title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Time to symptom resolution in young children treated for pulmonary tuberculosis. | Response to treatment may be useful for diagnostic confirmation of childhood tuberculosis (TB). We aimed to evaluate time to symptom resolution in children treated for pulmonary TB. We compared pulmonary TB cases and noncases, classified by a published diagnostic algorithm, in South African children younger than 2. TB treatment was prescribed independently on clinical grounds. We analyzed independent determinants of baseline symptom resolution by Cox regression. One hundred and ninety-one symptomatic children, median age 12 months, were prescribed for TB treatment. Chest radiograph features of TB were associated with longer time to resolution of cough (adjusted hazard ratio, AHR 0.31), wheeze (AHR 0.26) and failure to thrive (AHR 0.41), (all P < 0.05). However, median duration of baseline cough (63 vs. 70 days, P = 0.98), wheeze (62 vs. 68 days, P = 0.87) and failure to thrive (76 vs. 66 days, P = 0.59) did not differ in TB cases (n = 48) versus noncases (n = 46). Baseline symptoms take more than 60 days to resolve in the majority of young children after starting TB treatment. Furthermore, since time to resolution does not differentiate TB cases from noncases; clinical response to treatment is not an appropriate diagnostic criterion for pediatric trials of TB diagnostics, drugs and vaccines. | 25,144,794 | [
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Percutaneous microwave ablation for liver tumours adjacent to the marginal angle. | This study was designed to describe the technical essentials of microwave ablation (MWA) for tumours adjacent to the liver marginal angle (LMA) and to determine the feasibility, safety and efficacy of this approach. A total of 22 patients with primary or metastatic liver tumours adjacent to the LMA were enrolled. There were 19 small tumours (≤3 cm) and three larger tumours (>3 cm) with maximum diameters ranging from 0.7-2.7 cm (mean 1.7 ± 0.6 cm) and 4.7-6.6 cm (mean 5.4 ± 1.0 cm), respectively. For small tumours the entire acute angle was segmentally blocked utilising MWA. For larger tumours, the feeding arteries were initially blocked with ethanol before conformal ablation. Artificial ascites, real-time monitoring, small ethanol doses, colour Doppler flow imaging or contrast enhanced ultrasound guidance was used as an additional technique to assist with ablation. Contrast imaging was performed to evaluate the ablative efficacy. Treatment responses, local tumour progression (LTP) and complications were recorded. All patients achieved a complete response. LTP was identified in two cases (9.1%) during the 4.5 month median follow-up period (range 2-29 months). A total of five additional sessions were performed, and secondary effectiveness was achieved in patients with LTP. No major complications were observed. Percutaneous MWA is a new promising technique for tumours adjacent to the LMA, especially in cases with small tumours. Technical improvements to this procedure are expected to improve the results for large tumours abutting the LMA. | 25,144,820 | [
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Composition-dependent photoluminescence intensity and prolonged recombination lifetime of perovskite CH3NH3PbBr(3-x)Cl(x) films. | Mixed halide perovskites CH3NH3PbBr3-xClx (x = 0.6-1.2) with different compositions of halogens exhibit drastically changed optical properties. In particular, the thin films prepared with these perovskites demonstrate extraordinary photoluminescence emission intensities and prolonged recombination lifetimes up to 446 ns, which are desirable for light emitting and photovoltaic applications. | 25,144,835 | [
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Psychosocial, educational and communicative interventions for patients with cachexia and their family carers. | Cancer cachexia has a substantial impact on both patients and their family carers. It has been acknowledged as one of the two most frequent and devastating problems of advanced cancer. The impact of cachexia spans biopsychosocial realms. Symptom management in cachexia is fraught with difficulties and globally, there remains no agreed standard care or treatment for this client group. There is a need to address the psychosocial impact of cachexia for both patients and their family carers. Patients living at home and their family carers are often left to manage the distressing psychosocial impacts of cancer cachexia themselves. Successful symptom management requires healthcare professionals to address the holistic impact of cancer cachexia. High quality and rigorous research details the existential impact of cachexia on patients and their family carers. This information needs to inform psychosocial, educational and communicative supportive healthcare interventions to help both patients and their family carers better cope with the effects of cachexia. Supportive interventions need to inform both patients and their family carers of the expected impacts of cachexia, and address how to cope with them to retain a functional, supported family unit who are informed about and equipped to care for a loved one with cachexia. | 25,144,837 | [
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[Clinical aspects of the problem of vertebral metastases, possibilities of modern treatment methods, considering especially radiofrequency ablation]. | From 100,000 people in Germany, statistically calculated, 441 males and 350 females suffer from a cancer disease. In about 50 to 80 % of patients with breast or prostate carcinoma bone metastases are registered, which is connected, among others, with a high risk for pathological fractures and other debilitating diseases. The diagnosis of bone metastases is done by conventional X-ray equipment, CT, MRI, and especially with the help of skeletal scintigraphy. For therapy bisphosphonates, anti-hormones and chemotherapeutic agents as drugs are used. Furthermore, radiotherapy, radionuclides, surgery and ablative procedures are applied. A more recent technical method is the STAR™ Tumour Ablation System (RFA), by which minimally invasively an electrode is introduced into the vertebral bodies. The system ensures precise control and thus a targeted ablation of the metastases. Several publications and reports describing a combined application demonstrate the synergistic effectiveness of RFA and radiofrequency kyphoplasty. | 25,144,844 | [
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[The clinical outcome after occipitocervical fusion due to metastases of the upper cervical spine: a consecutive case series and a systematic review of the literature]. | Increasing incidences of osseous metastatic malignancies and higher life expectancy in patients are resulting in a raise of occipitocervical metastases. Those patients with infaust prognosis have a significantly reduced quality of life. In Germany, between 800 and 1680 new cases per year are expected. Treatment algorithms include the evaluation of the general condition, the operability of visceral metastases, the tumor localization, the sensitivity to chemo-/radiotherapy, the fracture risk and the extent of neurological deficits and myelopathies. A systematic review on clinical studies or case series in posterior occipitocervical fusions due to metastases to the craniocervical transition yielded nine publications with 48 patients without neurological deficit. The mean survival time in the given follow-up was 6.44 months (n = 26; SD: 5,28; 95 % CI: 4.3-8.57). When measured, the clinical outcome was improved towards the VAS, the DENIS Pain Scale and the quality of life through the activities of daily living (ADL). We searched our clinical database for occipitocervical stabilizations in patients with craniocervical metastases. The prospectively collected data included the preoperative Tokuhashi score, SIN score, neurological status, length of hospitalization, perioperative course/loss of blood/complication rate, as well as the Karnofsky- index and pain measured by VAS preoperatively and in follow-up. Six patients were treated in this consecutive case series. The median age was 72 years (min./max.: 65/82), the average BMI 31.75 (min./max.: 19.3/38.1). The mean preoperative Karnofsky-index was 35 % (min./max.: 23.99/46.01; 95 % CI: 8.39) the mean preoperative Tokuhashi-score 7 (min./max.: 4/10), the mean preoperative VAS7 (min./max.: 4.8/9.2; 95 % CI: 1.68). There were no perioperative complications. In the follow-up, one patient showed a loosening of the screws in the osteolytic massae laterales and one patient suffered from a construct failure after fall. Metastases of the craniocervical transition are rare. The initial treatment of instability includes the application of a rigid Miami-J-collar or a Halo fixator. The decision for an operative procedure must accurately assess the individual patient characteristics to provide him a balanced concept between operational risk and clinical benefit. The assessment should be based on the life expectation and the expected quality of life in dependency of the respective therapeutic concept and its risks. The sole posterior stabilization of craniocervical instability through occipitocervical fusion leads to a reduction of pain, has a low perioperative risk, and may prevent a hospitalization. It is justified for selected patients to receive this treatment to help alleviate pain and to improve their quality of life. From our experience, rare cases of pain without instability should undergo conservative treatment in the first line. Due to the low availability of data on the manifestation and the clinical course of craniocervical metastases, there is a need for the collection of both the descriptive patient data include the radiographic findings as well as the clinical outcome and socio-economic factors using appropriate scoring systems. | 25,144,845 | [
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[Outcomes after operative treatment of distal radius fractures - an analysis of 721 patients]. | Treatment strategies in distal radius fractures differ nationally and internationally. Conservative and operative treatment options compete as well as implants, postoperative therapy regimens and the necessity of implant removal. In our institution operative treatment is favoured. In the following the results of 721 surgically treated patients are presented. PATIENTS who underwent operative treatment of their distal radius fractures in our institution between 2008 and 2011 were retrospectively analysed. Following patient characteristics have been surveyed regarding age, sex, location of plate osteosynthesis, operation time, time of cast immobilisation and complications like infections, tendon ruptures, need of revision surgery. 721 patients (mean age: 59.03 years) were retrospectively analysed. 514 of them (71.29 %) were female. Time of operation was after a mean duration of 5.48 days. In 558 (77.39 %) patients we performed palmar plate osteosynthesis. 89 (12.34 %) had dorsal plate osteosynthesis and 74 (10.3 %) cases were treated with either K-wires or screws. 18 (2.5 %) patients had concomitant traumatic carpal tunnel syndrome and a concomitant SL rupture was seen in 38 (5.27 %) patients. 40 (5.55 %) patients underwent operative revision because of posttraumatic carpal tunnel syndrome (n = 15), tendon ruptures (n = 7), malposition of screws (n = 6), loss of reduction (n = 6) and infection (n = 3). Mean duration of in-hospital stay after operation was 6.6 days. Implant removal was performed in 77 (10.7) patients; 59 (8.2 %) patients had palmar plate osteosynthesis and 18 (2.5 %) patients had dorsal plating. Because of the low complication rate after operative treatment of distal radius fractures, osteosynthesis of this fracture seems to be warranted. Regarding the patients' higher age we have seen an unexpectedly long in-hospital stay with a mean time of 6.6 days. Herein attempts should be made to reduce time of in-hospital stay. In our opinion implant removal should not be recommended routinely. | 25,144,848 | [
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How confident do you feel? | In this issue of Neuron, Fetsch et al. (2014) show that microstimulation of motion-sensitive neurons in the visual cortex (MT/MST) of primates mimics the addition of sensory information for which the stimulated neurons are selective. Such microstimulation increases the confidence that monkeys have in their decisions about motion direction. | 25,144,869 | [
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Measuring the functional organization of the neocortex at large and small scales. | Sensory cortices are commonly structured topographically; however, the extent to which this organization principle is preserved at the microcircuit level is debated. In this issue of Neuron, Issa et al. (2014) revisit this question by combining calcium imaging in awake mice at large scales encompassing the whole auditory cortex and small scales providing single-cell resolution. | 25,144,871 | [
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Schizophrenia genetics comes of age. | The new GWAS from the Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) clearly validates a genetic approach to understanding schizophrenia. The challenge now remains to track down the contributing genes and to develop appropriate models to elucidate the biological effects of the contributing variants. | 25,144,873 | [
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Electrochemical control of a non-covalent binding between ferrocene and beta-cyclodextrin. | The forces required for the detachment of ferrocene (Fc) from β-cyclodextrin (βCD) in a single host (βCD)-guest (Fc) complex were investigated using force spectroscopy under electrochemical conditions. The redox state of the guest Fc moiety as well as the structure of the supporting matrix was found to decisively affect the nanomechanical properties of the complex. | 25,144,878 | [
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Transfusion-free management of gastrointestinal bleeding: the experience of a bloodless institute. | The Institute for Patient Blood Management and Bloodless Medicine at the Englewood Hospital has considerable experience in managing patients with gastrointestinal bleeding who do not accept blood-derived products. We present our data and experience over the last 8 years in managing such patients. There is paucity of data on management and outcomes of gastrointestinal bleeding in patients who do not accept blood-derived products. We performed a retrospective study of patients from 2003 to 2011 presenting with gastrointestinal bleeding who do not accept blood-derived products. Inclusion criteria were either overt bleeding with a presenting hemoglobin (Hb) of <12 g/dL or a decrease in Hb of >1.5 g/dL. Ninety-six patients who met the inclusion criteria were included. Forty-one upper and 48 lower gastrointestinal bleeding sources were identified. Mean Hb was 8.8 g/dL and mean nadir was 6.9 g/dL. Among 37 patients (80.5%) with Hb ≤6.0 g/dL, 30 (81%) survived. Four of 7 patients (57%) with a Hb <3 g/dL survived. The overall mortality rate was 10.4%. In unadjusted logistic regression models, age [1.06 (1.01-1.12 y)], admission to ICU [6.37(1.27-31.9)], and anticoagulation use [6.95 (1.57-30.6)] were associated with increased mortality. Initial Hb [0.68 (0.51-0.92)] and nadir Hb [0.48 (0.29-0.78)] inversely predicted mortality. These results suggest that transfusion-free management of gastrointestinal hemorrhage can be effective with mortality comparable with the general population accepting medically indicated transfusion. Management of these patients is challenging and requires a dedicated multidisciplinary team approach knowledgeable in techniques of blood conservation. | 25,144,897 | [
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C11/C9 helices in crystals of αβ hybrid peptides and switching structures between helix types by variation in the α-residue. | Close-packed helices with mixed hydrogen bond directionality are unprecedented in the structural chemistry of α-polypeptides. While NMR studies in solution state provide strong evidence for the occurrence of mixed helices in (ββ)n and (αβ)n sequences, limited information is currently available in crystals. The peptide structures presented show the occurrence of C11/C9 helices in (αβ)n peptides. Transitions between C11 and C11/C9 helices are observed upon varying the α-amino acid residue. | 25,144,906 | [
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Study of weathering effects on the distribution of aromatic steroid hydrocarbons in crude oils and oil residues. | The composition and distribution of triaromatic steroid hydrocarbons in oil residues after biodegradation and photo-oxidation processes were detected, and the diagnostic ratios for oil spill identification were developed and evaluated based on the relative standard deviation (RSD) and the repeatability limit. The preferential loss of C27 methyl triaromatic steranes (MTAS) relative to C28 MTAS and C29 MTAS was shown during the photo-oxidation process. In contrast to the photochemical degradation, the MTAS with the original 20R biological configuration was preferentially degraded during the biodegradation process. The RSD of most of the diagnostic ratios of MTAS ranged from 9 to 84% during the photo-oxidation process. However, the RSDs of such ratios derived from MTAS were all <5% even in high biodegradation, and such parameters may also provide new methods on oil spill identification. The parameters of monoaromatic sterane and monoaromatic sterane are not used well for oil spill identification after photo-oxidation. The triaromatic steroid hydrocarbons retained their molecular compositions after biodegradation and photo-oxidation and most of the diagnostic ratios derived from them could be efficiently used in oil spill identification. | 25,144,907 | [
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The effects of prior authorization policies on medicaid-enrolled children's use of antipsychotic medications: evidence from two mid-Atlantic states. | The purpose of this study was to examine the impact of prior authorization policies on the receipt of antipsychotic medication for Medicaid-enrolled children. Using de-identified administrative Medicaid data from two large, neighboring, mid-Atlantic states from November 2007 through June 2011, we identified subjects <18 years of age using antipsychotics, from the broader group of children and adolescents receiving behavioral health services or any psychotropic medication. Prior authorization for antipsychotics was required for children in State A <6 years of age from September 2008, and for children <13 years of age from August 2009. No such prior authorizations existed in State B during that period. Filled prescriptions were identified in the data using national drug codes. Using a triple-difference strategy (using differences among the states, time periods, and differences in antidepressant prescribing rates among states over the same time periods), we examined the effect of the prior authorization policy on the rate at which antipsychotic prescriptions were filled for Medicaid-enrolled children and adolescents. The impact of prior authorization policies on antipsychotic medication use varied by age: Among 6-12 year old children, the impact of the prior authorization policy on antipsychotic medication prescribing was a modest but statistically significant decrease of 0.47% after adjusting for other factors; there was no effect of the prior authorization among children 0-5 years. Prior authorization policies had a modest but statistically significant effect on antipsychotic use in 6-12 year old children, but had no impact in younger children. Future research is needed to understand the utilization and clinical effects of prior authorization and other policies and interventions designed to influence antipsychotic use in children. | 25,144,909 | [
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Structural Basis of the Toxicity of Chemicals in Cultured Human HeLa Cells. | The newly developed "chemical diversity approach" was used to determine whether or not it is likely that a panel of in vitro cell toxicity assays capable of predicting in vivo eye irritation could be assembled. The analyses, based upon available and validated structure-activity relationship models of toxicity in cultured human HeLa cells and murine Balb/c 3T3 cells, indicate that a battery of cytotoxicity tests could provide a viable alternative to the animal-based procedure. | 25,144,928 | [
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Shell-sheddable, pH-sensitive supramolecular nanoparticles based on ortho ester-modified cyclodextrin and adamantyl PEG. | We report a new type of pH-sensitive supramolecular aggregates which possess a programmable character of sequential dePEGylation and degradation. As a platform of designing and building multifunctional supramolecular nanoparticles, a family of 6-OH ortho ester-modified β-cyclodextrin (β-CD) derivatives have been synthesized via the facile reaction between β-CD and cyclic ketene acetals with different alkyl lengths. These asymmetric acid-labile β-CD derivatives formed amphiphilic supramolecules with adamantane-modified PEG through host-guest interaction in polar solvents such as ethanol. The supramolecules can self-assemble in water to form acid-labile supramolecular aggregates. The results of TEM and light scattering measurements demonstrate that the size and morphology of the aggregates are influenced by the alkyl or PEG length and the host-guest feed ratio. By carefully balancing the alkyl and PEG lengths and adjusting the host-guest ratio, well-dispersed vesicles (50-100 nm) or sphere-like nanoparticles (200-500 nm) were obtained. Zeta potential measurements reveal that these supramolecular aggregates are capable of being surface-functionalized via dynamic host-guest interaction. The supramolecular aggregates were stable at pH 8.4 for at least 12 h as proven by the (1)H NMR and LLS measurements. However, rapid dePEGylation occurred at pH 7.4 due to the hydrolysis of the ortho ester linkages locating at the interface, which resulted in aggregation of the dePEGylated hydrophobic inner cores. Upon further decreasing the pH to 6.4, the hydrophobic cores were further degraded due to the acid-accelerated hydrolysis of the ortho esters. The incubation stability of the acid-labile supramolecular aggregates in neutral buffer could be improved by incorporating hydrophobic poly(ε-caprolactone) into the core of the aggregates. | 25,144,934 | [
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In situ growth of matchlike ZnO/Au plasmonic heterostructure for enhanced photoelectrochemical water splitting. | In this paper, we report a novel matchlike zinc oxide (ZnO)/gold (Au) heterostructure with plasmonic-enhanced photoelectrochemical (PEC) activity for solar hydrogen production. The matchlike heterostructure with Au nanoparticles coated on the tip of ZnO nanorods is in situ grown on a zinc (Zn) substrate by using a facile hydrothermal and photoreduction combined approach. This unique heterostructure exhibits plasmonic-enhanced light absorption, efficient charge separation and transportation properties with tunable Au contents. The photocurrent density of the matchlike ZnO/Au heterostructure reaches 9.11 mA/cm(2) at an applied potential of 1.0 V (vs Ag/AgCl) with an Au/Zn atomic ratio of 0.039, which is much higher than that of the pristine ZnO nanorod array (0.33 mA/cm(2)). Moreover, the solar-to-hydrogen conversion efficiency of this special heterostructure can reach 0.48%, 16 times higher than that of the pristine ZnO nanorod array (0.03%). What is more, the efficiency could be further improved by optimizing the Au content of the heterostructure. The formation mechanism of such a unique heterostructure is proposed to explain the plasmonic-enhanced PEC performance. This study might contribute to the rational design of the visible-light-responsive plasmonic semiconductor/metal heterostructure photoanode to harvest the solar spectrum. | 25,144,940 | [
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Demographic, anthropometric and socioeconomic characteristics of functional constipation in Eastern Croatia. | Aim of the research is to establish the prevalence of constipation in Osjecko-baranjska County, to establish its specific characteristics and to determine the effect of demographic, anthropometric and socioeconomic factors. It is a cross-sectional study conducted in 2010. on systematic sample of 900 subjects between 20 and 69 years of age. Every subject was sent an invitation letter and a Rome III diagnostic questionnaire for one of the disorders. A scoring algorithm was used to confirm or exclude the diagnosis of functional constipation. The chi-square test (chi2 test), t-test and logistic regression were used for analysis. The prevalence of constipation in our study was 22.19%, which is higher than the prevalence in most other countries, where it ranges from 5% to 18%. In our study statistically significant variables were: place of current residence (urban), education level (high school), marital status (divorced people), a larger number of household members and a lower health status by self-assessment. According to t-test persons with constipation on average are older, have higher average BMI and lower average grade valued financial status of households and their health. There were a greater number of subjects that had at least one alarm symptom or some of the psychosocial factors and they often suffered from a chronic disease. Functional constipation presents a significant health problem. Rome III survey questionnaire proved to be an acceptable method for diagnosing this functional disorder in clinical-consilliary and primary health care, and for persons showing signs of alarm and needing further diagnostic treatment. | 25,144,985 | [
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Surgical treatment of prolactinomas--our experience. | The dilemma of whether to apply surgical or drug treatment to prolactinomas has been ongoing for the past 30 years. The aim of this study is to compare the early postoperative values of prolactin (PRL) in two groups of patients with prolactinomas: those who underwent primary surgical-treatment, and those who underwent surgery after a dopamine agonist (DA) therapy. We present the results of surgical treatment on a series of 161 patients with prolactinomas. Surgery was the primary treatment in 65 patients, while 96 patients had surgery following a long-term treatment with a DA. All surgically treated prolactinomas were operated in the standard transsphenoidal, microsurgical approach. The criteria for hyperprolactinemia remission was a PRL level under 25 ng/ml. Early normalization of PRL was achieved in 92% of those patients who underwent primary surgical-treatment, yet it was achieved in only 42% of patients who were operated on after receiving a long-term drug treatment with a DA. The highest prevalence of postoperative normalization of PRL was achieved in a group of patients with microadenomas who were primarily operated on (98%). The worst results in postoperative normalization of PRL were found in the group of patients with macroadenomas who received a long-term drug treatment with a DA first. These results show our surgical experience in treating prolactinomas. Using surgical treatment, the best clinical outcome was achieved with microprolactinomas and intrasellar, well-confined macroprolactinomas. Nevertheless, we stress the need of an individualized approach and recommend treatment in multidisciplinary centres for pituitary diseases. | 25,144,990 | [
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A study on utilization of oral contraceptives in the City of Zagreb (2008-2010). | Main aim of this study is to quantify and analyze the utilization and utilization trends of oral hormonal contraceptives in the City of Zagreb, 2008-2010, and to propose potential interventions, if necessary. Data gathered from Zagreb pharmacies were assessed by Anatomical Therapeutic Chemical Classification of drugs and Daily Defined Dose methodology. An alarming decrease in total utilization of hormonal contraceptives by 76% from 2008-2009 was found as the main result of this study. A major decrease by 95.5% in utilization of G03AB04 subgroup, sequential combined oral contraceptives, was noted in the year 2009. The subgroup G03AC0, progesterone-only pill group, showed a stable trend, and it became the most utilized subgroup in 2010, due to the decrease in utilization of both fixed and sequential combined oral contraceptives. Utilization of oral contraceptives in Croatia is not regulated adequately, since such dynamics in utilization can occur unnoticed. Measures need to take place in order to improve this situation. Proposed measures include organized farmacovigilance, prescription based on guidelines, and strict screening for risk factors in women seeking oral contraception. More research is required in Croatia to understand the pattern of utilization of hormonal contraceptives and to find the true cause of decrease in utilization of oral contraceptives. | 25,144,993 | [
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Respiratory distress syndrome in newborns of gestational age of over 32 weeks. | Albeit the aetiology of the respiratory distress syndrome (RDS) is well known, the paper shall demonstrate that the causes of RDS changed over the years 2006 and 2010. This retrospective study comprises analysis of the data collected from 60 newborns of over 32 weeks gestation with RDS in the Neonatal Intensive Care Unit at the Clinical Hospital Centre in Osijek. The focus of the paper lies in the difference in the incidence of RDS over two research periods (2006 and 2010), the most common and possible causes of RDS in newborns of over 32 weeks gestation as well as in the potential changes in the aetiology over the two research periods. An increase in the incidence of RDS was established in 2010, but it was statistically significant only for newborns of gestational age of 35 1/7 to 36 6/7 weeks. The most common cause of RDS in both research periods was sepsis, which decreased in its share in 2010, whereas the incidence of asphyxia and complications during pregnancy increased. The new potential cause in 2010 was maternal thrombophilia. The share of unknown causes of RDS decreased, although not significantly so. The results of the research indicate that the causes of RDS changed over the observed periods and that further research should focus on thrombophilia and other complications during pregnancy with the aim of reducing morbidity and improving neonatal outcomes as well as further reducing the incidence of RDS with unknown causes in newborns. | 25,144,999 | [
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A study on the quality of outpatient prescription of psychopharmaceuticals in the City of Zagreb 2006-2009. | The lack of Croatian studies which could determine the justifiability of excessive psychopharmaceutical utilization was an encouragement to conduct this research. Furthermore, regarding the conduction of this study, it would be possible to determine whether the trend of drug utilization has increased, decreased or perhaps stabilized. The data on the outpatient utilization of psycholeptics and psychoanaleptics were collected from all Zagreb pharmacies, 2006-2009. Based on the collected data for all N05 and N06 groups of drugs, the defined daily doses (DDD) and DDD per thousand inhabitants per day (DDD/TID) have been calculated using the Anatomical-Therapeutic-Chemical classification (ATC) for 2006, 2007, 2008 and 2009. To indicate the quality of drug prescription the Drug Utilization 90% (DU 90%) method was used. Moreover, in order to determine a more precise quality of individual drug group prescriptions, the indicators have been calculated by determining the proportion of the total utilization of individual therapeutic and pharmacological therapeutic subgroups in DDD/TID a day. The utilization of anxiolytics (N05B) accounts for most of the psycholeptic utilization in the City of Zagreb throughout the entire study period. In the study period, the utilization of antidepressants has slightly increased, by 10.5%, taking the first and the last years of the period into account. In 2006, 5 benzodiazepines and the hypnotic zolpidem, as well as 5 selective serotonin reuptake inhibitors (SSRIs) and 1 third generation antipsychotic (olanzapin) were found in the DU 90% segment. In 2009, the DU 90% segment also comprised 5 benzodiazepines and the hypnotic zolpidem, as well as 6 SSRIs and 1 third generation antipsychotic (olanzapin). In the City of Zagreb, a general insight into the quality of psychopharmaceutical prescriptions indicates stability in comparison to earlier studies. The ratio index of the first generation antipsychotic utilization, compared to the third generation antipsychotics, shows an increase in the quality of prescription. Also, the ratio index of total tricyclic antidepressants (TCA) and SSRI utilization indicates improvement in quality of prescription. The ratio index of the entire outpatient utilization of anxiolytics and antidepressants expressed in DDD/TID unfortunately shows a very mild increase of prescription quality. Benzodiazepines accounted for more than 50% of the outpatient utilization of psychopharmaceuticals throughout the study period, which proves the need for precise guidelines as the most significant means of drug rationalization and utilization. It is necessary to identify priorities and problems in order to solve them successfully, by monitoring drug utilization and prescription on a national level. Results demonstrate that within the primary health care system, there is a need for constant education on rational prescription of this drug group. | 25,145,013 | [
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Skeletal remains from late Roman period: "as old as Diocletian's Palace". | In 2000, human skeletal remains were discovered in Split (Croatia). As archaeologists confirmed, it was an ancient skeleton accompanied by ceramics and bracelet characteristic for late Roman period whose possible violent death was excluded. The bone sample was radiocarbon dated by AMS to 1750 years. DNA was successfully extracted from the bone sample and subsequently typed using mt DNA and STR systems. The metal content was determined by atomic absorption spectrometry (AAS) in flame mode. Mercury concentration was determined by direct consecutive measures taken with a mercury analyzer. According to our results, we consider that the bones could belong to the one of the last citizens of the Diocletian's Palace. | 25,145,017 | [
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Human papillomavirus-related diseases of the female lower genital tract: oncogenic aspects and molecular interaction. | The causal role of human papillomavirus (HPV) in all cancers of the uterine cervix has been firmly established biologically and epidemiologically. Most cancers of both the vulva and the vagina are also induced by HPV. Papillomaviruses are perfectly adapted to their natural host tissue, the differentiating epithelial cell of skin or mucosae, and exploit the cellular machinery for their own purposes. The infectious cycle is initiated once the infectious particles reach the basal layer of the epithelium, where they bind to and enter the cells. The critical molecules in the process of virus replication are the viral proteins E6 and E7, which interact with a number of cellular proteins. In experimental system these interactions have been shown to induce proliferation and eventually immortalization and malignant transformation of cells. Binding of E7 to pRb activates the E2F transcription factor, which then triggers the expression of proteins necessary for DNA replication. Unscheduled S-phase would normally lead to apoptosis by the action of p53. However, in HPV-infected cells, this process is counteracted by the viral E6 protein, which targets p53 for proteolytic degradation. Besides blocking p53 function in regulation of apoptosis, high-risk HPV proteins interact with both extrinsic and intrinsic apoptotic pathways. As an aberration of virus infection, constant activity of the viral proteins E6 and E7 leads to increasing genomic instability, accumulation of oncogene mutations, further loss of cell-growth control and ultimately cancer. The immune system uses innate and adaptive immunity to recognize and combat foreign agents that invade the body, but these methods are sometimes ineffective against human papillomavirus. HPV has several mechanisms for avoiding the immune system. Furthermore, HPV infections disrupt cytokine expression with the E6 and E7 oncoproteins, particularly targeting the expression of interferon genes. Approximately 10% of individuals develop a persistent infection, and it is this cohort who is at risk of cancer progression, with the development of high-grade precursor lesions and eventually invasive carcinoma. | 25,145,023 | [
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Personal exposure to mixtures of volatile organic compounds: modeling and further analysis of the RIOPA data. | Emission sources of volatile organic compounds (VOCs*) are numerous and widespread in both indoor and outdoor environments. Concentrations of VOCs indoors typically exceed outdoor levels, and most people spend nearly 90% of their time indoors. Thus, indoor sources generally contribute the majority of VOC exposures for most people. VOC exposure has been associated with a wide range of acute and chronic health effects; for example, asthma, respiratory diseases, liver and kidney dysfunction, neurologic impairment, and cancer. Although exposures to most VOCs for most persons fall below health-based guidelines, and long-term trends show decreases in ambient emissions and concentrations, a subset of individuals experience much higher exposures that exceed guidelines. Thus, exposure to VOCs remains an important environmental health concern. The present understanding of VOC exposures is incomplete. With the exception of a few compounds, concentration and especially exposure data are limited; and like other environmental data, VOC exposure data can show multiple modes, low and high extreme values, and sometimes a large portion of data below method detection limits (MDLs). Field data also show considerable spatial or interpersonal variability, and although evidence is limited, temporal variability seems high. These characteristics can complicate modeling and other analyses aimed at risk assessment, policy actions, and exposure management. In addition to these analytic and statistical issues, exposure typically occurs as a mixture, and mixture components may interact or jointly contribute to adverse effects. However most pollutant regulations, guidelines, and studies remain focused on single compounds, and thus may underestimate cumulative exposures and risks arising from coexposures. In addition, the composition of VOC mixtures has not been thoroughly investigated, and mixture components show varying and complex dependencies. Finally, although many factors are known to affect VOC exposures, many personal, environmental, and socioeconomic determinants remain to be identified, and the significance and applicability of the determinants reported in the literature are uncertain. To help answer these unresolved questions and overcome limitations of previous analyses, this project used several novel and powerful statistical modeling and analysis techniques and two large data sets. The overall objectives of this project were (1) to identify and characterize exposure distributions (including extreme values), (2) evaluate mixtures (including dependencies), and (3) identify determinants of VOC exposure. METHODS VOC data were drawn from two large data sets: the Relationships of Indoor, Outdoor, and Personal Air (RIOPA) study (1999-2001) and the National Health and Nutrition Examination Survey (NHANES; 1999-2000). The RIOPA study used a convenience sample to collect outdoor, indoor, and personal exposure measurements in three cities (Elizabeth, NJ; Houston, TX; Los Angeles, CA). In each city, approximately 100 households with adults and children who did not smoke were sampled twice for 18 VOCs. In addition, information about 500 variables associated with exposure was collected. The NHANES used a nationally representative sample and included personal VOC measurements for 851 participants. NHANES sampled 10 VOCs in common with RIOPA. Both studies used similar sampling methods and study periods. Specific Aim 1. To estimate and model extreme value exposures, extreme value distribution models were fitted to the top 10% and 5% of VOC exposures. Health risks were estimated for individual VOCs and for three VOC mixtures. Simulated extreme value data sets, generated for each VOC and for fitted extreme value and lognormal distributions, were compared with measured concentrations (RIOPA observations) to evaluate each model's goodness of fit. Mixture distributions were fitted with the conventional finite mixture of normal distributions and the semi-parametric Dirichlet process mixture (DPM) of normal distributions for three individual VOCs (chloroform, 1,4-DCB, and styrene). Goodness of fit for these full distribution models was also evaluated using simulated data. Specific Aim 2. Mixtures in the RIOPA VOC data set were identified using positive matrix factorization (PMF) and by toxicologic mode of action. Dependency structures of a mixture's components were examined using mixture fractions and were modeled using copulas, which address correlations of multiple components across their entire distributions. Five candidate copulas (Gaussian, t, Gumbel, Clayton, and Frank) were evaluated, and the performance of fitted models was evaluated using simulation and mixture fractions. Cumulative cancer risks were calculated for mixtures, and results from copulas and multivariate lognormal models were compared with risks based on RIOPA observations. Specific Aim 3. Exposure determinants were identified using stepwise regressions and linear mixed-effects models (LMMs). Specific Aim 1. Extreme value exposures in RIOPA typically were best fitted by three-parameter generalized extreme value (GEV) distributions, and sometimes by the two-parameter Gumbel distribution. In contrast, lognormal distributions significantly underestimated both the level and likelihood of extreme values. Among the VOCs measured in RIOPA, 1,4-dichlorobenzene (1,4-DCB) was associated with the greatest cancer risks; for example, for the highest 10% of measurements of 1,4-DCB, all individuals had risk levels above 10(-4), and 13% of all participants had risk levels above 10(-2). Of the full-distribution models, the finite mixture of normal distributions with two to four clusters and the DPM of normal distributions had superior performance in comparison with the lognormal models. DPM distributions provided slightly better fit than the finite mixture distributions; the advantages of the DPM model were avoiding certain convergence issues associated with the finite mixture distributions, adaptively selecting the number of needed clusters, and providing uncertainty estimates. Although the results apply to the RIOPA data set, GEV distributions and mixture models appear more broadly applicable. These models can be used to simulate VOC distributions, which are neither normally nor lognormally distributed, and they accurately represent the highest exposures, which may have the greatest health significance. Specific Aim 2. Four VOC mixtures were identified and apportioned by PMF; they represented gasoline vapor, vehicle exhaust, chlorinated solvents and disinfection byproducts, and cleaning products and odorants. The last mixture (cleaning products and odorants) accounted for the largest fraction of an individual's total exposure (average of 42% across RIOPA participants). Often, a single compound dominated a mixture but the mixture fractions were heterogeneous; that is, the fractions of the compounds changed with the concentration of the mixture. Three VOC mixtures were identified by toxicologic mode of action and represented VOCs associated with hematopoietic, liver, and renal tumors. Estimated lifetime cumulative cancer risks exceeded 10(-3) for about 10% of RIOPA participants. The dependency structures of the VOC mixtures in the RIOPA data set fitted Gumbel (two mixtures) and t copulas (four mixtures). These copula types emphasize dependencies found in the upper and lower tails of a distribution. The copulas reproduced both risk predictions and exposure fractions with a high degree of accuracy and performed better than multivariate lognormal distributions. Specific Aim 3. In an analysis focused on the home environment and the outdoor (close to home) environment, home VOC concentrations dominated personal exposures (66% to 78% of the total exposure, depending on VOC); this was largely the result of the amount of time participants spent at home and the fact that indoor concentrations were much higher than outdoor concentrations for most VOCs. In a different analysis focused on the sources inside the home and outside (but close to the home), it was assumed that 100% of VOCs from outside sources would penetrate the home. Outdoor VOC sources accounted for 5% (d-limonene) to 81% (carbon tetrachloride [CTC]) of the total exposure. Personal exposure and indoor measurements had similar determinants depending on the VOC. Gasoline-related VOCs (e.g., benzene and methyl tert-butyl ether [MTBE]) were associated with city, residences with attached garages, pumping gas, wind speed, and home air exchange rate (AER). Odorant and cleaning-related VOCs (e.g., 1,4-DCB and chloroform) also were associated with city, and a residence's AER, size, and family members showering. Dry-cleaning and industry-related VOCs (e.g., tetrachloroethylene [or perchloroethylene, PERC] and trichloroethylene [TCE]) were associated with city, type of water supply to the home, and visits to the dry cleaner. These and other relationships were significant, they explained from 10% to 40% of the variance in the measurements, and are consistent with known emission sources and those reported in the literature. Outdoor concentrations of VOCs had only two determinants in common: city and wind speed. Overall, personal exposure was dominated by the home setting, although a large fraction of indoor VOC concentrations were due to outdoor sources. City of residence, personal activities, household characteristics, and meteorology were significant determinants. Concentrations in RIOPA were considerably lower than levels in the nationally representative NHANES for all VOCs except MTBE and 1,4-DCB. Differences between RIOPA and NHANES results can be explained by contrasts between the sampling designs and staging in the two studies, and by differences in the demographics, smoking, employment, occupations, and home locations. (ABSTRACT TRUNCATED) | 25,145,040 | [
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An unusual presentation of Salmonella typhi bacteriuria in a 10 year old girl from North India. | Enteric fever caused mainly by Salmonella typhi (S. typhi), has a high incidence in India. We report a case of enteric fever in a ten year old patient presenting with clinical history of less than one week. Although blood culture, the most important diagnostic modality in early stage of enteric fever was sterile, S. typhi was isolated from culture of urine sample. Serum antibody titres against S. typhi were unusually raised considering that the infection was still in its early stage. Intravenous ceftriaxone therapy was given leading to complete recovery. | 25,145,066 | [
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Determination of pesticide residues in tea by gas chromatography/triple quadrupole mass spectrometry with solid-phase extraction. | An analytical method was developed for determination of multipesticide residues, including organophosphorus, organohalogen, pyrethroid, and organonitrogen, in tea at trace levels by GC coupled with triple quadrupole mass chromatography (QqQ-MS/MS). Scan time was selected in order to optimize QqQ-MS/MS conditions. The key parameters for controlling cleanup performance were optimized, including SPE cartridge type and elution solvent volume. Acetonitrile was the extraction solvent, and a novel multilayer SPE cartridge, Cleanert TPT, was used in the cleanup step. The recoveries of the studied pesticides at 5.0, 10.0, and 25.0 microg/kg were in the range of 77.8 to 103.8% with an RSD of less than 14%. Determination coefficient (R2) values between 0.9951 and 0.9998 were obtained for all target compounds. The LOD was between 0.002 and 1.0 microg/kg, and LOQs were 0.0066-3.3 microg/kg, which satisfied the maximum residue limits for pesticides in tea recommended by the European Union and Japan. The optimized method was applied to the analysis of real tea samples obtained from the local market. | 25,145,129 | [
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Determination of penicillin G in milk samples using its effect on cloud point extraction of triiodide ion. | A cloud point extraction (CPE) method for determination of trace amounts of penicillin G by spectrophotometry based on its effect on the triiodide ion (I3(-)) has been developed. Penicillin G is converted to the corresponding penicilloic acid by carrying out hydrolysis with sodium hydroxide solution, and treatment with acid yields D-penicillamine that is oxidized quantitatively by iodine to give rise to a disulfide. The 13- remaining in the solution is extracted into the surfactant Triton X-100, and the difference between absorbance of the working solution in the presence and absence of penicillin G is proportional to the amount of penicillin G. The effects of different variables, such as concentrations of sodium hydroxide, hydrochloric acid, surfactant, and I3(-) and the temperature and incubation time on the CPE were studied. The calibration graph was linear in the range of 50-1250 microg/L, and the LOD was 38 microg/L (n = 10). The RSD for 10 replicate determinations of 1000 microg/L of penicillin G was 1.0%. The method was applied to the determination of penicillin G in milk samples. | 25,145,162 | [
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Storage-based denitrification with municipal wastewater: influence of the denitrification stage duration. | Microbial polyhydroxyalkenoates (PHAs) degradation is the rate limiting step for denitrification which is based on microbial carbon storage. The influence ofdenitrification stage duration (3, 2 and 1.5 h) on PHA degradation kinetics and denitrification efficiency during PHA-based denitrification ofmunicipal wastewater and acetate-based synthetic wastewater was investigated. PHA degradation kinetics showed a good fit to first-order reaction, with higher rates at higher PHA concentrations. Decreasing the denitrification stage duration from 3 to 2 h resulted in an increase in biomass PHA content with the corresponding higher specific denitrification rate. Moreover, the daily denitrification rates increased by about 30% in both the acetate fed reactor and the wastewater fed reactor. Further decreasing the denitrification stage duration to 1.5 h resulted in a decrease in sludge PHA content in both reactors. The amount of filtered chemical oxygen demand removed by storage and PHA stored, remained similar regardless of the denitrification stage duration. | 25,145,169 | [
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Comparison of harvesting methods for microalgae Chlorella sp. and its potential use as a biodiesel feedstock. | Three methods for harvesting Chlorella sp. biomass were analysed in this paper--centrifugation, membrane microfiltration and coagulation: there was no significant difference between the total amount of biomass obtained by centrifugation and membrane microfiltration, i.e., 0.1174 +/- 0.0308 and 0.1145 +/- 0.0268 g, respectively. Almost the same total lipid content was obtained using both methods, i.e., 27.96 +/- 0.77 and 26.43 +/- 0.67% for centrifugation and microfiltration, respectively. However, harvesting by coagulation resulted in the lowest biomass and lipid content. Similar fatty acid profiles were obtained for all of the harvesting methods, indicating that the main components were palmitic acid (C16:0), oleic acid (C18:1) and linoleic acid (C18:2). However, the amounts of the individual fatty acids were higher for microfiltration than for centrifugation and coagulation; coagulation performed the most poorly in this regard by producing the smallest amount of fatty acids (41.61 +/- 6.49 mg/g dw). The harvesting method should also be selected based on the cost benefit and energy requirements. The membrane filtration method offers the advantages of currently decreasing capital costs, a high efficiency and low maintenance and energy requirements and is thus the most efficient method for microalgae harvesting. | 25,145,177 | [
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Recovery of struvite via coagulation and flocculation using natural compounds. | One of the major setbacks of struvite recovery processes is the difficulty in harvesting struvite crystals. This study evaluates the use of different coagulants to improve precipitation of struvite (MgNH4PO4.6H20) crystals. Chitosan and poly(diallyldimethyl ammonium chloride) (Poly-DADMAC) as a coagulant-flocculent and alginate and bentonite as a coagulant aid have been examined in jar tests. Also, a continuous three-phase process, i.e., struvite crystallization, coagulation/flocculation and precipitation process, was set up for real wastewater. Addition of chitosan as the coagulant and bentonite as the coagulant aid was significantly more efficient in forming struvite flocs in comparison to Poly-DADMAC alone or with coagulant aid, which did not show any positive effect. The calculated average settling velocity of struvite with chitosan-bentonite addition in synthetic and in real wastewater increased by approximately 5.3 and 2.8 folds, respectively, compared with that of no coagulant/flocculent addition. Phosphorus recovery of over 70% was achieved by the continuous process. Findings in this study clearly confirmed the possibility of using chitosan and bentonite as an efficient coagulant-flocculent to enhance the recovery of struvite crystals. | 25,145,182 | [
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Adsorption of hydrogen sulphide from aqueous solutions using modified nano/micro fibrillated cellulose. | In the present study, microfibrillated cellulose (MFC) was modified by aminopropyltriethoxysilane (APS), hydroxy-carbonated apatite (HAP), or epoxy in order to produce novel nanostructured adsorbents for the removal of hydrogen sulphide (H2S) from the aqueous solutions. Structural properties of the modified MFC materials were examined using a scanning electron microscope, Fourier transform infrared spectroscopy and acid/base titration. These methods were used to verify the presence of nanostructures on the adsorbents surfaces as well as functionalities suitable for H2S adsorption. Adsorption of H2S by prepared adsorbents was investigated in batch mode under different experimental conditions, i.e., varying pH and H2S concentrations. H2S uptake was found to be 103.95, 13.38 and 12.73 mg/g by APS/MFC, HAP/MFC and epoxy/MFC, respectively from 80 mg/L H2S solution. The equilibrium data were best described by the Langmuir isotherm for HAP/MFC and APS/MFC and the Sips isotherm for epoxy/MFC. | 25,145,187 | [
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Ultrasound-assisted surfactant-enhanced emulsification microextraction for the determination of Cd and Ni in tea and water samples. | A microextraction method based on ultrasound-assisted surfactant-enhanced emulsification using solidification of a floating organic droplet (UASEME-SFO) was evaluated for simultaneous determination of Cd and Ni in water and tea samples followed by flame atomic absorption spectrometry. In the UASEME-SFO technique, Triton X-100 was used as an emulsifier to accelerate the emulsification of the extraction solvent into a sample solution and hasten the mass transfer of the analytes. Analytes form a complex and are extracted into 1-dodecanol which was used as an extraction solvent. Some parameters such as type and volume of the extraction solvent, the type and concentration of the surfactant, ultrasound extraction time, reagent concentration, centrifuge conditions and salt concentration were investigated. Under optimum conditions, calibration curves were linear in the range of 0.3-100 and 0.6-180 microg L(-1) with detection limits of 0.11 and 0.20 microg L(-1) for Cd and Ni, respectively. The accuracy of the method was confirmed by parallel analyses using the certified reference material of water and tea samples. The recoveries of the analytes in tea leaves, tea infusions and water samples were in the range of 96.5-105.1%. | 25,145,194 | [
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Effects of ageing on elution behaviour of nitrogenous compounds in disposed wastes from landfill sites. | Comparative studies of elution and cation exchange capacity (CEC) tests were applied to aged and fresh municipal and industrial solid wastes to examine the effects of ageing on the long-term elution behaviour of nitrogen on leachate in municipal and industrial solid waste landfill sites. Nitrogen in the leachate gradually eluted as organic nitrogen, but not upon transformation of organic nitrogen to elutable inorganic nitrogen compounds in the solid waste. Ammonium in the solid waste, retained similar to its interaction with clay minerals in soil, elutes when exposed to leachate by being replaced with highly concentrated cations or loses its positive charge in high pH in the leachate, which percolates down from the upper layer of the disposed waste. The quantity of ammonium adsorbed into the aged wastes through CEC measurement process by replacement with ammonium acetate was higher than that onto the fresh wastes. That difference in quantities can serve as an index of the ability of the solid waste to withhold ammonium in the leachate that percolates down the landfill layer. Those results demonstrate that ammonification of organic nitrogen in the waste is not the crucial step of the elution of nitrogenous compounds into leachate. | 25,145,199 | [
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Comparative removal of commercial diclofenac sodium by electro-oxidation on platinum anode and combined electro-oxidation and electrocoagulation on stainless steel anode. | Aqueous solution of diclofenac sodium (DCFNa) from commercial analgesic pill was electro-oxidized on platinum and stainless steel (SS) anodes. On platinum anode, 66% degradation of the parent drug was achieved at pH 4.5 with a corresponding COD reduction of 49% for a specific charge of 4200 Coulombs/L. Degradation and COD reduction were less at higher pHs of 8.5 and 10.9. A number of intermediates were detected with some of them persisting at the end of the treatment. On SS anode, 84% drug removal and 80% COD decline were achieved for a specific charge of 4200 Coulombs/L at pH 10.9, owing to combined electro-oxidation and electrocoagulation. Contrary to platinum anode, here the drug removal and COD reduction were lesser at lower pHs of 8.5 and 4.5. Electrocoagulation was found to proceed with the organics directly forming complex with iron in the matrix of the SS anode with the iron oxidizing to Fe(III) at pH 10.9 and Fe(II) at pHs 8.5 and 4.5. Intermediates detected in residual liquid were much less in number and abundance. | 25,145,203 | [
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Thermophilic co-digestion feasibility of distillers grains and swine manure: effect of C/N ratio and organic loading rate during high solid anaerobic digestion (HSAD). | Anaerobic co-digestion of high solids containing distillers grains and swine manure (total solids, 27 +/- 2% and 18 +/- 2%, respectively) was evaluated in this study to assess the effect of C/N ratio and organic loading rate (OLR). Feed mixture was balanced to achieve a C/N ratio of 30/1 by mixing distillers grains and swine manure. Pilot-scale co-digestion of distillers grains and swine manure was carried out under thermophilic conditions in the continuous mode for seven different OLRs from R1 to R7 (3.5, 5, 6, 8, 10, 12 and 14 kg VS/m3 day) under high solid anaerobic digestion. The methane yield and volatile solid (VS) removal were consistent; ranging from 0.33 to 0.34 m3CH4/kg VS day and 50-53%, respectively, until OLR 8 kg VS/m3 day. After which methane yield and VS removal significantly decreased to 0.26 m3 CH4/kg VS day and 42%, respectively, when OLR was increased to 14 kg VS/m3 day. However, during operation, at OLR of 10 kg VS/m3 day, the methane yield and VS removal increased after the 19th day to 0.33 m3 CH4/kg VS day and 46%, respectively, indicating that a longer acclimatization period is required by methanogens at a higher loading rate. | 25,145,212 | [
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Impacts of tilling and covering treatments on the biosolids solar drying conversion from class B to class A. | The objective of this study was to evaluate the effects of tillage and cover treatments of solar drying on the conversion of class B treated sewage sludge to a class A product. The experiments were performed over two years at Green Valley, Arizona in steel-constructed sand-filled drying beds of 1.0 m (width) x 3.0 m (length) x 0.6 m (depth). Freshly produced aerobically and anaerobically digested biosolids from nearby wastewater treatment plants received tillage and cover treatments for expediting solar drying and microbial inactivation. During the summer drying, covered drying bed increased faecal inactivation rate by 26% over other treatments and automated rain shield abated faecal coliform regrowth from summer rains. Tilling accelerated evaporation of moisture from the biosolids and increased the inactivation rate of faecal coliforms during the summer season. An automated retractable roof to protect the biosolids from rain aided in maintaining class A criteria by preventing dried biosolids from re-wetting by rainfall. However, results from tilling and passive solar heating during the cold winter seasons did not improve the faecal coliform inactivation rate due mainly to lower ambient temperatures. Thus, tilling and cover treatments can be effective in accelerating biosolids solar drying and thus enhancing pathogen inactivation during the summer season. Investigation on the effects of tillage depth and frequency is recommended to determine optimal tilling practice. | 25,145,218 | [
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High-speed imaging use to predict spray retention on barley leaves. | Measuring spray retention by plant leaves was the aim of many experiments in plant protection researches. Different methods have been used to measure spray proportion retained on vegetative surfaces, such as chemical methods using dyes and other methods using image analysis. We conducted Laboratory studies in order to validate the effectiveness of using high-speed imaging method developed by Massinon and Lebeau (2012a) to replace chemical analysis by spectrofluorometry. Measurements were performed with a high speed camera coupled with a retro-LED lighting. Sizes and velocities of the drops were extracted by image analysis and drop impact behaviours were determined by the operator. Drops were produced with a flat-fan nozzle mounted on a movable ramp. Two surfactants (Break Thru 5240 and Li700) were sprayed to highlight the effect of the reduction of surface tension. Sprays contained a fluorescent tracer for the chemical analysis, fluorescein. Relative volume proportions were computed within of an energy scale based on the Weber number. Results of high-speed imaging were compared to those of the chemical analysis by spectrofluorometry. | 25,145,223 | [
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Secondary metabolites: applications on cultural heritage. | Biological sciences and related bio-technology play a very important role in research projects concerning protection and preservation of cultural heritage for future generations. In this work secondary metabolites of Burkholderia gladioli pv. agaricicola (Bga) ICMP 11096 strain and crude extract of glycoalkaloids from Solanaceae plants, were tested against a panel of microorganisms isolated from calcarenite stones of two historical bridges located in Potenza and in Campomaggiore (Southern Italy). The isolated bacteria belong to Bacillus cereus and Arthrobacter agilis species, while fungi belong to Aspergillus, Penicillium, Coprinellus, Fusarium, Rhizoctonio and Stemphylium genera. Bga broth (unfiltered) and glycoalkaloids extracts were able to inhibit the growth of all bacterial isolates. Bga culture was active against fungal colonies, while Solanaceae extract exerted bio-activity against Fusarium and Rhizoctonia genera. | 25,145,230 | [
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Vegephy: impact of vegetable oils used as extemporaneous additives on pesticide residues and their crop protection potential. | Within the framework of the VEGEPHY project set up to assess the effect of refined oils used as extemporaneous additives, both alone and in combination with oligosaccharides (guar, xanthan and carboxymethyl cellulose), on the quality of plant protection treatments for wheat, a study was conducted on the effect of combinations of additives on the level of pesticide residues in wheat plants and grain and their impact on treatment efficiency. The use of some of these additives gave efficiency results that were comparable with those obtained with additives that are currently used but are not bio-based. The use of refined oils as extemporaneous additives, both alone and combined with oligosaccharides, led to better penetration by the pesticide as well as longer persistence of its activity. The experiments were conducted with fungicides, herbicides, plant growth regulators and various types of formulation (EC, SC and WG). The results obtained were conclusive, but they did depend on the physico-chemical properties of the active substance. The risk of exceeding the maximum residue levels (MRLs) of pesticides was also evaluated. Even where the MRLs had not been not exceeded, the experiments showed that in some cases the treatment with these additives could lead to pesticide residues up to two times higher than those measured for the treatment without additives. It would be necessary, therefore, to reduce the treatment dose associated with the additive and/or have a long enough pre-harvest interval to avoid exceeding the MRLs. The use of green additives could be a useful and easy way to attain the European Union (EU) goal of reducing pesticide use by improving the retention of active substances on the plant and reducing the number of treatments. | 25,145,232 | [
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Essential oil compounds as stress reducing agents in rats. | Essential oil compounds were studied to demonstrate their potential as stress reducing agents against rats. Rats were intraperitoneal administered with Linalool, Cineole and Thymol, respectively. Anxiety-related behaviors were determined by open field test and elevated plus maze test. Thymol reduced anxiety-related behavior of the animals. Linalool had no effect in both sexes of rats in the open field test. Thus, the results suggested that Thymol and Linalool are safe to control pets without harming non-target mammals | 25,145,237 | [
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Effect of eucalyptus wood vinegar on rubberwood infestation by Asian subterranean termite, Coptotermes gestroi Isoptera: Rhinotermitidae). | Wood degradation caused by fungi, termites, and insects, is a major problem for the rubberwood industry. The potential of wood vinegar as rubberwood preservative was studied. The infestation rates of Coptotermes gestroi (Wasmann) (Isoptera: Rhinotermitidae) on rubberwood samples treated with 25%, 50% and 100% eucalyptus wood vinegar for 24 hours were observed in laboratory conditions. Both non-choice and choice experiments were included. The effects of eucalyptus wood vinegar treatment depended on its concentration. In the non-choice experiments, rubberwood samples treated with 100% eucalyptus wood vinegar had the highest resistance to C. gestroi infestation, with the lowest relative loss of mass, followed in rank order by 50% and 25% treatments. However, in the choice experiments the relative loss of mass did not differ significantly between the treatments with varied wood vinegar concentration. Untreated control samples were distinctly infested by C. gestroi in both non-choice and choice experiments, but their relative loss of mass in the non-choice experiments was not significantly different from samples treated with 25% eucalyptus wood vinegar. Hence, 25% eucalyptus wood vinegar was not effective as rubberwood preservative against C. gestroi attack. The results suggest that eucalyptus wood vinegar acts as a rubberwood preservative against termites, provided the treatment is done without dilution. About 50% dilution still has some efficacy, while lower concentrations are not effective. | 25,145,252 | [
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Toxicity of cypermethrin on the neotropical lacewing Chrysoperla externa (Neuroptera: Chrysopidae). | The generalist predator Chrysoperla externa (Neuroptera: Chrysopidae) is distributed in the Neotropical Region and presents a strong potential as a biological control agent due to its easily rearing, high voracity and tolerance to several pesticides. This species feeds on relevant pests such as aphids, whiteflies, trips and various lepidopterans. In Argentina, an indiscriminate chemical control with broad spectrum pesticides is still the first option for controlling pests causing resistance problems and reduction of beneficial organisms. Therefore, it would be desirable that predators or parasitoids develop tolerance or resistance as phytophagous pests for their maintenance in the agricultural ecosystems. The objective of this work was to evaluate the tolerance of C. externo to the pyrethroid cypermethrin by topical exposure in laboratory conditions. The symptoms evaluated were tremors, movement, knockdown, inability to walk due to being glued. Recovery from poisoning symptoms was also evaluated. Six different concentrations of the pesticide, including the full field one, were tested. The exposure method was by topical applications on third larval instar. A low toxicity on larvae at 24 h post-treatment was observed, even at the highest concentration evaluated. Most of treated individuals looked normal at 24 h post-treatment; those who were knocked down showed a complete recovery between 48 and 72 h post-treatment. C externa demonstrated a high tolerance to pyrethroids. This could be due to the activity involved in pyrethroids biotransformation (for example, esterases and mixed-function oxidases), or to a low sensitivity of the molecular target. Future studies should be addressed at biochemical and molecular levels to complete our knowledge about insecticide effects on this predator. | 25,145,256 | [
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Preliminary results on the ability of pentatomidae to transfer fire blight Erwinia amylovora under controlled conditions. | With their piercing-sucking mouthparts stink bugs (Heteroptera: Pentatomidae), a major pest in especially organic orchards, create wounds in fruit of pear trees. As Erwinia amylovora (Burrill, Winslow et al.), a wide spread bacterial disease affecting many rosaceous plants including pome fruit trees and hawthorn, enters through openings in flowers, leaves, shoots and fruit, feeding punctures caused by these bugs might be inoculated with Erwinia bacteria. In order to investigate the ability of the bugs Pentotoma rufipes L. and Polomena prasina L. to transmit fire blight, insects were caught in an organically managed orchard without fire blight, brought into contact with artificially inoculated immature pear fruit/slices and transferred to healthy, mechanically wounded pear fruit/slices. After an incubation period potential transmission of bacteria was examined by evaluation of symptom expression (necrosis, ooze production). To assess the presence of bacteria on the exoskeleton of the tested bugs, all bugs were forced to walk on a semiselective nutrient agar medium. In another experiment the viability of Ea on the exoskeleton was tested -after previous contact with ooze- through washing and plating of the wash water. All experiments were conducted under optimal climatological conditions and according to quarantine standards. Results demonstrated the ability of stink bugs to transfer E. amylovora to fruit and the viability of bacteria on stink bugs externally - both under lab conditions. | 25,145,257 | [
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Pharmacological inhibition of coronary restenosis: systemic and local approaches. | Percutaneous coronary intervention (PCI) with stent implantation has revolutionized the treatment of obstructive coronary artery disease. However, the main limitation of this therapy is stent failure, which is usually caused by in-stent restenosis. The aim of this article is to critically review the literature on the prevention of in-stent restenosis focusing on drug compounds that have reached clinical testing. The pathophysiological response following PCI includes many possible targets for antirestenosis treatment. Most notable success is seen with sirolimus (and its analogs) and paclitaxel, both of which target vascular smooth muscular cell proliferation. In view of the systemic side effects of both drugs, the high efficacy of local drug delivery methods reduced enthusiasm for systemic therapy. Cilastazol has shown benefit in restenosis reduction particularly in patients at high risk for stent failure, though further study in broader populations is warranted. Probucol showed variable results, but local drug delivery in combination with sirolimus seems promising. A hypothesized independent antirestenotic effect of pioglitazone in patients with diabetes has not been clearly demonstrated. Initial encouraging results with tranilast have not been replicated in a recent large-scale randomized trial. Colchicine and prednisone have shown promising results but require further investigation in larger clinical trials. | 25,145,263 | [
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Urinary excretion of arsenic following rice consumption. | Patterns of arsenic excretion were followed in a cohort (n = 6) eating a defined rice diet, 300 g per day d.wt. where arsenic speciation was characterized in cooked rice, following a period of abstinence from rice, and other high arsenic containing foods. A control group who did not consume rice were also monitored. The rice consumed in the study contained inorganic arsenic and dimethylarsinic acid (DMA) at a ratio of 1:1, yet the urine speciation was dominated by DMA (90%). At steady state (rice consumption/urinary excretion) ∼40% of rice derived arsenic was excreted via urine. By monitoring of each urine pass throughout the day it was observed that there was considerable variation (up to 13-fold) for an individual's total arsenic urine content, and that there was a time dependent variation in urinary total arsenic content. This calls into question the robustness of routinely used first pass/spot check urine sampling for arsenic analysis. | 25,145,278 | [
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Hydrogen-bond-directed-linking solving transparence-efficiency tradeoff in nonlinear optical molecule. | It is well known that settling transparency-efficiency tradeoff is important to design nonlinear optical (NLO) materials. In this work, we constructed one-dimensional polymeric cyanoacetylene (NCCCH)n by hydrogen-bond-directed-linking to understand this tradeoff from molecular level. Results show that the first hyperpolarizability of (NCCCH)n (n=2-8) gradually increased with the increase of n, and what is more important is that the red-shifts, associated with the increase of n, were very little. It is proposed that these polymeric structures possess double-degenerated charge transitions, which contribute to the hyperpolarizability in an additive fashion, and that the coupled oscillators are gradually improved, which lead to the increase of the first hyperpolarizability. Therefore, we propose the hydrogen-bond-directed-linking idea is helpful to develop the potential high-performance NLO materials. | 25,145,287 | [
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Comparison of effectiveness and cost between perventricular device occlusion and minimally invasive surgical repair for perimembranous ventricular septal defect. | Perventricular device occlusion and minimally invasive surgical repair for perimembranous ventricular septal defect (pmVSD) are two typical methods to reduce the invasiveness of the conventional operation through median sternotomy. However, few comparative studies have been made between them in terms of effectiveness and cost. A review was made of the inpatients with isolated pmVSD, who had undergone perventricular device occlusion or minimally invasive surgical repair from June 2011 and January 2013 for a comparative investigation between the two procedures. The two treatment groups had similar baseline characteristics. Procedural success was achieved in 163 (94.8%) of the perventricular and 137 (98.6%) of the surgical (P = 0.136). Major complications occurred in 2 (1.2%) of the perventricular and 4 (2.9 %) of the surgical (P = 0.497), and minor complications, in 57 (33%) of the percutaneous and 49 (35.2%) of the surgical (P = 0.696). In cost, the surgical repair was 30.5% cheaper than the device occlusion (Yuan 20139 ± 3760 vs. 28970 ± 3343, P < 0.001), where most of the cost was attributed to the occluder in the amount of Yuan 19,500. Compared with perventricular device closure, minimally invasive surgical repair can provide comparable efficacy and complication rates, without the potential for developing atrioventricular block at long-term follow-up. In addition, it is 30.5% cheaper than hybrid procedure. In the low-income countries where health-care resources are limited the medical resources must be judiciously allocated to the treatment that allows for effective treatment of the largest number of patients. | 25,145,293 | [
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Concise stereoselective synthesis of oxaspirocycles with 1-tosyl-1,2,3-triazoles: application to the total syntheses of (±)-Tuberostemospiroline and (±)-stemona-lactam R. | A 4-substituted-1-tosyl-1,2,3-triazole-based stereoselective synthesis of structurally diverse oxaspirocycles is reported. The synthesis involves Rh-catalyzed loss of nitrogen from 4-substituted-1-tosyl-1,2,3-triazoles, Grignard reaction, and a ring-closing metathesis reaction as key steps. By employing readily available and stable 4-substituted-1-tosyl-1,2,3-triazoles as surrogates of diazo compounds and nitrogen sources, two types of oxaspirocycles were obtained. The latter compounds, which contain adjacent nitrogen stereocenters, could serve as the core structures of many natural products. This chemistry has been successfully applied to the total syntheses of (±)-tuberostemospiroline and (±)-stemona-lactam R. | 25,145,296 | [
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Coming to work sick: a survey of hospital doctors in New Zealand. | To estimate the rate of sickness presenteeism in hospital doctors in a New Zealand tertiary hospital and to also identify reasons for why doctors continue to work whilst sick. An anonymous online survey about sickness presenteeism for all hospital doctors at one tertiary care hospital in New Zealand The response rate for the survey was 328/685 (47.8%). Sickness presenteeism was reported by 269/328 (82%) of respondents. The main reasons for sickness presenteeism were: not wanting to burden co-workers and the desire to ensure care for patients. Sickness presenteeism is highly prevalent in this survey. It is likely a change in attitudes by doctors towards their illnesses, and better allocation of staff resources are necessary to prevent this to avoid potential harm to patients and health care workers. | 25,145,303 | [
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Progress of successful New Zealand Registration Examination (NZREX Clinical) candidates during their first year of supervised clinical practice in New Zealand. | To determine the frequency and nature of clinical difficulties faced in the first year of supervised clinical practice by international medical graduates (IMGs) who have successfully passed NZREX Clinical in order to be able to practise in New Zealand. All doctors who successfully passed NZREX Clinical and who registered with the Medical Council of New Zealand (the Council) from 2005 to 2013 were identified. Supervisor reports for each of the four runs in the first year of practice were obtained and reports where concerns were raised over clinical performance analysed. Of 353 IMGs successful in NZREX Clinical, 316 (89.6%) completed the subsequent clinical year with no adverse reports. Those requiring more than one attempt to pass NZREX Clinical had an incremental increase in number of unsatisfactory reports, where areas of the IMGs' performance were rated as 'below the expected standard'. Less than 2% of IMGs had more than one unsatisfactory report. The majority of unsatisfactory reports were generated in the first half of the clinical year. Areas of concerns found were Clinical Knowledge and Skills (28%), Clinical Judgment (35%), Patient Communication (28%) and Professional Attitudes and Behaviour (9%). Most IMGs who were successful in NZREX Clinical performed well in the subsequent year of clinical practice. NZREX Clinical would appear to have acceptable criterion validity. | 25,145,304 | [
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A review of the Christchurch Hospital Breast Cancer Service in 2012: meeting the new Tumour Standards. | To determine whether patients diagnosed with breast cancer in 2012 received timely access to services at Christchurch Hospital when audited against Ministry of Health Tumour Standards of Service Provision (TS) (2013) and the Faster Cancer Treatment (FCT) indicators, and to discover factors which impeded patient pathways, and which would need to be addressed in order to meet the standards. Data on referrals, dates and treatment for patients diagnosed with breast cancer at Christchurch Hospital was extracted from the Christchurch Breast Cancer Patient Register and other hospital databases. In 2012, 288 breast cancer patients were treated at Christchurch Hospital, 60% referred by general practitioners, and 40% via the national screening programme. Some 2013 Tumour Standards were achieved. The FCT indicator 1 (TS 2.4) and 3 (TS 2.5) were met, with 87% (greater than or equal to 80%) receiving their first treatment within 62 days of referral, and 89% (greater than or equal to 80%) within 31 days of decision-to-treat. However, FCT indicator 2 (TS 2.1), requiring first specialist assessment within 14 days of referral, was met in 61% (greater than or equal to 90% required). Only 64% of women started adjuvant chemotherapy within 42 days of their surgery (TS 2.6, greater than or equal to 90%). The management of breast cancer patients by a multidisciplinary team is crucial to ensure patients receive timely and appropriate care. However, waiting for weekly multidisciplinary meetings and adequate anatomical pathology resource, together with other factors, were identified as delaying the patient pathway and solutions to resolve these are discussed. | 25,145,307 | [
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Modeling stroke in mice: permanent coagulation of the distal middle cerebral artery. | Stroke is the third most common cause of death and a main cause of acquired adult disability in developed countries. Only very limited therapeutical options are available for a small proportion of stroke patients in the acute phase. Current research is intensively searching for novel therapeutic strategies and is increasingly focusing on the sub-acute and chronic phase after stroke because more patients might be eligible for therapeutic interventions in a prolonged time window. These delayed mechanisms include important pathophysiological pathways such as post-stroke inflammation, angiogenesis, neuronal plasticity and regeneration. In order to analyze these mechanisms and to subsequently evaluate novel drug targets, experimental stroke models with clinical relevance, low mortality and high reproducibility are sought after. Moreover, mice are the smallest mammals in which a focal stroke lesion can be induced and for which a broad spectrum of transgenic models are available. Therefore, we describe here the mouse model of transcranial, permanent coagulation of the middle cerebral artery via electrocoagulation distal of the lenticulostriatal arteries, the so-called "coagulation model". The resulting infarct in this model is located mainly in the cortex; the relative infarct volume in relation to brain size corresponds to the majority of human strokes. Moreover, the model fulfills the above-mentioned criteria of reproducibility and low mortality. In this video we demonstrate the surgical methods of stroke induction in the "coagulation model" and report histological and functional analysis tools. | 25,145,316 | [
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RNA isolation from mouse pancreas: a ribonuclease-rich tissue. | Isolation of high-quality RNA from ribonuclease-rich tissue such as mouse pancreas presents a challenge. As a primary function of the pancreas is to aid in digestion, mouse pancreas may contain as much a 75 mg of ribonuclease. We report modifications of standard phenol/guanidine thiocyanate lysis reagent protocols to isolate RNA from mouse pancreas. Guanidine thiocyanate is a strong protein denaturant and will effectively disrupt the activity of ribonuclease under most conditions. However, critical modifications to standard protocols are necessary to successfully isolate RNA from ribonuclease-rich tissues. Key steps include a high lysis reagent to tissue ratio, removal of undigested tissue prior to phase separation and inclusion of a ribonuclease inhibitor to the RNA solution. Using these and other modifications, we routinely isolate RNA with RNA Integrity Number (RIN) greater than 7. The isolated RNA is of suitable quality for routine gene expression analysis. Adaptation of this protocol to isolate RNA from ribonuclease rich tissues besides the pancreas should be readily achievable. | 25,145,327 | [
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NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report. | NUP98/NSD1 has recently been reported in association with poor outcome in acute myeloid leukemia (AML). Previous studies also observed a high overlap between NUP98/NSD1 and FLT3/ITD, raising the question as to whether the reported poor outcome is due to NUP98/NSD1 or caused by the co-occurrence of these 2 genetic lesions. We aimed to determine the prognostic significance of NUP98/NSD1 in the context of FLT3/ITD AML. A total of 1421 patients enrolled in 5 consecutive Children's Oncology Group/Children's Cancer Group and SWOG trials were evaluated. NUP98/NSD1 was found in 15% of FLT3/ITD and 7% of cytogenetically normal (CN)-AML. Those with dual FLT3/ITD and NUP98/NSD1 (82% of NUP98/NSD1 patients) had a complete remission rate of 27% vs 69% in FLT3/ITD without NUP98/NSD1 (P < .001). The corresponding 3-year overall survival was 31% vs 48% (P = .011), respectively. In CN-AML, patients with concomitant NUP98/NSD1 and FLT3/ITD had a worse outcome than those harboring NUP98/NSD1 only. In multivariate analysis, the dual NUP98/NSD1 and FLT3/ITD remained an independent predictor of poor outcome, and NUP98/NSD1 without FLT3/ITD lost its prognostic significance. Our study demonstrates that it is the interaction between NUP98/NSD1 and FLT3/ITD that determines the poor outcome of patients with NUP98/NSD1 disease. | 25,145,343 | [
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Grail controls Th2 cell development by targeting STAT6 for degradation. | T helper (Th)-2 cells are the major players in allergic asthma; however, the mechanisms that control Th2-mediated inflammation are poorly understood. Here we find that enhanced expression of Grail, an E3 ubiquitin ligase, in Th2 cells depends on interleukin (IL)-4-signalling components, signal transducer and activator of transcription 6 (Stat6) and Gata3, that bind to and transactivate the Grail promoter. Grail deficiency in T cells leads to increased expression of Th2 effector cytokines in vitro and in vivo and Grail-deficient mice are more susceptible to allergic asthma. Mechanistically, the enhanced effector function of Grail-deficient Th2 cells is mediated by increased expression of Stat6 and IL-4 receptor α-chain. Grail interacts with Stat6 and targets it for ubiquitination and degradation. Thus, our results indicate that Grail plays a critical role in controlling Th2 development through a negative feedback loop. | 25,145,352 | [
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Backseat drivers: Regulation of dynein motility. | Control of the activity of the microtubule motor cytoplasmic dynein 1 is essential for its function in intracellular transport. A recent paper by McKenney et al. published in Science shows that activation of processive dynein motility requires the formation of cargo adaptor-dynein-dynactin complexes. | 25,145,357 | [
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Using drawing tests to explore the multidimensional psychological aspects of children with cancer. | In seeking to understand how life-threatening illness affects children psychologically, projective testing may be beneficial, particularly when attempting to identify psychological problems in younger adolescents. The advantages of projective testing are that it does not depend on patients' verbal ability and is not invasive. Three cancer inpatients from Kyoto Prefectural University of Medicine, aged between 10 and 16 years old, participated in the study. Projective testing was used to measure the depth of participants' distress and included a tree-drawing test, a person-drawing test and a free drawing test. Results from the tree- and person-drawing tests indicated energy loss, anxiety and a sense of emptiness. However, results from the free drawing test suggested that the children had hope and a desire to recover from their illness. The combination of drawing tests in this study may increase the understanding of the internal psychological difficulties faced by children hospitalized with cancer. | 25,145,380 | [
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Long noncoding RNAs in liver cancer: what we know in 2014. | Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with an estimated over half a million new cases diagnosed annually. Due to the difficulty in early diagnosis and lack of effective treatment options, HCC is currently ranked as the second highest neoplastic-related mortality in the world, with an extremely low 5-year survival rate of between 6 and 11%. Long noncoding RNAs (lncRNAs), are genes lacking protein coding ability, have recently emerged as pivotal participants in biological processes, often dysregulated in a range of cancers, including HCC. In this review, we highlight the recent findings of lncRNAs in HCC pathogenesis, with particular attention on epigenetic events. In silico analysis was utilized to emphasize intrinsic linkages within the ncRNA families associated with hepatocarcinogenesis. While our understanding of lncRNAs in the onset and progression of HCC is still in its infancy, there is no doubt that understanding the activities of ncRNAs will certainly secure strong biomarkers and improve treatment options for HCC patients. | 25,145,388 | [
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The role of general practitioners in the pre hospital setting, as experienced by emergency medicine technicians: a qualitative study. | Together with the ambulances staffed with emergency medical technicians (EMTs), general practitioners (GPs) on call are the primary resources for handling emergencies outside hospitals in Norway. The benefit of the GP accompanying the ambulance to pre-hospital calls is a matter of controversy in Norway. The purpose of the present study was to gain better insight into the EMT's experiences with the role of the GPs in the care for critically ill patients in the pre-hospital setting. We conducted four focus group interviews with EMTs at four different ambulance stations in Norway. Three of the stations were located at least 2 hours driving distance from the nearest hospital. The interviews were transcribed and analyzed using systematic text condensation. The EMTs described increasing confidence in emergency medicine during the last few years. However, they felt the need for GP participation in the ambulance when responding to a critically ill patient. The presence of GPs made the EMTs feel more confident, especially in unclear and difficult cases that did not fit into EMT guidelines. The main contributions of the GPs were described as diagnosis and decision-making. Bringing the physician to the patient shortened transportation time to the hospital and important medication could be started earlier. Several examples of sub-optimal treatment in the absence of the GP were given. The EMTs described discomfort with GPs not responding to the calls. They also experienced GPs responding to calls that did not function in the pre-hospital emergency setting. The EMTs reported a need for professional requirements for GPs taking part in out-of-hours work and mandatory interdisciplinary training on a regular basis. EMTs want GPs to be present in challenging pre-hospital emergency settings. The presence of GPs is perceived as improving patient care. However, professional requirements are needed for GPs taking part in out-of-hours work, and the informants suggested a formalized area for training between EMTs and GPs on call. | 25,145,390 | [
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Distinct subclades of Aux/IAA genes are direct targets of ARF5/MP transcriptional regulation. | The regulatory interactions between AUXIN RESPONSE FACTORS (ARFs) and Aux/IAA repressors play a central role in auxin signal transduction. Yet, the systems properties of this regulatory network are not well established. We generated a steroid-inducible ARF5/MONOPTEROS (MP) transgenic background to survey the involvement of this factor in the transcriptional regulation of the entire Aux/IAA family in Arabidopsis thaliana. Target genes of ARF5/MP identified by this approach were confirmed by chromatin immunoprecipitation, in vitro gel retardation assays and gene expression analyses. Our study shows that ARF5/MP is indispensable for the correct regulation of nearly one-half of all Aux/IAA genes, and that these targets coincide with distinct subclades. Further, genetic analyses demonstrate that the protein products of multiple Aux/IAA targets negatively feed back onto ARF5/MP activity. This work indicates that ARF5/MP broadly influences the expression of the Aux/IAA gene family, and suggests that such regulation involves the activation of specific subsets of redundantly functioning factors. These groups of factors may then act together to control various processes within the plant through negative feedback on ARF5. Similar detailed analyses of other Aux/IAA-ARF regulatory modules will be required to fully understand how auxin signal transduction influences virtually every aspect of plant growth and development. | 25,145,395 | [
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Cold exposure inhibits hypothalamic Kiss-1 gene expression, serum leptin concentration, and delays reproductive development in male Brandt's vole (Lasiopodomys brandtii). | Cold commonly affects growth and reproductive development in small mammals. Here, we test the hypothesis that low ambient temperature will affect growth and puberty onset, associated with altered hypothalamic Kiss-1 gene expression and serum leptin concentration in wild rodents. Male Brandt's voles (Lasiopodomys brandtii) were exposed to cold (4 ± 1 °C) and warm (23 ± 1 °C) conditions from the birth and sacrificed on different developmental stages (day 26, day 40, day 60, and day 90, respectively). Brandt's voles increased the thermogenic capacity of brown adipose tissue, mobilized body fat, decreased serum leptin levels, and delayed the reproductive development especially on day 40 in the cold condition. They increased food intake to compensate for the high energy demands in the cold. The hypothalamic Kiss-1 gene expression on day 26 was decreased, associated with lower wet testis mass and testis testosterone concentration on day 40, in the cold-exposed voles compared to that in the warm. Serum leptin was positively correlated with body fat, testis mass, and testosterone concentration. These data suggested that cold exposure inhibited hypothalamic Kiss-1 gene expression during the early stage of development, decreased serum leptin concentration, and delayed reproductive development in male Brandt's voles. | 25,145,442 | [
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Liquid crystal size selection of large-size graphene oxide for size-dependent N-doping and oxygen reduction catalysis. | Graphene oxide (GO) is aqueous-dispersible oxygenated graphene, which shows colloidal discotic liquid crystallinity. Many properties of GO-based materials, including electrical conductivity and mechanical properties, are limited by the small flake size of GO. Unfortunately, typical sonochemical exfoliation of GO from graphite generally leads to a broad size and shape distribution. Here, we introduce a facile size selection of large-size GO exploiting liquid crystallinity and investigate the size-dependent N-doping and oxygen reduction catalysis. In the biphasic GO dispersion where both isotropic and liquid crystalline phases are equilibrated, large-size GO flakes (>20 μm) are spontaneously concentrated within the liquid crystalline phase. N-Doping and reduction of the size-selected GO exhibit that N-dopant type is highly dependent on GO flake size. Large-size GO demonstrates quaternary dominant N-doping and the lowest onset potential (-0.08 V) for oxygen reduction catalysis, signifying that quaternary N-dopants serve as principal catalytic sites in N-doped graphene. | 25,145,457 | [
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A multicenter phase I dose escalation trial to evaluate safety and tolerability of intra-arterial temozolomide for patients with advanced extremity melanoma using normothermic isolated limb infusion. | L-phenylalanine mustard (LPAM) has been the standard for use in regional chemotherapy (RC) for unresectable in-transit melanoma. Preclinical data demonstrated that regional temozolomide (TMZ) may be more effective. Patients with AJCC Stage IIIB or IIIC extremity melanoma who failed previous LPAM-based RC were treated with TMZ via isolated limb infusion (ILI) according to a modified accelerated titration design. Drug pharmacokinetic (PK) analysis, tumor gene expression, methylation status of the O6-methylguanine methyltransferase (MGMT) promoter, and MGMT expression were evaluated. Primary objectives were to (1) determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of TMZ via ILI and (2) explore biomarker correlates of response. 28 patients completed treatment over 2.5 years at 3 institutions. 19 patients were treated at the MTD defined as 3,200 mg/m(2) [multiplied by 0.09 (arm), 0.18 (leg)]. Two of five patients had DLTs at the 3,600 mg/m(2) level while only grade 1 (n = 15) and grade 2 (n = 4) clinical toxicities occurred at the MTD. At 3-month post-ILI, 10.5 % (2/19) had CR, 5.3 % (1/19) had PR, 15.8 % (3/19) had SD, and 68.4 % (13/19) had PD. Neither PK parameters of TMZ nor MGMT levels were associated with response or toxicity. In this first ever use of intra-arterial TMZ in ILI for melanoma, the MTD was determined. While we could not define a marker for TMZ response, the minimal toxicity of TMZ ILI may allow for repeated treatments to increase the response rate as well as clarify the role of MGMT expression. | 25,145,500 | [
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Genome-wide association study of survival in early-stage non-small cell lung cancer. | Lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths all over the world. Studies have indicated that molecular biomarkers, including genetic variants, may provide additional values for the targeted treatments and clinical outcomes of NSCLC patients. To better understand the effects of molecular biomarkers on the treatment of NSCLC, we conducted a genome-wide analysis to investigate the prognostic implications of genetic variants in early-stage NSCLC patients with surgery. A genome wide scan of 906,703 single-nucleotide polymorphisms (SNPs) was conducted in a cohort with 365 early-stage NSCLC patients with surgery, followed by a fast-track replication in another independent cohort of 327 NSCLC patients from Nanjing, China. Cox models were used to screen and validate significant SNPs associated with the overall survival of early-stage NSCLC patients. We found that rs10023113 in calcium/calmodulin-dependent protein kinase II delta (CAMK2D) was consistently associated with survival of early-stage NSCLC in the GWAS scan and the replication cohort [GWAS scan: hazard ratio (HR) 2.84; 95 % confidence interval (CI) 1.90-4.23, P = 1.29 × 10(-6); replication cohort: HR 2.19, 95 % CI 1.15-4.21, P = 1.80 × 10(-2)]. When combining all the patients, the results showed that the variant allele of rs10023113 was significantly associated with poor prognosis of early-stage NSCLC with P value of 3.40 × 10(-7) (HR 2.30, 95 % CI 1.67-3.17). These findings suggest that CAMK2D rs10023113 may be a potentially prognostic marker for overall survival of early-stage NSCLC patients in Chinese population. | 25,145,502 | [
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Clinical significance of thrombocytosis before preoperative chemoradiotherapy in rectal cancer: predicting pathologic tumor response and oncologic outcome. | Thrombocytosis is considered an adverse prognostic factor in various malignancies. However, the clinical significance of thrombocytosis in rectal cancer patients is unknown. We investigated the predictive value of thrombocytosis for pathologic tumor response to preoperative chemoradiotherapy (CRT) and oncologic outcomes in patients with rectal cancer. A total of 314 patients who underwent preoperative CRT and subsequent rectal resection for rectal cancer were retrospectively evaluated at two tertiary institutions. Univariate and multivariate analyses of the clinical parameters were performed to identify markers predictive of a pathologic complete response (pCR). The Kaplan-Meier method was used to estimate 3-year disease-free and overall survival rates. Sixty-nine patients (22 %) had thrombocytosis before CRT, which significantly correlated with a large tumor size and advanced tumor depth. Thirty-nine patients (12.4 %) achieved a pCR. In the multivariate analyses, a platelet count of <370,000/μl (odds ratio 5.483; 95 % confidence interval, 1.271-23.653; P = 0.023) and a carcinoembryonic antigen (CEA) level of <5 ng/dl (odds ratio, 3.084; 95 % confidence interval, 1.291-7.368; P = 0.011) were identified as independent predictive factors for a pCR. Patients with pretreatment thrombocytosis had lower 3-year disease-free (P = 0.037) and overall survival (P = 0.001) rates than patients with normal pretreatment platelet counts. Thrombocytosis is a negative predictive factor for a pCR and has an adverse impact on survival in rectal cancer. The predictive value of this easily available clinical factor should not be underestimated, and better therapeutic strategies for these tumors are required. | 25,145,505 | [
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Mesenchymal stem cells, not conditioned medium, contribute to kidney repair after ischemia-reperfusion injury. | Studies have shown that stem cells exert their therapeutic effects on acute kidney injury (AKI) through paracrine/endocrine actions. If the protective effect is mediated in an endocrine manner, the injection of the factors that these cells secrete could be effective, but the effect of conditioned medium (CM) remains controversial. In this study, we cultured mesenchymal stem cells (MSCs) and then transplanted them into an ischemia-reperfusion (I/R) injury model. CM was also injected into mice, and the histological changes, level of cell proliferation, loss of peritubular capillaries and anti-inflammatory and anti-apoptotic effects were examined at different time points. The results showed that MSC infusion improved renal function and histological alterations, leading to significantly reduced mortality. MSC administration also promoted kidney microvasculature repair, attenuated kidney peritubular capillary loss, increased the proliferation of parenchymal cells and decreased CD68-positive macrophage infiltration and apoptotic cells. Although we determined that CM contained proangiogenic factors, including hepatocyte growth factor (HGF), vascular endothelial growth factor-A (VEGF-A) and insulin-like growth factor-1 (IGF-1), no favorable effects were observed during the course of repair. Our data show that MSC infusion promotes kidney repair in a variety of ways, including enhancement of the repair of peritubular capillaries and tubular epithelial cells and anti-inflammatory and anti-apoptotic effects. MSCs can secrete high levels of proangiogenic growth factors, but CM results in a nonsignificant improvement, indicating that MSCs play a role in kidney repair through paracrine rather than endocrine mechanisms. These results indicate that MSC infusion is a promising therapeutic strategy for promoting kidney repair after injury. | 25,145,540 | [
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Improved sensitivity of the nano ultra-high performance liquid chromatography-tandem mass spectrometric analysis of low-concentrated neuropeptides by reducing aspecific adsorption and optimizing the injection solvent. | Obtaining maximal sensitivity of nano UHPLC-MS/MS methods is primordial to quantify picomolar concentrations of neuropeptides in microdialysis samples. Since aspecific adsorption of peptides to Eppendorf tubes, pipette tips and UHPLC vials is detrimental for method sensitivity, a strategy is presented to reduce adsorption of these peptides during standard preparation. Within this respect, all procedural steps from dissolution of the lyophilized powder until the injection of the sample onto the system are investigated. Two peptides of the neuromedin family, i.e. neuromedin B and neuromedin N, and a neuromedin N-related neuropeptide, neurotensin, are evaluated. The first part of this study outlines a number of parameters which are known to affect peptide solubility. The main focus of the second part involves the optimization of the sample composition in the UHPLC vial by using design of experiments. Contradictory findings are observed concerning the influence of acetonitrile, salts and matrix components. They are found important for injection of the peptides into the system, but crucially need to be excluded from the dilution solvent. Furthermore, the type of surface material, temperature and the pipetting protocol considerably affect the adsorption phenomenon. Statistical analysis on the results of the central composite design reveals that the highest peptide responses are obtained with the injection solvent consisting of 13.1% V/V ACN and 4.4% V/V FA. This aspect of the optimization strategy can be identified as the main contributor to the gain in method sensitivity. Since the reduction of peptide adsorption and the optimization of the injection solvent resulted in a clear and quantifiable signal of the three peptides, optimization of both issues should be considered in the early stage of method development, in particular when the analysis of low-concentration peptide solutions is envisaged. | 25,145,562 | [
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Occurrence of turbulent flow conditions in supercritical fluid chromatography. | Having similar densities as liquids but with viscosities up to 20 times lower (higher diffusion coefficients), supercritical CO2 is the ideal (co-)solvent for fast and/or highly efficient separations without mass-transfer limitations or excessive column pressure drops. Whereas in liquid chromatography the flow remains laminar in both the packed bed and tubing, except in extreme cases (e.g. in a 75 μm tubing, pure acetonitrile at 5 ml/min), a supercritical fluid can experience a transition from laminar to turbulent flow in more typical operation modes. Due to the significant lower viscosity, this transition for example already occurs at 1.3 ml/min for neat CO2 when using connection tubing with an ID of 127 μm. By calculating the Darcy friction factor, which can be plotted versus the Reynolds number in a so-called Moody chart, typically used in fluid dynamics, higher values are found for stainless steel than PEEK tubing, in agreement with their expected higher surface roughness. As a result turbulent effects are more pronounced when using stainless steel tubing. The higher than expected extra-column pressure drop limits the kinetic performance of supercritical fluid chromatography and complicates the optimization of tubing ID, which is based on a trade-off between extra-column band broadening and pressure drop. One of the most important practical consequences is the non-linear increase in extra-column pressure drop over the tubing downstream of the column which leads to an unexpected increase in average column pressure and mobile phase density, and thus decrease in retention. For close eluting components with a significantly different dependence of retention on density, the selectivity can significantly be affected by this increase in average pressure. In addition, the occurrence of turbulent flow is also observed in the detector cell and connection tubing. This results in a noise-increase by a factor of four when going from laminar to turbulent flow (e.g. going from 0.5 to 2.5 ml/min for neat CO2). | 25,145,564 | [
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Perceived cancer risk and risk attributions among African-American residents of a low-income, predominantly African-American neighborhood. | In some national surveys, African-Americans have had lower scores on perceived cancer risk items than whites. Our goals were to confirm low perceptions of cancer risk in an African-American community sample and explore participants' attributions for their perceived cancer risk. Data were from three cross-sectional surveys. We report levels of perceived absolute and comparative cancer risk in a community sample of African-Americans (N = 88), and African-Americans (Ns = 655, 428) and whites (Ns = 5262, 1679) from two nationally representative Health Information National Trends Surveys (HINTS). We analyzed the content of spontaneously-provided explanations for perceived risk from the community sample. Perceived absolute and comparative cancer risk were lower in the community and national samples of African-Americans than in the national sample of whites. Participants' spontaneous attributions for low or lower than average risk included not having family history or behavioral risk factors, classes of attributions noted elsewhere in the literature. However, participants also explained that they wanted to avoid wishing cancer on themselves (positive affirmations) and hoped their risk was low (wishful thinking), responses rarely reported for majority-white samples. Results provide further evidence that cancer risk perceptions are lower among African-Americans than whites. Some participant explanations for low perceived risk (wishful thinking, affirmations) are inconsistent with behavioral scientists' assumptions about perceived risk questions. Results reveal a need to expand cancer risk attribution typologies to increase applicability to diverse populations, and may indicate that perceived cancer risk questions have lower validity in African-American populations. | 25,145,570 | [
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Multiplexed electrochemical detection of trypsin and chymotrypsin based on distinguishable signal nanoprobes. | In this work, we developed a novel multisignal output for simultaneous detection of multiple proteases by using nanoprobes labeled with distinguishable electrochemical probes. First, biotinylated peptide1 (S1) and biotinylated peptide2 (S2) were associated with biotinylated DNA1 and DNA2 via biotin-streptavidin interaction, forming DNA1-S1 and DNA2-S2, respectively. Two distinguishable signal nanoprobes (DNA1'-Au NPs-Thi and DNA2'-Au NPs-Fc) were prepared by initial assembling DNA1' and DNA2' on the Au NPs surface, respectively, and then carrying corresponding thionine (Thi) and 6-(Ferrocenyl)hexanethiol (Fc). Then, the peptide substrates (DNA1-S1 and DNA2-S2) were immobilized on gold electrode surface through Au-S bonds, and the DNA1'-Au NPs-Thi and DNA2'-Au NPs-Fc were assembled to the peptide-DNA-modified electrode surface via DNA hybridization. The targets of trypsin and chymotrypsin can specifically recognize and cleave peptides with different sequences, releasing DNA1'-Au NPs-Thi and DNA2'-Au NPs-Fc from the electrode surface into solution, thus decreasing the current of Thi and Fc. The decrease in the electrochemical currents of the two signal nanoprobes enables us to simultaneously and quantitatively determine the targets trypsin and chymotrypsin. More importantly, this strategy can be extended easily by designing various proteases-specific peptide substrates and utilizing corresponding electrochemical detectable elements for simultaneous multiplex protease assay in various biosystems. | 25,145,572 | [
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Development of a microsimulation of melanoma mortality for evaluating the effectiveness of population-based skin cancer screening. | A nationwide skin cancer screening (SCS) was implemented in Germany in 2008. It aims at improving early detection of melanoma in order to reduce melanoma mortality. While the idea of early detection is compelling, demonstrating the effectiveness of melanoma screening is crucial. Since it is not feasible to conduct epidemiological studies to investigate the impact of factors such as screening interval or targeted age groups, we developed a microsimulation model that is able to predict melanoma mortality in Germany under several SCS conditions. Using German cancer registry data, population data, and other published data on melanoma progression and screening participation, we developed a stochastic microsimulation model. With this model, 10,000 populations of 100,000 persons and their melanoma-related life histories were simulated separately for women and for men and calibrated to observed melanoma incidence. In a second step, life histories of melanoma were changed by an SCS. Compared with a nonscreening scenario (age-standardized mortality rate: 1.6 and 2.9 per 100,000 for women and men), a biennial SCS of the 35- to 85-year-old population with a participation probability of 20% for each screening-eligible individual and a test sensitivity of 80% reduced mortality by up to 0.7 and 1.4 deaths per 100,000 person-years for women and men, respectively, corresponding to a relative reduction of melanoma mortality by 45% in women and men. We developed a microsimulation model of melanoma mortality that can be used to evaluate the effectiveness of population-based skin cancer screening. The simulation provided plausible melanoma mortality predictions and is a tool for comparing different SCS scenarios. However, it does not provide estimates on total costs of SCS. | 25,145,574 | [
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Salivary cortisol and α-amylase responses to repeated bouts of downhill running. | To determine the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenal (SA) system response to repeated bouts of downhill running. Eleven active but untrained males (age: 19.7 ± 0.4 y; VO2peak 47.8 ± 3.6 ml/kg/min) performed two 60 min bouts of downhill running (-13.5% gradient), separated by 14 days, at a speed eliciting 75% of their VO2peak on a level grade. Saliva samples were collected before (baseline), after, and every hour for 12 h and every 24 h for 6 days after each run. Salivary cortisol and α-amylase levels were measured as markers of the HPA axis and SA response, respectively. Results were analyzed using repeated measures ANOVA (12 h period: 2 × 14; 24 h intervals 2 × 7, P ≤ 0.05) with Tukey post-hoc tests where appropriate. Paired samples t-tests were used to compare collapsed data vs. baseline measurements. There were no significant group × time interactions for cortisol or α-amylase for the hourly samples up to 12 h after each run, nor for the 24 h samples up to 6 days later. The 24 h samples for α-amylase showed a significant group effect between runs (Run 1: 69.77 ± 7.68 vs. Run 2: 92.19 ± 7.67 U/ml; P = 0.04). Significant time effects were measured for both cortisol (decreased 2 h to 12 h post-run) and α-amylase (elevated immediately after, 1 h and 2 h post-run) (P < 0.001). The 24 h period group effect for salivary α-amylase suggested an adaptation in the sympathoadrenal system that may alter the systemic inflammatory response to exercise-induced muscle damage but may also reflect enhanced mucosal immunity. | 25,145,588 | [
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The benzylperoxyl radical as a source of hydroxyl and phenyl radicals. | The benzyl radical (1) is a key intermediate in the combustion and tropospheric oxidation of toluene. Because of its relevance, the reaction of 1 with molecular oxygen was investigated by matrix-isolation IR and EPR spectroscopy as well as computational methods. The primary reaction product of 1 and O2 is the benzylperoxyl radical (2), which exists in several conformers that can easily interconvert even at cryogenic temperatures. Photolysis of radical 2 at 365 nm results in a formal [1,3]-H migration and subsequent cleavage of the O-O bond to produce a hydrogen-bonded complex between the hydroxyl radical and benzaldehyde (4). Prolonged photolysis produces the benzoyl radical (5) and water, which finally yield the phenyl radical (7), CO, and H2O. Thus, via a sequence of exothermic reactions 1 is transformed into radicals of even higher reactivity, such as OH and 7. Our results have implications for the development of models for the highly complicated process of combustion of aromatic compounds. | 25,145,605 | [
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Vagus nerve stimulation magnet activation for seizures: a critical review. | Some patients receiving VNS Therapy report benefit from manually activating the generator with a handheld magnet at the time of a seizure. A review of 20 studies comprising 859 subjects identified patients who reported on-demand magnet mode stimulation to be beneficial. Benefit was reported in a weighted average of 45% of patients (range 0-89%) using the magnet, with seizure cessation claimed in a weighted average of 28% (range 15-67%). In addition to seizure termination, patients sometimes reported decreased intensity or duration of seizures or the post-ictal period. One study reported an isolated instance of worsening with magnet stimulation (Arch Pediatr Adolesc Med, 157, 2003 and 560). All of the reviewed studies assessed adjunctive magnet use. No studies were designed to provide Level I evidence of efficacy of magnet-induced stimulation. Retrospective analysis of one pivotal randomized trial of VNS therapy showed significantly more seizures terminated or improved in the active stimulation group vs the control group. Prospective, controlled studies would be required to isolate the effect and benefit of magnet mode stimulation and to document that the magnet-induced stimulation is the proximate cause of seizure reduction. Manual application of the magnet to initiate stimulation is not always practical because many patients are immobilized or unaware of their seizures, asleep or not in reach of the magnet. Algorithms based on changes in heart rate at or near the onset of the seizure provide a methodology for automated responsive stimulation. Because literature indicates additional benefits from on-demand magnet mode stimulation, a potential role exists for automatic activation of stimulation. | 25,145,652 | [
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Systems level metabolic phenotype of methotrexate administration in the context of non-alcoholic steatohepatitis in the rat. | Adverse drug reactions (ADRs) represent a significant clinical challenge with respect to patient morbidity and mortality. We investigated the hepatotoxicity and systems level metabolic phenotype of methotrexate (MTX) in the context of a prevalent liver disease; non-alcoholic steatohepatitis (NASH). A nuclear magnetic resonance spectroscopic-based metabonomic approach was employed to analyze the metabolic consequences of MTX (0, 10, 40, and 100 mg/kg) in the urine and liver of healthy rats (control diet) and in a model of NASH (methionine-choline deficient diet). Histopathological analysis confirmed baseline (0 mg/kg) liver necrosis, liver inflammation, and lipid accumulation in the NASH model. Administration of MTX (40 and 100 mg/kg) led to liver necrosis in the control cohort, whereas the NASH cohort also displayed biliary hyperplasia and liver fibrosis (100 mg/kg), providing evidence of the synergistic effect of MTX and NASH. The complementary hepatic and urinary metabolic phenotypes of the NASH model, at baseline, revealed perturbation of multiple metabolites associated with oxidative and energetic stress, and folate homeostasis. Administration of MTX in both diet cohorts showed dose-dependent metabolic consequences affecting gut microbial, energy, nucleobase, nucleoside, and folate metabolism. Furthermore, a unique panel of metabolic changes reflective of the synergistic effect of MTX and NASH was identified, including the elevation of hepatic phenylalanine, urocanate, acetate, and both urinary and hepatic formiminoglutamic acid. This systems level metabonomic analysis of the hepatotoxicity of MTX in the context of NASH provided novel mechanistic insight of potential wider clinical relevance for further understanding the role of liver pathology as a risk factor for ADRs. | 25,145,655 | [
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Stage-dependent C-reflex, pain-like behavior and opioid analgesia during the induction of chronic arthritis in rats. | Chronic arthritis (CA) is a common clinical entity associated with persistent pain and limited response to opioid analgesic therapy. However, it is unknown whether these features of CA change depending on its stage of evolution. To address this, in a well-established animal model of CA we studied the time course of electromyographic responses to electrical stimulation of C fibers (C-reflex), pain-like behavior as a response to mechanical nociceptive stimulation, and the inhibition of both responses by a prototypic opioid analgesic, morphine. To induce CA, rats received a single injection of complete Freund's adjuvant into the ankle joint and the C-reflex responses to electrical stimuli or the nociceptive response to paw pressure test were studied 2, 4 or 6 weeks later. The C-reflexes evoked by threshold and supra-threshold electrical stimulation exhibited progressive increases together with enhancement of the nociceptive behavior to mechanical stimulation during induction of monoarthritis. Notably, while systemic morphine produced antinociceptive effects upon both experimental approaches, the effects were markedly reduced during the early stages of CA but enhanced at later stages. These data indicate that C-reflex and pain-like responses evolve in parallel, and are inhibited by morphine in a stage-dependent manner through the induction of CA. The present results may contribute to explain the enhanced pain response and variable analgesic efficacy of opioids that characterize arthritic pain in humans. | 25,145,673 | [
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Hyperammonia induces specific liver injury through an intrinsic Ca2+-independent apoptosis pathway. | Numerous pathological processes that affect liver function in patients with liver failure have been identified. Among them, hyperammonia is one of the most common phenomena.The purpose of this study was to determine whether hyperammonia could induced specific liver injury. Hyperammonemic cells were established using NH4Cl. The cells were assessed by MTT, ELISA, and flow cytometric analyses. The expression levels of selected genes and proteins were confirmed by quantitative RT-PCR and western blot analyses. The effects of 20 mM NH4Cl pretreatment on the cell proliferation and apoptosis of primary hepatocytes and other cells were performed by MTT assays and flow cytometric analyses. Significant increasing in cytotoxicity and apoptosis were only observed in hepatocytes. The cell damage was reduced after adding BAPTA-AM but unchanged after adding EGTA. The expression levels of caspase-3, cytochrome C, calmodulin, and inducible nitric oxide synthase were increased and that of bcl-2 was reduced. The Na+-K+-ATPase activities in hyperammonia liver cells was no signiaficant difference compaired with the control group, but was decreased in astrocytes. NH4Cl pretreatment of primary hepatocytes promoted the activation of mitochondrial permeability transition pores and the mitochondria swelled irregularly. Hyperammonia induces specific liver injury through an intrinsic Ca2+-independent apoptosis pathway. | 25,145,683 | [
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Addressing adolescent pregnancy with legislation. | Adolescent pregnancy is a concern among many women's health practitioners. While it is practical and appropriate to work to prevent adolescent pregnancy by educating adolescents in health care clinics, schools and adolescent-friendly community-based organizations, suggesting and supporting legislative efforts to reduce adolescent pregnancy can help address the issue on an even larger scale. This article aims to help nurses better understand current legislation that addresses adolescent pregnancy, and to encourage support of future adolescent pregnancy prevention legislation. | 25,145,716 | [
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Overview of latest evidence on uterine fibroids. | Uterine fibroids are the most common type of benign gynecologic mass, and are present in up to 80 percent of women. Research exploring risk factors for fibroids presents conflicting or inconclusive findings. Symptoms for up to 50 percent of women experiencing fibroids include heavy menstrual bleeding, pelvic pressure or pain and gastrointestinal and genitourinary changes. Diagnosis is made by history and symptoms, physical examination and imaging. Several treatment options are available, and are based on symptoms, preferences and reproductive plans. Given the high prevalence of fibroids and the potential for women's health implications, it is essential that clinicians are aware of the latest evidence regarding fibroids to provide the highest quality of care for women whose health is affected by this condition. | 25,145,720 | [
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A quality improvement project focused on women's perceptions of skin-to-skin contact after cesarean birth. | A quality improvement (QI) project was designed to identify women's perceptions of the benefits of skin-to-skin contact with newborns immediately following cesarean birth. Women reported positive experiences associated with skin-to-skin contact with their newborns. A major theme that emerged was that women who had cesarean birth felt that this QI project resulted in a birthing experience comparable to that of mothers who had vaginal deliveries. Participants also experienced decreased anxiety regarding the health and welfare of their newborns, as compared to a previous cesarean birth experience in which they did not have skin-to-skin contact. | 25,145,718 | [
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Population health outcome models in suicide prevention policy. | Suicide is a leading cause of death in the U.S. and results in immense suffering and significant cost. Effective suicide prevention interventions could reduce this burden, but policy makers need estimates of health outcomes achieved by alternative interventions to focus implementation efforts. To illustrate the utility of health outcome models to help in achieving goals defined by the National Action Alliance for Suicide Prevention's Research Prioritization Task Force. The approach is illustrated specifically with psychotherapeutic interventions to prevent suicide reattempt in emergency department settings. A health outcome model using decision analysis with secondary data was applied to estimate suicide attempts and deaths averted from evidence-based interventions. Under optimal conditions, the model estimated that over 1 year, implementing evidence-based psychotherapeutic interventions in emergency departments could decrease the number of suicide attempts by 18,737, and if offered over 5 years, it could avert 109,306 attempts. Over 1 year, the model estimated 2,498 fewer deaths from suicide, and over 5 years, about 13,928 fewer suicide deaths. Health outcome models could aid in suicide prevention policy by helping focus implementation efforts. Further research developing more sophisticated models of the impact of suicide prevention interventions that include a more complex understanding of suicidal behavior, longer time frames, and inclusion of additional outcomes that capture the full benefits and costs of interventions would be helpful next steps. | 25,145,731 | [
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A review of evidence-based follow-up care for suicide prevention: where do we go from here? | Follow-up services are an important component of a comprehensive, national strategy for suicide prevention. Increasing our knowledge of effective follow-up care has been identified as an Aspirational Goal by The National Action Alliance for Suicide Prevention's Research Prioritization Task Force. Several recent comprehensive reviews informed the selection of studies included in this brief review. Studies of follow-up services that reported significant effects for the outcomes of death by suicide, suicide attempts, or suicidal ideation were included. Although there is a paucity of research in this area, promising paradigms that have demonstrated effectiveness in preventing suicide and suicide attempts and reducing suicidal ideation will be discussed. The major limitations of the literature in this area include numerous methodological flaws in the design and analyses of such studies and the lack of replication of studies with positive findings. This paper identifies several breakthroughs that would be helpful for advancing this area of research and describes a comprehensive research pathway for achieving both short- and long-term research objectives. | 25,145,741 | [
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Adsorption-geometry induced transformation of self-assembled nanostructures of an aldehyde molecule on Cu(110). | From an interplay of high-resolution STM imaging/manipulation and DFT calculations, we have revealed that different self-assembled nanostructures of BA molecules on Cu(110) are attributable to specific molecular adsorption geometries, and thus the corresponding intermolecular hydrogen bonding patterns. The STM manipulations demonstrate the feasibility of switching such weak-hydrogen-bonding patterns. | 25,145,767 | [
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Decreasing hepatitis B viral load is associated with a risk of significant liver fibrosis in hepatitis B e antigen positive chronic hepatitis B. | Alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA levels and age are used commonly to assess liver histology in chronic hepatitis B. Increasing levels of HBV DNA are associated with the increasing prevalence of significant fibrosis in HBeAg-negative patients. It is unclear whether these data can be applied to HBeAg-positive patients. In present study, liver biopsies were performed and clinical parameters were measured in 234 treatment-naive chronic HBeAg-positive patients. The proportion of significant fibrosis in patients with ALT 1-2 × ULN was similar to in patients with ALT more than 2 × ULN (48.4% vs. 51.8%). Patients over 30 years of age (>30 years) had a higher prevalence of significant fibrosis than patients 30 years of age and younger (61.0% vs. 33.6%). Negative correlation between HBV DNA levels and significant fibrosis was observed in patients >30 years. The optimal level of serum HBV DNA to evaluate low risk of significant fibrosis was ≥6.7 log10 IU/ml. Patients with serum HBV DNA levels ≥8.5 log10 IU/ml all had no significant fibrosis, however, patients with HBV DNA levels <4.7 log10 IU/ml all had significant fibrosis. Logistic regressions showed that age, aspartate aminotransferase, platelet count, and HBV DNA levels were independent predictors of significant fibrosis. In summary, older age, elevated ALT, and lower HBV DNA levels are associated with significant fibrosis. Decreasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis in patients >30 years. The threshold of HBV DNA levels for treatment of HBeAg-positive patients needs to be combined with age. | 25,145,769 | [
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Adiponectin predicts MMP-2 activity independently of obesity. | Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, have been identified in atherosclerotic plaques and have been directly associated with plaque remodelling and vulnerability. Cardiovascular disease (CVD) is related to insulin resistance (IR) and obesity, characterized by changes in plasma levels of inflammatory markers, such as adiponectin and C-reactive protein (CRP). Our aim was to evaluate the impact of both proteins on MMP-2 and MMP-9 behaviour in individuals with IR. Plasma MMP-2 and MMP-9 activity, adiponectin and hs-CRP concentration and lipoprotein profile were determined in 52 patients with metabolic syndrome (MS) and 27 controls. Patients with MS presented significantly higher MMP-2 activity than controls: 0·95 ± 0·12 vs. 0·77 ± 0·15 relative units (RU) (P < 0·001), while MMP-9 activity was not detectable. MMP-2 activity decreased across quartiles of adiponectin, being significantly reduced in individuals with the highest levels of adiponectin in compared with the lowest levels (0·75 ± 0·17 vs. 0·93 ± 0·09 RU, P < 0·005). This difference persisted significant after adjusting by obesity markers. MMP-2 activity was significantly increased in individuals with the highest levels (G3) compared with those with the lowest levels (G1) of hs-CRP (0·94 ± 0·12 vs. 0·86 ± 0·12, P = 0·041) CONCLUSION: In this study, we observed that adiponectin levels predicted MMP-2 plasma activity independently of obesity. This finding suggests that the inflammatory process, associated with the highest CVD risk, would be involved in MMPs vascular production. | 25,145,771 | [
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Promotion of survival and differentiation of neural stem cells with fibrin and growth factor cocktails after severe spinal cord injury. | Neural stem cells (NSCs) can self-renew and differentiate into neurons and glia. Transplanted NSCs can replace lost neurons and glia after spinal cord injury (SCI), and can form functional relays to re-connect spinal cord segments above and below a lesion. Previous studies grafting neural stem cells have been limited by incomplete graft survival within the spinal cord lesion cavity. Further, tracking of graft cell survival, differentiation, and process extension had not been optimized. Finally, in previous studies, cultured rat NSCs were typically reported to differentiate into glia when grafted to the injured spinal cord, rather than neurons, unless fate was driven to a specific cell type. To address these issues, we developed new methods to improve the survival, integration and differentiation of NSCs to sites of even severe SCI. NSCs were freshly isolated from embryonic day 14 spinal cord (E14) from a stable transgenic Fischer 344 rat line expressing green fluorescent protein (GFP) and were embedded into a fibrin matrix containing growth factors; this formulation aimed to retain grafted cells in the lesion cavity and support cell survival. NSCs in the fibrin/growth factor cocktail were implanted two weeks after thoracic level-3 (T3) complete spinal cord transections, thereby avoiding peak periods of inflammation. Resulting grafts completely filled the lesion cavity and differentiated into both neurons, which extended axons into the host spinal cord over remarkably long distances, and glia. Grafts of cultured human NSCs expressing GFP resulted in similar findings. Thus, methods are defined for improving neural stem cell grafting, survival and analysis of in vivo findings. | 25,145,787 | [
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Investigating the physiological roles of low-efficiency D-mannonate and D-gluconate dehydratases in the enolase superfamily: pathways for the catabolism of L-gulonate and L-idonate. | The sequence/function space in the D-mannonate dehydratase subgroup (ManD) of the enolase superfamily was investigated to determine how enzymatic function diverges as sequence identity decreases [Wichelecki, D. J., et al. (2014) Biochemistry 53, 2722-2731]. That study revealed that members of the ManD subgroup vary in substrate specificity and catalytic efficiency: high-efficiency (kcat/KM = 10(3)-10(4) M(-1) s(-1)) for dehydration of D-mannonate, low-efficiency (kcat/KM = 10-10(2) M(-1) s(-1)) for dehydration of D-mannonate and/or D-gluconate, and no activity. Characterization of high-efficiency members revealed that these are ManDs in the D-glucuronate catabolic pathway {analogues of UxuA [Wichelecki, D. J., et al. (2014) Biochemistry 53, 4087-4089]}. However, the genomes of organisms that encode low-efficiency members of the ManDs subgroup encode UxuAs; therefore, these must have divergent physiological functions. In this study, we investigated the physiological functions of three low-efficiency members of the ManD subgroup and identified a novel physiologically relevant pathway for L-gulonate catabolism in Chromohalobacter salexigens DSM3043 as well as cryptic pathways for L-gulonate catabolism in Escherichia coli CFT073 and L-idonate catabolism in Salmonella enterica subsp. enterica serovar Enteritidis str. P125109. However, we could not identify physiological roles for the low-efficiency members of the ManD subgroup, allowing the suggestion that these pathways may be either evolutionary relics or the starting points for new metabolic potential. | 25,145,794 | [
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Bidirectional citation searching to completion: an exploration of literature searching methods. | Literature reviews underpin the majority of research projects in the health sciences, and yet relatively little analysis has been published as to the most appropriate method to identify relevant literature, outside of specialist information journals. The method of applying keyword search queries to bibliographic databases using Boolean logic dominates literature reviews due to its easy application to the major online databases. However, it is recognised increasingly as being problematic where the research question cannot be clearly defined or requires an element of exploration, due to its reliance on author's use of titling and keywords and is unable to identify topics other than those defined in the search query. This paper discusses the relative merits of a systematic citation searching approach as both an alternative and a concurrent method to keyword searching. A method of citation searching, both forwards and backwards, which is iterated to form a closed loop solution, is discussed. An illustrative example is presented of both methods, applying them to the topic of the UK National Institute for Health and Care Excellence (NICE) cost-effectiveness threshold. The case study finds the citation searching approach dominates the traditional keyword searching approach, finding 76 papers of relevance, including all 15 found by the alternative approach. Conceptually, and in the example presented, it is demonstrated that the proposed method can represent a dominant strategy to the more traditional approach in some situations, highlighting that, wherever possible, it is preferential to employ multiple methods of searching. However, it is clear that a better understanding is required as to how we can most efficiently search the ever-growing sea of literature. | 25,145,803 | [
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The effects of epistaxis on health-related quality of life in patients with hereditary hemorrhagic telangiectasia. | Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease mainly characterized by epistaxis in more than 96% of patients. Recently, a validated questionnaire known as the HHT Epistaxis Severity Score (ESS) was developed. However, little is known about the relationship between epistaxis and quality of life. We hypothesize that epistaxis severity is a major factor predicting health-related quality of life (HR-QoL) in HHT patients. This is a cross-sectional study. The ESS questionnaire and Medical Outcomes Study 36-item short form (SF-36) were administered to subjects through an Internet survey. All participants had a definitive diagnosis of HHT through Curaçao criteria or genetic testing. Demographic information, genetics, and extensive histories were also collected. Descriptive analyses were performed with calculations of means and standard deviations (SDs) for continuous variables and proportions for categorical variables. Linear regressions were then performed to assess the association between HR-QoL and ESS. A total of 604 subjects participated between April and August 2008. All patients reported epistaxis, 285 (47.2%) had telangiectasias, and 545 (90.2%) had a family history of HHT; 167 (27.6%) patients had mild epistaxis (ESS <4), 285 (47.2%) reported moderate epistaxis (≥4 ESS <7), and 152 (25.2%) reported severe epistaxis (ESS ≥7). Patients with severe epistaxis had lower scores for both the Physical Component Summary (PCS) and the Mental Component Summary (MCS) of HR-QoL when compared to those with mild epistaxis (p < 0.001, p < 0.001). The ESS is a major determinant of HR-QoL and should be considered as a measurement of treatment efficacy in HHT-related epistaxis. | 25,145,809 | [
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Minimally invasive esophagectomy for dysplastic Barrett's esophagus. | A substantial portion of patients diagnosed preoperatively with high grade dysplasia (HGD) alone will have occult esophageal adenocarcinoma on analysis of the surgical specimen. Therefore, because of an increased risk of disease progression and malignancy, patients with HGD should be referred for esophagectomy promptly when endoscopic therapy has failed. The required extent of lymphadenectomy in this cohort of patients is unknown because of the variable incidence of submucosal cancer observed. Improvements in perioperative care, adoption of a minimally invasive surgical approach, and centralization of esophageal cancer services have substantially reduced the rates of mortality and morbidity associated with esophagectomy in recent years. Minimally invasive esophagectomy should be considered the treatment of choice in patients with dysplastic Barrett's esophagus that is refractory to endoscopic therapy or those at high risk of invasive cancer. | 25,145,822 | [
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Is clinical performance adversely affected by wearing gloves during paediatric peripheral intravenous cannulation? | To investigate if wearing protective gloves during paediatric intravenous cannulation affects performance of the procedure. This was a prospective observational study. Peripheral intravenous cannulation (PIVC) performed within the Paediatric ED was observed and recorded over a 12 month period. Data were compared between those clinicians wearing gloves and those not wearing gloves during PIVC. One thousand and twenty paediatric cannulations were recorded during the observed period. The mean age of the children was 5.79 years. The overall success rate of cannulation was 86.18% and first attempt success rate 76.08%. Overall, gloves were used by 54.31% of clinicians to establish vascular access; glove use was lowest in the registrar group (41.11% compliance rate). The glove-wearing group had comparable overall success rate of 85.74% (475/554) to the no-gloves group of 86.70% (404/466). The difference was not statistically significant (P > 0.05). Higher incidence of significant blood spillage during the procedure was observed among clinicians wearing no gloves (16.74%) in comparison with their glove-wearing counterparts (9.03%, P < 0.05). One needlestick injury was recorded in the present study period. There was no difference in blood culture contamination rate between glove-wearing group and no-gloves group (3.94% vs 3.76%, P > 0.05). The present study shows that the use of protective gloves was not associated with adverse outcomes of clinical performance during paediatric cannulation. The low compliance rate of gloves use is alarming, and many clinicians might be exposed to potential blood-borne infections. Clinicians should be encouraged and supported to use gloves for paediatric cannulation. | 25,145,829 | [
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Kinetic resolution of 1,1'-biaryl-2,2'-diols and amino alcohols through NHC-catalyzed atroposelective acylation. | We present here a highly efficient NHC-catalyzed kinetic resolution of a wide range of 1,1'-biaryl-2,2'-diols and amino alcohols to provide them in uniformly ≥99% ee. This represents the first highly enantioselective catalytic acylation of axially chiral alcohols. The aldehyde backbone that is incorporated into the chiral acyl azolium intermediate was found to have a significant effect on the enantioselectivity of the process. | 25,145,856 | [
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Small molecule activation by POC(sp3)OP-nickel complexes. | This contribution describes the reactivities of CO2 , CO, O2 , and ArNC with the pincer-type complexes [(κ(P) ,κ(C) ,κ(P') -POC sp 3OP)NiX] (POC sp 3OP=(R2 POCH2 )2 CH; R=iPr; X=OSiMe3 , NArH; Ar=2,6-iPr2 C6 H3 ). Reaction of the amido derivative with CO2 and CO leads to a simple insertion into the NiN bond to give stable carbamate and carbamoyl derivatives, respectively, the pincer ligand backbone remaining intact in both cases. In contrast, the analogous reactions with the siloxide derivative produced kinetically labile insertion products that either revert to the starting material (in the case of CO2 ) or react further to give the mixed-valent, dinickel species [(POC sp 3OP)Ni(II) {μ,κ(O) ,κ(P) ,κ(P') -OCOCH(CH2 CH2 OPR2 )2 }Ni(0) (CO)2 ]. The zero-valent center in the latter compound is ligated by a new ligand arising from transformation of the POC sp 3OP ligand backbone. The carbonylation and carboxylation of the siloxido derivative also produced minor quantities of a side-product identified as the trinickel species, [{(η(3) -allyl)Ni(μ(O) ,κ(P) -R2 PO)2 }2 Ni], arising from total dismantling of the POC sp 3OP ligand. Similar reactivities were observed with isonitrile, ArNC: reaction with the siloxido derivative resulted in a complex sequence of steps involving initial insertion, a 1,3-hydrogen shift, and an Arbuzov rearrangement to give [Ni(CNAr)4 ] and a methacrylamide based on fragments of the POC sp 3OP ligand. Oxygenation of the amido and siloxido derivatives led to the phosphinate derivative, [(POC sp 3OP)Ni(OP(O)R2 )], arising from oxidative transformation of the original ligand frame; the reaction with the Ni-NHAr derivative also gave ArHNP(O)R2 through a complex NP bond-forming reaction. | 25,145,857 | [
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Expression of toll-like receptors and co-stimulatory molecules in lymphoid tissue during experimental infection of beef calves with bovine viral diarrhea virus of low and high virulence. | The objective of this study was to compare the mRNA expression of Toll-like receptors (TLR3 and TLR7), and costimulatory molecules involved in activation of lymphocytes and antigen presenting cells (CD80, CD86, CD28, and CD40L) after experimental infection of beef calves with low or high virulence noncytopathic (ncp) bovine viral diarrhea virus (BVDV) strains. Thirty BVDV-naïve, beef calves were intranasally inoculated with low (LV; n=10, SD-1) or high (HV; n=10, 1373) virulence ncp BVDV or with BVDV-free cell culture medium (Control, n=10). Calves were euthanized on day 5 post-inoculation and tracheo-bronchial lymph node (TBLN) and spleen samples were collected for mRNA expression through quantitative-RT-PCR. Levels of mRNA for TLR3 and TLR7 were increased in spleen of HV group (P<0.05), but not in LV group, compared to the control group. Expression of CD86 mRNA was up-regulated in TBLN of both LV and HV groups (P<0.05). A significant up-regulation of CD80 mRNA was observed in TBLN for LV calves (P<0.05), but not for HV calves. In conclusion, experimental inoculation with high virulence BVDV-2 1373 stimulated the expression of TLR3, TLR7 and CD86 in spleen and TBLN on day 5 post infection. In contrast, experimental challenge with the low virulence BVDV-1 SD-1 uniquely resulted in up-regulation of both CD80 and CD86 in TBLN samples on day 5 post infection. The observed differential expression during acute infection with high or low virulence BVDV might reflect differences in immune activation by these strains, which could be associated with differences in genotype and/or virulence. | 25,145,871 | [
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Masked smoothing using separable kernels for CT perfusion images. | CT perfusion images have a high contrast ratio between voxels representing different anatomy, such as tissue or vessels, which makes image segmentation of tissue and vascular regions relatively easy. However, grey and white matter tissue regions have relatively low values and can suffer from poor signal to noise ratios. While smoothing can improve the image quality of the tissue regions, the inclusion of much higher valued vascular voxels can skew the tissue values. It is thus desirable to smooth tissue voxels separately from other voxel types, as has been previously implemented using mean filter kernels. We created a novel Masked Smoothing method that performs Gaussian smoothing restricted to tissue voxels. Unlike previous methods, it is implemented as a combination of separable kernels and is therefore fast enough to consider for clinical work, even for large kernel sizes. We compare our Masked Smoothing method to alternatives using Gaussian smoothing on an unaltered image volume and Gaussian smoothing on an image volume with vascular voxels set to zero. Each method was tested on simulation data, collected phantom data, and CT perfusion data sets. We then examined tissue voxels for bias and noise reduction. Simulation and phantom experiments demonstrate that Masked Smoothing does not bias the underlying tissue value, whereas the other smoothing methods create significant bias. Furthermore, using actual CT perfusion data, we demonstrate significant differences in the calculated CBF and CBV values dependent on the smoothing method used. The Masked Smoothing is fast enough to allow eventual clinical usage and can remove the bias of tissue voxel values that neighbor blood vessels. Conversely, the other Gaussian smoothing methods introduced significant bias to the tissue voxels. | 25,145,879 | [
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High-load strength training improves outcome in patients with plantar fasciitis: A randomized controlled trial with 12-month follow-up. | The aim of this study was to investigate the effectiveness of shoe inserts and plantar fascia-specific stretching vs shoe inserts and high-load strength training in patients with plantar fasciitis. Forty-eight patients with ultrasonography-verified plantar fasciitis were randomized to shoe inserts and daily plantar-specific stretching (the stretch group) or shoe inserts and high-load progressive strength training (the strength group) performed every second day. High-load strength training consisted of unilateral heel raises with a towel inserted under the toes. Primary outcome was the foot function index (FFI) at 3 months. Additional follow-ups were performed at 1, 6, and 12 months. At the primary endpoint, at 3 months, the strength group had a FFI that was 29 points lower [95% confidence interval (CI): 6-52, P = 0.016] compared with the stretch group. At 1, 6, and 12 months, there were no differences between groups (P > 0.34). At 12 months, the FFI was 22 points (95% CI: 9-36) in the strength group and 16 points (95% CI: 0-32) in the stretch group. There were no differences in any of the secondary outcomes. A simple progressive exercise protocol, performed every second day, resulted in superior self-reported outcome after 3 months compared with plantar-specific stretching. High-load strength training may aid in a quicker reduction in pain and improvements in function. | 25,145,882 | [
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Intravascular lymphoma: an unusual cause of rapid cognitive decline and the role of brain biopsy. | Intravascular lymphoma (IVL) is a rare extra nodal variant of non Hodgkin's lymphoma characterised by neoplastic lymphoid cells growing inside the lumina of medium and small vessels. IVL limited to the central nervous system (CNS) is an extremely rare condition as IVL is usually found with systemic lesions. Most cases of IVL are not diagnosed until post mortem because of variable clinical presentation and non-specific laboratory findings. Even if diagnosed early the disease is clinically aggressive and usually fatal, even with early detection and treatment. We present a case of a 37-year-old woman with a short history of behavioural abnormality, rapidly progressive cognitive decline and seizures. There were no cutaneous manifestations. Diagnosis was established only after the brain biopsy. The case is presented for the rarity of its presentation and role of brain biopsy in diagnosis. | 25,145,897 | [
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Paragangliomas: presentation and management by radiotherapy at the Prince of Wales Hospital. | Paragangliomas are commonly treated with surgery, while radiotherapy is reserved for those that are inoperable or have relapsed. However, this retrospective study aims to determine whether radiotherapy is a viable initial treatment for paragangliomas. Of 73 tumours researched, 44 were diagnosed and treated from January 1967 to December 2012 at the Radiation Oncology Department at the Prince of Wales Hospital and thus were eligible for analysis. Median follow-up time was 3.5 years with a range of 1 to 40 years. Thirty-four tumours were treated with radiotherapy only, and 10 tumours were treated with both surgical resection and radiotherapy. Local control and cause-specific survival were the primary end points measured. Five-year local control rate for the population of 44 lesions was 89%; it was 100% in the group treated by radiotherapy alone, but only 50% in the group treated by surgery followed by radiotherapy, with radiation used for salvage. The difference in control rates between these two subset groups was found to be statistically significant (P < 0.001). Cause-specific survival rates for this eligible population at 5 and 10 years were 98% and 90%, respectively. After initial radiotherapy, 4 patients had improved cranial nerve function, there was clinical improvement in tinnitus, and one new cranial nerve deficit developed where a high dose was used. Radiotherapy has high local control rates and few complications. The local control and complication rates compare favourably to surgery. | 25,145,920 | [
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0.34... |
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