This suggests that cavin-1 expression altered the glycosylation modifications on PC3-EV surface. Finally, cavin-1 expression did not affect EV in vivo tissue targeting as both control and cavin-1-PC3-EVs were predominantly retained in the lung and bone 24 hours after injection into mice.
DISCUSSION
Taken together, our results reveal a novel pathway for EV cargo sorting, and highlight the potential of utilizing cavin-1-mediated pathways to attenuate metastatic prostate cancer.
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Retriever2771
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JOURNAL CLUB: Preoperative MRI Evaluation of Primary Rectal Cancer: Intrasubject Comparison With and Without Rectal Distention.
OBJECTIVE
The aim of this study was to determine whether rectal distention influences the accuracy of MRI for tumor staging and for measuring of maximal extramural depth of tumor spread and distance between tumor and mesorectal fascia (MRF).
SUBJECTS AND METHODS
Fifty patients with rectal carcinoma underwent MRI before and after rectal distention. Both sets of MR images were reviewed by two radiologists. The scores for depiction of the mass (1-4 scale), T and N category, distance from normal rectal wall to MRF, maximal extramural depth of tumor spread, and distance between tumor and MRF were evaluated.
RESULTS
The visualization scores on MR images obtained with the rectum distended were significantly higher than those on images obtained without distention (90% vs 58% for score 4, p < 0.001). The accuracy of T category assessed on distended images was slightly higher than the accuracy on nondistended images (88.6% vs 84.1% for observer 1, 84.1% vs 81.8% for observer 2), but the accuracy of N category was stable. The distance between normal rectal wall and MRF was significantly less on distended images than on nondistended images (p < 0.05). However, there was no significant difference between nondistended and distended images for maximal extramural depth and distance between tumor and MRF (p > 0.05).
CONCLUSION
Rectal distention significantly improved visualization of tumors on MR images. It also improved T category assessment to some extent. Although the distance between normal rectal wall and MRF was significantly less with rectal distention than without rectal distention, maximal extramural depth and the distance between tumor and MRF did not vary significantly with or without rectal distention.
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Retriever2772
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Acute effect of kinesiotaping on pain, balance and gait performance in patients with knee osteoarthritis: A randomized controlled study.
BACKGROUND
Kinesiotape application is one of the non-pharmacological methods frequently used in patients with knee OA. Guidelines do not have a consensus on its use in knee osteoarthritis (OA).
OBJECTIVE
In this study, we aimed to investigate the acute effect of kinesiotape application on pain, balance, and gait performance in patients with knee OA.
METHODS
We included 164 patients with grade 1-3 knee OA according to the Kellgren-Lawrence staging system in the study. Patients were evaluated with visual analog scale (VAS), 10-meter walking test (10MeWT), timed-up and go test (TUG-T), single leg stance test (SLST), and functional reach test (FRT) before and after taping.
RESULTS
There was a significant improvement in the post-taping scores of all evaluation parameters in the kinesiotaping group compared with pre-taping scores. Statistically significant improvement was found in all scores of evaluated parameters except FRT scores in the placebo taping group. We found a significant superiority in the mean recovery scores of the kinesiotaping group compared to the placebo-taping group in all parameters except for 10MeWT.
CONCLUSIONS
We found significant improvements in both groups. The mean improvement levels in pain and balance scores were better in the KT group than in the PT group.
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No neg
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Retriever2773
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Is there a doctor in the house? . . . Or the Senate? Physicians in US Congress, 1960-2004.
CONTEXT
The legislative and fiscal influences of Congress, as well as the continuing overall growth in health care spending as a portion of the gross domestic product, make congressional representation by physicians important because physicians have unique expertise in the impact of legislation on patient care and medical practice.
OBJECTIVES
To describe physician representation in the US Congress between 1960 and 2004 and relate the results to past representation of physicians in Congress.
DESIGN AND SETTING
A retrospective observational study of members of the US Congress from all 50 states and all represented territories, who served from January 1960 to April 2004 (including 108th Congress), using data available in public access databases and congressional biographical records.
MAIN OUTCOME MEASURES
Physician representation in Congress, including occupation before taking office, state/territory of representation, sex, party affiliation, and time served.
RESULTS
During the past 44 years, 25 (1.1%) of 2196 members of Congress were physicians. Physicians in Congress were more likely to be members of the Republican Party (60% vs 45.1% of all members, P = .007) and were similar to other members of Congress in mean years of service (9.2 years for physicians vs 12.3 years for all members, P = .09) and in sex distribution (4.0% female physicians vs 6.8% all female members, P = .57). Physicians in Congress represented 17 states, the Virgin Islands, and Puerto Rico.
CONCLUSIONS
Physician representation in Congress is low and is in stark contrast with physician roles during the first century of the United States. However, the 8 physicians currently serving in Congress may be indicative of a shift toward more direct influence of physicians in national politics.
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No pos
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No neg
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Retriever2774
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Plasma levels of beta-endorphin, adrenocorticotropic hormone and cortisol during early and late alcohol withdrawal.
Endogenous opioid peptides are thought to participate in the phenomena of alcohol tolerance and withdrawal. Since in the pituitary gland, beta-endorphin (beta-EP) and adrenocorticotropic hormone (ACTH) are produced from the same precursor molecule, pro-opiomelanocortin, it may be expected that alterations in plasma ACTH and cortisol levels should parallel changes in plasma beta-EP levels during alcohol withdrawal. The aim of the present study was to investigate the alterations of beta-EP, ACTH and cortisol secretion patterns in alcohol-dependent patients with heavy intake in the early withdrawal period and, if any, whether these changes remained stable on long-term withdrawal. Twenty-two hospitalized male patients (mean age +/- SD: 43.45 +/- 9.22 years, mean daily amount of alcohol +/- SD: 421.59 +/- 116.57 g) who were diagnosed to have alcohol withdrawal and 20 age-matched healthy men (mean age +/- SD: 38.35 +/- 7.63 years) were included in the study. Morning and night levels of plasma beta-EP, ACTH and cortisol were measured in the patients during the early (first week) and late (fourth week) withdrawal periods following alcohol cessation, and only once in the control subjects. It was found that both morning beta-EP and morning ACTH levels were reduced during both early and late withdrawals, whereas cortisol levels were increased in early withdrawal and normalized towards the late withdrawal period. The finding that beta-EP deficiency continued despite withdrawal symptoms subsiding in patients suggests that their beta-EP deficiency is independent of the withdrawal syndrome and that reduced beta-EP activity may be a trait contributing to alcohol craving.
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No pos
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No neg
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Retriever2775
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[Hungarian psychiatric care in the light of the closure of the National Institute of Psychiatry and Neurology, and the reduction of the number of hospital beds. A decade and a half under investigation].
The "Act on the Development of the Health Care System, CXXXII/2006" ordered a general reduction in the number of hospital beds, which sensitively affected the care of psychiatric inpatients, too. In this wave of downsizing, the National Institute of Psychiatry and Neurology, an institute with the traditions of one and a half centuries, also ceased to exist. Based on statistical data, the article examined the effect of the law on inpatient and outpatient psychiatric/ addictological care. The reduction in the number of beds had a long-term effect only upon the reduction in the capacity of acute inpatient care; while the number of acute patients treated decreased, the number of involuntary hospital admissions increased and oddly enough, bed occupancy also decreased. This last phenomenon can in part be attributed to a reduction in nursing time. The patient care decreased in both adult and pediatric psychiatric out - patient care, as did similarly the turnover of outpatient clinics for addicts. However, the changes observed in outpatient care were not related to the bed number reduction, but rather meant the continuation of previously started decline in psychiatric/addictological care. There were no detectable changes in the trends for other examined characteristics, such as homelessness and involuntary treatment. A temporary increase was observed only in the number of completed suicides, but the previously seen decreasing trend was restored in this respect after 2011. All in all, the reduction in the number of beds forced by law caused only temporary care disruptions and had no significant effect, either positive or negative, on the negative trends in psychiatric/addictological care that started earlier. However, the reasons for these negative trends observed in Hungarian psychiatric/addictological care, and which still persist to this day, are unclear.
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No pos
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No neg
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Retriever2776
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Lower practice effects as a marker of cognitive performance and dementia risk: A literature review.
BACKGROUND
Practice effects (PEs) are improvements in performance after repeated exposure to test materials, and typically viewed as a source of bias in repeated cognitive assessments. We aimed to determine whether characterizing PEs could also provide a useful marker of early cognitive decline.
METHODS
We conducted a systematic review of the literature, searching PsycInfo (Ebsco) and PubMed databases for articles studying PEs in aging and dementia populations. Articles published between 1920 and 2019 were included.
RESULT
We identified 259 articles, of which 27 studied PEs as markers of cognitive performance. These studies consistently showed that smaller, less-robust PEs were associated with current diagnostic status and/or future cognitive decline. In addition, lower PEs were associated with Alzheimer's disease risk factors and neurodegeneration biomarkers.
CONCLUSION
PEs provide a potentially useful marker of cognitive decline, and could prove valuable as part of a cost-effective strategy to select individuals who are at-risk for dementia for future interventions.
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No pos
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No neg
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Retriever2777
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Heparins and 2019-nCoV infection: a narrative review.
OBJECTIVE
Patients with 2019-nCoV infection have a high risk to develop venous thrombotic events. Several guidelines recommend the use of either unfractionated heparin or low molecular weight heparins in preventing thrombotic events in these patients. However, results from clinical studies, so far published, reached controversial conclusions on heparin efficacy in this kind of patients since the incidence of venous thromboembolism remains high despite prophylaxis. This narrative review aims to provide an overview of the antiviral and anti-inflammatory properties of heparins and their efficacy and safety in SARS-CoV-2 medical ward-patients. Moreover, anatomical findings and ongoing trials are also reported. Finally, this narrative review tries to explain why heparins fail to prevent venous thrombosis.
MATERIALS AND METHODS
We searched for the most relevant published studies on heparins and 2019-nCoV infected patients using the MEDLINE electronic database in the period between January and December 2020. Articles were preliminarily defined as eligible if they: a) were in English language, b) enrolled 250 or more medical ward-patients and 100 or more ICU-patients, c) reported results on patients treated with heparins in a percentage of at least 70% and d) performed an objectively confirmed diagnosis of VTE.
RESULTS
Data from medium to large scientific studies show that the incidence of venous thrombotic events in medical ward-patients with SARS-CoV-2 vary between 0% and 8.3%, while this rate is higher, from 6.2% to 49%, in Intensive Care Unit-patients. However, heparins reduce the mortality rate in these patients of about 50%. Histological findings show that thrombosis could affect capillaries, main and small-mid-sized vessels, and it is associated with diffuse alveolar damage.
CONCLUSIONS
Heparins have anti-inflammatory and anti-viral properties, which may be of help in reducing mortality in SARS-CoV-2 patients. Failure of heparins at prophylactic dosages in preventing VTE, especially in ICU-patients, could be due to the severity of the disease. Data on the use of heparins in an early phase of the 2019-nCoV infection are still lacking.
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No pos
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No neg
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Retriever2778
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The effect of epinephrine and dibutyryl cyclic AMP on glucose 1,6-bisphosphate levels and the activities of hexokinase, phosphofructokinase and phosphoglucomutase in the isolated rat diaphragm.
Based on previous studies which have revealed that glucose 1,6-bisphosphate (Glc-1,6-P2) is a potent inhibitor of muscle hexokinase and an activator (deinhibitor) of phosphofructokinase and phosphoglucomutase, the effect of epinephrine on the levels of this regulator in rat diaphragm muscle was investigated. It was found that epinephrine caused an increase in diaphragm Glc-1,6-P2 levels, accompanied by a reduction in the activity of hexokinase and an activation (deinhibition) of phosphofructokinase and phosphoglucomutase. N6-2'-O-dibutyryl cyclic AMP was able to mimic all these effects of epinephrine. The concentration of glucose-6-phosphate was not changed by epinephrine, under conditions in which the hormone produced an increase in cyclic AMP and Glc-1,6-P2 levels and the concomitant decrease in hexokinase activity. It was also shown that Glc-1,6-P, in the concentration range found after epinephrine, inhibited the diaphragm hexokinase and deinhibited phosphoglucomutase. These results may suggest a mechanism of epinephrine action by which the activities of hexokinase, phosphoglucomutase and phosphofructokinase, through the action of Glc-1,6-P2, are synchronized with the cyclic AMP-mediated activation of glycogen phosphorylase, to achieve an increase in total glycogenolysis and glycolysis and a concomitant reduction in glucose utilization by the muscle.
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No pos
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No neg
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Retriever2779
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[Research on aseptic condition of root canals after endodontic treatment].
Fifty infected root canals were examined whether they had been in aseptic condition or not after endodontic treatment. PLADIA was used for the examination of bacteriologic culture. Twenty eight cases were positive, 22 cases were negative, and the percentage of positive was 56%. Of the anterior teeth, 13 cases were positive in 23 cases (57%), In the posterior teeth, 15 cases were positive in 27 cases (56%), 5 cases were positive in 17 cases (29%) with clinical symptoms before treatment, 23 cases were positive in 33 cases (70%) without clinical symptoms before treatment. These results showed that the treated root canals which had been well adapted to root canal filling by clinical symptoms had a high percentage of positive of bacteriological culture.
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No pos
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No neg
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Retriever2780
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Accuracy of Suction Rectal Biopsy for Diagnosis of Hirschsprung's Disease in Neonates.
INTRODUCTION
Recent publications have questioned the sensitivity of suction rectal biopsy (SRB) for diagnosis of Hirschsprung's disease (HD) in newborns. A recent European survey reported that 39% of pediatric surgeons performed full-thickness transanal biopsies due to concerns about the accuracy of SRB. We sought to examine our contemporary SRB experience in infants.
MATERIALS AND METHODS
A review was performed (2007-2016) of patients under 6 months of age who had a SRB at our children's hospital. The cohort was subdivided by postmenstrual age at time of SRB: preterm (< 40 weeks, A), term neonate (40-44 weeks, B), and infant (> 44 weeks, C). The pathology reports from endorectal pull-through were used as gold standard confirmation. One-year follow-up of patients with negative SRB was used to confirm accurate diagnosis.
RESULTS
A total of 153 patients met the criteria and a total of 159 SRBs (< 2,500 g; n = 26) were performed (A = 60, B = 58, C = 35). Forty-three patients were diagnosed with HD (A = 25, B = 15, C = 3). A second SRB was performed in 6 (3.9%) patients due to inadequate tissue (A = 2, B = 2, C = 2) with HD diagnosed in 5. No complications occurred. Sensitivity and specificity of SRB was 100% in all age groups. Half of the patients with a negative SRB had at least 1 year follow-up, with none subsequently diagnosed with HD.
CONCLUSION
SRB results in adequate tissue for evaluation of HD in nearly all patients less than 6 months of age on the first attempt and is highly accurate in the preterm and newborn infants. No complications occurred, even among infants less than 2,500 g.
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No pos
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No neg
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Retriever2781
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[Histamine levels in the blood of humans experimental animals under normal conditions and following vaccination].
The authors present the results of study of the blood histamine content in intact rabbits and in the animals to which commercial vaccines with a different degree of reactogenic property for man were administered. The blood histamine level was also studied in practically healthy individuals and in those vaccinated with inactivated tick-borne encephalitis vaccine. The blood histamine content varied in intact rabbits from 4 to 10 microgram/ml, averaging 6.4 +/- 0.09 microgram/ml. Animal immunization caused elevation of the blood histamine content correlating with the reactogenic properties of the preparations for man: vaccines with low reactogenic properties--inactivated encephalitis and live measles vaccine produced no significant changes in the index under study; as to the typhoid vaccine with sextatoxoid, and smallpox vaccine with marked reactogenic properties--they stimulated significant histaminemia in rabbits. Revaccination of man against tick-borne encephalitis with the inactivated cultural vaccine caused an increase in the blood histamine content.
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No pos
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No neg
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Retriever2782
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Belimumab in the management of systemic lupus erythematosus - an update.
Belimumab is a fully humanised mAb against B lymphocyte stimulator (B-LyS). It is the first biological drug licensed and approved by the US FDA and the European Medicines Agency (EMA) for use in combination with standard immunosuppressants in autoantibody-positive systemic lupus erythematosus (SLE). Areas covered: This manuscript evalues the recent data concerning belimumab's safety and clinical effectiveness and its current place in the treatment of SLE. This includes an overview of the recent data coming from the post-hoc analyses of the BLISS trials, real-life experience with belimumab and the accumulating data on its safety. Attention is also paid to the progress made in the identification of predictors of response to belimumab, recent phase I/II/III studies with subcutaneous belimumab, and experience with B cell modulation coming from recent trials with other B cell modulating drugs. Expert opinion: Belimumab currently has its established role in the treatment of patients with SLE with serologic activity and clinical activity namely in mucocutaneous and musculoskeletal domains despite standard of care treatment. Better identification of patients who can benefit from treatment with belimumab is warranted. Data from ongoing studies in lupus nephritis and other data from observational studies are eagerly awaited.
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No pos
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No neg
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Retriever2783
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[Burns and scalds].
Every year, 20000 children and adults in Germany sustain serious bums resulting from the influence of strong heat on their skin. To cool down the burnt skin immediately relieves the pain and prevents further damage to deeper parts of the skin. According to the extent of the damage, different clinical degrees of burns are defined, which determine the appropriate therapeutic treatment.
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No pos
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No neg
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Retriever2784
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Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers.
Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non-small-cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which mainly included promoting angiogenesis, vasculogenic mimicry, energy metabolism reprogramming, epithelial-mesenchymal transition and modulating exosomes. The roles of myoferlin in both normal cells and cancer cells are of great significance to provide novel and efficient methods of tumour treatment. In this review, we summarize recent studies and findings of myoferlin and suggest that myoferlin is a novel potential candidate for clinical diagnosis and targeted cancer therapy.
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No pos
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No neg
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Retriever2785
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Heart rate adjustment of PR interval in middle-aged and older adults.
Prolonged PR interval has been associated with adverse cardiac events. Consequently, the scientific community and regulatory agencies have become concerned about PR interval prolongation induced by cardioactive agents. We evaluated PR dependence on heart rate (HR) in 5757 men and women aged 40 years and older from the US third National Health and Nutrition Survey with the objective to determine if rate adjustment for the PR interval is warranted as is the case with QT interval. Electrocardiograms were computer-processed in a central electrocardiogram laboratory. There was a statistically significant negative correlation between PR and HR (r = -0.15; P < .001); notably weaker than that between QT and HR (r = -0.76; P < .001). Evaluation of subgroups stratified by sex, race, and age revealed a significant interaction between PR and HR with age (P = .006). A subsequent search for optimal rate-adjusted PR (PRa) formula that eliminates PR dependence on HR within each age group produced the formula: PRa = PR + 0.26 (HR - 70) for age group younger than 60 years and PRa = PR + 0.42 (HR - 70) for age group 60 years or older. The application of this formula in the study population effectively made the PR interval rate-invariant (residual slope of regression, -0.0054; 95% confidence interval, -0.064 to 0.053; P = .86). Based on the distribution of PRa, the 98th percentile limit of 220 milliseconds would be a reasonable overall threshold for defining first-degree AV block, with the 95th percentile limit of 205 as a threshold for borderline PR prolongation. In conclusion, the association between PR and HR is age- and rate-dependent and a separate rate-adjustment formula is needed for adults in younger and older age groups. The prognostic significance of the rate-adjusted PR needs to be investigated.
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No pos
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No neg
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Retriever2786
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The porta hepatis as a site of recurrence of mucinous appendiceal neoplasms treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy.
BACKGROUND
A successful new treatment for a particular disease may change the natural history of that disease as patients go on to longer survival. The goal of this study was to investigate the porta hepatis as a site of recurrence of appendiceal mucinous neoplasms.
METHODS
A prospective database on patients with peritoneal dissemination of mucinous appendiceal neoplasms has been maintained for 21 years. In patients with complete cytoreduction, disease progression/recurrence in and around the porta hepatis has been noted as a new manifestation of this disease.
RESULTS
In 710 patients treated for mucinous appendiceal cancer with a complete cytoreduction, 140 developed recurrent disease. Seven patients (5%) had disease recurrence in and around the porta hepatis. Four of the seven had biliary obstruction and three had masses within the liver hilum not causing bile duct obstruction. Four of the seven patients were successfully palliated by surgical procedures within the liver and biliary tree. Two patients were successfully palliated using a biliary stent and one patient was not treated.
CONCLUSIONS
Progression of mucinous neoplasms within the porta hepatis may be related to imperfect cytoreduction technique. Reoperative surgical treatment and biliary stents were beneficial in some of these patients.
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No pos
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No neg
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Retriever2787
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Antidepressantlike effects of chronic nicotine on learned helplessness paradigm in rats.
BACKGROUND
The association between smoking and depression has been widely investigated. Smoking cessation is known to induce depression to a variable extent, and patients with a history of depression are more likely to experience depressive symptoms. To investigate the hypothesis that nicotine may have an antidepressantlike effect, we used learned helpless rats as an animal model of depression.
METHODS
Learned helplessness was produced according to our previous method. Learned helpless rats were implanted with nicotine and escape test was performed at 7 and 14 days after the implantation.
RESULTS
The number of escape failure in the rats receiving 1.5 mg/kg/day of nicotine was significantly reduced (p < .05) compared to control at day 14. Furthermore, this effect was blocked when the nicotinic receptor antagonist mecamylamine was coadministered.
CONCLUSIONS
These results suggest that chronic nicotine may act as an antidepressant, probably via nicotinic receptors.
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No pos
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No neg
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Retriever2788
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Comparison of Barefoot Walking and Shod Walking Between Children with and Without Flat Feet.
BACKGROUND
We sought to investigate the effect of wearing shoes on joint range of motion, ground reaction force (GRF), and muscle activity (electromyography) in children with flat and normal feet during walking.
METHODS
Nine children with flat feet and 12 children with normal feet aged 5 to 11 years were recruited. Each child was instructed to walk on a walkway in the barefoot and shod conditions. Joint range of motion, GRF, and electromyographic data within one gait cycle were collected simultaneously. Two-way analysis of variance was performed to evaluate the effects of foot type and shoe condition on the response measures.
RESULTS
Children with flat feet had greater joint motion and higher muscle activities in the lower extremity, as well as lower vertical GRF and longer duration of the first peak forces in vertical and mediolateral GRFs than children with normal feet while walking. Compared with the barefoot condition, shoe wearing in both groups of children showed an increase in ankle dorsiflexion at heel strike, a decrease in anteroposterior GRF and its duration, and an increase in leg muscle electromyographic activities. Pelvic tilt range of motion was affected by the interaction of foot type and shoe condition.
CONCLUSIONS
Gait performance in pelvic tilt, hip flexion, and ankle dorsiflexion were different between the two groups of children. Wearing shoes increased the muscle activities of the shin. This finding can provide important information for clinical assessment of and shoe design for children with flat feet.
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No pos
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No neg
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Retriever2789
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The Rubber Stopper: A Simple and Inexpensive Technique to Prevent Pin Tract Infection following Kirschner Wiring of Supracondylar Fractures of Humerus in Children.
Percutaneous pinning after closed reduction is commonly used to treat supracondylar fractures of the humerus in children. Minor pin tract infections frequently occur. The aim of this study was to prevent pin tract infections using a rubber stopper to reduce irritation of the skin against the Kirschner (K) wire following percutaneous pinning. Between July 2011 and June 2012, seventeen children with closed supracondylar fracture of the humerus of Gartland types 2 and 3 were treated with this technique. All patients were treated with closed reduction and percutaneous pinning and followed up prospectively. Only one patient, who was a hyperactive child, developed pin tract infection due to softening of the plaster slab. We found using the rubber stopper to be a simple and inexpensive method to reduce pin tract infections following percutaneous pinning.
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No pos
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No neg
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Retriever2790
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Comparing Methodologies in a Series of Speech Outcome Studies : Challenges and Lessons Learned.
BACKGROUND
Development of the speech audit tool Cleft Audit Protocol for Speech Augmented (CAPS-A) facilitated intercenter comparison of speech outcomes following cleft palate repair. The CAPS-A protocol recommends consensus listening by 3 speech and language therapists, 2 of whom must be CAPS-A trained. Allowing 15 minutes per sample, 15 to 20 samples can be assessed each day. Centers typically have resources to audit 15 to 75 samples per year but not to report speech outcomes of larger data sets for research. This 3-phased outcome study examines how the implementation of the CAPS-A protocol might be modified without compromising reliability.
METHODOLOGY
In phase 1, 2 external listeners independently rated 42 speech samples; in phase 2, 2 external listeners consensus listened 25% of 140 samples before 1 listener independently rated the remainder; phase 3 compared 124 Great Ormond Street Speech Assessment (GOS.SP.ASS'98) records from live assessments with CAPS-A-rated video samples.
RESULTS
Hypernasality, nasal airflow, and passive cleft speech characteristics were rated to identify signs of velopharyngeal dysfunction across all phases. Phase 1 demonstrated suboptimal correlation, intraclass correlation coefficient (ICC) ranging between 0.39 and 0.72. However, the "modified" CAPS-A consensus listening process in phase 2 achieved a mean ICC of 0.91. Phase 3 revealed only moderate agreement between GOS.SP.ASS'98 and CAPS-A.
CONCLUSION
A large data set of speech samples was successfully managed by establishing good interrater reliability on 25% of the data, which calibrated the listeners and validated a decision for only 1 of 2 listeners to rate the remaining speech samples. The recommended implementation of the CAPS-A protocol can therefore be modified for more efficient speech outcome reporting.
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No pos
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No neg
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Retriever2791
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Role of Helicobacter species in Chinese patients with inflammatory bowel disease.
Based on 16S rRNA gene PCR, no significant difference was observed in rates of detection of Helicobacter species in intestinal biopsy specimens from 160 Chinese inflammatory bowel disease (IBD) patients (10%) and 80 controls (6.3%). By using a [(13)C]urea breath test, the H. pylori infection rate in 208 Chinese IBD patients (19.7%) was found to be significantly lower than that in 416 controls (48.8%).
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No pos
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No neg
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Retriever2792
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Calix[4]arene-supported mononuclear lanthanide single-molecule magnet.
Three new single paramagnetic lanthanide-based complexes, [Ln(L)(LOEt)] (Ln(3+) = Dy(3+), Tb(3+), and Ho(3+)), are synthesized with the multidentate calix[4]arene ligand H2L (H2L = 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-dihydroxy-26,28-dimethoxycalix[4]arene) and Kläui's tripodal ligand LOEt(-) (LOEt(-) = (η(5)-cyclopentadienyl)tris(diethylphosphito-p)cobaltate(III)). All of the complexes have been characterized by single crystal X-ray diffraction analysis, thermal stability, absorption spectra, and magnetization measurements. The magnetic properties and magnetostructural correlation in this seven-coordinated system are investigated. The dysprosium complex 1 shows typical single-molecule magnetic behavior with characteristic magnetic hysteresis loops and the slow relaxation of magnetization.
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No pos
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No neg
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Retriever2793
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Growth rate is a dominant factor predicting the rhizosphere effect.
The root microbiome is shaped by plant root activity, which selects specific microbial taxa from the surrounding soil. This influence on the microorganisms and soil chemistry in the immediate vicinity of the roots has been referred to as the rhizosphere effect. Understanding the traits that make bacteria successful in the rhizosphere is critical for developing sustainable agriculture solutions. In this study, we compared the growth rate potential, a complex trait that can be predicted from bacterial genome sequences, to functional traits encoded by proteins. We analyzed 84 paired rhizosphere- and soil-derived 16S rRNA gene amplicon datasets from 18 different plants and soil types, performed differential abundance analysis, and estimated growth rates for each bacterial genus. We found that bacteria with higher growth rate potential consistently dominated the rhizosphere, and this trend was confirmed in different bacterial phyla using genome sequences of 3270 bacterial isolates and 6707 metagenome-assembled genomes (MAGs) from 1121 plant- and soil-associated metagenomes. We then identified which functional traits were enriched in MAGs according to their niche or growth rate status. We found that predicted growth rate potential was the main feature for differentiating rhizosphere and soil bacteria in machine learning models, and we then analyzed the features that were important for achieving faster growth rates, which makes bacteria more competitive in the rhizosphere. As growth rate potential can be predicted from genomic data, this work has implications for understanding bacterial community assembly in the rhizosphere, where many uncultivated bacteria reside.
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No pos
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No neg
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Retriever2794
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Two high-performance liquid chromatography-tandem mass spectrometry methods for determination of edaravone and taurine in human plasma: Application to drug-drug interaction and pharmacokinetic studies.
Two high-performance liquid chromatography-tandem mass spectrometry methods were developed and validated for the quantification of edaravone (method A) or taurine (method B) in human plasma. After protein precipitation, separations were achieved on an Ultimate XB-C8 (2.1 × 50 mm, 3.0 µm) column for edaravone and a ZORBAX SB-Aq column (2.1 × 100 mm, 3.5 µm) for taurine, respectively. The detection used electrospray ionization source via multiple reaction monitoring in positive-ion mode for edaravone and negative-ion mode for taurine, respectively. The lower limits of quantification were 10.0 ng/mL for edaravone and 3.00 μg/mL for taurine. The selectivity, accuracy, and precision of the methods were all within acceptable limits. Two methods were successfully applied to a drug-drug interaction study and a pharmacokinetic study of edaravone and taurine in healthy Chinese volunteers after intravenous infusion of single or compound injection. The results showed that co-administration of edaravone with taurine increased the Cmax and AUC0-24 of taurine in human plasma while taurine did not affect the systemic exposure of edaravone. Edaravone and taurine have the dose-dependent pharmacokinetic profiles in human.
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No pos
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No neg
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Retriever2795
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Phase II study of 5-fluorouracil, doxorubicin, and mitomycin C for metastatic small bowel adenocarcinoma.
BACKGROUND
Small bowel adenocarcinoma is a rare gastrointestinal malignancy that is treated primarily with surgery. Even with optimal resection, however, survival is poor and recurrences are common. Response rates to palliative combination chemotherapy are low, and the median duration of survival for metastatic disease is less than 1 year. This study aimed to document the response rate and survival time for patients with advanced small bowel adenocarcinoma who were not surgically curable and were treated with a regimen of 5-fluorouracil (5-FU), mitomycin C (Mutamycin; Bristol-Myers Squibb; Princeton, NJ), and doxorubicin (Adriamycin; Bedford Laboratories; Bedford, OH), the FAM regimen.
METHODS
This multi-institutional study was performed by the Eastern Cooperative Oncology Group (ECOG). Between November, 1983 and December, 1985, 39 patients with advanced or recurrent disease were enrolled. Chemotherapy was given as follows: 5-FU, 600 mg/m(2) on days 1, 8, 29 and 36; mitomycin C, 10 mg/m(2) on day 1; and doxorubicin, 30 mg/m(2) on days 1 and 29. Eligibility criteria included an ECOG performance status score of 0-2, measurable disease, and adequate baseline organ function. Prior chemotherapy was allowed. Response was measured by examination and imaging techniques. Survival time and time to progression were evaluated by the method of Kaplan and Meier, and these outcomes were stratified by clinical and laboratory covariates.
RESULTS
Of the 39 evaluated patients, 38 were eligible and 36 were evaluable for response. Grade 3-5 toxicities were experienced by a total of 26 patients (20 grade 3, 5 grade 4, 1 grade 5). The most common adverse events were neutropenia and vomiting. Responses were seen in a total of seven patients (2 complete responses, 5 partial responses), for a response rate of 18.4% (95% confidence interval of 7.8%-34.4%). The median survival time was 8 months.
CONCLUSIONS
The FAM regimen was active and tolerable for patients with advanced small bowel adenocarcinoma; however, the results were no better than those seen with other chemotherapy combinations.
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No pos
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No neg
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Retriever2796
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Exploratory survey of Florida pharmacists' experience, knowledge, and perception of HIV pre-exposure prophylaxis.
OBJECTIVE
To assess Florida pharmacists' experience, knowledge, and perception of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and to identify areas for pharmacist training.
DESIGN
Cross-sectional survey.
SETTING
Florida in March through July 2013.
PARTICIPANTS
Florida pharmacists.
INTERVENTION
In-person and online anonymous survey.
MAIN OUTCOME MEASURE
Florida pharmacists' experience, knowledge, and perceptions of PrEP.
RESULTS
225 completed surveys were analyzed. Survey respondents were predominantly community pharmacists with mean age of 45.7 years and less than 20 years of experience. Only 22% of respondents reported dispensing PrEP to patients. Although 75% had completed HIV-related continuing education in the last 2 years, 63% were unaware of Centers for Disease Control and Prevention PrEP guidelines and 71% answered that they did not have sufficient knowledge to counsel patients with PrEP prescriptions. Importantly, 47% of respondents answered they were uncomfortable counseling patients about PrEP. By self-report, most pharmacists agreed PrEP leads to risky behavior (68%) and increased rates of sexually transmitted infections (65%), and is too costly to promote patient access (92%).
CONCLUSION
Surveyed Florida pharmacists reported limited understanding of PrEP. As a widely accessible health care counseling resource, pharmacists are positioned to improve patient understanding, promote medication adherence, and enhance PrEP efficacy. Especially during PrEP implementation, when patients may receive PrEP prescriptions from non-HIV specialist prescribers, improving pharmacists' PrEP education presents a salient opportunity.
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No pos
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No neg
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Retriever2797
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The analysis of risk factors associated with tonsillitis in district Mardan, Pakistan.
OBJECTIVE
To assess the risk factors associated with tonsillitis.
METHODS
The cross-sectional study was conducted at Mardan Medical Complex and District Headquarter Hospital, Mardan, Pakistan, from January to June 2018, and comprised tonsillitis patients. Data was collected using a questionnaire which included different risk factors like age 1-10 years, gender, residential area, dietary habit etc. Data was analysed using SPSS 20.
RESULTS
Of the 325 subjects, 200(61.54%), were clinically diagnosed with tonsillitis; 138(69%) being males. Age, unhygienic living condition, balanced diet, stressful environment and the use of sore/spicy foods were identified as significantly associated factors (p<0.05).
CONCLUSIONS
Age, unhygienic living condition, balanced diet, stressful environment and the use of sore/spicy food were found to have a strong association with tonsillitis.
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No pos
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No neg
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Retriever2798
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Stimulation of transient receptor potential M3 (TRPM3) channels increases interleukin-8 gene promoter activity involving AP-1 and extracellular signal-regulated protein kinase.
Stimulation of Ca2+ permeable TRPM3 (transient receptor potential melastatin-3) channels with the steroid ligand pregnenolone sulfate activates stimulus-responsive transcription factors, including the transcription factor AP-1 (activator protein-1). As part of a search for AP-1-regulated target genes we analyzed the gene encoding interleukin-8 (IL-8) in HEK293 cells expressing TRPM3 channels. Here, we show that stimulation of TRPM3 channels activated transcription of an IL-8 promoter-controlled reporter gene that was embedded into the chromatin of the cells. Mutational analysis of the IL-8 promoter revealed that the AP-1 binding site of the IL-8 promoter was essential to connect TRPM3 stimulation with the transcription of the IL-8 gene. Genetic experiments revealed that the basic region leucine zipper proteins c-Jun and ATF2 and the ternary complex factor Elk-1 are essential to couple TRPM3 channel stimulation with the IL-8 gene. Moreover, we identified extracellular signal-regulated protein kinase (ERK1/2) as signal transducer connecting TRPM3 stimulation with enhanced transcription of the IL-8 gene. Furthermore, we show that stimulation of TRPC6 (transient receptor potential canonical-6) channels with its ligand hyperforin also increased IL-8 promoter activity, involving the AP-1 binding site within the IL-8 gene, suggesting that activation of IL-8 gene transcription may be a common theme following TRP channel stimulation.
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No pos
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No neg
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Retriever2799
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Co-localization of secretogranins/chromogranins with thyrotropin and luteinizing hormone in secretory granules of cow anterior pituitary.
We investigated the co-localization in secretory granules of secretogranins/chromogranins, thyrotropin, and luteinizing hormone in ultra-thin frozen sections of cow anterior pituitary by double immunoelectron microscopy, using specific antibodies and protein A-gold particles of different sizes. The distribution of secretogranin II, chromogranin A, and chromogranin B (secretogranin I) was largely similar. In cells containing secretory granules of relatively small size (100-300 nm) and low electron density (identified as thyrotrophs and gonadotrophs by immunolabeling for the respective hormone) and in cells containing both small (170-250 nm) and large (300-500 nm) secretory granules of low electron density (also identified as gonadotrophs), all three secretogranins/chromogranins were detected in most if not all granules, being co-localized with the hormone. In cells containing both relatively large (400-550 nm), electron-dense granules and small, less electron-dense secretory granules (150-300 nm), identified as somatomammotrophs by double immunolabeling for growth hormone and prolactin, all three secretogranins/chromogranins were predominantly detected in the subpopulation of small, less electron-dense granules containing neither growth hormone nor prolactin. Interestingly, this granule subpopulation of somatomammotrophs was also immunoreactive for thyrotropin and luteinizing hormone. These data show that somatomammotrophs of cow anterior pituitary are highly multihormonal, in that the same cell can produce and store in secretory granules up to four different hormones and, in addition, the three secretogranins/chromogranins. Moreover, selective localization of the secretogranins/chromogranins together with thyrotropin and luteinizing hormone in a subpopulation of secretory granules of somatomammotrophs indicates the preferential co-packaging of the secretogranins/chromogranins and these hormones during secretory granule formation.
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No pos
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No neg
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