Advanced manufacturing rules check (MRC) for fully automated assessment of complex reticle designs

NASA Astrophysics Data System (ADS)

Gladhill, R.; Aguilar, D.; Buck, P. D.; Dawkins, D.; Nolke, S.; Riddick, J.; Straub, J. A.

2005-11-01

Advanced electronic design automation (EDA) tools, with their simulation, modeling, design rule checking, and optical proximity correction capabilities, have facilitated the improvement of first pass wafer yields. While the data produced by these tools may have been processed for optimal wafer manufacturing, it is possible for the same data to be far from ideal for photomask manufacturing, particularly at lithography and inspection stages, resulting in production delays and increased costs. The same EDA tools used to produce the data can be used to detect potential problems for photomask manufacturing in the data. A production implementation of automated photomask manufacturing rule checking (MRC) is presented and discussed for various photomask lithography and inspection lines. This paper will focus on identifying data which may cause production delays at the mask inspection stage. It will be shown how photomask MRC can be used to discover data related problems prior to inspection, separating jobs which are likely to have problems at inspection from those which are not. Photomask MRC can also be used to identify geometries requiring adjustment of inspection parameters for optimal inspection, and to assist with any special handling or change of routing requirements. With this foreknowledge, steps can be taken to avoid production delays that increase manufacturing costs. Finally, the data flow implemented for MRC can be used as a platform for other photomask data preparation tasks.

Numerical study of flow, combustion and emissions characteristics in a 625 MWe tangentially fired boiler with composition of coal 70% LRC and 30% MRC

NASA Astrophysics Data System (ADS)

Sa'adiyah, Devy; Bangga, Galih; Widodo, Wawan; Ikhwan, Nur

2017-08-01

Tangential fired boiler is one of the methods that can produce more complete combustion. This method applied in Suralaya Power Plant, Indonesia. However, the boiler where supposed to use low rank coal (LRC), but at a given time must be mixed with medium rank coal (MRC) from another unit because of lack of LRC coal. Accordingly to the situation, the study about choosing the right position of LRC and MRC in the burner elevation must be investigated. The composition of coal is 70%LRC / 30%MRC where MRC will be placed at the lower (A & C - Case I)) or higher (E & G - Case II) elevation as the cases in this study. The study is carried out using Computational Fluid Dynamics (CFD) method. The simulation with original case (100%LRC) has a good agreement with the measurement data. As the results, MRC is more recommended at the burner elevation A & C rather than burner elevation E & G because it has closer temperature (880 K) compared with 100%LRC and has smaller local heating area between upper side wall and front wall with the range of temperature 1900 - 2000 K. For emissions, case I has smaller NOx and higher CO2 with 104 ppm and 15,6%. Moreover, it has samller O2 residue with 5,8% due to more complete combustion.

The influence of non-DNA-targeted effects on carbon ion–induced low-dose hyper-radiosensitivity in MRC-5 cells

PubMed Central

Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

2016-01-01

Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation–induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion–induced LDHRS. PMID:26559335

Protective Effect of Crocodile Hemoglobin and Whole Blood Against Hydrogen Peroxide-Induced Oxidative Damage in Human Lung Fibroblasts (MRC-5) and Inflammation in Mice.

PubMed

Phosri, Santi; Jangpromma, Nisachon; Patramanon, Rina; Kongyingyoes, Bunkerd; Mahakunakorn, Pramote; Klaynongsruang, Sompong

2017-02-01

A putative protective effect of cHb and cWb against H 2 O 2 -induced oxidative damage was evaluated in detail using MRC-5 cells. In addition, the carrageenan (Carr)-induced mouse paw edema model and the cotton pellet-induced granuloma model were employed to examine the in vivo anti-inflammatory activity of cHb and cWb in mice. It was demonstrated that both cHb and cWb treatments significantly increased cell viability and inhibited morphology alterations in MRC-5 cells exposed to H 2 O 2 . Orally administered cHb and cWb significantly reduced Carr-induced paw edema volume and cotton pellet-induced granuloma formation. Moreover, cHb and cWb decreased the expression levels of important pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), while only cWb was found to increase the expression of the anti-inflammatory cytokine IL-10 significantly. Finally, the activity of antioxidant enzymes (SOD, CAT, and GPx) in the liver improved after cHb and cWb treatment under acute and chronic inflammation. Taken collectively, the results of this study suggest that both cHb and cWb protect against hydrogen peroxide-induced damage in fibroblast cells. Moreover, cHb and cWb were found to exhibit anti-inflammatory activity in both the acute and chronic stages of inflammation and appear to enhance antioxidant enzyme activity and decrease lipid peroxidation in the livers of mice. Therefore, this study indicates that cHb and cWb have great potential to be used in the development of dietary supplements for the prevention of oxidative stress related to inflammatory disorders.

The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress

PubMed Central

Melnik, Andre; Wilson-Zbinden, Caroline; Schellhaas, René; Kastner, Lisa; Piwko, Wojciech; Dees, Martina; Picotti, Paola; Maric, Marija; Labib, Karim; Luke, Brian; Peter, Matthias

2016-01-01

Faithful DNA replication and repair requires the activity of cullin 4-based E3 ubiquitin ligases (CRL4), but the underlying mechanisms remain poorly understood. The budding yeast Cul4 homologue, Rtt101, in complex with the linker Mms1 and the putative substrate adaptor Mms22 promotes progression of replication forks through damaged DNA. Here we characterized the interactome of Mms22 and found that the Rtt101Mms22 ligase associates with the replisome progression complex during S-phase via the amino-terminal WD40 domain of Ctf4. Moreover, genetic screening for suppressors of the genotoxic sensitivity of rtt101Δ cells identified a cluster of replication proteins, among them a component of the fork protection complex, Mrc1. In contrast to rtt101Δ and mms22Δ cells, mrc1Δ rtt101Δ and mrc1Δ mms22Δ double mutants complete DNA replication upon replication stress by facilitating the repair/restart of stalled replication forks using a Rad52-dependent mechanism. Our results suggest that the Rtt101Mms22 E3 ligase does not induce Mrc1 degradation, but specifically counteracts Mrc1’s replicative function, possibly by modulating its interaction with the CMG (Cdc45-MCM-GINS) complex at stalled forks. PMID:26849847

Halomethane-induced cytotoxicity and cell proliferation in human lung MRC-5 fibroblasts and NL20-TA epithelial cells.

PubMed

Nájera-Martínez, Minerva; García-Latorre, Ethel A; Reyes-Maldonado, Elba; Domínguez-López, M Lilia; Vega-López, Armando

2012-09-01

Halomethanes (HMs) can be formed during the chlorination process to obtain drinking water. In liver cells, HMs had been shown to be mutagenic and carcinogenic; however, their bioactivation by CYP 2E1 and GSTT1 is required. Although inhalation is the most common pathway of exposure, reports on the toxic effects induced by HMs in human lung are contradictory. The aim of this study was therefore to evaluate in vitro cytotoxicity and cell proliferation induced by CH(2)Cl(2), CHCl(3) and BrCHCl(2) in human lung NL20-TA epithelial cells and MRC-5 fibroblasts, and their relationship with CYP 2E1 and GSTT1 activity. High concentrations of these HMs induced cytotoxicity, particularly in cells treated with BrCHCl(2). Low concentrations of BrCHCl(2) stimulated hyperproliferation of fibroblasts, the most probable consequence of which is regenerative proliferation related to collagen induction. Fibroblasts exposed to BrCHCl(2) exhibited low levels of CYP 2E1 activity suggesting that released bromine is able to alter this activity by affecting the active site or auto regulating the activity itself. GSTT1 was up to ten times more active than CYP 2E1 in both cell lines, indicating that potential lung damage is due to formation of pro-carcinogens such as formaldehyde.

Does age affect outcome in children with clavicle fracture treated conservatively? QuickDash and MRC evaluation of 131 consecutive cases.

PubMed

Pavone, Vito; DE Cristo, Claudia; Testa, Gianluca; Canavese, Federico; Lucenti, Ludovico; Sessa, Giuseppe

2018-04-12

Non-operative treatment with immobilization is the gold-standard for paediatric clavicular fractures. Purpose of this study is to evaluate functional outcomes and efficacy of non-operative treatment of clavicular fractures in a succession of 131 children. Between 2006 and 2012, we treated non-surgically 131 children for a clavicular fracture. All fractures have been classified according to Robinson classification. Clavicle shortening, range of movements and muscular strength through the Medical Research Council (MRC) scale were evaluated. To assess the outcomes, QuickDASH questionnaire, dividing the sample in 3 age-related group, was administered. The average follow-up was 26 months (8-84 months). Clavicle shortening at the time of injury occurred in 18 cases. All fractures reached union. Average time to union was 34 days. Mean time return to activity was 12.6 weeks. No cases of nonunion or delayed union were reported. Complications occurred in 21 cases. A shortening persisted in 2 cases. Only one patient had a slight functional restriction. Average QuickDASH score was 6.2±1.1 (range 4.3-9.4). All patients recovered to a MRC score of 5, except for one patient with a score of 4. Best QuickDASH scores were observed in the group aged under 8 years and in non-comminuted and lateral third fractures of the clavicle. Observing results, clavicle fractures have a satisfactory clinical healing as shown by the good scores at QuickDASH and MRC scale. Younger children under 8 years can achieve the best results with a conservative treatment in terms of bone healing and activity level.

A design of an interface board between a MRC thermistor probe and a personal computer.

DOT National Transportation Integrated Search

2013-09-01

The main purpose of this project was to design and build a prototype of an interface board between an MRC temperature probe : (thermistor array) and a personal laptop computer. This interface board replaces and significantly improve the capabilities ...

Outage Probability of MRC for κ-μ Shadowed Fading Channels under Co-Channel Interference.

PubMed

Chen, Changfang; Shu, Minglei; Wang, Yinglong; Yang, Ming; Zhang, Chongqing

2016-01-01

In this paper, exact closed-form expressions are derived for the outage probability (OP) of the maximal ratio combining (MRC) scheme in the κ-μ shadowed fading channels, in which both the independent and correlated shadowing components are considered. The scenario assumes the received desired signals are corrupted by the independent Rayleigh-faded co-channel interference (CCI) and background white Gaussian noise. To this end, first, the probability density function (PDF) of the κ-μ shadowed fading distribution is obtained in the form of a power series. Then the incomplete generalized moment-generating function (IG-MGF) of the received signal-to-interference-plus-noise ratio (SINR) is derived in the closed form. By using the IG-MGF results, closed-form expressions for the OP of MRC scheme are obtained over the κ-μ shadowed fading channels. Simulation results are included to validate the correctness of the analytical derivations. These new statistical results can be applied to the modeling and analysis of several wireless communication systems, such as body centric communications.

Outage Probability of MRC for κ-μ Shadowed Fading Channels under Co-Channel Interference

PubMed Central

Chen, Changfang; Shu, Minglei; Wang, Yinglong; Yang, Ming; Zhang, Chongqing

2016-01-01

In this paper, exact closed-form expressions are derived for the outage probability (OP) of the maximal ratio combining (MRC) scheme in the κ-μ shadowed fading channels, in which both the independent and correlated shadowing components are considered. The scenario assumes the received desired signals are corrupted by the independent Rayleigh-faded co-channel interference (CCI) and background white Gaussian noise. To this end, first, the probability density function (PDF) of the κ-μ shadowed fading distribution is obtained in the form of a power series. Then the incomplete generalized moment-generating function (IG-MGF) of the received signal-to-interference-plus-noise ratio (SINR) is derived in the closed form. By using the IG-MGF results, closed-form expressions for the OP of MRC scheme are obtained over the κ-μ shadowed fading channels. Simulation results are included to validate the correctness of the analytical derivations. These new statistical results can be applied to the modeling and analysis of several wireless communication systems, such as body centric communications. PMID:27851817

Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field

NASA Astrophysics Data System (ADS)

Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; D'Angelo, Raffaele; Zeni, Olga

2016-01-01

The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components.

Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field

PubMed Central

Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; d’Angelo, Raffaele; Zeni, Olga

2016-01-01

The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components. PMID:26762783

Isolation and characterization of trichothecin from corn cultures of Fusarium graminearum MRC 1125.

PubMed Central

Combrinck, S; Gelderblom, W C; Spies, H S; Burger, B V; Thiel, P G; Marasas, W F

1988-01-01

Trichothecin was isolated and purified from corn cultures of a toxic strain of Fusarium graminearum. This strain, designated MRC 1125, was obtained from corn in southern Africa. The brine shrimp toxicity assay was used throughout the isolation procedure to monitor the toxicity of the fractions. The compound was characterized by detailed 1H (500-MHz) and 13C (125-MHz) nuclear magnetic resonance spectroscopy and mass spectrometry. This is the first report of the production of trichothecin by a Fusarium species. PMID:3415233

Prevalence of overestimation or underestimation of the functional capacity using MRC score as compared to 6-minute walk test in patients with cardio-respiratory disorders.

PubMed

Callens, Etienne; Graba, Sémia; Essalhi, Mohamed; Gillet-Juvin, Karine; Chevalier-Bidaud, Brigitte; Chenu, Romain; Mahut, Bruno; Delclaux, Christophe

2014-09-01

The first objective of our study was to assess whether patients diagnosed with cardio-respiratory disorders report overestimation or underestimation on recall (Medical Research Council (MRC) dyspnea scale) of their true functional capacity (walked distance during a 6-minute walk test (6MWT)). The second objective was to assess whether the measurement of breathlessness at the end of a 6MWT (Borg score) may help to identify dyspneic patients on recall. The 6MWTs of 746 patients aged from 40 to 80 years who were diagnosed with either chronic obstructive pulmonary disease (COPD, n = 355), diffuse parenchymal lung disease (n = 140), pulmonary vascular diseases (n = 188) or congestive heart failure (n = 63) were selected from a prospective Clinical Database Warehouse. The percentage of patients who overestimated (MRC ≤ 2 with distance < lower limit of normal (LLN), 61/746, 8%; 95% confidence interval (CI): 6 to 10%) or underestimated (MRC > 2 with distance ≥LLN, 121/746, 16%; 95%CI: 14 to 19%) on recall their capacity was elevated. The overestimation seemed related to self-limitation, while the underestimation seemed related to patients who "work through" their breathing discomfort. These two latter groups of patients were mainly diagnosed with COPD. A Borg dyspnea score >3 (upper limit of normal) at the end of the 6MWT had 84% specificity for the prediction of a MRC score >1. Almost one fourth of patients suffering from cardio-pulmonary disorders overestimate or underestimate on recall their true functional capacity. An elevated Borg dyspnea score at the end of the 6MWT has a good specificity to predict dyspnea on recall.

The effect of prepartum antibiotics on the type of neonatal bacteraemia: insights from the MRC ORACLE trials.

PubMed

Gilbert, R E; Pike, K; Kenyon, S L; Tarnow-Mordi, W; Taylor, D J

2005-06-01

We analysed the type of bacteraemia before discharge from Neonatal Intensive Care Units in babies born to women randomised to the MRC ORACLE Trials. There was no evidence for an effect of oral antibiotics given prior to delivery on bacteraemia due to gram negative or enterococci bacteria, but Group B streptococcal (GBS) bacteraemia was significantly reduced in women with preterm prelabour rupture of the membranes (1.58% to 0.55%, relative risk 0.34; 95% CI: 0.17-0.70). There was no detectable effect in women in spontaneous preterm labour with intact membranes as the risk of GBS bacteraemia in their babies was very small regardless of treatment.

NASA'S SERVIR Gulf of Mexico Project: The Gulf of Mexico Regional Collaborative (GoMRC)

NASA Technical Reports Server (NTRS)

Quattrochi, Dale A.; Irwin, Daniel; Presson, Joan; Estes, Maury; Estes, Sue; Judd, Kathleen

2006-01-01

The Gulf of Mexico Regional Collaborative (GoMRC) is a NASA-funded project that has as its goal to develop an integrated, working, prototype IT infrastructure for Earth science data, knowledge and models for the five Gulf U.S. states and Mexico, and to demonstrate its ability to help decision-makers better understand critical Gulf-scale issues. Within this preview, the mission of this project is to provide cross cutting solution network and rapid prototyping capability for the Gulf of Mexico region, in order to demonstrate substantial, collaborative, multi-agency research and transitional capabilities using unique NASA data sets and models to address regional problems. SERVIR Mesoamerica is seen as an excellent existing framework that can be used to integrate observational and GIs data bases, provide a sensor web interface, visualization and interactive analysis tools, archival functions, data dissemination and product generation within a Rapid Prototyping concept to assist decision-makers in better understanding Gulf-scale environmental issues.

Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

PubMed Central

Maughan, Timothy S; Adams, Richard A; Smith, Christopher G; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Idziaszczyk, Shelley; Harris, Rebecca; Fisher, David; Kenny, Sarah L; Kay, Edward; Mitchell, Jenna K; Madi, Ayman; Jasani, Bharat; James, Michelle D; Bridgewater, John; Kennedy, M John; Claes, Bart; Lambrechts, Diether; Kaplan, Richard; Cheadle, Jeremy P

2011-01-01

Summary Background In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. Methods In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3–29·2] in the control group vs 17·0 months [9·4–30·1] in the cetuximab group; HR 1·04, 95% CI 0·87–1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0–12·5] in the control group vs 8·6 months [5·1–13·8] in the cetuximab group; HR 0·96, 0·82–1·12, p=0·60). Overall response rate increased from 57% (n=209

Body mass index does not influence post-treatment survival in early stage endometrial cancer: results from the MRC ASTEC trial.

PubMed

Crosbie, Emma J; Roberts, Chris; Qian, Wendi; Swart, Ann Marie; Kitchener, Henry C; Renehan, Andrew G

2012-04-01

Body mass index (BMI) is a major risk factor for endometrial cancer incidence but its impact on post-treatment survival is unclear. We investigated the relationships of BMI (categorised using the WHO definitions) with clinico-pathological characteristics and outcome in women treated within the MRC ASTEC randomised trial, which provides data from patients who received standardised allocated treatments and therefore reduces biases. The impact of BMI on both recurrence-free survival (RFS) and overall survival (OS) was analysed using the Cox regression models. An apriori framework of evaluating potential biases was explored. From 1408 participants, there were 1070 women with determinable BMI (median=29.1 kg/m(2)). Histological types were endometrioid (type 1) in 893 and non-endometrioid (type 2) in 146 women; the proportion of the latter decreasing with increasing BMI (8% versus 19% for obese III WHO category versus normal weight, p(trend)=0.003). For type 1 carcinomas, increasing BMI was associated with less aggressive histopathological features (depth of invasion, p=0.006; tumour grade, p=0.015). With a median follow-up of 34.3 months, there was no influence of BMI on RFS - adjusted HRs per 5 kg/m(2) were 0.98 (95% CI 0.86, 1.13) and 0.95 (0.74, 1.24), for type 1 and 2 carcinomas; and no influence on OS - adjusted HRs per 5 kg/m(2) were 0.96 (0.81, 1.14) and 0.92 (0.70, 1.23), respectively. These findings demonstrate an important principle: that an established link between an exposure (here, obesity) and increased incident cancer risk, does not necessarily translate into an inferior outcome following treatment for that cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Outcomes After Superior Rectus Transposition and Medial Rectus Recession Versus Vertical Recti Transposition for Sixth Nerve Palsy.

PubMed

Lee, Yeon-Hee; Lambert, Scott R

2017-05-01

To compare the effectiveness of superior rectus transposition and medial rectus recession (SRT/MRc) vs inferior and superior rectus transposition (VRT) for acquired sixth nerve palsy. Consecutive, interventional case series. The medical records of a consecutive series of patients with acquired sixth nerve palsy who underwent VRT or SRT/MRc by a single surgeon were reviewed. The preoperative and postoperative findings were compared between the 2 groups. Eight patients (mean age, 46.8 years) underwent SRT/MRc and 8 patients underwent VRT (mean age, 51.1 years). Lateral fixation was performed on all but 4 patients in the VRT group. Preoperative esotropia in primary position and abduction deficit were similar in both groups (SRT/MRc, 41.9 prism diopter [PD], -4.6; VRT, 55.6 PD, -4.5; P = .195, 1.0). The SRT/MRc group underwent a mean MR recession of 6 (range, 5-7) mm. Four patients in the VRT later underwent MR recession (mean 5.3 mm, range 5-6 mm). In addition, 5 patients in the VRT group had 1 or more botulinum toxin injections in the medial rectus muscle. No additional procedures were performed in the SRT/MR group. Fewer additional procedures were performed with SRT/MR (SRT/MR, 0; VRT, 1.8 ± 1.2; P < .010). At last follow-up, residual esotropia (SRT/MRc, 7.1 PD; VRT, 10.3 PD; P = .442) was similar in both groups, but abduction was better in the SRT/MRc group (SRT/MR, -3.0 ± 0.7; VRT, -3.8 ± 0.4; P = .038). There were no new persistent vertical deviations or torsional diplopia. Final outcomes were similar with SRT/MRc vs VRT. However, fewer additional surgical procedures were needed with SRT/MR. Copyright © 2017 Elsevier Inc. All rights reserved.

MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes.

PubMed

Kenyon, Sara; Brocklehurst, Peter; Jones, David; Marlow, Neil; Salt, Alison; Taylor, David

2008-04-24

The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660.

MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes

PubMed Central

Kenyon, Sara; Brocklehurst, Peter; Jones, David; Marlow, Neil; Salt, Alison; Taylor, David

2008-01-01

Background The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. Methods The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. Discussion This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. Trial registration The ORACLE Trial and Children Study is registered in the

Using 4+ to grade near-normal muscle strength does not improve agreement.

PubMed

O'Neill, Søren; Jaszczak, Sofie Louise Thomsen; Steffensen, Anne Katrine Søndergaard; Debrabant, Birgit

2017-01-01

Manual assessment of muscle strength is often graded using the ordinal Medical Research Council (MRC) scale. The scale has a number of inherent weaknesses, including poorly defined limits between grades '4' and '5' and very large differences in the span of muscle strength encompassed by each of the six grades. It is not necessarily obvious how to convert a manual muscle test finding into an MRC grade. Several modifications which include intermediate grades have been suggested to improve the MRC scale and the current study examines whether agreement improves and variation in ratings decrease, with an intermediate grade between '4' and '5', in circumstances where such a grade would seem appropriate. The present study examined the hypothesis, that a modified MRC-scale which included the commonly used '4+' option, resulted in greater agreement between clinicians compared to the standard MRC-scale. A questionnaire containing five simple clinical cases were distributed to a large convenience sample of chiropractors in Northern Europe, with instructions to grade the described muscle strength findings using the MRC scale. The scale was adapted (with/without an intermediate '4+' grade) depending on the preference of the individual respondent. The cases were designed in such a way as to suggest a muscle weakness in the grey area between '4' and '5', i.e. grade '4+' on the modified MRC scale. A total of 225 questionnaires were returned (7% response rate). The average percentage agreement (across cases) in the standard MRC group was 64% [range 51%: 73%] (grade '4' in all cases). In the modified MRC group, the corresponding findings was 48% [38%: 74%] (grade '4' or '4+' in all cases). The mean average deviation analogue in the standard MRC group was 0.34 (range 0.34: 0.40), compared to 0.51 (range 0.39: 0.73) in the modified MRC group, indicating greater dispersion of scores in the modified MRC group. The Fleiss kappa was 0.02 ( p  < 0.001) and 0.13 ( p  < 0

Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle

PubMed Central

Li, Wanbo; Dive, Marc; Tamma, Nico; Michaux, Charles; Druet, Tom; Huijbers, Ivo J.; Isacke, Clare M.; Coppieters, Wouter; Georges, Michel; Charlier, Carole

2009-01-01

We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed. PMID:19779552

School characteristics and adolescent smoking. Results from the MRC/Derbyshire Smoking Study 1974-8 and from a follow up in 1981.

PubMed Central

Murray, M; Kiryluk, S; Swan, A V

1984-01-01

In the MRC/Derbyshire Smoking Study a cohort of about 6000 adolescents was surveyed annually from 1974 when they entered secondary school aged 11-12 years until 1978 when they reached 15-16 years. In 1981 after the adolescents had left school they were again surveyed by post. Each year from 1974 to 1978 and again in 1981 they answered a questionnaire on their smoking behaviour and other issues. Information on the schools attended by these adolescents was obtained from their teachers and headteachers. This paper examines the relation between the school environment and the adolescents' smoking behaviour both before and after leaving school. The prevalence of smoking was higher among those boys who attended schools that were single sex, non-denominational, or had a parent-teacher association, no health education, no female teachers, or whose headteacher smoked cigarettes. Among girls the prevalence of smoking was higher if they attended a school that had optional school uniform and no health or antismoking education. The importance of these findings for the development of effective preventive measures is discussed. PMID:6747518

Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial.

PubMed

Ensor, Hannah M; Schwab, Claire; Russell, Lisa J; Richards, Sue M; Morrison, Heather; Masic, Dino; Jones, Lisa; Kinsey, Sally E; Vora, Ajay J; Mitchell, Christopher D; Harrison, Christine J; Moorman, Anthony V

2011-02-17

Deregulated expression of CRLF2 (CRLF2-d) arises via its juxtaposition to the IGH@ enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47], P < .001; OS 3.69 [2.34-5.84], P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31], P = .023; OS 2.86 [1.15-6.79], P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group.

Synthesis and cytotoxicity testing of new amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives.

PubMed

Sorra, Kumaraswamy; Chang, Chi-Fen; Pusuluri, Srinivas; Mukkanti, Khagga; Laiu, Min-Chiau; Bao, Bo-Ying; Su, Chia-Hao; Chuang, Ta-Hsien

2012-07-25

A series of amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives was synthesized from isatoic anhydride, and their cytotoxicity against the MRC-5 and Mahlavu cell lines was evaluated. The results suggest that compound PBDT-7i with the meta-trifluoromethylbenzoyl substituent can selectively inhibit the growth of Mahlavu cells and has low toxicity towards MRC-5 cells.

Magnetic resonance colonography without bowel cleansing: a prospective cross sectional study in a screening population

PubMed Central

Kuehle, Christiane A; Langhorst, Jost; Ladd, Susanne C; Zoepf, Thomas; Nuefer, Michael; Grabellus, Florian; Barkhausen, Joerg; Gerken, Guido; Lauenstein, Thomas C

2007-01-01

Background and aim To evaluate the diagnostic accuracy of magnetic resonance colonography (MRC) without bowel cleansing in a screening population and compare the results to colonoscopy as a standard of reference. Methods 315 screening patients, older than 50 years with a normal risk profile for colorectal cancer, were included in this study. For MRC, a tagging agent (5.0% Gastrografin, 1.0% barium sulphate, 0.2% locust bean gum) was ingested with each main meal within 2 days prior to MRC. No bowel cleansing was applied. For the magnetic resonance examination, a rectal water enema was administered. Data collection was based on contrast enhanced T1 weighted images and TrueFISP images. Magnetic resonance data were analysed for image quality and the presence of colorectal lesions. Conventional colonoscopy and histopathological samples served as reference. Results In 4% of all colonic segments, magnetic resonance image quality was insufficient because of untagged faecal material. Adenomatous polyps >5 mm were detected by means of MRC, with a sensitivity of 83.0%. Overall specificity was 90.2% (false positive findings in 19 patients). However, only 16 of 153 lesions <5 mm and 9 of 127 hyperplastic polyps could be visualised on magnetic resonance images. Conclusions Faecal tagging MRC is applicable for screening purposes. It provides good accuracy for the detection of relevant (ie, adenomatous) colorectal lesions >5 mm in a screening population. However, refinements to optimise image quality of faecal tagging are needed. PMID:17341542

MRI cisternography with gadolinium-containing contrast medium: its role, advantages and limitations in the investigation of rhinorrhoea.

PubMed

Aydin, K; Guven, K; Sencer, S; Jinkins, J R; Minareci, O

2004-01-01

Our purpose was to evaluate the utility of intrathecal gadopentetate dimeglumine -enhanced magnetic resonance cisternography (GdMRC). We injected 0.5 ml contrast medium into the subarachnoid space via lumbar puncture in 20 patients with suspected cerebrospinal fluid (CSF) rhinorrhoea. MRC showed CSF leakage in 14 patients with rhinorrhoea at the time of the examination, into the ethmoid air cells in nine, the sphenoid sinus in three and the frontal sinus in two cases. In 12 of these the site leakage was confirmed during surgical repair of the fistula. No leakage was observed in four patients with intermittent rhinorrhoea, not present at the time of the examination. GdMRC showed leakage in two patients with negative CT cisternography. GdMRC may prove better than CT cisternography, especially with slow CSF flow. We also showed low-dose GdMRC to be a feasible and relative safe way of confirming the presence of and localising active CSF leaks prior to surgical repair.

Preparatory study for the revaluation of the EQ-5D tariff: methodology report.

PubMed

Mulhern, Brendan; Bansback, Nick; Brazier, John; Buckingham, Ken; Cairns, John; Devlin, Nancy; Dolan, Paul; Hole, Arne Risa; Kavetsos, Georgios; Longworth, Louise; Rowen, Donna; Tsuchiya, Aki

2014-02-01

take place; or (5) satisfaction associated with the state. Furthermore, (6) exhaustion of lead time in the worst state was subject to substantial framing effects; (7) the five-level version of the EQ-5D (EQ-5D-5L) can be valued using DCE with duration as an attribute; and (8) binary choice LT-TTO can be administered in an online environment. Stage 2 found that although online surveys and CAPI surveys resulted in different compositions of respondents, at the aggregate, their responses to the experimental questions covering (1) to (7) above were not statistically significantly different from each other. Stages 3 and 4 found that TTO and LT-TTO were easier than DCE with duration; respondents did not necessarily trade across all attributes of EQ-5D; some respondents found it difficult to distinguish between the two worst levels of EQ-5D-5L, and some respondents may be thinking about the impact of their ill health on their family. In order for the National Institute for Health and Care Excellence to make the most appropriate decisions, the EQ-5D tariff needs to incorporate the latest understanding of health-state preferences. PRET contributed to the knowledge base on the conduct of health-state valuation studies. The Medical Research Council (MRC)-National Institute for Health Research (NIHR) Methodology Research Programme funded the PRET project (MRC ref. G0901500), and the EuroQol Group funded the PRET-AS project (Preparatory study for the Re-valuation of the EQ-5D Tariff project - Additional Sample) as an extension to the PRET project with formal agreement from the MRC.

[Evolution in muscle strength in critical patients with invasive mechanical ventilation].

PubMed

Via Clavero, G; Sanjuán Naváis, M; Menéndez Albuixech, M; Corral Ansa, L; Martínez Estalella, G; Díaz-Prieto-Huidobro, A

2013-01-01

To assess the evolution of muscle strength in critically ill patients with mechanical ventilation (MV) from withdrawal of sedatives to hospital discharge. A cohort study was conducted in two intensive care units in the Hospital Universitari de Bellvitge from November 2011 to March 2012. Consecutive patients with MV > 72h. Dependent outcome: Muscle strength measured with the Medical Research Council (MRC) scale beginning on the first day the patient was able to answer 3 out of 5 simple orders (day 1), every week, at ICU discharge and at hospital discharge or at day 60 Independent outcomes: factors associated with muscle strength loss, ventilator-free days, ICU length of stay and hospital length of stay. The patients were distributed into two groups (MRC< 48, MRC ≥ 48) after the first measurement. Thirty-four patients were assessed. Independent outcomes associated with muscle strength weakness were: days with cardiovascular SOFA >2 (P<.001) and days with costicosteroids (P<.001). Initial MRC in MRC<48 group was 38 (27-43), and 52 (50-54) in MRC ≥ 48. The largest muscle strength gain was obtained the first week (31% versus 52%). A MRC < 48 value was associated with more MV days (P<.007) and a longer ICU stay. (P<.003). The greatest muscle strength gain after withdrawing of the sedatives was achieved in the first week. Muscle strength loss was associated with a cardiovascular SOFA > 2 and costicosteroids. Patients with a MRC < 48 required more days with MV and a longer ICU stay. Copyright © 2013 Elsevier España, S.L. y SEEIUC. All rights reserved.

In vitro activities of plant extracts from Saudi Arabia against malaria, leishmaniasis, sleeping sickness and Chagas disease.

PubMed

Abdel-Sattar, Essam; Maes, Louis; Salama, Maha Mahmoud

2010-09-01

The in vitro activity of the methanol extracts of 51 plants randomly collected from the Kingdom of Saudi Arabia and some of their fractions (petroleum ether, chloroform, ethyl acetate and aqueous) were evaluated against Plasmodium falciparum, Trypanosoma brucei brucei, T. cruzi and Leishmania infantum, as well as toxicity against MRC-5 fibroblast cells. Ten crude methanolic extracts that demonstrated potent and adequately selective antiprotozoal activity were subjected to solvent fractionation using petroleum ether, ethyl acetate and chloroform. Only three samples showed promising antiprotozoal activity. Argemone ochroleuca (CHCl(3) fraction) showed pronounced activity against P. falciparum(GHA) (IC(50) 0.32 microg/mL) and T. cruzi (IC(50) 0.30 microg/mL) with low cytotoxicity against MRC-5 cells (CC(50) 11.6 microg/mL). Capparis spinosa (EtOAc fraction) showed pronounced activity against P. falciparum(GHA) with an IC(50) 0.50 microg/mL in the absence of toxicity against MRC-5 cell line (CC(50) > 30 microg/mL). Heliotropium curassavicum (CHCl(3) fraction) showed similar activity against P. falciparum (IC(50) 0.65 microg/mL; MRC-5 CC(50) > 30 microg /mL). These three extracts will be subjected for further extensive studies to isolate and identify their active constituents. Copyright 2010 John Wiley & Sons, Ltd.

Evaluation of different continuous cell lines in the isolation of mumps virus by the shell vial method from clinical samples

PubMed Central

Reina, J; Ballesteros, F; Mari, M; Munar, M

2001-01-01

Aims—To compare prospectively the efficacy of the Vero, LLC-MK2, MDCK, Hep-2, and MRC-5 cell lines in the isolation of the mumps virus from clinical samples by means of the shell vial method. Methods—During an epidemic outbreak of parotiditis 48 clinical samples (saliva swabs and CSF) were studied. Two vials of the Vero, LLC-MK2, MDCK, MRC-5, and Hep-2 cell lines were inoculated with 0.2 ml of the samples by the shell vial assay. The vials were incubated at 36°C for two and five days. The vials were then fixed with acetone at -20°C for 10 minutes and stained by a monoclonal antibody against mumps virus by means of an indirect immunofluorescence assay. Results—The mumps virus was isolated from 36 samples. The Vero and LLC-MK2 cell lines showed a 100% isolation capacity, MDCK showed 77.7%, MRC-5 showed 44.4%, and Hep-2 showed 22.2%. The Vero and LLC-MK2 lines were significantly different to the other cell lines (p < 0.001). The sensitivity for the Vero and LLC-MK2 lines at two and five days of incubation was identical (100%). The values obtained in the study of the quantitative isolation capacity (positive isolation with > 5 infectious foci) were 94.4% for Vero, 97.2% for LLC-MK2, 5.5% for MDCK, 5.5% for Hep-2, and 0% for MRC-5. Conclusions—The Vero and LLC-MK2 cell lines are equally efficient at two and five days incubation for the isolation of the mumps virus from clinical samples, and the use of the shell vial method considerably shortens the time of aetiological diagnosis with higher specificity. Key Words: mumps virus • Vero cell line • LLC-MK2 cell line • MDCK cell line • Hep-2 cell line • MRC-5 cell line • isolation • shell vial PMID:11729211

Genetic stability of RSV-F expression and the restricted growth phenotype of a live attenuated PIV3 vectored RSV vaccine candidate (MEDI-534) following restrictive growth in human lung cells.

PubMed

Nelson, Christine L; Tang, Roderick S; Stillman, Elizabeth A

2013-08-12

MEDI-534 is the first live, attenuated and vectored respiratory syncytial virus (RSV) vaccine to be evaluated in seronegative children. It consists of a bovine/human parainfluenza virus type 3 (PIV3) backbone with the RSV fusion glycoprotein (RSV-F) expressed from the second position. The PIV3 fusion and hemaglutinin-neuraminidase proteins are human-derived. No small animal appropriately replicates the restrictive growth of bovine PIV3 (bPIV3) based viruses relative to human PIV3 (hPIV3) observed in the respiratory tract of rhesus monkeys and humans, making analysis of the genetic stability of the attenuation phenotype and maintenance of RSV-F expression difficult. Screening of multiple cell-lines identified MRC-5 cells as supporting permissive growth of hPIV3 while restricting bPIV3 and MEDI-534 growth. In MRC-5 cells, the peak titers of MEDI-534 were more than 20-fold lower compared to hPIV3 peak titers. After more than 10 multicycle passages in MRC-5 cells, genetic alterations were detected in MEDI-534 that contributed to a partial loss in restricted growth in MRC-5 cells and a decrease in RSV-F expression. These adaptive mutations did not occur in the RSV-F gene but were found in the polyA sequence upstream of the transgene. MRC-5 adapted MEDI-534 viruses (1) lost some attenuation but did not replicate to the level of hPIV3 in this cell line, (2) did not completely lose RSV-F expression and (3) were able to elicit a protective anti-RSV immune response in hamsters despite lower levels of RSV-F expression. Interestingly analysis of shed MEDI-534 from a recent clinical trial indicates that in some recipients similar mutations arise by day 7 or day 12 post immunization (in press) suggesting that these mutations can arise rapidly in the human host. The utility and limits of MRC-5 cells for characterizing the attenuation and RSV-F expression of MEDI-534 is discussed. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Use of magnetic resonance cholangiography in the diagnosis of choledocholithiasis: prospective comparison with a reference imaging method

PubMed Central

Zidi, S; Prat, F; Le Guen, O; Rondeau, Y; Rocher, L; Fritsch, J; Choury, A; Pelletier, G

1999-01-01

Background—Magnetic resonance cholangiography (MRC) is a new technique for non-invasive imaging of the biliary tract. 
Aim—To assess the results of MRC in patients with suspected bile duct stones as compared with those obtained with reference imaging methods. 
Patients/Methods—70 patients (34 men and 36 women, mean (SD) age 71 (15.5) years; median 75) with suspected bile duct stones were included (cholangitis, 33; pancreatitis, three; suspected post-cholecystectomy choledocholithiasis, nine; cholestasis, six; stones suspected on ultrasound or computed tomography scan, 19). MR cholangiograms with two dimensional turbo spin echo sequences were acquired. Endoscopic retrograde cholangiography with or without sphincterotomy (n = 63), endosonography (n = 5), or intraoperative cho- langiography (n = 2) were the reference imaging techniques used for the study and were performed within 12 hours of MRC. Radiologists were blinded to the results of endoscopic retrograde cholangiography and previous investigations. 
Results—49 patients (70%) had bile duct stones on reference imaging (common bile duct, 44, six of which impacted in the papilla; intrahepatic, four; cystic duct stump, one). Stone size ranged from 1 to 20 mm (mean 6.1, median 5.5). Twenty seven patients (55%) had bile duct stones smaller than 6 mm. MRC diagnostic accuracy for bile duct lithiasis was: sensitivity, 57.1%; specificity, 100%; positive predictive value, 100%; negative predictive value, 50%. 
Conclusions—Stones smaller than 6 mm are still often missed by MRC when standard equipment is used. The general introduction of new technical improvements is needed before this method can be considered reliable for the diagnosis of bile duct stones. 

 Keywords: bile duct calculi; endoscopic retrograde cholangiography; magnetic resonance cholangiography PMID:9862837

Childhood Environment and Mental Wellbeing at Age 60-64 Years: Prospective Evidence from the MRC National Survey of Health and Development.

PubMed

Stafford, Mai; Gale, Catharine R; Mishra, Gita; Richards, Marcus; Black, Stephanie; Kuh, Diana L

2015-01-01

Mental wellbeing, conceptualised as positive affect, life satisfaction and realisation of needs that contribute to psychological growth, captures more than the absence of mental ill health. Several nations now aim to monitor and improve mental wellbeing. Whilst many studies document associations between adverse childhood experiences and mental disorders in adulthood, possible links between childhood experiences and adult mental wellbeing have so far received less attention. Using data from 1976 men and women in the MRC National Survey for Health and Development, we investigated prospective associations between childhood socioeconomic and psychosocial environments and the Warwick Edinburgh Mental Wellbeing Scale, designed to capture both hedonic and eudaimonic facets of wellbeing, at age 60-64. Whilst there was no evidence that childhood socioeconomic circumstances were related to later wellbeing independently of other childhood experiences, elements of childrearing and parenting, parental health and adjustment, and childhood illness were related. More advantaged socioeconomic position was associated with greater wellbeing but this did not explain the links between these childhood exposures and adult wellbeing, suggesting alternative explanatory pathways should be considered. Childhood illness and family psychosocial environment are associated with mental wellbeing in early older age, with effects sizes that are larger or comparable to socioeconomic circumstances in adulthood. Initiatives to improve the nation's mental wellbeing that include programmes targeted to supporting families and children may additionally have benefits that continue into older age.

Differential Effect of Modified Medical Research Council Dyspnea, COPD Assessment Test, and Clinical COPD Questionnaire for Symptoms Evaluation Within the New GOLD Staging and Mortality in COPD.

PubMed

Casanova, Ciro; Marin, Jose M; Martinez-Gonzalez, Cristina; de Lucas-Ramos, Pilar; Mir-Viladrich, Isabel; Cosio, Borja; Peces-Barba, German; Solanes-García, Ingrid; Agüero, Ramón; Feu-Collado, Nuria; Calle-Rubio, Miryam; Alfageme, Inmaculada; de Diego-Damia, Alfredo; Irigaray, Rosa; Marín, Margarita; Balcells, Eva; Llunell, Antonia; Galdiz, Juan Bautista; Golpe, Rafael; Lacarcel, Celia; Cabrera, Carlos; Marin, Alicia; Soriano, Joan B; Lopez-Campos, Jose Luis; Soler-Cataluña, Juan José; de-Torres, Juan P

2015-07-01

The modified Medical Research Council (mMRC) dyspnea, the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by GOLD (Global Initiative for Chronic Obstructive Lung Disease) for assessing symptoms in patients with COPD. However, there are no data on the prognostic value of these tools in terms of mortality. We endeavored to evaluate the prognostic value of the CAT and CCQ scores and compare them with mMRC dyspnea. We analyzed the ability of these tests to predict mortality in an observational cohort of 768 patients with COPD (82% men; FEV1, 60%) from the COPD History Assessment in Spain (CHAIN) study, a multicenter observational Spanish cohort, who were monitored annually for a mean follow-up time of 38 months. Subjects who died (n = 73; 9.5%) had higher CAT (14 vs 11, P = .022), CCQ (1.6 vs 1.3, P = .033), and mMRC dyspnea scores (2 vs 1, P < .001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and mMRC dyspnea scores were associated with higher mortality (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores ≥ 17 and CCQ scores > 2.5 provided a similar sensitivity than mMRC dyspnea scores ≥ 2 to predict all-cause mortality. The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with COPD, but were inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores based on mortality risk that could be useful for the new GOLD grading classification. ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Diagnostic value of Gd-EOB-DTPA-enhanced MR cholangiography in non-invasive detection of postoperative bile leakage.

PubMed

Kul, Melahat; Erden, Ayşe; Düşünceli Atman, Ebru

2017-04-01

To assess the diagnostic value of dynamic T 1 weighted (T1w) gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced MR cholangiography (MRC) for the detection of active bile leaks. A total of 28 patients with suspected biliary leakage who underwent routine T 2 weighted (T2w) MRC and T1w GD-EOB-DTPA-enhanced MRC at our institution from February 2013 to June 2016 were included in this study. The image sets were retrospectively analyzed in consensus by three radiologists. T1w Gd-EOB-DTPA-enhanced MRC findings were correlated with clinical data, follow-up examinations and findings of invasive/surgical procedures. Patients with positive bile leak findings in Gd-EOB-DTPA-enhanced MRC were divided into hepatobiliary phase (HBP) (20-30 min) and delayed phase (DP) (60-390 min) group according to elapsed time between Gd-EOB-DTPA injection and initial bile leak findings in MRC images. These groups were compared in terms of laboratory test results (total bilirubin, liver enzymes) and the presence of bile duct dilatation in T2w MRC images. In each patient, visualization of bile ducts was sufficient in the HBP. The accuracy, sensitivity and specificity of dynamic Gd-EOB-DTPA-enhanced T1w MRC in the detection of biliary leaks were 92.9%, 90.5% and 100%, respectively (p < 0.001). 19 of 28 patients had bile leak findings in T1w Gd-EOB-DTPA-enhanced MRC [HBP group: N = 7 (36.8%), DP group: N = 12 (63.2%)]. There was no statistically significant difference in terms of laboratory test results and the presence of bile duct dilatation between HBP and DP group (p > 0.05). Three patients, each of them in DP group, showed normal laboratory test results and bile duct diameters. Dynamic T1w Gd-EOB-DTPA-enhanced MRC is a useful non-invasive diagnostic tool to detect bile leak. Advances in knowledge: Prolonged DP imaging may be required for bile leak detection even if visualization of biliary tree is sufficient in HBP and liver function tests

Mitochondria-rich cells adjustments and ionic balance in the Neotropical fish Prochilodus lineatus exposed to titanium dioxide nanoparticles.

PubMed

Carmo, Talita L L; Azevedo, Vinícius C; Siqueira, Priscila R; Galvão, Tiago D; Santos, Fabrício A; Martinez, Cláudia B R; Appoloni, Carlos R; Fernandes, Marisa N

2018-07-01

Manufactured titanium dioxide nanoparticles (TiO 2 -NP) have been intensely applied in numerous industrial products and may be a risk for aquatic systems as they are not completely removed from domestic and industrial wastes after water treatment. This study evaluated the osmo- and ionic balance, Na + /K + -ATPase, H + -ATPase and carbonic anhydrase activities and the mitochondria-rich cells (MRC) in the gills and kidney of the Neotropical fish Prochilodus lineatus after 2 (acute) and 14 (subchronic) days of exposure to nominal 0, 1, 5, 10 and 50 mg L -1 TiO 2 -NP. The nominal concentrations corresponded to 0.0, 0.6, 1.6, 2.7 and 18.1 mg L -1 suspended TiO 2 -NP, respectively, in the water column one hour after NP introduction and were maintained for at least 24 h. Acute exposure to TiO 2 -NP decreased plasma osmolality and Ca 2+ levels. Na + /K + -ATPase, H + -ATPase and carbonic anhydrase activities were inhibited in the gills, but not in the kidney. Total MRC density did not change in gills and kidneys. At gill surface, total MRC density decreased in fish exposed to 50 mg L -1 TiO 2 -NP and the total MRC fractional surface area unchanged although, there were some changes in the fractional area of MRC with apical microvilli (MRCm) and MRC with apical sponge-like structure (MRCs). MRCm was more abundant than MRCs. After subchronic exposure, there was no change in plasma osmolality, ionic balance and enzyme activities. Total gill MRC density increased in the filament epithelium and renal tubules. In the gills, MRC contacting water exhibited some adjustments. Total MRC and fractional surface area unchanged, but there was an increase of MRCs contacting water at gill surface after exposure to10 and 50 mg L -1 TiO 2 -NP. MRC proliferation in filament epithelium and in renal tubules as well as the increasing MRCs at gill surface may have contributed to avoid change in plasma osmolality, ionic balance and enzyme activities and suggested a cellular physiological

Clinical Outcomes following median to radial nerve transfers

PubMed Central

Ray, Wilson Z.; Mackinnon, Susan E.

2010-01-01

Purpose In this study the authors evaluate the clinical outcomes in patients with radial nerve palsy who underwent nerve transfers utilizing redundant fascicles of median nerve (innervating the flexor digitorum superficialis and flexor carpi radialis muscles) to the posterior interosseous nerve and the nerve to the extensor carpi radialis brevis. Methods A retrospective review of the clinical records of 19 patients with radial nerve injuries who underwent nerve transfer procedures using the median nerve as a donor nerve were included. All patients were evaluated using the Medical Research Council (MRC) grading system. Results The mean age of patients was 41 years (range 17 – 78 years). All patients received at least 12 months of follow-up (20.3 ± 5.8 months). Surgery was performed at a mean of 5.7 ± 1.9 months post-injury. Post-operative functional evaluation was graded according to the following scale: grades MRC 0/5 - MRC 2/5 were considered poor outcomes, while MRC of 3/5 was a fair result, MRC grade 4/5 was a good result, and grade 4+/5 was considered an excellent outcome. Seventeen patients (89%) had a complete radial nerve palsy while two patients (11%) had intact wrist extension but no finger or thumb extension. Post-operatively all patients except one had good to excellent recovery of wrist extension. Twelve patients recovered good to excellent finger and thumb extension, two patients had fair recovery, five patients had a poor recovery. Conclusions The radial nerve is a commonly injured nerve, causing significant morbidity in affected patients. The median nerve provides a reliable source of donor nerve fascicles for radial nerve reinnervation. This transfer was first performed in 1999 and evolved over the subsequent decade. The important nuances of both surgical technique and motor re-education critical for to the success of this transfer have been identified and are discussed. PMID:21168979

The potential of imaging techniques as a screening tool for colorectal cancer: a cost-effectiveness analysis.

PubMed

Greuter, Marjolein J E; Berkhof, Johannes; Fijneman, Remond J A; Demirel, Erhan; Lew, Jie-Bin; Meijer, Gerrit A; Stoker, Jaap; Coupé, Veerle M H

2016-07-01

Imaging may be promising for colorectal cancer (CRC) screening, since it has test characteristics comparable with colonoscopy but is less invasive. We aimed to assess the potential of CT colonography (CTC) and MR colonography (MRC) in terms of (cost-effectiveness) using the Adenoma and Serrated pathway to Colorectal CAncer model. We compared several CTC and MRC strategies with 5- or 10-yearly screening intervals with no screening, 10-yearly colonoscopy screening and biennial faecal immunochemical test (FIT) screening. We assumed trial-based participation rates in the base-case analyses and varied the rates in sensitivity analyses. Incremental lifetime costs and health effects were estimated from a healthcare perspective. The health gain of CTC and MRC was similar and ranged from 0.031 to 0.048 life-year gained compared with no screening, for 2-5 screening rounds. Lifetime costs per person for MRC strategies were €60-110 higher than those for CTC strategies with an equal number of screening rounds. All imaging-based strategies were cost-effective compared with no screening. FIT screening was the dominant screening strategy, leading to most LYG and highest cost-savings. Compared with three rounds of colonoscopy screening, CTC with five rounds was found to be cost-effective in an incremental analysis of imaging strategies. Assumptions on screening participation have a major influence on the ordering of strategies in terms of costs and effects. CTC and MRC have potential for CRC screening, compared with no screening and compared with three rounds of 10-yearly colonoscopy screening. When taking FIT screening as the reference, imaging is not cost-effective. Participation is an important driver of effectiveness and cost estimates. This is the first study to assess the cost-effectiveness of MRC screening for CRC.

The Radio Spectral Energy Distribution and Star-formation Rate Calibration in Galaxies

NASA Astrophysics Data System (ADS)

Tabatabaei, F. S.; Schinnerer, E.; Krause, M.; Dumas, G.; Meidt, S.; Damas-Segovia, A.; Beck, R.; Murphy, E. J.; Mulcahy, D. D.; Groves, B.; Bolatto, A.; Dale, D.; Galametz, M.; Sandstrom, K.; Boquien, M.; Calzetti, D.; Kennicutt, R. C.; Hunt, L. K.; De Looze, I.; Pellegrini, E. W.

2017-02-01

We study the spectral energy distribution (SED) of the radio continuum (RC) emission from the Key Insight in Nearby Galaxies Emitting in Radio (KINGFISHER) sample of nearby galaxies to understand the energetics and origin of this emission. Effelsberg multi-wavelength observations at 1.4, 4.8, 8.4, and 10.5 GHz combined with archive data allow us, for the first time, to determine the mid-RC (1-10 GHz, MRC) bolometric luminosities and further present calibration relations versus the monochromatic radio luminosities. The 1-10 GHz radio SED is fitted using a Bayesian Markov Chain Monte Carlo technique leading to measurements for the nonthermal spectral index ({S}ν ˜ {ν }-{α {nt}}) and the thermal fraction ({f}{th}) with mean values of {α }{nt}=0.97 +/- 0.16(0.79 +/- 0.15 for the total spectral index) and {f}{th} = (10 ± 9)% at 1.4 GHz. The MRC luminosity changes over ˜3 orders of magnitude in the sample, 4.3× {10}2 {L}⊙ < MRC < 3.9× {10}5 {L}⊙ . The thermal emission is responsible for ˜23% of the MRC on average. We also compare the extinction-corrected diagnostics of the star-formation rate (SFR) with the thermal and nonthermal radio tracers and derive the first star-formation calibration relations using the MRC radio luminosity. The nonthermal spectral index flattens with increasing SFR surface density, indicating the effect of the star-formation feedback on the cosmic-ray electron population in galaxies. Comparing the radio and IR SEDs, we find that the FIR-to-MRC ratio could decrease with SFR, due to the amplification of the magnetic fields in star-forming regions. This particularly implies a decrease in the ratio at high redshifts, where mostly luminous/star-forming galaxies are detected.

Childhood Environment and Mental Wellbeing at Age 60-64 Years: Prospective Evidence from the MRC National Survey of Health and Development

PubMed Central

Stafford, Mai; Gale, Catharine R.; Mishra, Gita; Richards, Marcus; Black, Stephanie; Kuh, Diana L.

2015-01-01

Background Mental wellbeing, conceptualised as positive affect, life satisfaction and realisation of needs that contribute to psychological growth, captures more than the absence of mental ill health. Several nations now aim to monitor and improve mental wellbeing. Whilst many studies document associations between adverse childhood experiences and mental disorders in adulthood, possible links between childhood experiences and adult mental wellbeing have so far received less attention. Methods Using data from 1976 men and women in the MRC National Survey for Health and Development, we investigated prospective associations between childhood socioeconomic and psychosocial environments and the Warwick Edinburgh Mental Wellbeing Scale, designed to capture both hedonic and eudaimonic facets of wellbeing, at age 60-64. Results Whilst there was no evidence that childhood socioeconomic circumstances were related to later wellbeing independently of other childhood experiences, elements of childrearing and parenting, parental health and adjustment, and childhood illness were related. More advantaged socioeconomic position was associated with greater wellbeing but this did not explain the links between these childhood exposures and adult wellbeing, suggesting alternative explanatory pathways should be considered. Conclusions Childhood illness and family psychosocial environment are associated with mental wellbeing in early older age, with effects sizes that are larger or comparable to socioeconomic circumstances in adulthood. Initiatives to improve the nation’s mental wellbeing that include programmes targeted to supporting families and children may additionally have benefits that continue into older age. PMID:26030929

Metabolic cooperation between co-cultured lung cancer cells and lung fibroblasts.

PubMed

Koukourakis, Michael I; Kalamida, Dimitra; Mitrakas, Achilleas G; Liousia, Maria; Pouliliou, Stamatia; Sivridis, Efthimios; Giatromanolaki, Alexandra

2017-11-01

Cooperation of cancer cells with stromal cells, such as cancer-associated fibroblasts (CAFs), has been revealed as a mechanism sustaining cancer cell survival and growth. In the current study, we focus on the metabolic interactions of MRC5 lung fibroblasts with lung cancer cells (A549 and H1299) using co-culture experiments and studying changes of the metabolic protein expression profile and of their growth and migration abilities. Using western blotting, confocal microscopy and RT-PCR, we observed that in co-cultures MRC5 respond by upregulating pyruvate dehydrogenase (PDH) and the monocarboxylate transporter MCT1. In contrast, cancer cells increase the expression of glucose transporters (GLUT1), LDH5, PDH kinase and the levels of phosphorylated/inactivated pPDH. H1299 cells growing in the same culture medium with fibroblasts exhibit a 'metastasis-like' phenomenon by forming nests within the fibroblast area. LDH5 and pPDH were drastically upregulated in these nests. The growth rate of both MRC5 and cancer cells increased in co-cultures. Suppression of LDHA or PDK1 in cancer cells abrogates the stimulatory signal from cancer cells to fibroblasts. Incubation of MRC5 fibroblasts with lactate resulted in an increase of LDHB and of PDH expression. Silencing of PDH gene in fibroblasts, or silencing of PDK1 or LDHA gene in tumor cells, impedes cancer cell's migration ability. Overall, a metabolic cooperation between lung cancer cells and fibroblasts has been confirmed in the context of direct Warburg effect, thus the fibroblasts reinforce aerobic metabolism to support the intensified anaerobic glycolytic pathways exploited by cancer cells.

Mannose Receptor 2 Attenuates Renal Fibrosis

PubMed Central

López-Guisa, Jesús M.; Cai, Xiaohe; Collins, Sarah J.; Yamaguchi, Ikuyo; Okamura, Daryl M.; Bugge, Thomas H.; Isacke, Clare M.; Emson, Claire L.; Turner, Scott M.; Shankland, Stuart J.

2012-01-01

Mannose receptor 2 (Mrc2) expresses an extracellular fibronectin type II domain that binds to and internalizes collagen, suggesting that it may play a role in modulating renal fibrosis. Here, we found that Mrc2 levels were very low in normal kidneys but subsets of interstitial myofibroblasts and macrophages upregulated Mrc2 after unilateral ureteral obstruction (UUO). Renal fibrosis and renal parenchymal damage were significantly worse in Mrc2-deficient mice. Similarly, Mrc2-deficient Col4α3−/− mice with hereditary nephritis had significantly higher levels of total kidney collagen, serum BUN, and urinary protein than Mrc2-sufficient Col4α3−/− mice. The more severe phenotype seemed to be the result of reduced collagen turnover, because procollagen III (α1) mRNA levels and fractional collagen synthesis in the wild-type and Mrc2-deficient kidneys were similar after UUO. Although Mrc2 associates with the urokinase receptor, differences in renal urokinase activity did not account for the increased fibrosis in the Mrc2-deficient mice. Treating wild-type mice with a cathepsin inhibitor, which blocks proteases implicated in Mrc2-mediated collagen degradation, worsened UUO-induced renal fibrosis. Cathepsin mRNA profiles were similar in Mrc2-positive fibroblasts and macrophages, and Mrc2 genotype did not alter relative cathepsin mRNA levels. Taken together, these data establish an important fibrosis-attenuating role for Mrc2-expressing renal interstitial cells and suggest the involvement of a lysosomal collagen turnover pathway. PMID:22095946

Screening of agelasine D and analogs for inhibitory activity against pathogenic protozoa; identification of hits for visceral leishmaniasis and Chagas disease.

PubMed

Vik, Anders; Proszenyák, Agnes; Vermeersch, Marieke; Cos, Paul; Maes, Louis; Gundersen, Lise-Lotte

2009-01-08

There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T. cruzi, as well as for toxicity against MRC-5 fibroblast cells. Many compounds displayed high general toxicity towards both the protozoa and MRC-5 cells. However, two compounds exhibited more selective inhibitory activity against L. infantum (IC(50) <0.5 microg/mL) while two others displayed IC(50) <1 microg/mL against T. cruzi in combination with relatively low toxicity against MRC-5 cells. According to criteria set up by the WHO Special Programme for Research & Training in Tropical Diseases (TDR), these compounds could be classified as hits for leishmaniasis and for Chagas disease, respectively. Identification of the hits as well as other SAR data from this initial screening will be valuable for design of more potent and selective potential drugs against these neglected tropical diseases.

In vitro cytotoxicity of carbon black nanoparticles synthesized from solution plasma on human lung fibroblast cells

NASA Astrophysics Data System (ADS)

Panomsuwan, Gasidit; Chokradjaroen, Chayanaphat; Rujiravanit, Ratana; Ueno, Tomonaga; Saito, Nagahiro

2018-01-01

Carbon black nanoparticles (CB-NPs) have been synthesized from liquid benzene by a solution plasma method at room temperature and atmospheric pressure. The morphological observation by scanning electron microscopy revealed the agglomeration of aggregated fine particles. The synthesized CB-NPs were predominantly amorphous as confirmed by X-ray diffraction. The in vitro cytotoxicity of CB-NPs on the human lung fibroblast (MRC-5) cell line was assessed by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and systematically compared with those of two types of commercial carbon blacks (i.e., Vulcan XC-72 and Ketjenblack EC-600JD). Cell viabilities were studied at different concentrations of 32.5, 65, 125, and 250 µg/mL. It was found that the CB-NPs derived from solution plasma exhibited a lower cytotoxicity on the MRC-5 cells than the other two comparative carbon blacks. The viability of MRC-5 cells exposed to CB-NPs remained higher than 90% even at a high concentration of 250 µg/mL. This result preliminarily confirmed the biosafety and potential use of CB-NPs in the field of biological applications.

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study.

PubMed

Lai, Chih-Jou; Wang, Chih-Pin; Tsai, Po-Yi; Chan, Rai-Chi; Lin, Shan-Hui; Lin, Fu-Gong; Hsieh, Chin-Yi

2015-01-01

To identify the effective predictors for therapeutic outcomes based on intermittent theta-burst stimulation (iTBS). A sham-controlled, double-blind parallel study design. A tertiary hospital. People with stroke (N=72) who presented with unilateral hemiplegia. Ten consecutive sessions of real or sham iTBS were implemented with the aim of enhancing hand function. Patients were categorized into 4 groups according to the presence (MEP+) or absence (MEP-) of motor-evoked potentials (MEPs) and grip strength according to the Medical Research Council (MRC) scale. Cortical excitability, Wolf Motor Function Test (WMFT), finger-tapping task (FT), and simple reaction time were performed before and after the sessions. MEPs and the MRC scale were predictive of iTBS therapeutic outcomes. Group A (MEP+, MRC>1) exhibited the greatest WMFT change (7.6±2.3, P<.001), followed by group B (MEP-, MRC>1; 5.2±2.2 score change) and group C (MEP-, MRC=0; 2.3±1.5 score change). These improvements were correlated significantly with baseline motor function and ipsilesional maximum MEP amplitude. The effectiveness of iTBS modulation for poststroke motor enhancement depends on baseline hand grip strength and the presence of MEPs. Our findings indicate that establishing neurostimulation strategies based on the proposed electrophysiological and clinical criteria can allow iTBS to be executed with substantial precision. Effective neuromodulatory strategies can be formulated by using electrophysiological features and clinical presentation information as guidelines. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

3D T2-weighted and Gd-EOB-DTPA-enhanced 3D T1-weighted MR cholangiography for evaluation of biliary anatomy in living liver donors.

PubMed

Cai, Larry; Yeh, Benjamin M; Westphalen, Antonio C; Roberts, John; Wang, Zhen J

2017-03-01

To investigate whether the addition of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced 3D T1-weighted MR cholangiography (T1w-MRC) to 3D T2-weighted MRC (T2w-MRC) improves the confidence and diagnostic accuracy of biliary anatomy in living liver donors. Two abdominal radiologists retrospectively and independently reviewed pre-operative MR studies in 58 consecutive living liver donors. The second-order bile duct visualization on T1w- and T2w-MRC images was rated on a 4-point scale. The readers also independently recorded the biliary anatomy and their diagnostic confidence using (1) combined T1w- and T2w-MRC, and (2) T2w-MRC. In the 23 right lobe donors, the biliary anatomy at imaging and the imaging-predicted number of duct orifices at surgery were compared to intra-operative findings. T1w-MRC had a higher proportion of excellent visualization than T2w-MRC, 66% vs. 45% for reader 1 and 60% vs. 31% for reader 2. The median confidence score for biliary anatomy diagnosis was significantly higher with combined T1w- and T2w-MRC than T2w-MRC alone for both readers (Reader 1: 3 vs. 2, p < 0.001; Reader 2: 3 vs. 1, p < 0.001). Compared to intra-operative findings, the accuracy of imaging-predicted number of duct orifices using combined T1w-and T2w-MRC was significantly higher than that using T2w-MRC alone (p = 0.034 for reader 1, p = 0.0082 for reader 2). The addition of Gd-EOB-DTPA-enhanced 3D T1w-MRC to 3D T2w-MRC improves second-order bile duct visualization and increases the confidence in biliary anatomy diagnosis and the accuracy in the imaging-predicted number of duct orifices acquired during right lobe harvesting.

The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

PubMed

Krivokrysenko, Vadim I; Toshkov, Ilia A; Gleiberman, Anatoli S; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K; Narizhneva, Natalya V; Singh, Vijay K; Whitnall, Mark H; Purmal, Andrei A; Shakhov, Alexander N; Gudkov, Andrei V; Feinstein, Elena

2015-01-01

There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters.

Geologic Controls of Sand Boil Formation at Buck Chute, Mississippi

DTIC Science & Technology

2017-06-30

12 Figure 6. 1915 MRC hydrographic survey of Buck Chute (Modified from MRC 1975, sheet 48). ............ 13 Figure 7. 1926 MRC...hydrographic survey of Buck Chute (Modified from MRC 1975, sheet 48). ............ 14 Figure 8. Diagram of the evolution of the Mississippi River...library). .................... 17 Figure 11. AGI SuperSting 8 ERT survey equipment

Chronic obstructive pulmonary disease (COPD) assessment test scores corresponding to modified Medical Research Council grades among COPD patients.

PubMed

Lee, Chang-Hoon; Lee, Jinwoo; Park, Young Sik; Lee, Sang-Min; Yim, Jae-Joon; Kim, Young Whan; Han, Sung Koo; Yoo, Chul-Gyu

2015-09-01

In assigning patients with chronic obstructive pulmonary disease (COPD) to subgroups according to the updated guidelines of the Global Initiative for Chronic Obstructive Lung Disease, discrepancies have been noted between the COPD assessment test (CAT) criteria and modified Medical Research Council (mMRC) criteria. We investigated the determinants of symptom and risk groups and sought to identify a better CAT criterion. This retrospective study included COPD patients seen between June 20, 2012, and December 5, 2012. The CAT score that can accurately predict an mMRC grade ≥ 2 versus < 2 was evaluated by comparing the area under the receiver operating curve (AUROC) and by classification and regression tree (CART) analysis. Among 428 COPD patients, the percentages of patients classified into subgroups A, B, C, and D were 24.5%, 47.2%, 4.2%, and 24.1% based on CAT criteria and 49.3%, 22.4%, 8.9%, and 19.4% based on mMRC criteria, respectively. More than 90% of the patients who met the mMRC criteria for the 'more symptoms group' also met the CAT criteria. AUROC and CART analyses suggested that a CAT score ≥ 15 predicted an mMRC grade ≥ 2 more accurately than the current CAT score criterion. During follow-up, patients with CAT scores of 10 to 14 did not have a different risk of exacerbation versus those with CAT scores < 10, but they did have a lower exacerbation risk compared to those with CAT scores of 15 to 19. A CAT score ≥ 15 is a better indicator for the 'more symptoms group' in the management of COPD patients.

Evolution of an Expanded Mannose Receptor Gene Family

PubMed Central

Staines, Karen; Hunt, Lawrence G.; Young, John R.; Butter, Colin

2014-01-01

Sequences of peptides from a protein specifically immunoprecipitated by an antibody, KUL01, that recognises chicken macrophages, identified a homologue of the mammalian mannose receptor, MRC1, which we called MRC1L-B. Inspection of the genomic environment of the chicken gene revealed an array of five paralogous genes, MRC1L-A to MRC1L-E, located between conserved flanking genes found either side of the single MRC1 gene in mammals. Transcripts of all five genes were detected in RNA from a macrophage cell line and other RNAs, whose sequences allowed the precise definition of spliced exons, confirming or correcting existing bioinformatic annotation. The confirmed gene structures were used to locate orthologues of all five genes in the genomes of two other avian species and of the painted turtle, all with intact coding sequences. The lizard genome had only three genes, one orthologue of MRC1L-A and two orthologues of the MRC1L-B antigen gene resulting from a recent duplication. The Xenopus genome, like that of most mammals, had only a single MRC1-like gene at the corresponding locus. MRC1L-A and MRC1L-B genes had similar cytoplasmic regions that may be indicative of similar subcellular migration and functions. Cytoplasmic regions of the other three genes were very divergent, possibly indicating the evolution of a new functional repertoire for this family of molecules, which might include novel interactions with pathogens. PMID:25390371

Prospective associations of psychosocial adversity in childhood with risk factors for cardiovascular disease in adulthood: the MRC National Survey of Health and Development.

PubMed

Anderson, Emma L; Caleyachetty, Rishi; Stafford, Mai; Kuh, Diana; Hardy, Rebecca; Lawlor, Debbie A; Fraser, Abigail; Howe, Laura D

2017-09-07

Studies assessing associations of childhood psychosocial adversity (e.g. sexual abuse, physical neglect, parental death), as opposed to socioeconomic adversity, with cardiovascular disease (CVD) risk factors in adulthood are scarce. We aimed to assess associations of various forms of psychosocial adversity and cumulative adversity in childhood, with multiple CVD risk factors in mid-life. Participants were from the MRC National Survey of Health and Development. Childhood psychosocial risk factors were reported prospectively by parents from 1950-1957, and retrospectively by participants at mean age 43 years in 1989. CVD risk factors were assessed at mean age 60-64 years in 2006-2011. Associations of a summary score of total psychosocial adversity and CVD risk in adulthood were assessed. There was no consistent evidence that cumulative psychosocial adversity, nor any specific form of psychosocial adversity in childhood, was associated with CVD risk factors in late adulthood. There was some evidence that parental death in the first 15 years was associated with higher SBP (Beta: 0.23, 95% confidence interval: 0.06 to 0.40, P=0.01) and DBP (Beta: 0.15, 95% confidence interval: -0.01 to 0.32, P=0.07). We found no evidence that exposure to greater psychosocial adversity, or specific forms of psychosocial adversity during childhood is associated with adult CVD risk factors. Further large population studies are needed to clarify whether parental death is associated with higher systolic and diastolic blood pressure.

Visualization of heterogeneity and regional grading of gliomas by multiple features using magnetic resonance-based clustered images.

PubMed

Inano, Rika; Oishi, Naoya; Kunieda, Takeharu; Arakawa, Yoshiki; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu

2016-07-26

Preoperative glioma grading is important for therapeutic strategies and influences prognosis. Intratumoral heterogeneity can cause an underestimation of grading because of the sampling error in biopsies. We developed a voxel-based unsupervised clustering method with multiple magnetic resonance imaging (MRI)-derived features using a self-organizing map followed by K-means. This method produced novel magnetic resonance-based clustered images (MRcIs) that enabled the visualization of glioma grades in 36 patients. The 12-class MRcIs revealed the highest classification performance for the prediction of glioma grading (area under the receiver operating characteristic curve = 0.928; 95% confidential interval = 0.920-0.936). Furthermore, we also created 12-class MRcIs in four new patients using the previous data from the 36 patients as training data and obtained tissue sections of the classes 11 and 12, which were significantly higher in high-grade gliomas (HGGs), and those of classes 4, 5 and 9, which were not significantly different between HGGs and low-grade gliomas (LGGs), according to a MRcI-based navigational system. The tissues of classes 11 and 12 showed features of malignant glioma, whereas those of classes 4, 5 and 9 showed LGGs without anaplastic features. These results suggest that the proposed voxel-based clustering method provides new insights into preoperative regional glioma grading.

An Overdensity of Massive, Dusty Starbursts Associated with the High-Redshift Radio Galaxy MRC1138-262 at z = 2.16

NASA Astrophysics Data System (ADS)

Altieri, Bruno; Dannerbauer, Helmut

We present Herschel and APEX LABOCA 870 μm imaging of the field of the high-redshift radio galaxy MRC1138 at z = 2.16. We detect 16 submillimeter galaxies in this ˜140 arcmin2 large bolometer map, with flux densities in the range 3-11 mJy. The pure number counts indicate an overdensity of SMGs by a factor of five compared to blank field surveys. Based on an exquisite multi-wavelength database including VLA 1.4 GHz radio and infrared observations, we verifiy whether these sources are members of the proto-cluster structure at z = 2.2 or not. Based on Herschel PACS+ SPIRE and Spitzer MIPS photometry, we derived reliable far-infrared photometric redshifts for all of our sources. VLT-ISAAC near-infrared spectroscopic observations confirmed redshifts of z ≈ 2.2 for four of these SMGs. We conclude that in total at least seven sources are part of this proto-cluster at z = 2.16. We measure a star formation rate density S FRD ˜ 1500 M⊙ yr-1 Mpc-3, four magntiudes higher compared to the global SFRD at this redshift. Striklingly, these seven sources are concentrated within a region of 2 Mpc (the typical size of clusters in the local universe) and are not distributed in the filaments as predicted by theories and traced by the Hα emitters at z ≈ 2.2. This concentration of massive, dusty starbursts is not centered on the radio galaxy which is submm bright. A significant fraction, six out of 11 SMGs with z ≈ 2.2 Hα imaging coverage are associated with Hα emitters, demonstrating the potential of tracing SMG counterparts with this source population. Our results demonstrate that indeed submm observations enable us to reveal clusters of massive, dusty starbursts and will pave the road for systematic and detailed investigations with this technique in the future.

Developing strong response capacity: training volunteers in the medical reserve corps.

PubMed

Ye, Jiali; Stanford, Stacy; Gousse, Tahlia; Tosatto, Robert J

2014-12-01

The success of the Medical Reserve Corps (MRC) is dependent on the ability of volunteers to respond in a timely and effective manner. This study aimed to assess the current status of MRC volunteer training and to examine the association between MRC characteristics and provision of training. The data for this study were drawn from the 2013 Network Profile Survey of the MRC, which was administered to active MRC unit leaders or designated alternates of 962 units across the country in April to May of 2013. Over 80% of MRCs had a training plan. Ninety-one percent of MRCs offered one or more training courses to volunteers, and 73% indicated requirements for mandatory training. Approximately 84% of MRC units collaborated with other organizations to conduct trainings. Units with more volunteers (>150) were 3 times as likely to have a plan for volunteer training as were those with fewer volunteers (≤50). Compared to units with a full-time leader, those with leaders who were volunteers were only 0.57 times as likely to have a training plan. An overwhelming majority of MRC units provide critical training to their volunteers prior to an emergency deployment. To further strengthen the overall MRC capacities, it is important for MRC units to have a training plan tailored to their community needs and features, make full use of available training resources, and collaborate with partner organizations.

Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus

PubMed Central

Lihoradova, Olga A.; Indran, Sabarish V.; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A.; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L.; Freiberg, Alexander N.; Ikegami, Tetsuro

2013-01-01

Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus.

PubMed

Lihoradova, Olga A; Indran, Sabarish V; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

2013-01-01

Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

Safety and immunogenicity of two inactivated poliovirus vaccines in combination with an acellular pertussis vaccine and diphtheria and tetanus toxoids in seventeen- to nineteen-month-old infants.

PubMed

Halperin, S A; Davies, H D; Barreto, L; Guasparini, R; Meekison, W; Humphreys, G; Eastwood, B J

1997-04-01

To compare the safety and immunity of an acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, 69 kd protein, fimbriae 2 and 3 combined with diphtheria and tetanus toxoids given as single or separate injection with inactivated poliovirus vaccine (MRC-5-or Vero cell-derived) or live attenuated polio vaccine. A total of 425 healthy children between 17 and 19 months of age who were receiving the fourth dose of their routine immunization series were randomly allocated to receive either the acellular pertussis vaccine and oral poliovirus vaccine or one of two inactivated poliovirus vaccines as a combined injection or separate injections. Although minor adverse events were commonly reported, differences between the groups were few. Fever and decreased feeding were less common in recipients of live attenuated poliovirus vaccine than the combination vaccine containing MRC-5 cell-derived inactivated poliovirus vaccine. A significant antibody response was demonstrated in all groups against all the antigens contained in the vaccines. Antibodies against poliovirus were higher in the groups immunized with the inactivated poliovirus vaccine than the live attenuated vaccine. Anti-69 kd protein antibodies were higher in the group given the MRC-5 cell-derived inactivated poliovirus vaccine as a combined injection than in the group given the separate injection or the group immunized with the live attenuated poliovirus vaccine. The five-component acellular pertussis vaccine combined with diphtherid and tetanus toxoids is safe and immunogenic when combined with either MRC-5- or Vero cell-derived inactivated poliovirus vaccine. This will facilitate the implementation of acellular pertussis vaccine and the movement to inactivated poliovirus vaccine programs.

Ultrahigh-field imaging of the biliary tract at 7 T: initial results of gadoxetic acid-enhanced magnetic resonance cholangiography.

PubMed

Fischer, Anja; Kraff, Oliver; Orzada, Stephan; Nensa, Felix; Schäfer, Lena C; Ladd, Mark E; Umutlu, Lale; Lauenstein, Thomas C

2014-05-01

The objectives of this study were to assess the feasibility of magnetic resonance cholangiography (MRC) using biliary-secreted gadoxetic acid at 7 T and to compare it with T2-weighted (w) MRC at 3 T. Ten healthy volunteers were examined on a 7-T whole-body magnetic resonance system. T2-weighted turbo-spin-echo sequence, T1-w volume-interpolated breath-hold examination (VIBE), and fast low-angle shot (FLASH) with inversion recovery (IR) were acquired in coronal orientation. For dynamic imaging, gadoxetic acid was administrated and data were collected for a period of 5 to 40 minutes after injection. The volunteers underwent subsequent T2-w respiratory-gated MRC at 3 T. For qualitative analysis, a 5-point scale was used. Contrast ratios (CRs) were calculated for quantitative assessment. Contrast-enhanced T1-w MRC at 7 T showed a homogeneous depiction of the intrahepatic and extrahepatic biliary tract with a maximum enhancement of 20 minutes after contrast. Volume-interpolated breath-hold examination and FLASH IR provided a good image quality for the intrahepatic (VIBE, 3.60; FLASH IR, 3.67) and extrahepatic bile ducts (VIBE, 3.50; FLASH IR, 3.72). The quantitative analysis revealed high CR values for FLASH IR (intrahepatic CR, 0.41; extrahepatic CR, 0.45) because of an effective suppression of hepatic tissue and vessels. The T2-w TSE at 7 T showed only a poor image quality without diagnostic potential (intrahepatic, 2.22; extrahepatic, 1.93). Seven-tesla VIBE and FLASH revealed superiority in the depiction of the intrahepatic bile ducts, whereas 3-T MRC was superior in the delineation of the extrahepatic biliary tract. Our results demonstrate the feasibility of contrast-enhanced imaging of the biliary ducts at 7 T.

[Diagnostic performance of biliary ultrasound vs. magnetic resonance cholangiogram in patients with recurrent biliary obstruction.].

PubMed

Chávez-Valencia, V; Espinosa-Ortega, H F; Espinoza-Peralta, D; Arce-Salinas, C A

2009-01-01

Obstructive jaundice in patients with previous cholecystectomy requires a precise diagnosis. In the diagnostic algorithm, biliary ultrasound (BUS) and magnetic resonance cholangiogram (MRC) are used, although the accuracy of each method is unknown in our setting. No previous comparison of US and MRC in subjects with cholecystectomy has been made. To determine diagnostic accuracy of BUS and MRC in patients with recurrent biliary obstruction. Patients with endoscopic retrograde cholangiopacreatography (ERCP) demonstrating recurrent biliary obstruction by stones were included. All patients underwent BUS and MRC. We determined the diagnostic performance of each image study compared with ERCP. Twenty-seven patients with a mean age of 62.9 +/- 17.3 years-old were included. Sensitivity and specificity of BUS were 0.12 and 0.58, respectively. Figures for MRC were 0.88 and 0.82. Diagnostic agreement between ERCP and MRC was k= 0.66 whereas BUS had a k of only 0.26. MRC had good diagnostic performance for recurrent choledocolithiasis. BUS demonstrated lower accuracy compared with previous reports, so should not be considered in the initial approach of recurrent choledocus obstruction.

Discrepancies between modified Medical Research Council dyspnea score and COPD assessment test score in patients with COPD

PubMed Central

Rhee, Chin Kook; Kim, Jin Woo; Hwang, Yong Il; Lee, Jin Hwa; Jung, Ki-Suck; Lee, Myung Goo; Yoo, Kwang Ha; Lee, Sang Haak; Shin, Kyeong-Cheol; Yoon, Hyoung Kyu

2015-01-01

Background and objective According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, either a modified Medical Research Council (mMRC) dyspnea score of ≥2 or a chronic obstructive pulmonary disease (COPD) assessment test (CAT) score of ≥10 is considered to represent COPD patients who are more symptomatic. We aimed to identify the ideal CAT score that exhibits minimal discrepancy with the mMRC score. Methods A receiver operating characteristic curve of the CAT score was generated for an mMRC scores of 1 and 2. A concordance analysis was applied to quantify the association between the frequencies of patients categorized into GOLD groups A–D using symptom cutoff points. A κ-coefficient was calculated. Results For an mMRC score of 2, a CAT score of 15 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.70 and 0.66, respectively (area under the receiver operating characteristic curve [AUC] 0.74; 95% confidence interval [CI], 0.70–0.77). For an mMRC score of 1, a CAT score of 10 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.77 and 0.65, respectively (AUC 0.77; 95% CI, 0.72–0.83). The κ value for concordance was highest between an mMRC score of 1 and a CAT score of 10 (0.66), followed by an mMRC score of 2 and a CAT score of 15 (0.56), an mMRC score of 2 and a CAT score of 10 (0.47), and an mMRC score of 1 and a CAT score of 15 (0.43). Conclusion A CAT score of 10 was most concordant with an mMRC score of 1 when classifying patients with COPD into GOLD groups A–D. However, a discrepancy remains between the CAT and mMRC scoring systems. PMID:26316736

Correlation Between Bile Reflux Gastritis and Biliary Excreted Contrast Media in the Stomach.

PubMed

Hyun, Jong Jin; Yeom, Suk Keu; Shim, Euddeum; Cha, Jaehyung; Choi, Inyoung; Lee, Seung Hwa; Chung, Hwan Hoon; Cha, Sang Hoon; Lee, Chang Hee

This study aimed to evaluate the relationship between biliary excreted contrast media in the stomach and the presence of bile reflux gastritis. Consecutive 111 patients who underwent both gadoxetic acid-enhanced magnetic resonance cholangiography (gadoxetic MRC) and gastric endoscopy were included in this study. We performed a review of the gadoxetic-MRC image sets acquired 60 minutes after intravenous injection of contrast media and endoscopic images. We recorded amount of contrast media in the stomach. The sensitivity, specificity, and accuracy of duodenogastric bile reflux diagnosis were evaluated for the gadoxetic MRC. Statistical analysis was performed using the Fisher exact test and the linear-by-linear association test. Among the 111 patients, 39 had 60-minute delayed images showing the presence of contrast media in the stomach. Of these 39 patients, 13 had bile reflux gastritis and 5 showed bile in the stomach without evidence of erythematous gastritis. Of the 72 patients who did not show contrast media in the stomach, none had bile reflux gastritis and 2 patients showed bile staining in the stomach without evidence of erythematous gastritis. Bile reflux gastritis was significantly more frequent in patients with contrast media in the stomach on gadoxetic MRC than in those without. Patients with high-grade extension of contrast media in the stomach had significantly frequent bile reflux gastritis than did those with low-grade extension. Biliary excreted contrast media in the stomach on 60-minute delayed gadoxetic MRC has a correlation with the presence of bile reflux gastritis on endoscopic examination.

Detection of Apoptosis and Necrosis in Normal Human Lung Cells Using 1H NMR Spectroscopy

NASA Astrophysics Data System (ADS)

Shih, Chwen-Ming; Ko, Wun-Chang; Yang, Liang-Yo; Lin, Chien-Ju; Wu, Jui-Sheng; Lo, Tsui-Yun; Wang, Shwu-Huey; Chen, Chien-Tsu

2005-05-01

This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P < 0.01). In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.

Driving a Semiautonomous Mobile Robotic Car Controlled by an SSVEP-Based BCI.

PubMed

Stawicki, Piotr; Gembler, Felix; Volosyak, Ivan

2016-01-01

Brain-computer interfaces represent a range of acknowledged technologies that translate brain activity into computer commands. The aim of our research is to develop and evaluate a BCI control application for certain assistive technologies that can be used for remote telepresence or remote driving. The communication channel to the target device is based on the steady-state visual evoked potentials. In order to test the control application, a mobile robotic car (MRC) was introduced and a four-class BCI graphical user interface (with live video feedback and stimulation boxes on the same screen) for piloting the MRC was designed. For the purpose of evaluating a potential real-life scenario for such assistive technology, we present a study where 61 subjects steered the MRC through a predetermined route. All 61 subjects were able to control the MRC and finish the experiment (mean time 207.08 s, SD 50.25) with a mean (SD) accuracy and ITR of 93.03% (5.73) and 14.07 bits/min (4.44), respectively. The results show that our proposed SSVEP-based BCI control application is suitable for mobile robots with a shared-control approach. We also did not observe any negative influence of the simultaneous live video feedback and SSVEP stimulation on the performance of the BCI system.

New parasite inhibitors encompassing novel conformationally-locked 5'-acyl sulfamoyl adenosines.

PubMed

Dixit, Shailesh S; Upadhayaya, Ram Shankar; Chattopadhyaya, Jyoti

2012-08-14

We describe the design, synthesis and biological evaluation of conformationally-locked 5'-acyl sulfamoyl adenosine derivatives as new parasitic inhibitors against Trypanosoma and Leishmania. The conformationally-locked (3'-endo, North-type) nucleosides have been synthesized by covalently attaching a 4'-CH(2)-O-2' bridge () across C2'-C4' of adenosine in order to reduce the conformational flexibility of the pentose ring. This is designed to decrease the entropic penalty for complex formation with the target protein, which may improve free-energy of stabilization of the complex leading to improved potency. Conformationally-locked 5'-acyl sulfamoyl adenosine derivatives (16-22) were tested against parasitic protozoans for the first time in this work, and showed potent inhibition of Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma rhodesiense and Leishmania infantum with IC(50) = 0.25-0.51 μM. In particular, the potent 5'-pentanyl acyl sulfamoyl adenosine derivative 17 (IC(50) = 0.25 μM) against intracellular L. infantum amastigotes and Trypanosoma subspecies is interesting in view of its almost insignificant cytotoxicity in murine macrophage host cells (CC(50) >4 μM) and in diploid human fibroblasts MRC-5 cell lines (CC(50) 4 μM). This work also suggests that variable alkyl chain length of the acyl group on the acylsulfamoyl side chain at 5' can modulate the toxicity of 5'-O-sulfamoylnucleoside analogues. This conformationally-locked sulfamoyl adenosine scaffold presents some interesting possibilities for further drug design and lead optimization.

Use of Medical Reserve Corps Volunteers in a Hospital-based Disaster Exercise.

PubMed

Gist, Ramon; Daniel, Pia; Grock, Andrew; Lin, Chou-Jui; Bryant, Clarence; Kohlhoff, Stephan; Roblin, Patricia; Arquilla, Bonnie

2016-06-01

Introduction The Medical Reserve Corps (MRC) is a national network of community-based volunteer groups created in 2002 by the Office of the United States Surgeon General (Rockville, Maryland USA) to augment the nation's ability to respond to medical and public health emergencies. However, there is little evidence-based literature available to guide hospitals on the optimal use of medical volunteers and hesitancy on the part of hospitals to use them. Hypothesis/Problem This study sought to determine how MRC volunteers can be used in hospital-based disasters through their participation in a full-scale exercise. A full-scale exercise was designed as a "Disaster Olympics," in which the Emergency Medicine residents were divided into teams tasked with completing one of the following five challenges: victim decontamination, mass casualty/decontamination tent assembly, patient triage and registration during a disaster, point of distribution (POD) site set-up and operation, and infection control management. A surge of patients potentially exposed to avian influenza was the scenario created for the latter three challenges. Some MRC volunteers were assigned clinical roles. These roles included serving as members of the suit support team for victim decontamination, distributing medications at the POD, and managing infection control. Other MRC volunteers functioned as "victim evaluators," who portrayed the potential avian influenza victims while simultaneously evaluating various aspects of the disaster response. The MRC volunteers provided feedback on their experience and evaluators provided feedback on the performance of the MRC volunteers using evaluation tools. Twenty-eight (90%) MRC volunteers reported that they worked well with the residents and hospital staff, felt the exercise was useful, and were assigned clearly defined roles. However, only 21 (67%) reported that their qualifications were assessed prior to role assignment. For those MRC members who functioned as

Modification of the hTERT promoter by heat shock elements enhances the efficiency and specificity of cancer targeted gene therapy.

PubMed

Wang, Xiaolong; Zhou, PeiHua; Sun, XueJun; Wei, GuangBing; Zhang, Li; Wang, Hui; Yao, JianFeng; Jia, PengBo; Zheng, JianBao

2016-05-01

One of the current challenges facing cancer gene therapy is the tumour-specific targeting of therapeutic genes. Effective targeting in gene therapy requires accurate spatial and temporal control of gene expression. To develop a sufficient and accurate tumour-targeting method for cancer gene therapy, we have investigated the use of hyperthermia to control the expression of a transgene under the control of the human telomerase reverse transcriptase (hTERT) promoter and eight heat shock elements (8HSEs). Luciferase reporters were constructed by inserting eight HSEs and the hTERT promoter (8HSEs-hTERTp) upstream of the pGL4.20 vector luciferase gene. The luciferase activity of the hTERT promoter and 8HSEs-hTERT promoter were then compared in the presence and absence of heat. The differences in luciferase activity were analysed using dual luciferase assays in SW480 (high hTERT expression), MKN28 and MRC-5 cells (low hTERT expression). The luciferase activity of the Hsp70B promoter was also compared to the 8HSEs-hTERT promoter in the above listed cell lines. Lentiviral vector and heat-induced expression of EGFP expression under the control of the 8HSEs-hTERT promoter in cultured cells and mouse tumour xenografts was measured by reverse transcription polymerase (RT-PCR), Western blot and immunofluorescence assays. hTERT promoter activity was higher in SW480 cells than in MKN28 or MRC-5 cells. At 43 °C, the luciferase activity of the 8HSEs-hTERT promoter was significantly increased in SW480 cells, but not in MKN28 or MRC-5 cells. Importantly, the differences in luciferase activity were much more obvious in both high (SW480) and low (MKN28 and MRC-5) hTERT expressing cells when the activity of the 8HSEs-hTERT promoter was compared to the Hsp70B promoter. Moreover, under the control of 8HSEs-hTERT promoter in vitro and in vivo, EGFP expression was obviously increased by heat treatment in SW480 cells but not in MKN28 or MRC-5 cells, nor was expression increased under

Value of three-dimensional gradient-echo magnetic resonance cholangiography in diagnosing choledocholithiasis.

PubMed

Rawat, B; Loewy, J

1996-08-01

To evaluate the role of magnetic resonance cholangiography (MRC) in patients with suspected choledocholithiasis. Twenty-six consecutive patients with suspected choledocholithiasis (11 men and 15 women ranging in age from 25 to 81 years) underwent three-dimensional gradient-echo MRC; each patient also underwent endoscopic retrograde cholangiography or operative cholangiography. Each set of images for each patient was reviewed independently by a radiologist who was unaware of the results of the other type of imaging. Diagnostic-quality MRC images were obtained for 17 of the patients. Of these, 13 had stones in the common bile duct, as confirmed by another imaging method, and MRC indicated the presence of these stones in all 13 patients. In the other four patients bile duct obstruction was due to either acute pancreatitis (in three) or cholangiocarcinoma (in one). For seven of the nine nondiagnostic-quality MRC studies, the bile duct was not obstructed, so there was no bile stasis and the MRC images could not be obtained. Motion artifacts due to inability to hold the breath were the limiting factors in the other two patients. Although MRC has some limitations, this new noninvasive technique may be used as a screening test in selected patients with suspected choledocholithiasis.

77 FR 57088 - Agency Information Collection Activities; Proposed Collection; Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... States, and to continue planning for future emergencies that are national in scope, detailed information... the Surgeon General. MRC Unit Leaders are asked to update this information on the MRC Web site at... Total burden respondents respondent per response hours MRC Unit Leader 1,000 6 1.0 6,000 Keith A. Tucker...

Functional Consequences of Mannose and Asialoglycoprotein Receptor Ablation*

PubMed Central

Mi, Yiling; Coonce, Marcy; Fiete, Dorothy; Steirer, Lindsay; Dveksler, Gabriela; Townsend, R. Reid; Baenziger, Jacques U.

2016-01-01

The mannose receptor (ManR, Mrc1) and asialoglycoprotein receptor (ASGR, Asgr1 and Asgr2) are highly abundant endocytic receptors expressed by sinusoidal endothelial cells and parenchymal cells in the liver, respectively. We genetically manipulated either receptor individually or in combination, revealing phenotypic changes in female and male mice associated with changes in circulating levels of many glycoproteins. Both receptors rise and fall in response to progesterone during pregnancy. Thirty percent of Asgr2−/− and 65% of Mrc1−/−Asgr2−/− mice are unable to initiate parturition at the end of pregnancy, whereas Mrc1−/− mice initiate normally. Twenty five percent of Mrc1−/−Asgr2−/− male mice develop priapism when mating due to thrombosis of the penile vein, but neither Mrc1−/− nor Asgr2−/− mice do so. The half-life for luteinizing hormone (LH) clearance increases in Mrc1−/− and Mrc1−/−Asgr2−/− mice but not in Asgr2−/− mice; however, LH and testosterone are elevated in all three knockouts. The ManR clears LH thus regulating testosterone production, whereas the ASGR appears to mediate clearance of an unidentified glycoprotein that increases LH levels. More than 40 circulating glycoproteins are elevated >3.0-fold in pregnant Mrc1−/−Asgr2−/− mice. Pregnancy-specific glycoprotein 23, undetectable in WT mice (<50 ng/ml plasma), reaches levels of 1–10 mg/ml in the plasma of Mrc1−/−Asgr2−/− and Asgr2−/− mice, indicating it is cleared by the ASGR. Elevation of multiple coagulation factors in Mrc1−/−Asgr2−/− mice may account for priapism seen in males. These male and female phenotypic changes underscore the key roles of the ManR and ASGR in controlling circulating levels of numerous glycoproteins critical for regulating reproductive hormones and blood coagulation. PMID:27405760

Cytotoxic constituents of Pachyrhizus tuberosus from Peruvian amazon.

PubMed

Leuner, Olga; Havlik, Jaroslav; Budesinsky, Milos; Vrkoslav, Vladimir; Chu, Jessica; Bradshaw, Tracey D; Hummelova, Jana; Miksatkova, Petra; Lapcik, Oldrich; Valterova, Irena; Kokoska, Ladislav

2013-10-01

Investigations into the chemical constituents of the seeds of the neglected tuber crop Pachyrhizus tuberosus (Leguminosae) resulted in the isolation of seven components: five rotenoids [12a-hydroxyerosone (1), 12a-hydroxydolineone (2), erosone (3), 12a-hydroxyrotenone (4) and rotenone (6)], a phenylfuranocoumarin [pachyrrhizine (5)] and an isoflavanone [neotenone (7)]. The compounds were isolated using several chromatography techniques and characterized and verified by NMR and HPLC/MS. The MTT assay was used to examine the selective cytotoxic effects of the methanolic P. tuberosus extract and isolated compounds in two human cancer cell lines [breast (MCF-7) and colorectal (HCT-116)] and in non-transformed human fibroblasts (MRC-5); IC50 values were calculated. The methanolic P. tuberosus extract displayed respectable cytotoxic effects against HCT-116 and MCF-7 cells with IC50 values of 7.3 and 6.3 microg/mL, respectively. Of the compounds, 6 exacted greatest cytotoxicity and selectivity towards the cancer cell lines tested, yielding IC50 values of 0.3 microg/mL against both MCF-7 and HCT-116 cells, and a 6-fold reduced activity against MRC-5 fibroblasts. Compound 4 also demonstrated cytotoxicity against MCF-7 and HCT-116 (1.1 and 1.8 microg/mL, respectively), and reduced cytotoxicity towards MRC-5 cells (7.5 mirog/mL). The results revealed from the in vitro cytotoxic MTT assay are worthy of further antitumor investigation.

Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment

PubMed Central

Zhong, Ting; Zhang, Li-ying; Wang, Zeng-yan; Wang, Yue; Song, Feng-mei; Zhang, Ya-hong; Yu, Jing-hua

2017-01-01

Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication

Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment.

PubMed

Zhong, Ting; Zhang, Li-Ying; Wang, Zeng-Yan; Wang, Yue; Song, Feng-Mei; Zhang, Ya-Hong; Yu, Jing-Hua

2017-03-01

Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication

Rotenone-stimulated superoxide release from mitochondrial complex I acutely augments L-type Ca2+ current in A7r5 aortic smooth muscle cells

PubMed Central

Dhagia, Vidhi; Lakhkar, Anand; Patel, Dhara; Wolin, Michael S.; Gupte, Sachin A.

2016-01-01

Voltage-gated L-type Ca2+ current (ICa,L) induces contraction of arterial smooth muscle cells (ASMCs), and ICa,L is increased by H2O2 in ASMCs. Superoxide released from the mitochondrial respiratory chain (MRC) is dismutated to H2O2. We studied whether superoxide per se acutely modulates ICa,L in ASMCs using cultured A7r5 cells derived from rat aorta. Rotenone is a toxin that inhibits complex I of the MRC and increases mitochondrial superoxide release. The superoxide content of mitochondria was estimated using mitochondrial-specific MitoSOX and HPLC methods, and was shown to be increased by a brief exposure to 10 μM rotenone. ICa,L was recorded with 5 mM BAPTA in the pipette solution. Rotenone administration (10 nM to 10 μM) resulted in a greater ICa,L increase in a dose-dependent manner to a maximum of 22.1% at 10 μM for 1 min, which gradually decreased to 9% after 5 min. The rotenone-induced ICa,L increase was associated with a shift in the current-voltage relationship (I-V) to a hyperpolarizing direction. DTT administration resulted in a 17.9% increase in ICa,L without a negative shift in I–V, and rotenone produced an additional increase with a shift. H2O2 (0.3 mM) inhibited ICa,L by 13%, and additional rotenone induced an increase with a negative shift. Sustained treatment with Tempol (4-hydroxy tempo) led to a significant ICa,L increase but it inhibited the rotenone-induced increase. Staurosporine, a broad-spectrum protein kinase inhibitor, partially inhibited ICa,L and completely suppressed the rotenone-induced increase. Superoxide released from mitochondria affected protein kinases and resulted in stronger ICa,L preceding its dismutation to H2O2. The removal of nitric oxide is a likely mechanism for the increase in ICa,L. PMID:26873970

Impact Evaluation of the Minnesota Reading Corps K-3 Program

ERIC Educational Resources Information Center

Markovitz, Carrie E.; Hernandez, Marc W.; Hedberg, Eric C.; Silberglitt, Benjamin

2014-01-01

Minnesota Reading Corps (MRC) is the largest AmeriCorps State program in the country. The goal of MRC is to ensure that students become successful readers and meet reading proficiency targets by the end of the third grade. To meet this goal, the MRC program, and its host organization, ServeMinnesota Action Network, recruit, train, place and…

Comparison of the amount of bioaccessible fumonisin B1 and B2 in maize and rice inoculated with Fusarium verticillioides (MRC 826) and determined by in vitro digestion-preliminary results.

PubMed

Szabó-Fodor, J; Bors, I; Szabó, A; Kovács, M

2016-08-01

In this study the occurrence of hidden fumonisin B1 (FB1) and fumonisin B2 (FB2) was analysed, on two cereal substrates (maize and rice), inoculated with Fusarium verticillioides (MRC 826), in order to determine the ratio of hidden FB1 and FB2. Two parallel methods were applied: an in vitro human digestion sample pre-treatment and the routine extraction procedure, in both cases with subsequent LC-MS analysis. It was found that all samples showed higher concentration of total fumonisin B1 after digestion, as compared to that of free fumonisin analysed only after extraction. The percentage of the hidden form by maize was 18.8 % (±2.4) for FB1 and 36.8 % (±3.8) for FB2, while for rice it was 32.3 % (±11.3) and 58.0 (±6.8), respectively, expressed as the proportion to total fumonisin B1, for the total dataset. Significant differences were found in the FB1 and FB2 concentration measured after the different digestion phases (saliva, gastric and duodenal) in case of both matrixes. The results are useful for human risk assessment, since both humans and animals may be exposed to markedly higher toxin load, as determined merely by conventional analytical methods.

Development of model reference adaptive control theory for electric power plant control applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mabius, L.E.

1982-09-15

The scope of this effort includes the theoretical development of a multi-input, multi-output (MIMO) Model Reference Control (MRC) algorithm, (i.e., model following control law), Model Reference Adaptive Control (MRAC) algorithm and the formulation of a nonlinear model of a typical electric power plant. Previous single-input, single-output MRAC algorithm designs have been generalized to MIMO MRAC designs using the MIMO MRC algorithm. This MRC algorithm, which has been developed using Command Generator Tracker methodologies, represents the steady state behavior (in the adaptive sense) of the MRAC algorithm. The MRC algorithm is a fundamental component in the MRAC design and stability analysis.more » An enhanced MRC algorithm, which has been developed for systems with more controls than regulated outputs, alleviates the MRC stability constraint of stable plant transmission zeroes. The nonlinear power plant model is based on the Cromby model with the addition of a governor valve management algorithm, turbine dynamics and turbine interactions with extraction flows. An application of the MRC algorithm to a linearization of this model demonstrates its applicability to power plant systems. In particular, the generated power changes at 7% per minute while throttle pressure and temperature, reheat temperature and drum level are held constant with a reasonable level of control. The enhanced algorithm reduces significantly control fluctuations without modifying the output response.« less

Driving a Semiautonomous Mobile Robotic Car Controlled by an SSVEP-Based BCI

PubMed Central

2016-01-01

Brain-computer interfaces represent a range of acknowledged technologies that translate brain activity into computer commands. The aim of our research is to develop and evaluate a BCI control application for certain assistive technologies that can be used for remote telepresence or remote driving. The communication channel to the target device is based on the steady-state visual evoked potentials. In order to test the control application, a mobile robotic car (MRC) was introduced and a four-class BCI graphical user interface (with live video feedback and stimulation boxes on the same screen) for piloting the MRC was designed. For the purpose of evaluating a potential real-life scenario for such assistive technology, we present a study where 61 subjects steered the MRC through a predetermined route. All 61 subjects were able to control the MRC and finish the experiment (mean time 207.08 s, SD 50.25) with a mean (SD) accuracy and ITR of 93.03% (5.73) and 14.07 bits/min (4.44), respectively. The results show that our proposed SSVEP-based BCI control application is suitable for mobile robots with a shared-control approach. We also did not observe any negative influence of the simultaneous live video feedback and SSVEP stimulation on the performance of the BCI system. PMID:27528864

N-glycan profiles in H9N2 avian influenza viruses from chicken eggs and human embryonic lung fibroblast cells.

PubMed

Chen, Wentian; Zhong, Yaogang; Su, Rui; Qi, Huicai; Deng, Weina; Sun, Yu; Ma, Tianran; Wang, Xilong; Yu, Hanjie; Wang, Xiurong; Li, Zheng

2017-11-01

N-glycosylation can affect the host specificity, virulence and infectivity of influenza A viruses (IAVs). In this study, the distribution and evolution of N-glycosylation sites in the hemagglutinin (HA) and neuraminidase (NA) of H9N2 virus were explored using phylogenetic analysis. Then, one strain of the H9N2 subtypes was proliferated in the embryonated chicken eggs (ECE) and human embryonic lung fibroblast cells (MRC-5) system. The proliferated viral N-glycan profiles were analyzed by a glycomic method that combined the lectin microarray and MALDI-TOF/TOF-MS. As a result, HA and NA of H9N2 viruses prossess six and five highly conserved N-glycosylation sites, respectively. Sixteen lectins (e.g., MAL-II, SNA and UEA-I) had increased expression levels of the glycan structures in the MRC-5 compared with the ECE system; however, 6 lectins (e.g., PHA-E, PSA and DSA) had contrasting results. Eleven glycans from the ECE system and 13 glycans from the MRC-5 system were identified. Our results showed that the Fucα-1,6GlcNAc(core fucose) structure was increased, and pentaantennary N-glycans were only observed in the ECE system. The SAα2-3/6Gal structures were highly expressed and Fucα1-2Galβ1-4GlcNAc structures were only observed in the MRC-5 system. We conclude that the existing SAα2-3/6Gal sialoglycans make the offspring of the H9N2 virus prefer entially attach to each other, which decreases the virulence. Alterations in the glycosylation sites for the evolution and role of IAVs have been widely described; however, little is known about the exact glycan structures for the same influenza strain from different hosts. Our findings may provide a novel way for further discussing the molecular mechanism of the viral transmission and virulence associated with viral glycosylation in avian and human hosts as well as vital information for designing a vaccine against influenza and other human viruses. Copyright © 2017. Published by Elsevier B.V.

Explosive safety criteria at a Department of Energy contractor facility

NASA Astrophysics Data System (ADS)

Krach, F.

1984-08-01

Monsanto Research Corporation (MRC) operates the Mound facility in Miamisburg, Ohio, for the Department of Energy. Small explosive components are manufactured at MRC, and stringent explosive safety criteria have been developed for their manufacturing. The goals of these standards are to reduce employee injuries and eliminate fenceline impacts resulting from accidental detonations. The manner in which these criteria were developed and what DOD standards were incorporated into MRC's own design criteria are described. These design requirements are applicable to all new construction at MRC. An example of the development of the design of a Component Test Facility is presented to illustrate the application of the criteria.

Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients.

PubMed

Ogawa, Erika; Shimura, Masaru; Fushimi, Takuya; Tajika, Makiko; Ichimoto, Keiko; Matsunaga, Ayako; Tsuruoka, Tomoko; Ishige, Mika; Fuchigami, Tatsuo; Yamazaki, Taro; Mori, Masato; Kohda, Masakazu; Kishita, Yoshihito; Okazaki, Yasushi; Takahashi, Shori; Ohtake, Akira; Murayama, Kei

2017-09-01

Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It is clinically diagnosed by typical manifestations and characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS is essential for deeper understanding of the disease, which may lead to the development of new therapies and cure. The aim of this study was to evaluate the clinical validity of various diagnostic tools in confirming MRC disorder in LS and Leigh-like syndrome (LL). The results of enzyme assays, molecular analysis, and cellular oxygen consumption rate (OCR) measurements were examined. Of 106 patients, 41 were biochemically and genetically verified, and 34 had reduced MRC activity but no causative mutations. Seven patients with normal MRC complex activities had mutations in the MT-ATP6 gene. Five further patients with normal activity in MRC were identified with causative mutations. Conversely, 12 out of 60 enzyme assays performed for genetically verified patients returned normal results. No biochemical or genetic background was confirmed for 19 patients. OCR was reduced in ten out of 19 patients with negative enzyme assay results. Inconsistent enzyme assay results between fibroblast and skeletal muscle biopsy samples were observed in 33% of 37 simultaneously analyzed cases. These data suggest that highest diagnostic rate is reached using a combined enzymatic and genetic approach, analyzing more than one type of biological materials where suitable. Microscale oxygraphy detected MRC impairment in 50% cases with no defect in MRC complex activities.

Baseline Severity as Predictor of Change in St George’s Respiratory Questionnaire Scores in Trials of Long-acting Bronchodilators with COPD Patients

PubMed Central

Jones, Paul W.; Gelhorn, Heather; Karlsson, Niklas; Menjoge, Shailendra; Müllerova, Hana; Rennard, Stephen I.; Tal-Singer, Ruth; Wilson, Hilary; Merrill, Debora; Tabberer, Maggie

2017-01-01

Background: In trials oflong-acting bronchodilators, health status is an important trial outcome, however the influence of baseline severity on response measured by St George’s Respiratory Questionnaire (SGRQ) is not known. We have compared SGRQ changes between patients with chronic obstructive pulmonary disease (COPD) of mild-moderate severity or dyspnea (Global initiative for chronic Obstructive Lung disease [GOLD] grades 1 and 2; modified Medical Research Council [mMRC] grades 1 and 2) to those with severe-very severe severity or dyspnea (GOLD grades 3 and 4; mMRC grades 3 and 4). Methods: Combined individual patient data from the COPD Biomarkers Qualification Consortium database (trials of long-acting bronchodilators) were used comprising of patients from short-term (≤1-year duration; n=10802) and medium-term (2-4 years’ duration; n=8963) studies. A repeated measures analysis of variance (ANOVA) was used to determine the effects of baseline severity (GOLD/mMRC) on SGRQ response to treatment. All treatment arms were combined. Results: In short-term studies, milder patients showed a greater response than those with more severe disease in terms of GOLD grade (partial Eta2 = 0.03, p < 0.0001) and mMRC grade (partial Eta2 = 0.05, p < 0.0001). Similar results were seen in the medium-term studies (partial Eta2 = 0.02, p < 0.0001; mMRC: partial Eta2 = 0.05, p < 0.0001,). Conclusions: Patients with less severe airflow limitation and less severe dyspnea showed larger improvements in SGRQ score than more severely obstructed or dyspneic patients. Although these severity influences are small (2%-5% of the variance in SGRQ score), they do suggest that pre-specified separate analyses are warranted to test for differences in response, based on baseline severity. PMID:28848922

Outcomes of clinical decision support (CDS) and correlates of CDS use for home care patients with high medication regimen complexity: A randomized trial

PubMed Central

McDonald, Margaret V.; Feldman, Penny H.; Barrón-Vayá, Yolanda; Peng, Timothy R.; Sridharan, Sridevi; Pezzin, Liliana E.

2017-01-01

Objective To assess the outcomes of a clinical decision support (CDS) intervention designed for home care patients with high medication regimen complexity (MRC) and to examine the correlates of CDS use and its relationship to patient outcomes. Method The intervention randomized nurses upon identification of an eligible patient. The CDS consisted of a computerized algorithm that identified high MRC patients, electronic clinician alerts, and a care management module. Analyses were completed on full intention to treat and intervention group-only samples. Regression-adjusted outcomes were hospitalization, emergency department use and reduction in MRC. Data sources included health records and administrative data. Results Five hundred nurses were randomized with 7,919 of their patients. Approximately 20% of the intervention group was hospitalized versus 21% in the control group; 16.5% of the intervention group had an emergency department visit versus 16.7% in the control group; and 6% in each group dropped below the high MRC threshold. No statistically significant differences were found in the intention to treat analysis. Eighty-two percent of intervention nurses used the CDS but for only 42% of their patients. Among intervention patients, CDS use (versus non-use) was associated with reduced MRC and hospitalization. CDS use was more likely among older nurses, those with higher study-patient caseload and, marginally, among salaried nurses and those with longer tenure. Significant patient characteristics were clinical conditions, payer, episode length, care continuity and race. Conclusion CDS use was limited, thus negating the impact of the intervention overall. The findings on correlates of CDS use and the relationship between CDS use and positive outcomes suggest that CDS use and outcomes could be enhanced by avoiding very short patient lengths of stay, improving continuity of care, increasing reliance on salaried nurses and/or increasing per diem nurses’ incentives to

The effect of artichoke (Cynara scolymus L.) extract on respiratory chain system activity in rat liver mitochondria.

PubMed

Juzyszyn, Z; Czerny, B; Myśliwiec, Z; Pawlik, A; Droździk, M

2010-06-01

The effect of artichoke extract on mitochondrial respiratory chain (MRC) activity in isolated rat liver mitochondria (including reaction kinetics) was studied. The effect of the extract on the activity of isolated cytochrome oxidase was also studied. Extract in the range of 0.68-2.72 microg/ml demonstrated potent and concentration-dependent inhibitory activity. Concentrations > or =5.4 microg/ml entirely inhibited MRC activity. The succinate oxidase system (MRC complexes II-IV) was the most potently inhibited, its activity at an extract concentration of 1.36 microg/ml being reduced by 63.3% compared with the control (p < 0.05). The results suggest a complex inhibitory mechanism of the extract. Inhibition of the succinate oxidase system was competitive (K(i) = 0.23 microg/ml), whereas isolated cytochrome oxidase was inhibited noncompetitively (K(i) = 126 microg/ml). The results of this study suggest that the salubrious effects of artichoke extracts may rely in part on the effects of their active compounds on the activity of the mitochondrial respiratory chain system.

Comparison of the predictability of refractive cylinder correction by laser in situ keratomileusis in eyes with low or high ocular residual astigmatism.

PubMed

Archer, Timothy J; Reinstein, Dan Z; Piñero, David P; Gobbe, Marine; Carp, Glenn I

2015-07-01

To compare the manifest refractive cylinder (MRC) predictability of myopic astigmatism laser in situ keratomileusis (LASIK) between eyes with low and high ocular residual astigmatism (ORA). London Vision Clinic, London, United Kingdom. Retrospective case study. The ORA was considered the vector difference between the MRC and the corneal astigmatism. The index of success (IoS), difference vector ÷ MRC, was analyzed for different groups as follows: stage 1, low ORA (ORA ÷ MRC <1), high ORA (ORA ÷ MRC ≥1); stage 2, low ORA group reduced to match the high ORA group for MRC; stage 3, grouped by ORA magnitude with low ORA (<0.50 diopters [D]), mid ORA (0.50 to 1.24 D), and high ORA (≥1.25 D); stage 4, high ORA group subdivided into low (<0.75 D) and high (≥0.75 D) corneal astigmatism. For stage 1, the mean preoperative MRC and mean IoS were -1.32 D ± 0.65 (SD) (range -0.55 to -3.77 D) and 0.27, respectively, for low ORA and -0.79 ± 0.20 D (range -0.56 to -2.05 D) and 0.37, respectively, for high ORA. For stage 2, the mean IoS increased to 0.32 for low ORA. For stage 3, the mean IoS was 0.28, 0.29, and 0.31 for low ORA, mid ORA, and high ORA, respectively. For stage 4, the mean IoS was 0.20 for high ORA/low corneal astigmatism and 0.35 for high ORA/high corneal astigmatism. The MRC predictability was slightly worse in eyes with high ORA when grouped by the ORA ÷ MRC. Matching for the MRC and grouping by ORA magnitude resulted in similar predictability; however, eyes with high ORA and high corneal astigmatism were less predictable. Dr. Reinstein is a consultant to Carl Zeiss Meditec AG, has a proprietary interest in the Artemis technology (Arcscan, Inc.), and is an author of patents related to very-high-frequency digital ultrasound administered by the Center for Technology Licensing at Cornell University, Ithaca, New York, USA. No other author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS

Differential response of two cell lines sequentially irradiated with low X-ray doses.

PubMed

Güerci, A M; Dulout, F N; Grillo, C A; Seoane, A I

2005-05-01

An experiment was designed to compare the effect of repeated low doses of X-rays in two different cell lines: one transformed, epithelial like and aneuploid Chinese hamster ovary K-1 (CHO-K1); the other originated from a human primary culture, fibroblast, diploid and non-transformed, MRC-5. CHO and MRC-5 cells were cultured for 14 or eight passages, respectively. Irradiation was performed once per passage when cells were in the quiescent state (90 - 95% in G1/G0). Cells were exposed to 10.0 mSv X-ray doses. Ionizing radiation did not induce apoptosis or necrosis in the exposed CHO cell population. Significant increases of low-level damaged cells (degrees 1 and 2) were found for the 14 cycles of radiation when compared with controls, except for the first irradiation cycle. No significant increases in the frequency of cells with severe damage were observed. The frequency of MRC-5 cells with low-level damage increased significantly when compared with controls for radiation cycles seven and eight. Significant increases of apoptosis, necrosis and severe damage were found only for the highest dose. Transformed and non-transformed cell types responded differently to direct and indirect damage using low-dose repeat exposures to ionizing radiation. Though more investigation is needed to understand the mechanisms of radiation effects in chronic low-dose-exposed cell populations, cellular type should be taken into account in the design of in vitro experiments for understanding low-dose-irradiation effects.

Effect and mechanism of calpains on pediatric lobar pneumonia.

PubMed

Yin, Genquan; Zeng, Qiang; Zhao, Haijin; Wu, Peiqiong; Cai, Shaoxi; Deng, Li; Jiang, Wenhui

2017-07-04

Lobar pneumonia, one of the community-acquired pneumonia (CAP), is a common pediatric low respiratory tract infection. Calpains are Ca 2+ -activated cysteine proteases whose activation mechanism is elusive. The present study was undertaken to detect the role and mechanism of calpains in pediatric lobar pneumonia. The human acute lung infection model (ALIM) was constructed and infected by Streptococcus. Enzyme-linked immunosorbent assay (ELISA) was used to measure interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α. We observed the lactate dehydrogenase (LDH) release, calpains activity and calpain inhibitor effects in ALIM. The expression of proliferating cell nuclear antigen (PCNA) protein was quantified by western blotting. Then the effects of calpain 1 and 2 knockdown on expressions of inflammation factors and PCNA protein, LDH release and apoptosis were evaluated in lung MRC-5 cells. In constructed ALIM, expressions of IL-6 (P < 0.01), IL-8 (P < 0.01), TNF-α (P < 0.05) and PCNA protein (P < 0.05) were significantly reduced by the calpain inhibitor. Expressions of IL-6, IL-8, TNF-α, PCNA protein and relative LDH release were statistically reduced by the small interfering (si) RNA-calpain 1 and 2 in MRC-5 cells (P < 0.05). Calpains silence increased apoptotic cells from 5% (negative control) to more than 20% in MRC-5 cells. The present study suggests that calpains possess a significant effect on inflammations, cell proliferation and apoptosis. Suppression of calpains may provide a potential therapeutic target of lobar pneumonia.

MIDWESTERN REGIONAL CENTER OF THE DOE NATIONAL INSTITUTE FOR CLIMATIC CHANGE RESEARCH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burton, Andrew J.

2014-02-28

The goal of NICCR (National Institute for Climatic Change Research) was to mobilize university researchers, from all regions of the country, in support of the climatic change research objectives of DOE/BER. The NICCR Midwestern Regional Center (MRC) supported work in the following states: North Dakota, South Dakota, Nebraska, Kansas, Oklahoma, Minnesota, Iowa, Missouri, Wisconsin, Illinois, Michigan, Indiana, and Ohio. The MRC of NICCR was able to support nearly $8 million in climatic change research, including $6,671,303 for twenty projects solicited and selected by the MRC over five requests for proposals (RFPs) and $1,051,666 for the final year of ten projectsmore » from the discontinued DOE NIGEC (National Institute for Global Environmental Change) program. The projects selected and funded by the MRC resulted in 135 peer-reviewed publications and supported the training of 25 PhD students and 23 Masters students. Another 36 publications were generated by the final year of continuing NIGEC projects supported by the MRC. The projects funded by the MRC used a variety of approaches to answer questions relevant to the DOE’s climate change research program. These included experiments that manipulated temperature, moisture and other global change factors; studies that sought to understand how the distribution of species and ecosystems might change under future climates; studies that used measurements and modeling to examine current ecosystem fluxes of energy and mass and those that would exist under future conditions; and studies that synthesized existing data sets to improve our understanding of the effects of climatic change on terrestrial ecosystems. In all of these efforts, the MRC specifically sought to identify and quantify responses of terrestrial ecosystems that were not well understood or not well modeled by current efforts. The MRC also sought to better understand and model important feedbacks between terrestrial ecosystems, atmospheric chemistry, and

Simulation study of the second-generation MR-compatible SPECT system based on the inverted compound-eye gamma camera design

NASA Astrophysics Data System (ADS)

Lai, Xiaochun; Meng, Ling-Jian

2018-02-01

In this paper, we present simulation studies for the second-generation MRI compatible SPECT system, MRC-SPECT-II, based on an inverted compound eye (ICE) gamma camera concept. The MRC-SPECT-II system consists of a total of 1536 independent micro-pinhole-camera-elements (MCEs) distributed in a ring with an inner diameter of 6 cm. This system provides a FOV of 1 cm diameter and a peak geometrical efficiency of approximately 1.3% (the typical levels of 0.1%-0.01% found in modern pre-clinical SPECT instrumentations), while maintaining a sub-500 μm spatial resolution. Compared to the first-generation MRC-SPECT system (MRC-SPECT-I) (Cai 2014 Nucl. Instrum. Methods Phys. Res. A 734 147-51) developed in our lab, the MRC-SPECT-II system offers a similar resolution with dramatically improved sensitivity and greatly reduced physical dimension. The latter should allow the system to be placed inside most clinical and pre-clinical MRI scanners for high-performance simultaneous MRI and SPECT imaging.

Study of the in vitro antiplasmodial, antileishmanial and antitrypanosomal activities of medicinal plants from Saudi Arabia.

PubMed

Al-Musayeib, Nawal M; Mothana, Ramzi A; Al-Massarani, Shaza; Matheeussen, An; Cos, Paul; Maes, Louis

2012-09-25

The present study investigated the in vitro antiprotozoal activity of sixteen selected medicinal plants. Plant materials were extracted with methanol and screened in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. Cytotoxic activity was determined against MRC-5 cells to assess selectivity. The criterion for activity was an IC₅₀ < 10 μg/mL (<5 μg/mL for T. brucei) and a selectivity index of ≥4. Antiplasmodial activity was found in the extracts of Prosopis juliflora and Punica granatum. Antileishmanial activity against L. infantum was demonstrated in Caralluma sinaica and Periploca aphylla. Amastigotes of T. cruzi were affected by the methanol extract of Albizia lebbeck pericarp, Caralluma sinaica, Periploca aphylla and Prosopius juliflora. Activity against T. brucei was obtained in Prosopis juliflora. Cytotoxicity (MRC-5 IC₅₀ < 10 μg/mL) and hence non-specific activities were observed for Conocarpus lancifolius.

Investigating sensitivity, specificity, and area under the curve of the Clinical COPD Questionnaire, COPD Assessment Test, and Modified Medical Research Council scale according to GOLD using St George's Respiratory Questionnaire cutoff 25 (and 20) as reference.

PubMed

Tsiligianni, Ioanna G; Alma, Harma J; de Jong, Corina; Jelusic, Danijel; Wittmann, Michael; Schuler, Michael; Schultz, Konrad; Kollen, Boudewijn J; van der Molen, Thys; Kocks, Janwillem Wh

2016-01-01

In the GOLD (Global initiative for chronic Obstructive Lung Disease) strategy document, the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC) scale are recommended for the assessment of symptoms using the cutoff points of CCQ ≥1, CAT ≥10, and mMRC scale ≥2 to indicate symptomatic patients. The current study investigates the criterion validity of the CCQ, CAT and mMRC scale based on a reference cutoff point of St George's Respiratory Questionnaire (SGRQ) ≥25, as suggested by GOLD, following sensitivity and specificity analysis. In addition, areas under the curve (AUCs) of the CCQ, CAT, and mMRC scale were compared using two SGRQ cutoff points (≥25 and ≥20). Two data sets were used: study A, 238 patients from a pulmonary rehabilitation program; and study B, 101 patients from primary care. Receiver-operating characteristic (ROC) curves were used to assess the correspondence between the recommended cutoff points of the questionnaires. Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥25 were: study A, 0.99, 0.43, and 0.96 for CCQ ≥1, 0.92, 0.48, and 0.89 for CAT ≥10, and 0.68, 0.91, and 0.91 for mMRC ≥2; study B, 0.87, 0.77, and 0.9 for CCQ ≥1, 0.76, 0.73, and 0.82 for CAT ≥10, and 0.21, 1, and 0.81 for mMRC ≥2. Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥20 were: study A, 0.99, 0.73, and 0.99 for CCQ ≥1, 0.91, 0.73, and 0.94 for CAT ≥10, and 0.66, 0.95, and 0.94 for mMRC ≥2; study B, 0.8, 0.89, and 0.89 for CCQ ≥1, 0.69, 0.78, and 0.8 for CAT ≥10, and 0.18, 1, and 0.81 for mMRC ≥2. Based on data from these two different samples, this study showed that the suggested cutoff point for the SGRQ (≥25) did not seem to correspond well with the established cutoff points of the CCQ or CAT scales, resulting in low specificity levels. The correspondence with the mMRC scale seemed satisfactory, though not optimal. The SGRQ threshold of ≥20

Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

PubMed Central

Demeyer, Heleen; Gimeno-Santos, Elena; Rabinovich, Roberto A.; Hornikx, Miek; Louvaris, Zafeiris; de Boer, Willem I.; Karlsson, Niklas; de Jong, Corina; Van der Molen, Thys; Vogiatzis, Ioannis; Janssens, Wim; Garcia-Aymerich, Judith; Troosters, Thierry; Polkey, Michael I.

2016-01-01

Background The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient’s distribution in relation to the questionnaire used. Methods 136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. Results GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. Conclusions Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. Clinical Trial Registration ClinicalTrials.gov NCT01388218 PMID:26974332

Wave Action and Breakwater Location, Taconite Harbor (Two Islands), Lake Superior, Minnesota: Hydraulic Model Investigation

DTIC Science & Technology

1955-05-01

president, Taconite Contractors, Erie. Mining Company, Duluth, Minnesota The model study was conducted in the Hydraulics Division of the Waterways...CORPS OF ENGINEERS. U. S. ARMY WAVE ACTION AND BREAKWATER LOCATION TACONITE HARBOR (TWO ISLANDS) LAKE SUPERIOR, MINNESOTA ARIIIY-MRC VICKSBURG...Breakwater Location, Taconite Harbor (Two Islands), Lake Superior, Minnesota : Hydraulic Model Investigation 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

Fine-needle aspiration cytology of mucous retention cyst of the tongue: distinction from other cystic lesions of the tongue.

PubMed

De Las Casas, L E; Bardales, R H

2000-05-01

Mucous retention cyst (MRC) is a common submucosal lesion of the oral cavity that, when deeply seated, simulates a neoplasm. This report describes the fine-needle aspiration cytology findings of a lingual MRC of complex architecture and with metaplastic epithelium. In addition, we emphasize its cytologic differential diagnosis from other benign and malignant cystic lesions of the tongue. To the best of our knowledge, this is the first report of aspiration cytology of a complex MRC of the tongue. Copyright 2000 Wiley-Liss, Inc.

Quinol derivatives as potential trypanocidal agents

PubMed Central

Capes, Amy; Patterson, Stephen; Wyllie, Susan; Hallyburton, Irene; Collie, Iain T.; McCarroll, Andrew J.; Stevens, Malcolm F.G.; Frearson, Julie A.; Wyatt, Paul G.; Fairlamb, Alan H.; Gilbert, Ian H.

2012-01-01

Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. PMID:22264753

Chemical characterization, antioxidant, genotoxic and in vitro cytotoxic activity assessment of Juniperus communis var. saxatilis.

PubMed

Vasilijević, Bojana; Knežević-Vukčević, Jelena; Mitić-Ćulafić, Dragana; Orčić, Dejan; Francišković, Marina; Srdic-Rajic, Tatjana; Jovanović, Marina; Nikolić, Biljana

2018-02-01

Chemical composition and antioxidative, genotoxic and cytotoxic potential of essential oil (EO) and post-distillation waste (PDW) of Serbian Juniperus communis L. var. saxatilis Pall. was studied in human lung carcinoma (A549) and normal lung fibroblast (MRC-5) cells. GC-MS analysis identified 93.95% of total EO content and determined α-pinen as a dominant component (23.61%). LC-MS/MS analysis of PDW pointed at rutin (12.2 mg g -1 ) and quinic acid (11.1 mg g -1 ) as the most abundant. Antioxidativity of PDW was strong in DPPH (IC 50 was 5.27 μg mL -1 ), and moderate in TBA and FRAP assays. Both substances were more cytotoxic to A549 than to MRC-5 cells. Obtained IC 50 values were 69.4 μg mL -1 and 120 μg mL -1 for EO, and 1.27 mg mL -1 and 2.86 mg mL -1 for PDW, respectively. PDW was genotoxic (0.3 mg mL -1 and 1 mg mL -1 in A549 and MRC-5 cells, respectively) and induced apoptosis and arrested cell cycle in G2/M phase in A549 cells (0.3 mg mL -1 ). In mixtures with doxorubicin cytotoxicity of EO and PDW increased, and combination index values (0.12-0.18) revealed clear synergistic effect, stronger in cancer cells. This indicates that J. communis var. saxatilis could decrease the chemotherapeutic doses of doxorubicin, potentially reducing its side effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advanced bearing materials for cryogenic aerospace engine turbopump requirements

NASA Technical Reports Server (NTRS)

Friedman, G.; Bhat, B. N.

1986-01-01

The properties of eleven alloys were investigated to select an improved bearing material for the High Pressure Oxygen Turbo Pump which delivers liquid oxygen to the Space Shuttle Main Engine. The alloys, selected through detailed literature analysis, X 405, MRC-2001, T440V, 14-4/6V, D-5, V-M Pyromet 350, Stellite 3, FerroTic CS-40, Tribaloy 800, WD-65, and CBS-600. The alloys were tested in hardness, corrosion resistance, wear resistance, fatigue resistance, and fracture toughness tests, and their performance was compared with the baseline 440C test alloy. As a result, five alloys were eliminated, leaving the remaining six (X 405, MRC-2001, T440V, 14-4/6V, D-5, and WD-65 to be evaluated in the next phase of NASA tests which will include fracture toughness, rolling contact fatigue, wear resistance, and corrosion resistance. From these, three alloys will be selected, which will be made into ninety bearings for subsequent testing.

Biological and Phytochemical Investigations on Caesalpinia benthamiana, a Plant Traditionally Used as Antimalarial in Guinea

PubMed Central

Loua, Jean; Traore, Mohamed Sahar; Camara, Aissata; Balde, Mamadou Aliou; Maes, Louis; Pieters, Luc

2017-01-01

Caesalpinia benthamiana is widely used as antimalarial in Guinean traditional medicine. Leaf extracts of the plant were tested for their in vitro antiprotozoal activity against Trypanosoma brucei brucei and T. cruzi and the chloroquine-sensitive Ghana strain of Plasmodium falciparum along with their cytotoxicity on MRC-5 cells. The methanolic extract showed the strongest antiprotozoal activity against P. falciparum (IC50 4 μg/ml), a good activity against T. brucei (IC50 13 μg/ml), and a moderate activity against T. cruzi (IC50 31 μg/ml) along with an IC50 on human MRC-5 cells of 32 μg/ml. Bioassay-guided fractionation from the methanolic extract led to antiplasmodially active subfractions. A prospective, placebo-controlled ethnotherapeutic trial assessed the antimalarial effectiveness and tolerability of C. benthamiana syrup administered orally to children with uncomplicated malaria as compared with chloroquine syrup. Phytochemical screening of the leaf extracts indicated the presence of flavonoids, terpenoids, tannins, saponins, and iridoids. PMID:29081823

Dyspnea in Chronic Fatigue Syndrome (CFS): Comparison of Two Prospective Cross-Sectional Studies

PubMed Central

Ravindran, Murugan K.; Adewuyi, Oluwatoyin; Zheng, Yin; Rayhan, Rakib U.; Le, Uyenphuong; Timbol, Christian R.; Merck, Samantha; Esteitie, Rania; Cooney, Michelle; Read, Charles; Baraniuk, James N.

2013-01-01

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements. Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea. In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness. In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms. PMID:23445698

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies.

PubMed

Ravindran, Murugan; Adewuyi, Oluwatoyin; Zheng, Yin; Rayhan, Rakib U; Le, Uyenphuong; Timbol, Christian; Merck, Samantha; Esteitie, Rania; Read, Charles; Cooney, Michelle; Baraniuk, James

2012-12-12

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements. Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea. In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness. In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

PubMed

Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

2016-09-01

Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients' activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

Prescriptions for medical research. I--Management within the Medical Research Council.

PubMed Central

Gillett, R; Harrow, J

1993-01-01

In their submission to the government in advance of the white paper on science policy in the United Kingdom the Medical Research Council commends the MRC's own approach to managing directly funded research. But a series of semi-structured interviews with the directors of some of the MRC's units suggests a gap between the MRC's model of managed research and the reality. Although such units are theoretically managed from MRC head office (and units are charged an overhead for this), in practice each unit runs its own affairs. Between major reviews average contact time with the head office contact person is seven hours a year. The first paper argues that a purchaser-provider split would recognise the benefits of decentralisation and allow units to bid for research funds from several sources, the successful ones guaranteeing their survival through a rolling series of research programmes. The second paper criticises the MRC's cumbersome peer review system. Reliance on outside experts atrophies the scientific skills of head office staff and builds delays into decision making. A purchaser-provider model would allow the head office scientific staff to act like commercial research and development managers, commissioning research, and using the outcome, rather than peer review, as a criterion for continued funding. PMID:8324441

Mechanism of development of ionocytes rich in vacuolar-type H+-ATPase in the skin of zebrafish larvae

PubMed Central

Esaki, Masahiro; Hoshijima, Kazuyuki; Nakamura, Nobuhiro; Munakata, Keijiro; Tanaka, Mikiko; Ookata, Kayoko; Asakawa, Kazuhide; Kawakami, Koichi; Wang, Weiyi; Weinberg, Eric S.; Hirose, Shigehisa

2009-01-01

Mitochondrion-rich cells (MRCs), or ionocytes, play a central role in aquatic species, maintaining body fluid ionic homeostasis by actively taking up or excreting ions. Since their first description in 1932 in eel gills, extensive morphological and physiological analyses have yielded important insights into ionocyte structure and function, but understanding the developmental pathway specifying these cells remains an ongoing challenge. We previously succeeded in identifying a key transcription factor, Foxi3a, in zebrafish larvae by database mining. In the present study, we analyzed a zebrafish mutant, quadro (quo), deficient in foxi1 gene expression and found that foxi1 is essential for development of an MRC subpopulation rich in vacuolar-type H+-ATPase (vH-MRC). foxi1 acts upstream of Delta-Notch signaling that determines sporadic distribution of vH-MRC and regulates foxi3a expression. Through gain- and loss-of-function assays and cell transplantation experiments, we further clarified that (1) the expression level of foxi3a is maintained by a positive feedback loop between foxi3a and its downstream gene gcm2 and (2) Foxi3a functions cell-autonomously in the specification of vH-MRC. These observations provide a better understanding of the differentiation and distribution of the vH-MRC subtype. PMID:19268451

Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors

PubMed Central

Kim, Do Young; Vallejo, Johana; Rho, Jong M

2010-01-01

Abstract Ketones have previously shown beneficial effects in models of neurodegenerative disorders, particularly against associated mitochondrial dysfunction and cognitive impairment. However, evidence of a synaptic protective effect of ketones remains lacking. We tested the effects of ketones on synaptic impairment induced by mitochondrial respiratory complex (MRC) inhibitors using electrophysiological, reactive oxygen species (ROS) imaging and biochemical techniques. MRC inhibitors dose-dependently suppressed both population spike (PS) and field potential amplitudes in the CA1 hippocampus. Pre-treatment with ketones strongly prevented changes in the PS, whereas partial protection was seen in the field potential. Rotenone (Rot; 100 nmol/L), a MRC I inhibitor, suppressed synaptic function without altering ROS levels and PS depression by Rot was unaffected by antioxidants. In contrast, antioxidant-induced PS recovery against the MRC II inhibitor 3-nitropropionic acid (3-NP; 1 mmol/L) was similar to the synaptic protective effects of ketones. Ketones also suppressed ROS generation induced by 3-NP. Finally, ketones reversed the decreases in ATP levels caused by Rot and 3-NP. In summary, our data demonstrate that ketones can preserve synaptic function in CA1 hippocampus induced by MRC dysfunction, likely through an antioxidant action and enhanced ATP generation. PMID:20374433

Mutagenicity in Salmonella of a Simulated Urban-Smog Atmosphere Generated Using a Mobile Reaction Chamber

EPA Science Inventory

The EPA Mobile Reaction Chamber (MRC) is a 24-foot trailer containing a 14.3-m3 Teflon lined photochemical chamber used to generate simulated urban atmospheres. Photochemistry in the MRC is catalyzed by 120 fluorescent bulbs evenly mixed with black light bulbs and UV bulbs (300 &...

Magnetic resonance cholangiography in the assessment and management of biliary complications after OLT.

PubMed

Girometti, Rossano; Cereser, Lorenzo; Bazzocchi, Massimo; Zuiani, Chiara

2014-07-28

Despite advances in patient and graft management, biliary complications (BC) still represent a challenge both in the early and delayed period after orthotopic liver transplantation (OLT). Because of unspecific clinical presentation, imaging is often mandatory in order to diagnose BC. Among imaging modalities, magnetic resonance cholangiography (MRC) has gained widespread acceptance as a tool to represent the reconstructed biliary tree noninvasively, using both the conventional technique (based on heavily T2-weighted sequences) and contrast-enhanced MRC (based on the acquisition of T1-weighted sequences after the administration of hepatobiliary contrast agents). On this basis, MRC is generally indicated to: (1) avoid unnecessary procedures of direct cholangiography in patients with a negative examination and/or identify alternative complications; and (2) provide a road map for interventional procedures or surgery. As illustrated in the review, MRC is accurate in the diagnosis of different types of biliary complications, including anastomotic strictures, non-anastomotic strictures, leakage and stones.

Characteristics of a COPD population categorised using the GOLD framework by health status and exacerbations.

PubMed

Jones, Paul W; Nadeau, Gilbert; Small, Mark; Adamek, Lukasz

2014-01-01

GOLD proposed a COPD assessment framework focussed on symptoms measured by the COPD Assessment Test™ (CAT) or the mMRC and on exacerbation risk based on poor lung function (FEV1 <50%) or a history of ≥2 exacerbations in the previous year. This analysis examined the characteristics of COPD patients recruited from routine clinical settings and classified using the GOLD framework. 1041 European COPD patients (38.5% from primary care) from the Adelphi Respiratory Disease Specific Programme with information on CAT, mMRC, spirometry and exacerbation history in the previous year were analysed. Their mean age was 64.9 ± 9.9 years and mean FEV1 was 62.5 ± 17.8% predicted; 80% were in GOLD 2 spirometric grade or milder. CAT and mMRC cut points identified different groups of patients; using CAT, the composition was: Group A 9.3%, Group B 48.5%, Group C 0.7% and Group D 41.5%. 80% were classified as high risk based on exacerbation history and 25% of patients in a low risk category (GOLD A and B) had 1 exacerbation in the previous year. The incidence of diabetes, hypertension and hyperlipidaemia rose with worsening GOLD group (all p < 0.0001); diabetes GOLD A 4%, GOLD B 16%, GOLD D 29%; hypertension GOLD A 38%, GOLD B 55%, GOLD D 65%; hyperlipidaemia GOLD A 13%, GOLD B 30%, GOLD D 37%. In patients seen in routine clinical settings, 25% of GOLD low risk patients had one exacerbation per year and the incidence of cardio-vascular and metabolic diseases increases with worsening GOLD group. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Attentional Demands on Motor-Respiratory Coordination

ERIC Educational Resources Information Center

Hessler, Eric E.; Amazeen, Polemnia G.

2009-01-01

Athletic performance requires the pacing of breathing with exercise, known as motor-respiratory coordination (MRC). In this study, we added cognitive and physical constraints while participants intentionally controlled their breathing locations during rhythmic arm movement. This is the first study to examine a cognitive constraint on MRC.…

Improved antioxidative and cytotoxic activities of chamomile (Matricaria chamomilla) florets fermented by Lactobacillus plantarum KCCM 11613P.

PubMed

Park, Eun-Hye; Bae, Won-Young; Eom, Su-Jin; Kim, Kee-Tae; Paik, Hyun-Dong

Antioxidative and cytotoxic effects of chamomile (Matricaria chamomilla) fermented by Lactobacillus plantarum were investigated to improve their biofunctional activities. Total polyphenol (TP) content was measured by the Folin-Denis method, and the antioxidant activities were assessed by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and β-carotene bleaching method. AGS, HeLa, LoVo, MCF-7, and MRC-5 (normal) cells were used to examine the cytotoxic effects by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. The TP content of fermented chamomile reduced from 21.75 to 18.76 mg gallic acid equivalent (mg GAE)/g, but the DPPH radical capturing activity of fermented chamomile was found to be 11.1% higher than that of nonfermented chamomile after 72 h of fermentation. Following the β-carotene bleaching, the antioxidative effect decreased because of a reduction in pH during fermentation. Additionally, chamomile fermented for 72 h showed a cytotoxic effect of about 95% against cancer cells at 12.7 mg solid/ml of broth, but MRC-5 cells were significantly less sensitive against fermented chamomile samples. These results suggest that the fermentation of chamomile could be applied to develop natural antioxidative and anticancer products.

Microwave and Electron Beam Computer Programs

DTIC Science & Technology

1988-06-01

Research (ONR). SCRIBE was adapted by MRC from the Stanford Linear Accelerator Center Beam Trajectory Program, EGUN . oTIC NSECE Acc !,,o For IDL1C I...achieved with SCRIBE. It is a ver- sion of the Stanford Linear Accelerator (SLAC) code EGUN (Ref. 8), extensively modified by MRC for research on

The Relative Importance of Children's Criteria for Representational Adequacy in the Perception of Simple Sonic Stimuli

ERIC Educational Resources Information Center

Verschaffel, Lieven; Reybrouck, Mark; Degraeuwe, Goedele; Van Dooren, Wim

2013-01-01

This study investigates children's metarepresentational competence (MRC) with regard to listening to and making sense of simple sonic stimuli. Using diSessa's (2002) seminal work on MRC in mathematics and sciences as background, it aims to assess the relative importance children attribute to several criteria for representational adequacy…

Impact Evaluation: Minnesota Reading Corps K-3 Program. Appendices

ERIC Educational Resources Information Center

Markovitz, Carrie E.; Hernandez, Marc W.; Hedberg, Eric C.; Silberglitt, Benjamin

2014-01-01

Minnesota Reading Corps (MRC) is the largest AmeriCorps State program in the country. The goal of MRC is to ensure that students become successful readers and meet reading proficiency targets by the end of the third grade. Starting in 2011, the "Corporation for National and Community Service" (CNCS) sponsored a randomized controlled…

Reaction Rate Data. Number 63. Resume of FY 78 DNA-Sponsored Chemistry/Physics Reaction Rate Research Programs.

DTIC Science & Technology

1977-12-01

related progress p reports concerning the DNA-sponsored effo rt s described herein. - ~~~ Submission of other pertinent informat ion of a related nature...Work Unit 06). 5 5. Atmospheric Chemical Sensitivity and Modeling Invesriga nons—M. Scheibe, MRC (Work Unit 09). 5 6. Low Energy Cross Sections for...Debris Metal Ions—R. Neynaber, D. Vroom . and l.A. Rutherford, IRT, Inc. (Work Unit 12). 5 7. E and F Region Rate Coefficients for Excited Positive

Respiratory health status is impaired in UK HIV-positive adults with virologically suppressed HIV infection.

PubMed

Brown, J; McGowan, J A; Chouial, H; Capocci, S; Smith, C; Ivens, D; Johnson, M; Sathia, L; Shah, R; Lampe, F C; Rodger, A; Lipman, M

2017-09-01

We sought to evaluate whether people living with HIV (PLWH) using effective antiretroviral therapy (ART) have worse respiratory health status than similar HIV-negative individuals. We recruited 197 HIV-positive and 93 HIV-negative adults from HIV and sexual health clinics. They completed a questionnaire regarding risk factors for respiratory illness. Respiratory health status was assessed using the St George's Respiratory Questionnaire (SGRQ) and the Medical Research Council (MRC) breathlessness scale. Subjects underwent spirometry without bronchodilation. PLWH had worse respiratory health status: the median SGRQ Total score was 12 [interquartile range (IQR) 6-25] in HIV-positive subjects vs. 6 (IQR 2-14) in HIV-negative subjects (P < 0.001); breathlessness was common in the HIV-positive group, where 47% compared with 24% had an MRC breathlessness score ≥ 2 (P = 0.001). Eighteen (11%) HIV-positive and seven (9%) HIV-negative participants had airflow obstruction. In multivariable analyses (adjusted for age, gender, smoking, body mass index and depression), HIV infection remained associated with higher SGRQ and MRC scores, with an adjusted fold-change in SGRQ Total score of 1.54 [95% confidence interval (CI) 1.14-2.09; P = 0.005] and adjusted odds ratio of having an MRC score of ≥ 2 of 2.45 (95% CI 1.15-5.20; P = 0.02). Similar findings were obtained when analyses were repeated including only HIV-positive participants with a viral load < 40 HIV-1 RNA copies/mL. Despite effective ART, impaired respiratory health appears more common in HIV-positive adults, and has a significant impact on health-related quality of life. © 2017 The Authors HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Biodiversity of Spongosorites coralliophaga (Stephens, 1915) on coral rubble at two contrasting cold-water coral reef settings

NASA Astrophysics Data System (ADS)

Kazanidis, Georgios; Henry, Lea-Anne; Roberts, J. Murray; Witte, Ursula F. M.

2016-03-01

Cold-water coral reefs (CWRs) in the northeast Atlantic harbor diverse sponge communities. Knowledge of deep-sea sponge ecology is limited and this leaves us with a fragmented understanding of the ecological roles that sponges play in CWR ecosystems. We present the first study of faunal biodiversity associated with the massive demosponge Spongosorites coralliophaga (Stephens, 1915) that typically colonizes coral debris fields of CWRs. Our study focused on the sessile fauna inhabiting sponges mixed with coral rubble at two contrasting settings in the northeast Atlantic: the shallow inshore (120-190 m water depth) Mingulay Reef Complex (MRC) and the deep offshore (500-1200 m) Logachev Mound (LM) coral province. MRC is dominated by the scleractinian Lophelia pertusa, while LM is dominated by L. pertusa and Madrepora oculata. Nine sponge-coral rubble associations were collected from MRC and four from LM. Measurements of abundance, species richness, diversity, evenness, dry biomass, and composition of sessile fauna on sponge and coral rubble microhabitats were undertaken. Differences in community composition between the two regions were mainly a response to changes in fauna with depth. Fauna composition was also different between sponge and coral rubble within each region. Infauna constituted a minor component of the sponge-associated fauna in MRC but had a higher contribution in LM. Sponge and coral rubble sessile fauna in both regions was mainly composed of cnidarians and molluscs, similarly to some previous studies. Sponges' outer surfaces at MRC were colonized by a species-rich community with high abundance and biomass suggesting that S. coralliophaga at MRC acts as a settlement surface for various organisms but such a role is not the case at LM. This difference in the role of S. coralliophaga as a biological structure is probably related to differences in fauna composition with depth, bottom current speed, and the quantity/quality of food supplied to the benthos.

Why the Medical Research Council refused Robert Edwards and Patrick Steptoe support for research on human conception in 1971

PubMed Central

Johnson, Martin H.; Franklin, Sarah B.; Cottingham, Matthew; Hopwood, Nick

2010-01-01

BACKGROUND In 1971, Cambridge physiologist Robert Edwards and Oldham gynaecologist Patrick Steptoe applied to the UK Medical Research Council (MRC) for long-term support for a programme of scientific and clinical ‘Studies on Human Reproduction’. The MRC, then the major British funder of medical research, declined support on ethical grounds and maintained this policy throughout the 1970s. The work continued with private money, leading to the birth of Louise Brown in 1978 and transforming research in obstetrics, gynaecology and human embryology. METHODS The MRC decision has been criticized, but the processes by which it was reached have yet to be explored. Here, we present an archive-based analysis of the MRC decision. RESULTS We find evidence of initial support for Edwards and Steptoe, including from within the MRC, which invited the applicants to join its new directly funded Clinical Research Centre at Northwick Park Hospital. They declined the offer, preferring long-term grant support at the University of Cambridge, and so exposed the project to competitive funding mode. Referees and the Clinical Research Board saw the institutional set-up in Cambridge as problematic with respect to clinical facilities and patient management; gave infertility a low priority compared with population control; assessed interventions as purely experimental rather than potential treatments, and so set the bar for safety high; feared fatal abnormalities and so wanted primate experiments first; and were antagonized by the applicants’ high media profile. The rejection set MRC policy on IVF for 8 years, until, after the birth of just two healthy babies, the Council rapidly converted to enthusiastic support. CONCLUSIONS This analysis enriches our view of a crucial decision, highlights institutional opportunities and constraints and provides insight into the then dominant attitudes of reproductive scientists and clinicians towards human conception research. PMID:20657027

Application of the new GOLD COPD staging system to a US primary care cohort, with comparison to physician and patient impressions of severity.

PubMed

Mapel, Douglas W; Dalal, Anand A; Johnson, Phaedra T; Becker, Laura K; Hunter, Alyssa Goolsby

2015-01-01

In 2011, the traditional Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD spirometry-based severity classification system was revised to also include exacerbation history and COPD Assessment Test (CAT) and modified Medical Research Council Dyspnea Scale (mMRC) scores. This study examined how COPD patients treated in primary care are reclassified by the new GOLD system compared to the traditional system, and each system's level of agreement with patient's or physician's severity assessments. In this US multicenter cross-sectional study, COPD patients were recruited by 83 primary care practitioners (PCPs) to complete spirometry testing and a survey. Patients were classified by the traditional spirometry-based system (stages 1-4) and under the new system (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. Concordance between physician and patient-reported severity, spirometry stage, and ABCD grade based on either mMRC or CAT scores was examined. Data from 445 patients with spirometry-confirmed COPD were used. As compared to the traditional system, the GOLD mMRC system reclassifies 47% of patients, and GOLD CAT system reclassifies 41%, but the distributions are very different. The GOLD mMRC system resulted in relatively equal distributions by ABCD grade (33%, 22%, 19%, 26%, respectively), but the GOLD CAT system put most into either B or D groups (9%, 45%, 4%, and 42%). The addition of exacerbation history reclassified only 19 additional patients. Agreement between PCPs' severity rating or their patients' self-assessment and the new ABCD grade was very poor (κ=0.17 or less). As compared to the traditional system, the GOLD 2011 multidimensional system reclassified nearly half of patients, but how they were reclassified varied greatly by whether the mMRC or CAT questionnaire was chosen. Either way, the new system had little correlation with the PCPs or their patients' impressions about the COPD severity.

Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.

PubMed

Blake, P; Swart, Ann Marie; Orton, J; Kitchener, H; Whelan, T; Lukka, H; Eisenhauer, E; Bacon, M; Tu, D; Parmar, M K B; Amos, C; Murray, C; Qian, W

2009-01-10

Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years

Implementation and effects of Movement-oriented Restorative Care in a nursing home - a quasi-experimental study.

PubMed

Henskens, Marinda; Nauta, Ilse M; Scherder, Erik J A; Oosterveld, Frits G J; Vrijkotte, Susan

2017-10-23

The prevalence of dementia is expected to increase rapidly, and institutionalization is a common consequence of the disease. Dependence in activities of daily living (ADL) is a predictor for institutionalization and a determinant for the quality of life (QoL). A promising method to increase functional independence in nursing homes is a restorative care or function focused care (FFC) approach. Movement-oriented restorative care (MRC) is derived from the concept of FFC and restorative care and focuses on the integration of physical activity in the daily lives of nursing home residents with dementia using a multidisciplinary approach. The objective of this study was to assess the effectiveness of MRC in preservation of ADL independence and QoL in nursing home residents with dementia. In this quasi-experimental 12-month study, the effects of MRC were compared to care as usual in 61 nursing home residents with moderate to severe dementia. The outcome measures were ADL independence and QoL. These outcomes were measured five times (i.e. at baseline, and after 3, 6, 9, and 12 months). Additionally, data was collected regarding the degree of implementation, and the barriers to the implementation process. The effect of the intervention was analyzed using linear mixed model analyses. There was no significant overall intervention effect on ADL independence and QoL. A significant group-by-time interaction was found for the QoL subscale positive self-image: after a 12 month intervention period, the MRC group scored significantly better than the control group on positive self-image. Regarding the other subscales and the total score of the QoL, as well as ADL, no significant group-by-time interactions were found. MRC did not demonstrate significant improvements in ADL or QoL. After a 12-month intervention period, residents who received MRC showed higher scores on positive self-image compared to the control group. This study contributes to the limited research regarding the

Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis

PubMed Central

2009-01-01

Summary Background Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. Methods Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40–46 Gy in 20–25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). Findings After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1·05 (95% CI 0·75–1·48; p=0·77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1·04; 95% CI 0·84–1·29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local

Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial

PubMed Central

Brundage, Michael; Sydes, Matthew R.; Parulekar, Wendy R.; Warde, Padraig; Cowan, Richard; Bezjak, Andrea; Kirkbride, Peter; Parliament, Matthew; Moynihan, Clare; Bahary, Jean-Paul; Parmar, Mahesh K.B.; Sanders, Karen; Chen, Bingshu E.; Mason, Malcolm D.

2015-01-01

Purpose The NCIC CTG PR3/MRC PR07 randomized phase III trial compared androgen-deprivation therapy (ADT) alone versus ADT with radiotherapy (RT) for patients with locally advanced prostate cancer. This article reports the health-related quality-of-life (HRQOL) outcomes of this trial. Patients and Methods A total of 1,205 patients were randomly allocated to either ADT alone or ADT with RT. HRQOL was assessed at baseline and every 6 months thereafter using the European Organisation for Research and Treatment of Cancer Core Questionnaire and a prostate cancer–specific checklist or the Functional Assessment of Cancer Therapy–Prostate questionnaire. Mean changes from baseline scores for five function domains and nine symptom domains were analyzed as those most relevant to ADT and RT. The proportions of patients with improved, stable, or worsened HRQOL scores according to instrument-specific minimal important differences were calculated. Results Baseline questionnaires were completed by 1,028 patients (88%). At 6 months, RT had a statistically significant impact on mean score for bowel symptoms (P = .02), diarrhea (P < .001), urinary function (P = .003), and erectile dysfunction (P = .008); by 3 years, however, there were no significant between-group differences in any domain. Generalized linear mixed modeling revealed no significant between-arm differences in any of the function scales but showed significant deterioration in both arms over time for Functional Assessment of Cancer Therapy–Prostate total score, treatment outcome index, and physical and functional well-being. Conclusion The addition of RT to ADT for patients with locally advanced prostate cancer significantly improved overall survival and had only modest and transient negative impact on relevant domains of HRQOL. PMID:26014295

Evaluation of genotoxic potential of avarol, avarone, and its methoxy and methylamino derivatives in prokaryotic and eukaryotic test models.

PubMed

Kolarević, Stoimir; Milovanović, Dragana; Kračun-Kolarević, Margareta; Kostić, Jovana; Sunjog, Karolina; Martinović, Rajko; Đorđević, Jelena; Novaković, Irena; Sladić, Dušan; Vuković-Gačić, Branka

2018-01-04

In this study, mutagenic and genotoxic potential of anti-tumor compounds avarol, avarone, and its derivatives 3'-methoxyavarone, 4'-(methylamino)avarone and 3'-(methylamino)avarone was evaluated and compared to cytostatics commonly used in chemotherapy (5-fluorouracil, etoposid, and cisplatin). Mutagenic potential of selected hydroquinone and quinones was assessed in prokaryotic model by the SOS/umuC assay in Salmonella typhimurium TA1535/pSK1002. Genotoxic potential was also assessed in eukaryotic models using comet assay in human fetal lung cell line (MRC-5), human adenocarcinoma epithelial cell line (A549), and in human peripheral blood cells (HPBC). The results indicated that avarol and avarone do not exert mutagenic/genotoxic potential. Among the studied avarone derivatives, mutagenic potential was detected by SOS/umuC test for 3'-(methylamino)avarone, but only after metabolic activation. The results of comet assay indicated that 3'-methoxyavarone and 3'-(methylamino)avarone have a significant impact on the level of DNA damage in the MRC-5 cell line. Genotoxic potential was not observed in A549 cells or HPBC probably due to a different uptake rate for the compounds and lower in metabolism rate within these cells.

Statistical shape modelling of hip and lumbar spine morphology and their relationship in the MRC National Survey of Health and Development.

PubMed

Pavlova, Anastasia V; Saunders, Fiona R; Muthuri, Stella G; Gregory, Jennifer S; Barr, Rebecca J; Martin, Kathryn R; Hardy, Rebecca J; Cooper, Rachel; Adams, Judith E; Kuh, Diana; Aspden, Richard M

2017-08-01

The anatomical shape of bones and joints is important for their proper function but quantifying this, and detecting pathological variations, is difficult to do. Numerical descriptions would also enable correlations between joint shapes to be explored. Statistical shape modelling (SSM) is a method of image analysis employing pattern recognition statistics to describe and quantify such shapes from images; it uses principal components analysis to generate modes of variation describing each image in terms of a set of numerical scores after removing global size variation. We used SSM to quantify the shapes of the hip and the lumbar spine in dual-energy x-ray absorptiometry (DXA) images from 1511 individuals in the MRC National Survey of Health and Development at ages 60-64 years. We compared shapes of both joints in men and women and hypothesised that hip and spine shape would be strongly correlated. We also investigated associations with height, weight, body mass index (BMI) and local (hip or lumber spine) bone mineral density. In the hip, all except one of the first 10 modes differed between men and women. Men had a wider femoral neck, smaller neck-shaft angle, increased presence of osteophytes and a loss of the femoral head/neck curvature compared with women. Women presented with a flattening of the femoral head and greater acetabular coverage of the femoral head. Greater weight was associated with a shorter, wider femoral neck and larger greater and lesser trochanters. Taller height was accompanied by a flattening of the curve between superior head and neck and a larger lesser trochanter. Four of the first eight modes describing lumbar spine shape differed between men and women. Women tended to have a more lordotic spine than men with relatively smaller but caudally increasing anterior-posterior (a-p) vertebral diameters. Men were more likely to have a straighter spine with larger vertebral a-p diameters relative to vertebral height than women, increasing cranially

Rod stiffness as a risk factor of proximal junctional kyphosis after adult spinal deformity surgery: comparative study between cobalt chrome multiple-rod constructs and titanium alloy two-rod constructs.

PubMed

Han, Sanghyun; Hyun, Seung-Jae; Kim, Ki-Jeong; Jahng, Tae-Ahn; Lee, Subum; Rhim, Seung-Chul

2017-07-01

Little is known about the effect of rod stiffness as a risk factor of proximal junctional kyphosis (PJK) after adult spinal deformity (ASD) surgery. The aim of this study was to compare radiographic outcomes after the use of cobalt chrome multiple-rod constructs (CoCr MRCs) and titanium alloy two-rod constructs (Ti TRCs) for ASD surgery with a minimum 1-year follow-up. Retrospective case-control study in two institutes. We included 54 patients who underwent ASD surgery with fusion to the sacrum in two academic institutes between 2002 and 2015. Radiographic outcomes were measured on the standing lateral radiographs before surgery, 1 month postoperatively, and at ultimate follow-up. The outcome measures were composed of pre- and postoperative sagittal vertical axis (SVA), pre- and postoperative lumbar lordosis (LL), pre- and postoperative thoracic kyphosis (TK)+LL+pelvic incidence (PI), pre- and postoperative PI minus LL, level of uppermost instrumented vertebra (UIV), evaluation of fusion after surgery, the presence of PJK, and the occurrence of rod fracture. We reviewed the medical records of 54 patients who underwent ASD surgery. Of these, 20 patients had CoCr MRC and 34 patients had Ti TRC. Baseline data and radiographic measurements were compared between the two groups. The Mann-Whitney U test, the chi-square test, and the Fisher exact test were used to compare outcomes between the groups. The patients of the groups were similar in terms of age, gender, diagnosis, number of three-column osteotomy, levels fused, bone mineral density, preoperative TK, pre- and postoperative TK+LL+PI, SVA difference, LL change, pre- and postoperative PI minus LL, and location of UIV (upper or lower thoracic level). However, there were significant differences in the occurrence of PJK and rod breakage (PJK: CoCr MRC: 12 [60%] vs. Ti TRC: 9 [26.5%], p=.015; occurrence of rod breakage: CoCr MRC: 0 [0%] vs. Ti TRC: 11 [32.4%], p=.004). The time of PJK was less than 12 months after

Low-dose, Chronic Exposure to Silver Nanoparticles Causes Mild Mitochondrial Alterations in the Liver of Sprague-Dawley Rat

DTIC Science & Technology

2014-05-10

of Sprague-Dawley rat CARLOS PALMEIRA CENTRO DE NEUROCIENCIAS E BIOLOGIA CELULAR (CNC) DEPARTAMENTO DE ZOOLOGIA COIMBRA 3000 - 329...CENTRO DE NEUROCIENCIAS E BIOLOGIA CELULAR (CNC) DEPARTAMENTO DE ZOOLOGIA COIMBRA 3000 - 329 PORTUGAL 8. PERFORMING ORGANIZATION REPORT NUMBER

Pulmonary toxoplasmosis after allogeneic bone marrow transplantation: case report and review.

PubMed

Saad, R; Vincent, J F; Cimon, B; de Gentile, L; Francois, S; Bouachour, G; Ifrah, N

1996-07-01

We report an isolated case of toxoplasma pneumonitis in a 27-year-old man. This acute infection occurred after induction chemotherapy for AMLo relapsing 3 years post-allogeneic BMT. The detection of Toxoplasma gondii in the bronchoalvolar lavage (BAL), by culture in fibroblast cell line MRC5 enabled us to make the diagnosis. Pyrimethamine and sulfadiazine were effective.

Chemical Characterization and Cytotoxic Activity of Blueberry Extracts (cv. Misty) Cultivated in Brazil.

PubMed

Massarotto, Giovana; Barcellos, Thiago; Garcia, Charlene Silvestrin Celi; Brandalize, Ana Paula Carneiro; Moura, Sidnei; Schwambach, Joséli; Henriques, João Antonio Pêgas; Roesch-Ely, Mariana

2016-08-01

Vaccinium corymbosum (L.) varieties cultivation is relatively recent in Brazil, but its production has been intensified given its good adaptability to the Southern Brazil climate. Blueberries are a rich source of phenolic compounds and contain significant levels of anthocyanins, flavonols, chlorogenic acids, and procyanidins, which lead to different biological activities. Chemical identification of skin and whole hydroalcoholic blueberry extracts (ExtSB and ExtWB) revealed the presence of anthocyanins concentrated in the skin and others chemicals compounds as quercetin glycosides, proanthocyanins dimers, citric, and chlorogenic acid in the pulp. Selectivity for tumor cell lines (Hep-2, HeLa, HT-29) using ExtSB and ExtWB extracts was observed through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after 24 h of treatment when compared to nontumor cells (MRC-5). Morphological changes and late stages of apoptotic and necrosis process were seen in HT-29 cell line after ExtWB treatment, compared to nontumor cell line MRC-5. These results are in agreement with other studies that indicate the activity of compounds such as anthocyanins and other molecules found in Southern Highbush blueberry variety, attributed to promote beneficial effects on health that may respond as cytotoxic natural agent and contribute to cancer treatment. © 2016 Institute of Food Technologists®

Improved antioxidative and cytotoxic activities of chamomile (Matricaria chamomilla) florets fermented by Lactobacillus plantarum KCCM 11613P*

PubMed Central

Park, Eun-Hye; Bae, Won-Young; Eom, Su-Jin; Kim, Kee-Tae; Paik, Hyun-Dong

2017-01-01

Antioxidative and cytotoxic effects of chamomile (Matricaria chamomilla) fermented by Lactobacillus plantarum were investigated to improve their biofunctional activities. Total polyphenol (TP) content was measured by the Folin-Denis method, and the antioxidant activities were assessed by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and β-carotene bleaching method. AGS, HeLa, LoVo, MCF-7, and MRC-5 (normal) cells were used to examine the cytotoxic effects by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. The TP content of fermented chamomile reduced from 21.75 to 18.76 mg gallic acid equivalent (mg GAE)/g, but the DPPH radical capturing activity of fermented chamomile was found to be 11.1% higher than that of nonfermented chamomile after 72 h of fermentation. Following the β-carotene bleaching, the antioxidative effect decreased because of a reduction in pH during fermentation. Additionally, chamomile fermented for 72 h showed a cytotoxic effect of about 95% against cancer cells at 12.7 mg solid/ml of broth, but MRC-5 cells were significantly less sensitive against fermented chamomile samples. These results suggest that the fermentation of chamomile could be applied to develop natural antioxidative and anticancer products. PMID:28124843

New technique targeting the C5 nerve root proximal to the traditional interscalene sonoanatomical approach is analgesic for outpatient arthroscopic shoulder surgery.

PubMed

Dobie, Katherine H; Shi, Yaping; Shotwell, Matthew S; Sandberg, Warren S

2016-11-01

Regional anesthesia and analgesia for shoulder surgery is most commonly performed via interscalene nerve block. We developed an ultrasound-guided technique that specifically targets the C5 nerve root proximal to the traditional interscalene block and assessed its efficacy for shoulder analgesia. Prospective case series. Vanderbilt Bone and Joint Surgery Center. Patients undergoing shoulder arthroscopy at an ambulatory surgery center. Thirty-five outpatient shoulder arthroscopy patients underwent an analgesic nerve block using a new technique where ultrasound visualization of the C5 nerve root served as the primary target at a level proximal to the traditional interscalene approach. The block was performed with 15mL of 0.5% plain ropivicaine. Post anesthesia care unit pain scores, opioid consumption, hand strength, and duration of block were recorded. Cadaver dissection after injection with methylene blue confirmed that the primary target under ultrasound visualization was the C5 nerve root. Pain scores revealed 97% patients had 0/10 pain at arrival to PACU, with 91% having a pain score of 3/10 or less at discharge from PACU. Medical Research Council (MRC) hand strength mean (SD) score was 4.17 (0.92) on a scale of 1-5. The mean (SD) duration of the block was 13.9 (3.5) hours. A new technique for ultrasound-guided blockade at the level of the C5 nerve root proximal to the level of the traditional interscalene block is efficacious for shoulder post-operative pain control. Copyright © 2016 Elsevier Inc. All rights reserved.

Global magnetosphere simulations using constrained-transport Hall-MHD with CWENO reconstruction

NASA Astrophysics Data System (ADS)

Lin, L.; Germaschewski, K.; Maynard, K. M.; Abbott, S.; Bhattacharjee, A.; Raeder, J.

2013-12-01

We present a new CWENO (Centrally-Weighted Essentially Non-Oscillatory) reconstruction based MHD solver for the OpenGGCM global magnetosphere code. The solver was built using libMRC, a library for creating efficient parallel PDE solvers on structured grids. The use of libMRC gives us access to its core functionality of providing an automated code generation framework which takes a user provided PDE right hand side in symbolic form to generate an efficient, computer architecture specific, parallel code. libMRC also supports block-structured adaptive mesh refinement and implicit-time stepping through integration with the PETSc library. We validate the new CWENO Hall-MHD solver against existing solvers both in standard test problems as well as in global magnetosphere simulations.

SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization.

PubMed

Gougat, Jean; Ferrari, Bernard; Sarran, Lionel; Planchenault, Claudine; Poncelet, Martine; Maruani, Jeanne; Alonso, Richard; Cudennec, Annie; Croci, Tiziano; Guagnini, Fabio; Urban-Szabo, Katalin; Martinolle, Jean-Pierre; Soubrié, Philippe; Finance, Olivier; Le Fur, Gérard

2004-05-01

The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B(1) receptor, SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride] were evaluated. SSR240612 inhibited the binding of [(3)H]Lys(0)-des-Arg(9)-BK to the B(1) receptor in human fibroblast MRC5 and to recombinant human B(1) receptor expressed in human embryonic kidney cells with inhibition constants (K(i)) of 0.48 and 0.73 nM, respectively. The compound selectivity for B(1) versus B(2) receptors was in the range of 500- to 1000-fold. SSR240612 inhibited Lys(0)-desAr(9)-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC(50) of 1.9 nM. It also antagonized des-Arg(9)-BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA(2) of 8.9 and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited des-Arg(9)-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B(1) receptor antagonist.

Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella-Zoster Virus Lytic Infection.

PubMed

Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan; Venkatesan, Arun; Cohen, Jeffrey I

2018-01-01

Varicella-zoster virus (VZV) is highly cell associated when grown in culture and has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio in vitro than herpes simplex virus (HSV). In contrast, VZV is highly infectious in vivo by airborne transmission. Neurons are major targets for VZV in vivo ; in neurons, the virus can establish latency and reactivate to produce infectious virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free wild-type (WT) VZV, we demonstrated that neurons are nearly 100 times more permissive for WT VZV infection than very-early-passage human embryonic lung cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production or virus isolation. The peak titers achieved after infection were ∼10-fold higher in human neurons than in MRC-5 cells, and the viral genome copy number-to-PFU ratio for VZV in human neurons was 500, compared with 50,000 for MRC-5 cells. Thus, VZV may not necessarily have a higher particle-to-PFU ratio than other herpesviruses; instead, the cells previously used to propagate virus in vitro may have been suboptimal. Furthermore, based on electron microscopy, neurons infected with VZV produced fewer defective or incomplete viral particles than MRC-5 cells. Our data suggest that neurons derived from hESC may have advantages compared to other cells for studies of VZV pathogenesis, for obtaining stocks of virus with high titers, and for isolating VZV from clinical specimens. IMPORTANCE Varicella-zoster virus (VZV) causes chickenpox and shingles. Cell-free VZV has been difficult to obtain, both for in vitro studies and for vaccine production. While numerous cells lines have been tested for their ability to produce high titers of VZV, the number of total virus particles relative to the number of viral particles that can form plaques in culture has been reported to be extremely high relative to that in other viruses. We show that VZV grows to much higher titers in human

Mental health research, ethics and multiculturalism.

PubMed

Bailes, Marion J; Minas, I Harry; Klimidis, Steven

2006-01-01

In this paper we examine ethical issues relevant to conducting mental health research with refugees and immigrant communities that have cultural orientations and social organisation that are substantially different to those of the broader Australian community, and we relate these issues to NH&MRC Guidelines. We describe the development and conduct of a mental health research project carried out recently in Melbourne with the Somali community, focusing on ethical principles involved, and relating these to the NH&MRC National Statement on Ethical Conduct in Research Involving Humans, and the NH&MRC document Values and Ethics: Guidelines for Ethical Conduct in Aboriginal and Torres Strait Islander Health Research. The experience of conducting mental health research with the Somali community highlights the fact that the principles of inclusion and benefit enunciated in the NH&MRC document Values and Ethics are particularly pertinent when conducting research with refugees and immigrant communities that are culturally distant to those of the broader Australian community. These principles inform issues of research design and consent, as well as guiding respectful engagement with the participating community and communication of the research findings.

Application of the new GOLD COPD staging system to a US primary care cohort, with comparison to physician and patient impressions of severity

PubMed Central

Mapel, Douglas W; Dalal, Anand A; Johnson, Phaedra T; Becker, Laura K; Hunter, Alyssa Goolsby

2015-01-01

Background In 2011, the traditional Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD spirometry-based severity classification system was revised to also include exacerbation history and COPD Assessment Test (CAT) and modified Medical Research Council Dyspnea Scale (mMRC) scores. This study examined how COPD patients treated in primary care are reclassified by the new GOLD system compared to the traditional system, and each system’s level of agreement with patient’s or physician’s severity assessments. Methods In this US multicenter cross-sectional study, COPD patients were recruited by 83 primary care practitioners (PCPs) to complete spirometry testing and a survey. Patients were classified by the traditional spirometry-based system (stages 1–4) and under the new system (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. Concordance between physician and patient-reported severity, spirometry stage, and ABCD grade based on either mMRC or CAT scores was examined. Results Data from 445 patients with spirometry-confirmed COPD were used. As compared to the traditional system, the GOLD mMRC system reclassifies 47% of patients, and GOLD CAT system reclassifies 41%, but the distributions are very different. The GOLD mMRC system resulted in relatively equal distributions by ABCD grade (33%, 22%, 19%, 26%, respectively), but the GOLD CAT system put most into either B or D groups (9%, 45%, 4%, and 42%). The addition of exacerbation history reclassified only 19 additional patients. Agreement between PCPs’ severity rating or their patients’ self-assessment and the new ABCD grade was very poor (κ=0.17 or less). Conclusion As compared to the traditional system, the GOLD 2011 multidimensional system reclassified nearly half of patients, but how they were reclassified varied greatly by whether the mMRC or CAT questionnaire was chosen. Either way, the new system had little correlation with the PCPs or their patients�

International Conference on Partitioning in Aqueous Two-Phase Systems: Advances in Separation in Biochenistry, Cell Biology and Biotechnology (7th) Held in New Orleans, Louisiana on 2-7 June 1991.

DTIC Science & Technology

1991-06-27

de Bioquimica y Biologia Molecular y Celular . Facultad de Veterinaria. Universidad de Zaragoza. SPAIN Homogenization of brain tissue results in nerve...and M. J. L6pez-Pirez. Departamento de Bioquimica y Biologia Molecular y Celular . Facultad de Veterinaria. Universidad de Zaragoza. SPAIN Previous

State Defense Force Monograph Series. Winter 2006, Medical Support Teams

DTIC Science & Technology

2006-01-01

Research Organization, 1981). By 1955, the escalating Cold War saw the formal revival of the classic all-volunteer state militia. But growth was...officer. It was at this point that the MDDF MRC project action officer petitioned the OSG for the formal audit that was required for official MRC...increased need (December, 2006). Shortages of primary caregivers , acute care beds, ventilators, vaccines and antiviral medicines, coupled with the

Psoralidin, a dual inhibitor of COX-2 and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflammation.

PubMed

Yang, Hee Jung; Youn, HyeSook; Seong, Ki Moon; Yun, Young Ju; Kim, Wanyeon; Kim, Young Ha; Lee, Ji Young; Kim, Cha Soon; Jin, Young-Woo; Youn, BuHyun

2011-09-01

Radiotherapy is the most significant non-surgical cure for the elimination of tumor, however it is restricted by two major problems: radioresistance and normal tissue damage. Efficiency improvement on radiotherapy is demanded to achieve cancer treatment. We focused on radiation-induced normal cell damage, and are concerned about inflammation reported to act as a main limiting factor in the radiotherapy. Psoralidin, a coumestan derivative isolated from the seed of Psoralea corylifolia, has been studied for anti-cancer and anti-bacterial properties. However, little is known regarding its effects on IR-induced pulmonary inflammation. The aim of this study is to investigate mechanisms of IR-induced inflammation and to examine therapeutic mechanisms of psoralidin in human normal lung fibroblasts and mice. Here, we demonstrated that IR-induced ROS activated cyclooxygenases-2 (COX-2) and 5-lipoxygenase (5-LOX) pathway in HFL-1 and MRC-5 cells. Psoralidin inhibited the IR-induced COX-2 expression and PGE(2) production through regulation of PI3K/Akt and NF-κB pathway. Also, psoralidin blocked IR-induced LTB(4) production, and it was due to direct interaction of psoralidin and 5-lipoxygenase activating protein (FLAP) in 5-LOX pathway. IR-induced fibroblast migration was notably attenuated in the presence of psoralidin. Moreover, in vivo results from mouse lung indicate that psoralidin suppresses IR-induced expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-6 and IL-1 α/β) and ICAM-1. Taken together, our findings reveal a regulatory mechanism of IR-induced pulmonary inflammation in human normal lung fibroblast and mice, and suggest that psoralidin may be useful as a potential lead compound for development of a better radiopreventive agent against radiation-induced normal tissue injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Antimalarial efficacy of Albizia lebbeck (Leguminosae) against Plasmodium falciparum in vitro & P. berghei in vivo

PubMed Central

Kalia, Shagun; Walter, Neha Sylvia; Bagai, Upma

2015-01-01

Background & objectives: Albizia lebbeck Benth. (Leguminosae) has long been used in Indian traditional medicine. The current study was designed to test antimalarial activity of ethanolic bark extract of A. lebbeck (EBEAL). Methods: EBEAL was prepared by soxhlet extraction and subjected to phytochemical analysis. The extract was evaluated for its in vitro antimalarial activity against Plasmodium falciparum chloroquine (CQ) sensitive (MRC2) and CQ resistant (RKL9) strains. Cytotoxicity (CC50) of extract against HeLa cells was evaluated. Median lethal dose (LD50) was determined to assess safety of EBEAL in BALB/c mice. Schizonticidal (100-1000 mg/kg) and preventive (100-750 mg/kg) activities of EBEAL were evaluated against P. berghei. Curative activity (100-750 mg/kg) of extract was also evaluated. Results: Phytochemical screening revealed presence of alkaloids, flavonoids, phenols, saponins, terpenes and phytosterols. The extract exhibited IC50 of 8.2 μg/ml (MRC2) and 5.1 μg/ml (RKL9). CC50 of extract on HeLa cell line was calculated to be >1000 μg/ml. EBEAL showed selectivity indices (SI) of >121.9 and >196.07 against MRC2 and RKL9 strains of P. falciparum, respectively. LD50 of EBEAL was observed to be >5 g/kg. Dose-dependent chemosuppression was observed with significant (P<0.001) schizonticidal activity at 1000 mg/kg with ED50 >100 mg/kg. Significant (P<0.001) curative and repository activities were exhibited by 750 mg/kg concentration of extract on D7. Interpretation & conclusions: The present investigation reports antiplasmodial efficacy of EBEAL in vitro against P. falciparum as evident by high SI values. ED50 of <100 mg/kg against P. berghei categorizes EBEAL as active antimalarial. Further studies need to be done to exploit its antiplasmodial activity further. PMID:26905234

Comparison of Different Magnetic Resonance Cholangiography Techniques in Living Liver Donors Including Gd-EOB-DTPA Enhanced T1-Weighted Sequences

PubMed Central

Kinner, Sonja; Steinweg, Verena; Maderwald, Stefan; Radtke, Arnold; Sotiropoulos, Georgios; Forsting, Michael; Schroeder, Tobias

2014-01-01

Objectives Preoperative evaluation of potential living liver donors (PLLDs) includes the assessment of the biliary anatomy to avoid postoperative complications. Aim of this study was to compare T2-weighted (T2w) and Gd-EOB-DTPA enhanced T1-weighted (T1w) magnetic resonance cholangiography (MRC) techniques in the evaluation of PLLDs. Materials and Methods 30 PLLDs underwent MRC on a 1.5 T Magnetom Avanto (Siemens, Erlangen, Germany) using (A) 2D T2w HASTE (Half Fourier Acquisition Single Shot Turbo Spin Echo) fat saturated (fs) in axial plane, (B) 2D T2w HASTE fs thick slices in coronal plane, (C) free breathing 3D T2w TSE (turbo spin echo) RESTORE (high-resolution navigator corrected) plus (D) maximum intensity projections (MIPs), (E) T2w SPACE (sampling perfection with application optimized contrasts using different flip angle evolutions) plus (F) MIPs and (G) T2w TSE BLADE as well as Gd-EOB-DTPA T1w images without (G) and with (H) inversion recovery. Contrast enhanced CT cholangiography served as reference imaging modality. Two independent reviewers evaluated the biliary tract anatomy on a 5-point scale subjectively and objectively. Data sets were compared using a Mann-Whitney-U-test. Kappa values were also calculated. Results Source images and maximum intensity projections of 3D T2w TSE sequences (RESTORE and SPACE) proved to be best for subjective and objective evaluation directly followed by 2D HASTE sequences. Interobserver variabilities were good to excellent (k = 0.622–0.804). Conclusions 3D T2w sequences are essential for preoperative biliary tract evaluation in potential living liver donors. Furthermore, our results underline the value of different MRCP sequence types for the evaluation of the biliary anatomy in PLLDs including Gd-EOB-DTPA enhanced T1w MRC. PMID:25426932

Tethering of SCFDia2 to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase

PubMed Central

Maculins, Timurs; Nkosi, Pedro Junior; Nishikawa, Hiroko; Labib, Karim

2015-01-01

Summary Disassembly of the Cdc45-MCM-GINS (CMG) DNA helicase, which unwinds the parental DNA duplex at eukaryotic replication forks, is the key regulated step during replication termination but is poorly understood [1, 2]. In budding yeast, the F-box protein Dia2 drives ubiquitylation of the CMG helicase at the end of replication, leading to a disassembly pathway that requires the Cdc48 segregase [3]. The substrate-binding domain of Dia2 comprises leucine-rich repeats, but Dia2 also has a TPR domain at its amino terminus that interacts with the Ctf4 and Mrc1 subunits of the replisome progression complex [4, 5], which assembles around the CMG helicase at replication forks [6]. Previous studies suggested two disparate roles for the TPR domain of Dia2, either mediating replisome-specific degradation of Mrc1 and Ctf4 [4] or else tethering SCFDia2 (SCF [Skp1/cullin/F-box protein]) to the replisome to increase its local concentration at replication forks [5]. Here, we show that SCFDia2 does not mediate replisome-specific degradation of Mrc1 and Ctf4, either during normal S phase or in response to replication stress. Instead, the tethering of SCFDia2 to the replisome progression complex increases the efficiency of ubiquitylation of the Mcm7 subunit of CMG, both in vitro and in vivo. Correspondingly, loss of tethering reduces the efficiency of CMG disassembly in vivo and is synthetic lethal in combination with a disassembly-defective allele of CDC48. Residual ubiquitylation of Mcm7 in dia2-ΔTPR cells is still CMG specific, highlighting the complex regulation of the final stages of chromosome replication, about which much still remains to be learned. PMID:26255844

Short-Term Prognosis of Mechanically Ventilated Patients With Guillain–Barré Syndrome Is Worsened by Corticosteroids as an Add-On Therapy

PubMed Central

Wu, Xiujuan; Zhang, Bing; Li, Chunrong; Shen, Donghui; Liu, Kangding; Zhu, Jie; Zhang, Hong-Liang

2015-01-01

Abstract Intravenous immunoglobulin (IVIg) has been proven most effective in treating Guillain–Barré syndrome (GBS). Corticosteroids as an add-on therapy have been prescribed in severe GBS cases. However, the efficacy of intravenous corticosteroids combined with IVIg in dealing with severe GBS remains unclear. We explored the therapeutic effects of different therapeutic regimens on the short-term prognosis of GBS patients, especially the severe cases. We retrospectively analyzed the clinical data of 527 adult patients with GBS who were prescribed to different treatments from 2003 to 2014. The therapeutic effect of a treatment was evaluated by the improvement of Hughes Functional Grading Scale (HFGS) and Medical Research Council (MRC) sum score. With comparable incidence of infectious complications (P > 0.05), more mechanically ventilated patients were found improvement after IVIg treatment than combination IVIg with intravenous corticosteroids (MRC: 97% vs. 72.4%, P < 0.05; HFGS: 97% vs. 72.4%, P < 0.05). As to bedridden patients without mechanical ventilation, incidence of infectious complications (P > 0.05) and ratio of patients who were improved after IVIg were insignificantly different from the combination therapy (MRC: 89.6% vs. 86.5%; HFGS: 69.6% vs. 61.5%; both P > 0.05), even if the intravenous corticosteroids were initiated within 7 days after onset (P > 0.05). In addition, supportive treatment was sufficient for patients who were able to walk with help (HFGS = 3) and mildly affected (HFGS < 3) when compared with IVIg and intravenous corticosteroids. IVIg is sufficient to GBS patients who are unable to walk (HFGS > 3), while corticosteroids are detrimental for short-term prognosis in mechanically ventilated patients when used in combination with IVIg. Further prospective and randomized studies are warranted to validate this finding. PMID:26512609

Antimalarial efficacy of Albizia lebbeck (Leguminosae) against Plasmodium falciparum in vitro & P. berghei in vivo.

PubMed

Kalia, Shagun; Walter, Neha Sylvia; Bagai, Upma

2015-12-01

Albizia lebbeck Benth. (Leguminosae) has long been used in Indian traditional medicine. The current study was designed to test antimalarial activity of ethanolic bark extract of A. lebbeck (EBEAL). EBEAL was prepared by soxhlet extraction and subjected to phytochemical analysis. The extract was evaluated for its in vitro antimalarial activity against Plasmodium falciparum chloroquine (CQ) sensitive (MRC2) and CQ resistant (RKL9) strains. Cytotoxicity (CC 50 ) of extract against HeLa cells was evaluated. Median lethal dose (LD 50 ) was determined to assess safety of EBEAL in BALB/c mice. Schizonticidal (100-1000 mg/kg) and preventive (100-750 mg/kg) activities of EBEAL were evaluated against P. berghei. Curative activity (100-750 mg/kg) of extract was also evaluated. Phytochemical screening revealed presence of alkaloids, flavonoids, phenols, saponins, terpenes and phytosterols. The extract exhibited IC 50 of 8.2 µg/ml (MRC2) and 5.1 µg/ml (RKL9). CC 50 of extract on HeLa cell line was calculated to be >1000 µg/ml. EBEAL showed selectivity indices (SI) of >121.9 and >196.07 against MRC2 and RKL9 strains of P. falciparum, respectively. LD 50 of EBEAL was observed to be >5 g/kg. Dose-dependent chemosuppression was observed with significant ( p<0.001) schizonticidal activity at 1000 mg/kg with ED 50 >100 mg/kg. Significant (P<0.001) curative and repository activities were exhibited by 750 mg/kg concentration of extract on D7. The present investigation reports antiplasmodial efficacy of EBEAL in vitro against P. falciparum as evident by high SI values. ED 50 of <100 mg/kg against P. berghei categorizes EBEAL as active antimalarial. Further studies need to be done to exploit its antiplasmodial activity further.

Short-Term Prognosis of Mechanically Ventilated Patients With Guillain-Barré Syndrome Is Worsened by Corticosteroids as an Add-On Therapy.

PubMed

Wu, Xiujuan; Zhang, Bing; Li, Chunrong; Shen, Donghui; Liu, Kangding; Zhu, Jie; Zhang, Hong-Liang

2015-10-01

Intravenous immunoglobulin (IVIg) has been proven most effective in treating Guillain-Barré syndrome (GBS). Corticosteroids as an add-on therapy have been prescribed in severe GBS cases. However, the efficacy of intravenous corticosteroids combined with IVIg in dealing with severe GBS remains unclear. We explored the therapeutic effects of different therapeutic regimens on the short-term prognosis of GBS patients, especially the severe cases.We retrospectively analyzed the clinical data of 527 adult patients with GBS who were prescribed to different treatments from 2003 to 2014. The therapeutic effect of a treatment was evaluated by the improvement of Hughes Functional Grading Scale (HFGS) and Medical Research Council (MRC) sum score.With comparable incidence of infectious complications (P > 0.05), more mechanically ventilated patients were found improvement after IVIg treatment than combination IVIg with intravenous corticosteroids (MRC: 97% vs. 72.4%, P < 0.05; HFGS: 97% vs. 72.4%, P < 0.05). As to bedridden patients without mechanical ventilation, incidence of infectious complications (P > 0.05) and ratio of patients who were improved after IVIg were insignificantly different from the combination therapy (MRC: 89.6% vs. 86.5%; HFGS: 69.6% vs. 61.5%; both P > 0.05), even if the intravenous corticosteroids were initiated within 7 days after onset (P > 0.05). In addition, supportive treatment was sufficient for patients who were able to walk with help (HFGS = 3) and mildly affected (HFGS < 3) when compared with IVIg and intravenous corticosteroids.IVIg is sufficient to GBS patients who are unable to walk (HFGS > 3), while corticosteroids are detrimental for short-term prognosis in mechanically ventilated patients when used in combination with IVIg. Further prospective and randomized studies are warranted to validate this finding.

Caffeic acid attenuates rat liver reperfusion injury through sirtuin 3-dependent regulation of mitochondrial respiratory chain.

PubMed

Mu, Hong-Na; Li, Quan; Pan, Chun-Shui; Liu, Yu-Ying; Yan, Li; Hu, Bai-He; Sun, Kai; Chang, Xin; Zhao, Xin-Rong; Fan, Jing-Yu; Han, Jing-Yan

2015-08-01

Sirtuin 3 (Sirt3) plays critical roles in regulating mitochondrial oxidative metabolism. However, whether Sirt3 is involved in liver ischemia and reperfusion (I/R) injury remains elusive. Caffeic acid (CA) is a natural antioxidant derived from Salvia miltiorrhiza. Whether CA protects against liver I/R injury through regulating Sirt3 and the mitochondrial respiratory chain (MRC) is unclear. This study investigated the effect of CA on liver I/R injury, microcirculatory disturbance, and potential mechanisms, particularly focusing on Sirt3-dependent MRC. Liver I/R of male Sprague-Dawley rats was established by occlusion of portal area vessels for 30 min followed by 120 min of reperfusion. CA (15 mg/kg/h) was continuously infused via the femoral vein starting 30 min before ischemia. After I/R, Sirt3 expression, and MRC activity decreased, acetylation of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 and succinate dehydrogenase complex, subunit A, flavoprotein variant provoked, and the liver microcirculatory disturbance and injury were observed. Treatment with CA attenuated liver injury, inhibited Sirt3 down-expression, and up-regulated MRC activity. CA attenuated rat liver microcirculatory disturbance and oxidative injury through regulation of Sirt3 and the mitochondrial respiratory chain. Copyright © 2015 Elsevier Inc. All rights reserved.

Tendon transfer to reconstruct wrist extension in children with obstetric brachial plexus palsy.

PubMed

Al-Qattan, M M

2003-04-01

This study reports on 20 children with obstetric brachial plexus palsy who underwent a tendon transfer to reconstruct wrist extension. The mean age at the time of tendon transfer was 8 years. There were seven patients with Erb's palsy and the remaining 13 had total palsy. The flexor carpi ulnaris was utilized 15 times and the flexor carpi radialis five times. The transferred tendon was sutured to the tendon of the extensor carpi radialis brevis. The result of the transfer was assessed according to a modified Medical Research Council (MRC) muscle grading system. A good result was obtained in 18 patients (modified MRC grade of 4) and a fair result (modified MRC grade of 3) in two. The choice of tendon transfer to reconstruct the wrist drop deformity in various conditions including adult traumatic brachial plexus injuries is discussed.

Exploring cellular uptake of iron oxide nanoparticles associated with rhodium citrate in breast cancer cells.

PubMed

Chaves, Natalia L; Estrela-Lopis, Irina; Böttner, Julia; Lopes, Cláudio Ap; Guido, Bruna C; de Sousa, Aparecido R; Báo, Sônia N

2017-01-01

Nanocarriers have the potential to improve the therapeutic index of currently available drugs by improving their efficacy and achieving therapeutic steady-state levels over an extended period. The association of maghemite-rhodium citrate (MRC) nanoparticles (NPs) has the potential to increase specificity of the cytotoxic action. However, the interaction of these NPs with cells, their uptake mechanism, and subcellular localization need to be elucidated. This work evaluates the uptake mechanism of MRC NPs in metastatic and nonmetastatic breast cancer-cell models, comparing them to a nontumor cell line. MRC NPs uptake in breast cancer cells was more effective than in normal cells, with regard to both the amount of internalized material and the achievement of more strategic intracellular distribution. Moreover, this process occurred through a clathrin-dependent endocytosis pathway with different basal expression levels of this protein in the cell lines tested.

After slow start, project to channel drug company funds to universities builds steam.

PubMed

Berkowitz, P

1996-08-01

Drug companies appear to have been listening when researchers began complaining about their lack of participation in the MRC/PMAC Health Program, for the 30-month-old project appears to have taken on new life. It is designed to increase collaboration between university and pharmaceutical industry researchers by directing more of the industry's growing investment in Canada through the MRC's peer-review process. By mid-May, program commitments stood at $60 million.

Army Engineers in Memphis District: A Documentary Chronicle

DTIC Science & Technology

1982-05-01

Treasure Island and Drinkwater Sewer, Missouri; Hickman, Kentucky; Helena, Arkansas; and on the lower White River, Reelfoot Lake , and the West...of navigation," be permanently closed. 26 The MRC decided to begin its program of river improvement at two points. One was the Lake Providence reach...levees. The MRC employed 350 men and supplied 50,000 sacks to be used for sandbags to help the Reelfoot Levee District hold its levees. Although the

Fidelity of DNA Replication in Normal and Malignant Human Brest Cells.

DTIC Science & Technology

1995-08-31

cellular DNA replication machinery, we have initiated experiments that utilize a multiprotein DNA replication complex (MRC) isolated from breast cancer...gene in an in vitro DNA replication assay. By utilizing the target gene in a bacterial mutant selection assay we have begun to determine the...frequency with which mutational sequence errors occur as a result of the in vitro DNA replication mediated by the breast cancer cell MRC and the normal breast

EMPReSS: European mouse phenotyping resource for standardized screens.

PubMed

Green, Eain C J; Gkoutos, Georgios V; Lad, Heena V; Blake, Andrew; Weekes, Joseph; Hancock, John M

2005-06-15

Standardized phenotyping protocols are essential for the characterization of phenotypes so that results are comparable between different laboratories and phenotypic data can be related to ontological descriptions in an automated manner. We describe a web-based resource for the visualization, searching and downloading of standard operating procedures and other documents, the European Mouse Phenotyping Resource for Standardized Screens-EMPReSS. Direct access: http://www.empress.har.mrc.ac.uk e.green@har.mrc.ac.uk.

Upon Their Shoulders: A History of the Mississippi River Commission from Its Inception through the Advent of the Modern Mississippi River and Tributaries Project

DTIC Science & Technology

2004-01-01

up the mantle in the Senate the following year . Overton, of Louisiana, was a relative newcomer...Davidson in Harper ’s Weekly, March 5, 1884. In the years following the War of 1812, high cotton prices and a gen- eral return to prosperity provided...Harrison resigned from the MRC less than a year later, ostensibly to make a run for the U.S . Senate. Following his resignation,

Birth weight and growth from infancy to late adolescence in relation to fat and lean mass in early old age: findings from the MRC National Survey of Health and Development.

PubMed

Bann, D; Wills, A; Cooper, R; Hardy, R; Aihie Sayer, A; Adams, J; Kuh, D

2014-01-01

High birth weight and greater weight gain in infancy have been associated with increased risk of obesity as assessed using body mass index, but few studies have examined associations with direct measures of fat and lean mass. This study examined associations of birth weight and weight and height gain in infancy, childhood and adolescence with fat and lean mass in early old age. A total of 746 men and 812 women in England, Scotland and Wales from the MRC National Survey of Health and Development whose heights and weights had been prospectively ascertained across childhood and adolescence and who had dual energy X-ray absorptiometry measures at age 60-64 years. Associations of birth weight and standardised weight and height (0-2 (weight only), 2-4, 4-7, 7-11, 11-15, 15-20 years) gain velocities with outcome measures were examined. Higher birth weight was associated with higher lean mass and lower android/gynoid ratio at age 60-64 years. For example, the mean difference in lean mass per 1 standard deviation increase in birth weight was 1.54 kg in males (95% confidence interval=1.04, 2.03) and 0.78 kg in females (0.41, 1.14). Greater weight gain in infancy was associated with higher lean mass, whereas greater gains in weight in later childhood and adolescence were associated with higher fat and lean mass, and fat/lean and android/gynoid ratios. Across growth intervals greater height gain was associated with higher lean but not fat mass, and with lower fat/lean and android/gynoid ratios. Findings suggest that growth in early life may have lasting effects on fat and lean mass. Greater weight gain before birth and in infancy may be beneficial by leading to higher lean mass, whereas greater weight gain in later childhood and adolescence may be detrimental by leading to higher fat/lean and android/gynoid ratios.

[Emodin inhibits the proliferation, transdifferentiation and collagen synthesis of pulmonary fibroblasts].

PubMed

Liu, Lijing; Yin, Huiming; He, Jianbin; Xie, Maofeng; Wang, Zaiyan; Xiao, Hua

2016-07-01

Objective To explore the effect of emodin on the proliferation, differentiation into myofibroblasts and collagen synthesis of pulmonary fibroblasts and the underlying mechanisms. Methods Human pulmonary fibroblasts MRC-5 were cultured in vitro, then the cells were inoculated with dimethyl sulfoxide (DMSO) added with 0, 10, 20, 40, 80 and 160 μmol/L emodin for 24, 48 and 72 hours. Inhibitory rate of cell proliferation was analyzed by MTT assay. Based on the results of cell proliferation experiment, MRC-5 cells were treated with DMSO (control group) and 40, 80 μmol/L emodin (in DMSO) for 48 hours. Fluorescence real-time quantitative PCR was then used to measure the mRNA expressions of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1), collagen type 1 (Col1) and collagen type 3 (Col3). The protein expressions of the above mentioned factors were also measured by Western blotting. Results In a concentration- and time-dependent manner, emodin inhibited MRC-5 cell proliferation. After 48 hours of co-culture, in comparison with control group, the mRNA and protein expression levels of α-SMA, TGF-β1, Col1 and Col3 significantly decreased, while the mRNA and protein expression levels of ADAMTS-1 significantly increased in 40 and 80 μmol/L emodin-treated groups. Moreover, in comparison with 40 μmol/L emodin-treated group, the mRNA and protein expressions of α-SMA, TGF-β1, Col1 and Col3 were significantly downregulated, but ADAMTS-1 mRNA and protein expressions were significantly upregulated in 80 μmol/L emodin-treated group. Conclusion Emodin can block pulmonary fibroblast proliferation and differentiation into myofibroblasts, and reduce the synthesis of Col1 and Col3 by inhibiting TGF-β1/ADAMTS-1 signaling pathway.

The Expression of AQP1 IS Modified in Lung of Patients With Idiopathic Pulmonary Fibrosis: Addressing a Possible New Target.

PubMed

Galán-Cobo, Ana; Arellano-Orden, Elena; Sánchez Silva, Rocío; López-Campos, José Luis; Gutiérrez Rivera, César; Gómez Izquierdo, Lourdes; Suárez-Luna, Nela; Molina-Molina, María; Rodríguez Portal, José A; Echevarría, Miriam

2018-01-01

Activation of the epithelial-mesenchymal transition process (EMT) by which alveolar cells in human lung tissue undergo differentiation giving rise to a mesenchymal phenotype (fibroblast/miofibroblasts) has been well recognized as a key element in the origin of idiopathic pulmonary fibrosis (IPF). Here we analyzed expression of AQP1 in lung biopsies of patients diagnosed with IPF, and compared it to biopsies derived from patients with diverse lung pneumonies, such as hypersensitivity pneumonitis, sarcoidosis or normal lungs. Immunostaining for AQP1 showed a clear increment of AQP1 localized in the alveolar epithelium in biopsies from IPF patients alone. Moreover, to examine the possible participation of AQP1 in the pathophysiology of IPF, we evaluated its role in the pro-fibrotic transformation induced by transforming growth factor (TGF-β) in vitro . Human alveolar epithelial cells (A549), and fibroblasts derived from an IPF patient (LL29), or fibroblasts from healthy normal lung tissue (MRC-5), were treated with TGF-β, and levels of expression of AQP1, as well as those of E-cadherin, vimentin, α-SMA and collagen were analyzed by RT-qPCR, western blot and immunohistochemistry. An increase of AQP1 mRNA and protein after TGF-β treatment (4-72h) was observed either in A549 or IPF fibroblast-LL29 but not in MRC-5 fibroblasts. A gradual reduction of E-cadherin, and increased expression of vimentin, with no changes in α-SMA levels were observed in A549. Whereas in LL29 and MRC-5, TGF-β1 elicited a large production of collagen and α-SMA that was significantly greater in IPF fibroblast-LL29. Changes observed are consistent with activation of EMT by TGF-β, but whether modifications in AQP1 expression are responsible or independent events occurring at the same time is still unknown. Our results suggest that AQP1 plays a role in the pro-fibrotic TGF-β action and contributes to the etiology and pathophysiology of IPF. Understanding AQP1's role will help us comprehend

LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

PubMed

Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

2015-02-15

Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development. Copyright © 2015 the American Physiological

Magnetic resonance cholangiogram patterns and clinical profiles of ketamine-related cholangiopathy in drug users.

PubMed

Seto, Wai-Kay; Mak, Siu-King; Chiu, Keith; Vardhanabhuti, Varut; Wong, Ho-Fai; Leong, Heng-Tat; Lee, Paul S F; Ho, Y C; Lee, Chi-Kei; Cheung, Ka-Shing; Yuen, Man-Fung; Leung, Wai K

2018-07-01

Recreational ketamine use has emerged as an important health and social issue worldwide. Although ketamine is associated with biliary tract damage, the clinical and radiological profiles of ketamine-related cholangiopathy have not been well described. Chinese individuals who had used ketamine recreationally at least twice per month for six months in the previous two years via a territory-wide community network of charitable organizations tackling substance abuse were recruited. Magnetic resonance cholangiography (MRC) was performed, and the findings were interpreted independently by two radiologists, with the findings analysed in association with clinical characteristics. Among the 343 ketamine users referred, 257 (74.9%) were recruited. The mean age and ketamine exposure duration were 28.7 (±5.8) and 10.5 (±3.7) years, respectively. A total of 159 (61.9%) had biliary tract anomalies on MRC, categorized as diffuse extrahepatic dilatation (n = 73), fusiform extrahepatic dilatation (n = 64), and intrahepatic ductal changes (n = 22) with no extrahepatic involvement. Serum alkaline phosphatase (ALP) level (odds ratio [OR] 1.007; 95% CI 1.002-1.102), lack of concomitant recreational drug use (OR 1.99; 95% CI 1.11-3.58), and prior emergency attendance for urinary symptoms (OR 1.95; 95% CI 1.03-3.70) had high predictive values for biliary anomalies on MRC. Among sole ketamine users, ALP level had an AUC of 0.800 in predicting biliary anomalies, with an optimal level of ≥113 U/L having a positive predictive value of 85.4%. Cholangiographic anomalies were reversible after ketamine abstinence, whereas decompensated cirrhosis and death were possible after prolonged exposure. We have identified distinctive MRC patterns in a large cohort of ketamine users. ALP level and lack of concomitant drug use predicted biliary anomalies, which were reversible after abstinence. The study findings may aid public health efforts in combating the growing epidemic of ketamine

Circulation effect: response of precipitation δ18O to the ENSO cycle in monsoon regions of China

NASA Astrophysics Data System (ADS)

Tan, Ming

2014-02-01

Inter-annual variation in the ratio of 18O to 16O of precipitation (δ18Op) in the monsoon regions of China (MRC, area approximately east of 100°E) has not yet been fully analyzed. Based on an analysis of the relationships between the time series of amount-weighted mean annual δ18O in precipitation (δ18Ow) and meteorological variables such as temperature, precipitation as well as atmospheric/oceanic circulation indices, it is recognized that the El Niño-Southern Oscillation (ENSO) cycle appears to be the dominant control on the inter-annual variation in δ18Op in the MRC. Further analysis shows that the trade wind plays a role in governing δ18Ow through affecting the intensity of the different summer monsoon circulations which are closely linked to the weakening (weaker than normal) and strengthening (stronger than normal) of the trade wind and gives the δ18Ow different values at or over inter-annual timescales. The southwest monsoon (SWM) drives long-distance transport of water vapor from Indian Ocean to the MRC, and along this pathway increasing rainout leads to more negative δ18Ow via Rayleigh distillation processes. In contrast, the southeast monsoon (SEM), which is consistent with the changes in the strength of the West Pacific subtropical high, drives short-distance water vapor transport from the West Pacific Ocean to the MRC and leads to less negative δ18Ow. Therefore, the δ18Ow value directly reflects the differences in influence between the SWM, which is strong when the SE trade wind is strong, and the SEM, which is strong when the SE trade wind is weak. In addition, the South China Sea Monsoon also transports local water vapor as well as plays a role in achieving the synchronization between the δ18Ow and ENSO. The author thus terms the δ18Op rhythm in the MRC the "circulation effect". In turn, the δ18Op variation in the MRC has the potential to provide information on atmospheric circulation and the signal of δ18Op recorded in natural archives

Nuclear Tubulin: A Novel Target for Breast Cancer Chemotherapy

DTIC Science & Technology

2001-05-01

A. Castillo1, R.F. Luduena 3, and I. Meza 2 ’Departamentos de Biologia Celular and 2 Biomedicina Molecular, CINVESTA V del /PN, M6xico, D. F...resistance. J Biol Chem 270: 31269-31275. Hyams JS, Lloyd CW. 1994.-.The role of multiple tubulin isoforms in celular microtubule function. In: Raff E editor

A Novel Model System to Examine Agents Used in Breast Cancer Therapy.

DTIC Science & Technology

1995-07-01

We have recently characterized a multiprotein DNA replication complex (MRC) that was purified from NODA NIB 468 human breast cancer cells by a series...proliferating cell nuclear antigen (PCNA), RE-C RP-A and DNA topoisomerase I. Based upon its requirements for DNA replication activity and its...SV4O) origin sequences, the MRC executes all of the steps required for the in vitro, bidirectional replication of the SV4O genome. Several of the DNA

Exploring cellular uptake of iron oxide nanoparticles associated with rhodium citrate in breast cancer cells

PubMed Central

Chaves, Natalia L; Estrela-Lopis, Irina; Böttner, Julia; Lopes, Cláudio AP; Guido, Bruna C; de Sousa, Aparecido R; Báo, Sônia N

2017-01-01

Nanocarriers have the potential to improve the therapeutic index of currently available drugs by improving their efficacy and achieving therapeutic steady-state levels over an extended period. The association of maghemite–rhodium citrate (MRC) nanoparticles (NPs) has the potential to increase specificity of the cytotoxic action. However, the interaction of these NPs with cells, their uptake mechanism, and subcellular localization need to be elucidated. This work evaluates the uptake mechanism of MRC NPs in metastatic and nonmetastatic breast cancer-cell models, comparing them to a nontumor cell line. MRC NPs uptake in breast cancer cells was more effective than in normal cells, with regard to both the amount of internalized material and the achievement of more strategic intracellular distribution. Moreover, this process occurred through a clathrin-dependent endocytosis pathway with different basal expression levels of this protein in the cell lines tested. PMID:28814867

Who Will Experience the Most Alcohol Problems in College? The Roles of Middle and High School Drinking Tendencies.

PubMed

Scaglione, Nichole M; Mallett, Kimberly A; Turrisi, Rob; Reavy, Racheal; Cleveland, Michael J; Ackerman, Sarah

2015-10-01

Previous work examining college drinking tendencies has identified a disproportionately small (20%), but uniquely high-risk group of students who experience nearly 50% of the reported alcohol-related consequences (i.e., the multiple repeated consequences, or MRC, group). With the goal of reducing drinking-related consequences later in college, this study sought to identify potential MRC group members in their first semester by examining: (i) early-risk subgroups based on analysis of early-risk screening constructs (e.g., age of drinking onset, middle school alcohol exposure, high school drinking, and consequences); and (ii) their association with MRC criteria early in the first semester of college. A random sample of 2,021 first-year college student drinkers (56% female) completed a web-based drinking survey in their first semester on campus. Latent class analysis revealed 4 early-risk subgroups: (i) an early-onset risk group who endorsed early age of drinking onset and engaged in heavy middle and high school drinking (10%); (ii) a late-onset risk group who engaged in weekend drinking and drunkenness and experienced 6 or more unique consequences as seniors in high school (32%); (iii) an early-onset limited risk group who only endorsed early age of onset and middle school drinking (3%); and (iv) a minimal risk group who did not engage in any early-risk behaviors (55%). Members of both the early- and late-onset risk groups had significantly higher odds of MRC membership in their first semester of college (9.85 and 6.79 greater, respectively). Results suggest age of onset, middle and high school drinking and drunkenness, and frequency of unique consequences could be particularly useful in brief screening tools. Further, findings support early screening and prevention efforts for MRC membership prior to college matriculation. Copyright © 2015 by the Research Society on Alcoholism.

A two-site filtration model for silica nanoaggregate mobility in porous media under high salinity conditions

NASA Astrophysics Data System (ADS)

Taghavy, Amir; Kim, Ijung; Huh, Chun; DiCarlo, David A.

2018-06-01

A variable-viscosity colloid transport simulator is developed to model the mobility behavior of surface-engineered nanosilica aggregates (nSiO2) under high salinity conditions. A two-site (2S) filtration approach was incorporated to account for heterogeneous particle-collector surface interactions. 2S model was then implemented along with the conventional clean bed filtration (CFT) and maximum retention capacity (MRC) particle filtration models to simulate the results of a series of column tests conducted in brine (8% wt. NaCl and 2% wt. CaCl2)-saturated Ottawa sand columns at various pore velocities (7 to 71 m/day). Simulation results reveal the superiority of the MRC and 2S model classes over CFT model with respect to numerical performance criteria; a general decrease of normalized sum of squared residuals (ca. 20-90% reduction) and an enhanced degree of normality of model residuals were detected for 2S and MRC over CFT in all simulated experiments. Based on our findings, conformance with theories underpinning colloid deposition in porous media was the ultimate factor that set 2S and MRC model classes apart in terms of explaining the observed mobility trends. MRC and 2S models were evaluated based on the scaling of the fitted maximum retention capacity parameter with variation of experimental conditions. Two subclasses of 2S that consider a mix of favorable and unfavorable attachment sites with irreversible attachment to favorable sites (with and without physical straining effects) were found most consistent with filtration theory and shadow zone predictions, yielding theoretical conformity indices of 0.6 and higher, the highest among all implemented models. An explanation for such irreversible favorable deposition sites on the surface of silica nanoaggregates might be a partial depletion of stabilizing steric forces that had led to the formation of these aggregates.

Feasibility of Home-Based Functional Status Assessment of Chronic Obstructive Pulmonary Disease Patients Recovering From an Exacerbation.

PubMed

Valeiro, Beatriz; Hernández, Carme; Barberán-Garcia, Anael; Rodríguez, Diego A; Aibar, Jesús; Llop, Lourdes; Vilaró, Jordi

2016-05-01

The Glittre Activities of Daily Living Test (ADL-Test) is a reliable functional status measurement for stable chronic obstructive pulmonary disease (COPD) patients in a laboratory setting. We aimed to adapt the test to the home setting (mADL-Test) and to follow-up the functional status recovery of post-exacerbation COPD patients included in a home hospitalization (HH) program. We assessed 17 exacerbated moderate-to-very-severe COPD patients in 3 home visits: at discharge to HH (V0), 10days (V10post) and 1month after discharge (V30post). Patients completed the mADL-Test (laps, VO2 and VE), COPD assessment test (CAT), London Chest ADL Test (LCADL), modified Medical Research Council (mMRC) and upper limb strength (handgrip). The number of laps of the mADL-Test (4, 5 and 5, P<.05), CAT (19, 12 and 12, P<.01), mMRC (2, 1.5 and 1, P<.01) and the self-care domain of the LCADL (6, 5 and 5, P<.01) improved during follow-up (V0, V10post and V30post, respectively). No significant changes were evidenced in VO2, VE or handgrip. Our results suggest that the mADL-test can be performed in the home setting after a COPD exacerbation, and that functional status continues to improve 10days after discharge to HH. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.

Daunorubicin and Cytarabine Liposome in Newly Diagnosed Therapy-Related Acute Myeloid Leukemia (AML) or AML With Myelodysplasia-Related Changes.

PubMed

Kim, Miryoung; Williams, Sherry

2018-03-01

To evaluate the efficacy and safety of daunorubicin and cytarabine liposome in older adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). A literature search of PubMed and MEDLINE (January 2017 to January 2018) was performed using the terms CPX-351, Vyxeos, daunorubicin and cytarabine liposome, and acute myeloid leukemia. Phase I, II, and III clinical trials evaluating the efficacy and safety of daunorubicin and cytarabine liposome were reviewed with a specific focus on its use in older patients with newly diagnosed AML. All peer-reviewed articles with clinically relevant information were evaluated for inclusion. The phase II trial demonstrated that daunorubicin and cytarabine liposome improved response rates (RR), but there was no difference in event-free survival and overall survival in the overall patient population. However, clinical benefit was most pronounced in secondary AML with an increased RR and survival. The phase III trial illustrated that daunorubicin and cytarabine liposome improved survival and RR with tolerable toxicity compared with standard 7 plus 3 (daunorubicin and cytarabine) in patients 60 to 75 years of age with t-AML or AML-MRC. More patients proceeded to a stem cell transplant, and 30-day and 60-day mortality was lower with daunorubicin and cytarabine liposome. Grade 3 to 5 toxicities were similar between the 2 groups, except daunorubicin and cytarabine liposome had prolonged cytopenia and a higher risk of hemorrhage. Daunorubicin and cytarabine liposome improves RR and survival, with tolerable toxicity in older patients with t-AML or AML-MRC.

MR colonography with fecal tagging: do individual patient characteristics influence image quality?

PubMed

Kinner, Sonja; Kuehle, Christiane A; Langhorst, Jost; Ladd, Susanne C; Nuefer, Michael; Barkhausen, Joerg; Lauenstein, Thomas C

2007-05-01

To evaluate if different patient characteristics influence performance of fecal tagging (a new MR colonography (MRC) technique to label stool to avoid bowel cleansing) and, consecutively, MR image quality. A total of 333 patients (mean age = 61 years) underwent MRC with fecal tagging. Four segments of the large bowel (ascending, transverse, descending, and sigmoid colon) were assessed as for the presence of nontagged stool particles, which can impede an assessment of the colonic wall. Ratings were correlated with patients' characteristics including patient age (<55 vs. > or =55 years), body mass index (BMI) (<25 vs. > or =25), gender, and acceptance levels for fecal tagging. Statistical analysis was performed using a Mann-Whitney U-test. A total of 1332 colonic segments were evaluated. Among them, 327 segments (25%) did not contain any visible stool particles. Considerably reduced image quality was found in 61 segments (5%). Best image quality was found in the sigmoid colon (mean value = 1.9), while image quality of the ascending colon turned out to be worst (mean value = 2.6). Fecal tagging effectiveness showed a reverse correlation with patient age. However, all other characteristics did not have a statistically significant influence on fecal tagging outcome. MRC in conjunction with barium-based fecal tagging led to diagnostic image quality in 95% of all colonic segments. Since tagging results were significantly decreased in patients > or =55 years, tagging protocols should to be modified in this group, i.e., by increasing the time interval of tagging administration. (c) 2007 Wiley-Liss, Inc.

Cellular Effects of Endotoxin in Vitro: Mobility of Endotoxin in the Plasma Membrane of Hepatocytes and Neuroblastoma Cells

DTIC Science & Technology

1985-01-01

initiates ain.otoxin eqxpocar In the pteet work. we have celular perturbations. remains to be determined. I In vivo stdahawe shown that the liver is an...1977) Scismos 195. 307-309 tomn at the Celular LAve (Majde. JA.. ad.). Mp 81-95. 30 SdchminW. J., SebchaW. Y- Casacasas. P. Wminsa Alan I. Liss. New

Acute myeloid leukaemia with myelodysplastic features in children: a report of Japanese Paediatric Leukaemia/Lymphoma Study Group.

PubMed

Kinoshita, Akitoshi; Miyachi, Hayato; Matsushita, Hiromichi; Yabe, Miharu; Taki, Tomohiko; Watanabe, Tomoyuki; Saito, Akiko M; Tomizawa, Daisuke; Taga, Takashi; Takahashi, Hiroyuki; Matsuo, Hidemasa; Kodama, Kumi; Ohki, Kentaro; Hayashi, Yasuhide; Tawa, Akio; Horibe, Keizo; Adachi, Souichi

2014-10-01

The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found 'AML with myelodysplasia-related changes' (AML-MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia-related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with 'AML, not otherwise specified' (AML-NOS), patients with 'AML-MRC' presented at a younger age, with a lower white blood cell count, higher incidence of 20-30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), NPM1 and CEBPA mutations. Complete remission rate and 3-year probability of event-free survival were significantly worse in 'AML-MRC' patients (67·7 vs. 85·6%, P < 0·01, 37·1% vs. 53·8%, P = 0·02, respectively), but 3-year overall survival and relapse-free survival were comparable with 'AML-NOS' patients. By multivariate analysis, FLT3-ITD was solely associated with worse overall survival. These results support the distinctive features of the category 'AML-MRC' even in children. © 2014 John Wiley & Sons Ltd.

Comparative immunohistologic studies in an adoptive transfer model of acute rat cardiac allograft rejection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forbes, R.D.; Lowry, R.P.; Gomersall, M.

1985-07-01

It has been shown that fulminant acute rejection of rat cardiac allografts across a full haplotype disparity may occur as a direct result of adoptive transfer of sensitized W3/25+ MRC OX8- SIg- T helper/DTH syngeneic spleen cells to sublethally irradiated recipients. In order to establish the immunohistologic parameters of this form of rejection, allografts and recipient lymphoid tissue were analyzed using a panel of monoclonal antibodies of known cellular distribution. These data were compared with those obtained following reconstitution of irradiated allograft recipients with unseparated sensitized spleen cells, with unreconstituted irradiated donor recipient pairs, with unmodified first-set rejection, and withmore » induced myocardial infarction of syngeneic heart grafts transplanted to normal and to sublethally irradiated recipients. Rejecting cardiac allografts transplanted to all reconstituted irradiated recipients were characterized by extensive infiltration with MRC OX8+ (T cytotoxic-suppressor, natural killer) cells even when this subset was virtually excluded from the reconstituting inocula. A similar proportional accumulation of MRC OX8+ cells observed at the infarct margins of syngeneic heart grafts transplanted to irradiated unreconstituted recipients greatly exceeded that present in normal nonirradiated controls. These data provide evidence that under conditions of heavy recipient irradiation, MRC OX8+ cells may be sequestered within heart grafts in response to nonspecific injury unrelated to the rejection process.« less

An Examination of the Relationship between Consequence-Specific Normative Belief Patterns and Alcohol-Related Consequences among College Students

PubMed Central

Reavy, Racheal; Cleveland, Michael J.; Mallett, Kimberly A.; Scaglione, Nichole M.; Sell, Nichole M.; Turrisi, Rob

2016-01-01

Background Research has previously identified a high-risk subgroup of college students who experience high levels of multiple and repeated alcohol-related consequences (MRC group). The purpose of this study was to examine the association between consequence-specific normative influences and experiencing multiple and repeated drinking-related consequences using a person-centered approach. Normative subgroups were identified using latent profile analysis (LPA), which were then used to predict MRC group status at 6-month follow-up. Methods First-year college student drinkers (N=2024) at a large northeastern university completed online surveys during the fall and spring semesters of their freshman year. Retention was high with 92% of invited participants completing T2, of which the MRC group accounted for 27%. Results Three student profiles were identified from LPA on T1 data: Non Permissive Parents (77%), Positive Peer and Parent Norms (20%), and Permissive Parents (3%). Logistic regression revealed that both the Positive Peer and Parent Norms and Permissive Parents profiles had significantly higher odds of MRC group membership at follow-up (1.81 and 2.78 times greater, respectively). Conclusions The results suggest value in prevention efforts that include normative beliefs about alcohol-related consequences. Further, parental norms in particular have the potential to enhance interventions, especially through direct communication of disapproval for experiencing consequences. PMID:27805274

Selective Modification of Adenovirus Replication Can Be Achieved through Rational Mutagenesis of the Adenovirus Type 5 DNA Polymerase

PubMed Central

Capella, Cristina; Beltejar, Michael-John; Brown, Caitlin; Fong, Vincent; Daddacha, Waaqo; Kim, Baek

2012-01-01

Mutations that reduce the efficiency of deoxynucleoside (dN) triphosphate (dNTP) substrate utilization by the HIV-1 DNA polymerase prevent viral replication in resting cells, which contain low dNTP concentrations, but not in rapidly dividing cells such as cancer cells, which contain high levels of dNTPs. We therefore tested whether mutations in regions of the adenovirus type 5 (Ad5) DNA polymerase that interact with the dNTP substrate or DNA template could alter virus replication. The majority of the mutations created, including conservative substitutions, were incompatible with virus replication. Five replication-competent mutants were recovered from 293 cells, but four of these mutants failed to replicate in A549 lung carcinoma cells and Wi38 normal lung cells. Purified polymerase proteins from these viruses exhibited only a 2- to 4-fold reduction in their dNTP utilization efficiency but nonetheless could not be rescued, even when intracellular dNTP concentrations were artificially raised by the addition of exogenous dNs to virus-infected A549 cells. The fifth mutation (I664V) reduced biochemical dNTP utilization by the viral polymerase by 2.5-fold. The corresponding virus replicated to wild-type levels in three different cancer cell lines but was significantly impaired in all normal cell lines in which it was tested. Efficient replication and virus-mediated cell killing were rescued by the addition of exogenous dNs to normal lung fibroblasts (MRC5 cells), confirming the dNTP-dependent nature of the polymerase defect. Collectively, these data provide proof-of-concept support for the notion that conditionally replicating, tumor-selective adenovirus vectors can be created by modifying the efficiency with which the viral DNA polymerase utilizes dNTP substrates. PMID:22811532

Tumour-marker levels and prognosis in malignant teratoma of the testis.

PubMed Central

Germa-Lluch, J. R.; Begent, R. H.; Bagshawe, K. D.

1980-01-01

The effect of 6 putative prognostic factors on survival was studied in patients with Stages III and IV malignant teratoma of the testis. Differences between survival curves were tested for statistical significance. A diameter greater than 5 cm in the largest tumour mass, and greater than 8 pulmonary metastases were adverse prognostic factors (P = 0.004 and 0.008 respectively). Patients with malignant teratoma, trophoblastic, fared worse than those with malignant teratoma, undifferentiated, and malignant teratoma, intermediate (P = 0.011 and 0.023 respectively). Previous chemotherapy or radiotherapy had no significant effect. Serum alpha-foetoprotein (AFP) above 10(3) MRC u/ml and serum beta subunit of human chorionic gonadotrophin (hCG) above 10(5) miu/ml, were found to predict a poor prognosis (P = 0.010 and 0.001 respectively). A combination of measurements of the tumour markers gave the most consistent indication of prognosis, in that patients with either AFP greater than 10(3) MRC u/ml or hCG greater than 10(5) miu/ml, or both, fared much worse than those with neither factor (P = 0.001). Serum concentrations of AFP and hCG should be stated in reports of treatment of testicular teratoma in order to provide a basis for comparison with other series. Regular and frequent measurements of these markers are appropriate throughout the clinical management of patients with malignant teratoma. PMID:6161630

Bone marrow VEGFC expression is associated with multilineage dysplasia and several prognostic markers in adult acute myeloid leukemia, but not with survival.

PubMed

Guillem, Vicent; Calabuig, Marisa; Brunet, Salut; Esteve, Jordi; Escoda, Lourdes; Gallardo, David; Ribera, Josep-Maria; Queipo de Llano, María Paz; Arnan, Montserrat; Pedro, Carme; Amigo, María Luz; Martí-Tutusaus, Josep M; García-Guiñón, Antoni; Bargay, Joan; Sampol, Antonia; Salamero, Olga; Font, Llorenç; Talarn, Carme; Hoyos, Montserrat; Díaz-Beyá, Marina; Garrido, Ana; Navarro, Blanca; Nomdédeu, Josep; Sierra, Jordi; Tormo, Mar

2018-01-18

Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell proliferation and survival, and promotes angiogenesis. We studied VEGFC expression in bone marrow samples from 353 adult acute myeloid leukemia (AML) patients and its relationship with several clinical, cytogenetic, and molecular variables. We also studied the expression of 84 genes involved in VEGF signaling in 24 patients. We found that VEGFC expression was higher in AML patients with myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We also found an association between VEGFC expression and the patient cytogenetic risk group, with those with a worse prognosis having higher VEGFC expression levels. No correlation was observed between VEGFC expression and survival or complete remission. VEGFC expression strongly correlated with expression of the VEGF receptors FLT1, KDR, and NRP1. Thus, in this series, VEGFC expression was increased in AML-MRC and in subgroups with a poorer prognosis, but has no impact on survival.

Variations in AmLi source spectra and their estimation utilizing the 5 Ring Multiplicity Counter

NASA Astrophysics Data System (ADS)

Weinmann-Smith, R.; Beddingfield, D. H.; Enqvist, A.; Swinhoe, M. T.

2017-06-01

Active-mode assay systems are widely used for the safeguards of uranium items to verify compliance with the Non-Proliferation Treaty. Systems such as the Active-Well Coincidence Counter (AWCC) and the Uranium Neutron Coincidence Collar (UNCL) use americium-lithium (AmLi) neutron sources to induce fissions which are measured to determine the sample mass. These systems have historically relied on calibrations derived from well-defined standards. Recently, restricted access to standards or more difficult measurements have resulted in a reliance on modeling and simulation for the calibration of systems, which introduces potential simulation biases. The AmLi source energy spectra commonly used in the safeguards community do not accurately represent measurement results and the spectrum uncertainty can represent a large contribution to the total modeling uncertainty in active-mode systems. The 5-Ring Multiplicity Counter (5RMC) has been used to measure 17 AmLi sources. The measurements showed a significant spectral variation between different sources. Utilization of a spectrum that is specific to an individual source or a series of sources will give improved results over historical general spectra when modeling AmLi sources. Candidate AmLi neutron spectra were calculated in MCNP and SOURCES4C for a range of physical AmLi characteristics. The measurement and simulation data were used to fit reliable and accurate AmLi spectra for use in the simulation of active-mode systems. Spectra were created for average Gammatron C, Gammatron N, and MRC series sources, and for individual sources. The systematic uncertainty introduced by physical aspects of the AmLi source were characterized through simulations. The accuracy of spectra from the literature was compared.

Application of powder metallurgy technique to produce improved bearing elements for cryogenic aerospace engine turbopumps

NASA Technical Reports Server (NTRS)

Moxson, V. S.; Moracz, D. J.; Bhat, B. N.; Dolan, F. J.; Thom, R.

1987-01-01

Traditionally, vacuum melted 440C stainless steel is used for high performance bearings for aerospace cryogenic systems where corrosion due to condensation is a major concern. For the Space Shuttle Main Engine (SSME), however, 440C performance in the high-pressure turbopumps has been marginal. A basic assumption of this study was that powder metallurgy, rather than cast/wrought, processing would provide the finest, most homogeneous bearing alloy structure. Preliminary testing of P/M alloys (hardness, corrosion resistance, wear resistance, fatigue resistance, and fracture toughness) was used to 'de-select' alloys which did perform as well as baseline 440C. Five out of eleven candidate materials (14-4/6V, X-405, MRC-2001, T-440V, and D-5) based on preliminary screening were selected for the actual rolling-sliding five-ball testing. The results of this test were compared with high-performance vacuum-melted M50 bearing steel. The results of the testing indicated outstanding performance of two P/M alloys, X-405 and MRC-2001, which eventually will be further evaluated by full-scale bearing testing.

Inactivation of Influenza A virus, Adenovirus, and Cytomegalovirus with PAXgene tissue fixative and formalin.

PubMed

Kap, Marcel; Arron, Georgina I; Loibner, M; Hausleitner, Anja; Siaulyte, Gintare; Zatloukal, Kurt; Murk, Jean-Luc; Riegman, Peter

2013-08-01

Formalin fixation is known to inactivate most viruses in a vaccine production context, but nothing is published about virus activity in tissues treated with alternative, non-crosslinking fixatives. We used a model assay based on cell culture to test formalin and PAXgene Tissue fixative for their virus-inactivating abilities. MDCK, A549, and MRC-5 cells were infected with Influenza A virus, Adenovirus, and Cytomegalovirus, respectively. When 75% of the cells showed a cytopathic effect (CPE), the cells were harvested and incubated for 15 min, or 1, 3, 6, or 24 hours, with PBS (positive control), 4% formalin, or PAXgene Tissue Fix. The cells were disrupted and the released virus was used to infect fresh MDCK, A549, and MRC-5 cells cultured on cover slips in 24-well plates. The viral cultures were monitored for CPE and by immunocytochemistry (ICC) to record viral replication and infectivity. Inactivation of Adenovirus by formalin occurred after 3 h, while Influenza A virus as well as Cytomegalovirus were inactivated by formalin after 15 min. All three virus strains were inactivated by PAXgene Tissue fixative after 15 min. We conclude that PAXgene Tissue fixative is at least as effective as formalin in inactivating infectivity of Influenza A virus, Adenovirus, and Cytomegalovirus.

Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

PubMed Central

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Lee, In Kyung; Nam, Seon Young

2017-01-01

Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation. PMID:28122968

Voluntary authority set up.

PubMed

Clarke, M

The British Medical Research Council (MRC), in association with the Royal College of Obstetricians and Gynaecologists, has responded to the Warnock report on human fertilization and embryology by setting up a voluntary authority to license such research. MRC also seeks to define the term "embryo" and to include as research "new and untried treatment." Possible lines of investigation include studies on infertility, genetic and congenital diseases, and contraceptive methods. However, if Enoch Powell's Parliamentary bill should become law, all research on human embryos would be illegal.

Fermi LAT detection of renewed and strong GeV gamma-ray flares from blazars PKS 0903-57 and PKS 0346-27

NASA Astrophysics Data System (ADS)

Ciprini, Stefano

2018-05-01

The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed high-level gamma-ray activity from sources positionally consistent with the active galaxy PKS 0903-57 (also known as MRC 0903-573 and 3FGL J0904.8-5734, Acero et al. 2015, ApJS, 218, 23) and with the flat spectrum radio quasar PKS 0346-27 (also known as OE -278, TXS 0346-279, MRC 0346-279 and 3FGL J0348.6-2748).

Erectile dysfunction in COPD patients

PubMed Central

Ure, Iyimser; Turan, Pakize Ayse

2015-01-01

Sexual dysfunction is a common problem in chronic obstructive pulmonary disease (COPD). We aimed to assess the presence of erectile dysfunction (ED) in COPD patients. Ninety-three outpatients who had been diagnosed as COPD and followed in Bolvadin State Hospital, Afyon, Turkey, were included in the study. All patients underwent pulmonary function tests and arterial blood gas analysis. They completed International Physical Activity Questionnaire (IPAQ), Medical Research Council (MRC) Dyspnea Scale, Short Form 36-item Scale (SF-36), and International Index of Erectile Function (IIEF) Questionnaire. The mean age of 10 (10.8%) mild, 46 (49.5%) moderate, 28 (30.1%) severe, and 9 (9.7%) very severe COPD patients was 61.4 ± 9.8 years. Varying degrees of ED were detected in 67.7% of COPD patients. All patients with hypoxemia had ED. IPAQ score and all SF-36 parameters were low in patients with ED, while MRC score was high. Forced expiratory volume in one second, forced vital capacity, partial pressure of oxygen in blood, oxygen (O2) saturation, IPAQ score, and role-physical parameters were statistically low in ED patients (p = 0.04, 0.02, <0.01, <0.01, 0.02, and 0.04, respectively); MRC score was statistically higher in patients with ED (p = 0.02). Patients with moderate and severe ED had statistically lower score of mental health (p < 0.01 and p = 0.02, respectively). There was a positive correlation between IIEF score and IPAQ scores (p < 0.01), MRC scores (p = 0.01), general health (p < 0.01), role-physical (p < 0.01), role-emotional (p < 0.01), physical functioning (p < 0.01), and mental health (p < 0.01) parameters in SF-36. ED is frequently seen in COPD patients. Hypoxemia, smoking, and limitation of physical activity are thought to be associated with ED in COPD as mechanisms. Quality of life and the functional capacity are negatively affected with the presence of ED. It is important for a physician to question the sexual functions in patients with COPD. The

Erectile dysfunction in COPD patients.

PubMed

Turan, Onur; Ure, Iyimser; Turan, Pakize Ayse

2016-02-01

Sexual dysfunction is a common problem in chronic obstructive pulmonary disease (COPD). We aimed to assess the presence of erectile dysfunction (ED) in COPD patients. Ninety-three outpatients who had been diagnosed as COPD and followed in Bolvadin State Hospital, Afyon, Turkey, were included in the study. All patients underwent pulmonary function tests and arterial blood gas analysis. They completed International Physical Activity Questionnaire (IPAQ), Medical Research Council (MRC) Dyspnea Scale, Short Form 36-item Scale (SF-36), and International Index of Erectile Function (IIEF) Questionnaire. The mean age of 10 (10.8%) mild, 46 (49.5%) moderate, 28 (30.1%) severe, and 9 (9.7%) very severe COPD patients was 61.4 ± 9.8 years. Varying degrees of ED were detected in 67.7% of COPD patients. All patients with hypoxemia had ED. IPAQ score and all SF-36 parameters were low in patients with ED, while MRC score was high. Forced expiratory volume in one second, forced vital capacity, partial pressure of oxygen in blood, oxygen (O2) saturation, IPAQ score, and role-physical parameters were statistically low in ED patients (p = 0.04, 0.02, <0.01, <0.01, 0.02, and 0.04, respectively); MRC score was statistically higher in patients with ED (p = 0.02). Patients with moderate and severe ED had statistically lower score of mental health (p < 0.01 and p = 0.02, respectively). There was a positive correlation between IIEF score and IPAQ scores (p < 0.01), MRC scores (p = 0.01), general health (p < 0.01), role-physical (p < 0.01), role-emotional (p < 0.01), physical functioning (p < 0.01), and mental health (p < 0.01) parameters in SF-36. ED is frequently seen in COPD patients. Hypoxemia, smoking, and limitation of physical activity are thought to be associated with ED in COPD as mechanisms. Quality of life and the functional capacity are negatively affected with the presence of ED. It is important for a physician to question the sexual functions in patients with COPD. The

Experiments on the Dynamics and Hydrodynamic Instabilities of Ablatively Accelerated Targets.

DTIC Science & Technology

1983-02-01

pressure and velocities obtained using the double foil tech - diance nonuniformities has been investigated previously and 430 Appi P"v$ Lett.. Vol 41. No, 5...NRL is evaluating for the Department of Energy the feasibility of using direct laser drive to Implode fusion pellets.t Mission Research Corporation...MRC) has contracted to support this experiment by using its best effort to perform the tasks summarized below: A parametric study shall be performed

Correlation between ICDAS and histology: Differences between stereomicroscopy and microradiography with contrast solution as histological techniques

PubMed Central

Campos, Samara de Azevedo Gomes; Vieira, Maria Lúcia Oliveira

2017-01-01

Detection of occlusal caries with visual examination using ICDAS correlates strongly with histology under stereomicroscopy (SM), but dentin aspects under SM are ambiguous regarding mineral content. Thus, our aim was to test two null hypotheses: SM and microradiography result in similar correlations between ICDAS and histology; SM and microradiography result in similar positive (PPV) and negative predictive values (NPV) of ICDAS cut-off 1–2 (scores 0–2 as sound) with histological threshold D3 (demineralization in the inner third of dentin). Occlusal surfaces of extracted permanent teeth (n = 115) were scored using ICDAS. Undemineralized ground sections were histologically scored using both SM without contrast solution and microradiography after immersion in Thoulet’s solution 1.47 for 24 h (MRC). Correlation between ICDAS and histology differed from SM (0.782) to MRC (0.511) (p = 0.0002), with a large effect size “q” of 0.49 (95% CI: 0.638/0.338). For ICDAS cut-off 1–2 and D3, PPV from MRC (0.56) was higher than that from SM (0.28) (p< 0.00001; effect size h = 0.81), and NPV from MRC (0.72) was lower than that from SM (1,00) (p < 0.00001; effect size h = 1.58). In conclusion, SM overestimated the correlation between ICDAS and lesion depth, and underestimated the number of occlusal surfaces with ICDAS cut-off 1–2 and deep dentin demineralization. PMID:28841688

Reliability of TMS metrics in patients with chronic incomplete spinal cord injury.

PubMed

Potter-Baker, K A; Janini, D P; Frost, F S; Chabra, P; Varnerin, N; Cunningham, D A; Sankarasubramanian, V; Plow, E B

2016-11-01

Test-retest reliability analysis in individuals with chronic incomplete spinal cord injury (iSCI). The purpose of this study was to examine the reliability of neurophysiological metrics acquired with transcranial magnetic stimulation (TMS) in individuals with chronic incomplete tetraplegia. Cleveland Clinic Foundation, Cleveland, Ohio, USA. TMS metrics of corticospinal excitability, output, inhibition and motor map distribution were collected in muscles with a higher MRC grade and muscles with a lower MRC grade on the more affected side of the body. Metrics denoting upper limb function were also collected. All metrics were collected at two sessions separated by a minimum of two weeks. Reliability between sessions was determined using Spearman's correlation coefficients and concordance correlation coefficients (CCCs). We found that TMS metrics that were acquired in higher MRC grade muscles were approximately two times more reliable than those collected in lower MRC grade muscles. TMS metrics of motor map output, however, demonstrated poor reliability regardless of muscle choice (P=0.34; CCC=0.51). Correlation analysis indicated that patients with more baseline impairment and/or those in a more chronic phase of iSCI demonstrated greater variability of metrics. In iSCI, reliability of TMS metrics varies depending on the muscle grade of the tested muscle. Variability is also influenced by factors such as baseline motor function and time post SCI. Future studies that use TMS metrics in longitudinal study designs to understand functional recovery should be cautious as choice of muscle and clinical characteristics can influence reliability.

Evaluation of the Tobacco Heating System 2.2. Part 6: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of a mentholated version compared with mentholated and non-mentholated cigarette smoke.

PubMed

Oviedo, Alberto; Lebrun, Stefan; Kogel, Ulrike; Ho, Jenny; Tan, Wei Teck; Titz, Bjoern; Leroy, Patrice; Vuillaume, Gregory; Bera, Monali; Martin, Florian; Rodrigo, Gregory; Esposito, Marco; Dempsey, Ruth; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

2016-11-30

The toxicity of a mentholated version of the Tobacco Heating System (THS2.2M), a candidate modified risk tobacco product (MRTP), was characterized in a 90-day OECD inhalation study. Differential gene and protein expression analysis of nasal epithelium and lung tissue was also performed to record exposure effects at the molecular level. Rats were exposed to filtered air (sham), to THS2.2M (at 15, 23 and 50 μg nicotine/l), to two mentholated reference cigarettes (MRC) (at 23 μg nicotine/l), or to the 3R4F reference cigarette (at 23 μg nicotine/l). MRCs were designed to meet 3R4F specifications. Test atmosphere analyses demonstrated that aldehydes were reduced by 75%-90% and carbon monoxide by 98% in THS2.2M aerosol compared with MRC smoke; aerosol uptake was confirmed by carboxyhemoglobin and menthol concentrations in blood, and by the quantities of urinary nicotine metabolites. Systemic toxicity and alterations in the respiratory tract were significantly lower in THS2.2M-exposed rats compared with MRC and 3R4F. Pulmonary inflammation and the magnitude of the changes in gene and protein expression were also dramatically lower after THS2.2M exposure compared with MRCs and 3R4F. No menthol-related effects were observed after MRC mainstream smoke-exposure compared with 3R4F. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

NASA Astrophysics Data System (ADS)

Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua; Zheng, Yuanjin

2015-09-01

Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF) stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC) stimulation, magnetic stimulation (MS) and transcutaneous electrical nerve stimulation (TENS) are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissue voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.

Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua

Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF) stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC) stimulation, magnetic stimulation (MS) and transcutaneous electrical nerve stimulation (TENS) are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissuemore » voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.« less

NASTRAN User’s Colloquium (12th), Held in Orlando, FLorida on May 7-11, 1984

DTIC Science & Technology

1984-08-01

Tennessee Eastman Company) 10.K-FINITE ELEMENT PREDICTION OF ACOUSTIC SCATTERING AND RADIATION FROM SUBMERGED ELASTIC STRUCTURES ... ...... .192 by...MCB’Iee) 2 (MRC*Ivv+MRR*O+MRB’ ) (MRC*H(R+MRRIRR+MRBFIBR) (MRCO+MRRO+MRBIee) p + LL(MBC I vv+ MBR *O+MBB*O) (MBCHCR+ MBR *IRR+MBB*HBR) (MBC’O+ MBR *O+MBB*Iee)J I...for the reed would consist of the partition MRR only and would be devoid of MCR and MBR and so would their transposes; i.e., no mass coupling between

Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

PubMed Central

Adams, Richard A; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Madi, Ayman; Fisher, David; Kenny, Sarah L; Kay, Edward; Hodgkinson, Elizabeth; Pope, Malcolm; Rogers, Penny; Wasan, Harpreet; Falk, Stephen; Gollins, Simon; Hickish, Tamas; Bessell, Eric M; Propper, David; Kennedy, M John; Kaplan, Richard; Maughan, Timothy S

2011-01-01

Summary Background When cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim. Methods COIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1·162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15·8 months (IQR 9·4–26·1) in arm A and 14·4 months (8·0–24·7) in arm C (hazard ratio [HR] 1·084, 80% CI 1·008–1·165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19·6 months (13·0–28·1) in arm A and 18·0 months (12·1–29·3) in arm C (HR 1·087, 0·986–1·198). The upper limits of CIs for HRs

Predictors for mechanical ventilation and short-term prognosis in patients with Guillain-Barré syndrome.

PubMed

Wu, Xiujuan; Li, Chunrong; Zhang, Bing; Shen, Donghui; Li, Ting; Liu, Kangding; Zhang, Hong-Liang

2015-09-02

Guillain-Barré syndrome (GBS) is an immune-mediated disorder of the peripheral nervous system. Respiratory failure requiring mechanical ventilation (MV) is a serious complication of GBS. Identification of modifiable risk factors for MV and poor short-term prognosis in mechanically ventilated patients with GBS may contribute to the individualized management and may help improve the outcome of the patients. We retrospectively analyzed the clinical data of 541 patients who were diagnosed with GBS from 2003 to 2014. Independent predictors for MV and short-term prognosis in mechanically ventilated patients were identified via multivariate logistic regression analysis. The mean age was 41.6 years with a male predilection (61.2%). Eighty patients (14.8%) required MV. Multivariate analysis revealed that shorter interval from onset to admission (p < 0.05), facial nerve palsy (p < 0.01), glossopharyngeal and vagal nerve deficits (p < 0.01) and lower Medical Research Council (MRC) sum score at nadir (p < 0.01) were risk factors for MV; disease occurrence in summer (p < 0.01) was a protective factor. As to prognostic factors, absence of antecedent infections (p < 0.01) and lower MRC sum score at nadir (p < 0.01) were predictors of poor short-term prognosis in mechanically ventilated patients regardless of treatment modality. We further investigated the predictors of poor short-term prognosis in patients requiring MV with different nadir MRC sum scores. Combined use of intravenous corticosteroids with intravenous immunoglobulin (odds ratio 10.200, 95% confidence interval 1.068-97.407, p < 0.05) was an independent predictor of poor short-term prognosis in mechanically ventilated patients with a nadir MRC sum score from 0 to 12 points, regardless of existence of antecedent infection. Clinical predictors of MV and poor short-term prognosis in mechanically ventilated GBS patients were distinct. Add-on use of intravenous corticosteroids was a risk factor for poor short

Technical report: gadoxetate-disodium-enhanced 2D R2* mapping: a novel approach for assessing bile ducts in living donors.

PubMed

Fazeli Dehkordy, Soudabeh; Fowler, Kathryn J; Wolfson, Tanya; Igarashi, Saya; Lamas Constantino, Carolina P; Hooker, Jonathan C; Hong, Cheng W; Mamidipalli, Adrija; Gamst, Anthony C; Hemming, Alan; Sirlin, Claude B

2017-10-31

Gadoxetate-disodium (Gd-EOB-DTPA)-enhanced 3D T1- weighted (T1w) MR cholangiography (MRC) is an efficient method to evaluate biliary anatomy due to T1 shortening of excreted contrast in the bile. A method that exploits both T1 shortening and T2* effects may produce even greater bile duct conspicuity. The aim of our study is to determine feasibility and compare the diagnostic performance of two-dimensional (2D) T1w multi-echo (ME) spoiled gradient-recalled-echo (SPGR) derived R2* maps against T1w MRC for bile duct visualization in living liver donor candidates. Ten potential living liver donor candidates underwent pretransplant 3T MRI and were included in our study. Following injection of Gd-EOBDTPA and a 20-min delay, 3D T1w MRC and 2D T1w ME SPGR images were acquired. 2D R2* maps were generated inline by the scanner assuming exponential decay. The 3D T1w MRC and 2D R2* maps were retrospectively and independently reviewed in two separate sessions by three radiologists. Visualization of eight bile duct segments was scored using a 4-point ordinal scale. The scores were compared using mixed effects regression model. Imaging was tolerated by all donors and R2* maps were successfully generated in all cases. Visualization scores of 2D R2* maps were significantly higher than 3D T1w MRC for right anterior (p = 0.003) and posterior (p = 0.0001), segment 2 (p < 0.0001), segment 3 (p = 0.0001), and segment 4 (p < 0.0001) ducts. Gd-EOB-DTPA-enhanced 2D R2* mapping is a feasible method for evaluating the bile ducts in living donors and may be a valuable addition to the living liver donor MR protocol for delineating intrahepatic biliary anatomy.

Moderate replacement of carbohydrates by dietary fats affects features of metabolic syndrome: a randomized crossover clinical trial.

PubMed

Rajaie, Somayeh; Azadbakht, Leila; Khazaei, Majid; Sherbafchi, Mostafa; Esmaillzadeh, Ahmad

2014-01-01

Earlier studies on the management of metabolic syndrome (MetS) have mostly focused on very low carbohydrate diets, whereas long-term adherence to such diets is difficult for apparently healthy people. The aim of this study was to examine the effects of moderate replacement of carbohydrates by dietary fats on insulin resistance and features of MetS among women. This randomized crossover clinical trial was performed with 30 overweight or obese (body mass index [BMI] > 25 kg/m(2)) women with MetS. After a 2-wk run-in period, participants were randomly assigned to consume either a calorie-restricted high-carbohydrate (HC) diet (60%-65% of energy from carbohydrates and 20%-25% from fats) or a calorie-restricted moderately restricted carbohydrate (MRC) diet (43%-47% of total calories as carbohydrate and 36%-40% as dietary fats) for 6 wk. Protein contents of both diets were 15% to 17% of total energy. A 2-wk washout period was applied following which participants were crossed over to the alternate treatment arm for an additional 6 wk. Anthropometric, blood pressure, and biochemical measurements were performed before and after each phase of intervention. Mean age and BMI of study participants was 42.4 y and 33 kg/m(2), respectively. A trend toward greater reduction in waist (-3.9 versus -2.6 cm; P = 0.07) and hip circumferences (-2.7 versus -1.5 cm; P = 0.07) as well as serum triglyceride (TG) levels (-31.3 versus 0.13 mg/dL; P = 0.07) was observed after consumption of an MRC diet compared with an HC diet. The TG to high-density lipoprotein cholesterol (HDL-C) ratio had a tendency to improve with the MRC diet rather than the HC diet (-0.9 versus -0.1; P = 0.06). Consumption of the MRC diet resulted in a greater reduction of systolic blood pressure (-8.93 versus -2.97 mm Hg; P = 0.06) and diastolic blood pressure (-12.7 versus -1.77 mm Hg; P = 0.001) compared with the HC diet. The prevalence of MetS was significantly decreased following the consumption of the MRC diet (P

International Conference on Partitioning in Aqueous Two-Phase Systems in Biochemistry Cell Biology and Biotechnology (7th) Held in New Orleans, Louisiana on June 2-7, 1991.

DTIC Science & Technology

1991-11-30

and Virus Like Particles (VLPs, cloned in yeast presently being used for the development of an AIDS vaccine). This paper will describe partition...PARTITIONING OF CEREBROCORTICAL SYNAPTOSOMES M. J. L6pez.P6rez Departamento de Bioquimica y Biologia Molecular y Celular . Facultad de Veterinaria...Pascual, T. Muifio-Blanco, J. A. Cebriin-Pdrez and M. J. L6pez-Pdrez. Departamento de Bioqufmica y Biologia Molecular y Celular . Facultad de

Development of Special Biological Products

DTIC Science & Technology

1981-01-01

Rocky Mountain Spotted Fever (RMSF) 20. Continued B. Tissue Culture / ?Two production lots of FRhL-2 dnd three of MRC-5 were stabilized...104) was potency tested. J. Q Fever Vaccine Storage Stability Potency Testing Q fever vaccine (NDBR 105) was put on potency test. K. Rocky Mountain Spotted Fever (RMSF...Fever Vaccine Storage Stability Potency Testing Two lots of Q fever vaccine (NDBR 105) were put on potency test. K. Rocky Mountain Spotted Fever

Chemically Modified Microelectrode Arrays. New Kinds of Electronic Devices.

DTIC Science & Technology

1987-08-05

switching. Figure 1 shows a typical process for the fabrication of a microelectrode array consisting of eight, individually addressable Au (or Pt...S4r... -n - 2 ORGANIC CLEAN MRC SPUTTERING PHOTOLITHOGRAPHY _Suttred SI.N, & DRY ETCH _LorVO S1. 1.2 pm Figure 1. Flow chart for fabrication of...microelectrochemical devices, including polypyrrole, 14 poly(N-methylpyrrole), 14b poly(3-methylthiophene), 1 5 and polyaniline .15b,16 These materials can all be made by

Electrochemical Behavior and Surface Chemistry of Nonequilibrium Aluminum Alloys: Passivity Mechanism and Fabrication Methods

DTIC Science & Technology

1994-01-17

alartl.rdentifvb bjock nurrber) FtELD GROUP SUB-GROUP Appreveo for LUDic release; OSirlOUtion unllmilTe. Reproduction in whole or in part is pemitted for any...INSPECTED 5 0eeesson For Mr.c EAi 0 Justi fioaL fo p ,l INTRODUCTION Aluminum alloys are generally designed for improved mechanical properties which...during spraying. The specifications for these samples are given in Table 1. In this report, W concentrations used to denote samples refer to design

Nerve Ultrasound and Electrophysiology for Therapy Monitoring in Chronic Inflammatory Demyelinating Polyneuropathy.

PubMed

Kerasnoudis, Antonios; Pitarokoili, Kalliopi; Gold, Ralf; Yoon, Min-Suk

2015-01-01

We evaluated prospectively nerve ultrasound and electrophysiology as monitoring methods of intravenous immunoglobulin (IVIG) therapy in chronic inflammatory demyelinating polyneuropathy (CIDP). Overall 15 healthy subjects and 11 CIDP patients undergoing IVIG therapy were recruited in the study. All patients underwent clinical, ultrasound, and electrophysiological evaluation at the time point of first onset of symptoms (<6 weeks of symptoms) and 4, 8, and 12 months after onset. The intranerve cross-sectional area (CSA) variability of each nerve, but not the CSA alone, correlated with the MRC Scale score during 12-month follow-up. On the other hand, none of the electrophysiological parameters correlated with the MRC Scale Score in each of the peripheral nerves. Interestingly, in ¾ of the CIDP patients, the resolution of the conduction block correlated with the improvement in the MRC Sum score. Nerve ultrasound and in particular the intranerve CSA variability seems to be a useful method in monitoring CIDP patients. Although the sample size is small, the intranerve CSA variability seems to be more promising than neurophysiology. Copyright © 2015 by the American Society of Neuroimaging.

Nonlinear Diamagnetic Stabilization of Double Tearing Modes in Cylindrical MHD Simulations

NASA Astrophysics Data System (ADS)

Abbott, Stephen; Germaschewski, Kai

2014-10-01

Double tearing modes (DTMs) may occur in reversed-shear tokamak configurations if two nearby rational surfaces couple and begin reconnecting. During the DTM's nonlinear evolution it can enter an ``explosive'' growth phase leading to complete reconnection, making it a possible driver for off-axis sawtooth crashes. Motivated by similarities between this behavior and that of the m = 1 kink-tearing mode in conventional tokamaks we investigate diamagnetic drifts as a possible DTM stabilization mechanism. We extend our previous linear studies of an m = 2 , n = 1 DTM in cylindrical geometry to the fully nonlinear regime using the MHD code MRC-3D. A pressure gradient similar to observed ITB profiles is used, together with Hall physics, to introduce ω* effects. We find the diamagnetic drifts can have a stabilizing effect on the nonlinear DTM through a combination of large scale differential rotation and mechanisms local to the reconnection layer. MRC-3D is an extended MHD code based on the libMRC computational framework. It supports nonuniform grids in curvilinear coordinates with parallel implicit and explicit time integration.

Essential Oil Content of the Rhizome of Curcuma purpurascens Bl. (Temu Tis) and Its Antiproliferative Effect on Selected Human Carcinoma Cell Lines

PubMed Central

Hong, Sok-Lai; Lee, Guan-Serm; Ahmed Hamdi, Omer Abdalla; Awang, Khalijah; Aznam Nugroho, Nurfina

2014-01-01

Curcuma purpurascens Bl., belonging to the Zingiberaceae family, is known as temu tis in Yogyakarta, Indonesia. In this study, the hydrodistilled dried ground rhizome oil was investigated for its chemical content and antiproliferative activity against selected human carcinoma cell lines (MCF7, Ca Ski, A549, HT29, and HCT116) and a normal human lung fibroblast cell line (MRC5). Results from GC-MS and GC-FID analysis of the rhizome oil of temu tis showed turmerone as the major component, followed by germacrone, ar-turmerone, germacrene-B, and curlone. The rhizome oil of temu tis exhibited strong cytotoxicity against HT29 cells (IC50 value of 4.9 ± 0.4 μg/mL), weak cytotoxicity against A549, Ca Ski, and HCT116 cells (with IC50 values of 46.3 ± 0.7, 32.5 ± 1.1, and 35.0 ± 0.3 μg/mL, resp.), and no inhibitory effect against MCF7 cells. It exhibited mild cytotoxicity against a noncancerous human lung fibroblast cell line (MRC5), with an IC50 value of 25.2 ± 2.7 μg/mL. This is the first report on the chemical composition of this rhizome's oil and its selective antiproliferative effect on HT29. The obtained data provided a basis for further investigation of the mode of cell death. PMID:25177723

Strategy optimization for mask rule check in wafer fab

NASA Astrophysics Data System (ADS)

Yang, Chuen Huei; Lin, Shaina; Lin, Roger; Wang, Alice; Lee, Rachel; Deng, Erwin

2015-07-01

Photolithography process is getting more and more sophisticated for wafer production following Moore's law. Therefore, for wafer fab, consolidated and close cooperation with mask house is a key to achieve silicon wafer success. However, generally speaking, it is not easy to preserve such partnership because many engineering efforts and frequent communication are indispensable. The inattentive connection is obvious in mask rule check (MRC). Mask houses will do their own MRC at job deck stage, but the checking is only for identification of mask process limitation including writing, etching, inspection, metrology, etc. No further checking in terms of wafer process concerned mask data errors will be implemented after data files of whole mask are composed in mask house. There are still many potential data errors even post-OPC verification has been done for main circuits. What mentioned here are the kinds of errors which will only occur as main circuits combined with frame and dummy patterns to form whole reticle. Therefore, strategy optimization is on-going in UMC to evaluate MRC especially for wafer fab concerned errors. The prerequisite is that no impact on mask delivery cycle time even adding this extra checking. A full-mask checking based on job deck in gds or oasis format is necessary in order to secure acceptable run time. Form of the summarized error report generated by this checking is also crucial because user friendly interface will shorten engineers' judgment time to release mask for writing. This paper will survey the key factors of MRC in wafer fab.

The Glittre-ADL Test Cut-Off Point to Discriminate Abnormal Functional Capacity in Patients with COPD.

PubMed

Gulart, Aline Almeida; Munari, Anelise Bauer; Klein, Suelen Roberta; Santos da Silveira, Lucas; Mayer, Anamaria Fleig

2018-02-01

The study objective was to determine a cut-off point for the Glittre activities of daily living (ADL)test (TGlittre) to discriminate patients with normal and abnormal functional capacity. Fifty-nine patients with moderate to very severe COPD (45 males; 65 ± 8.84 years; BMI: 26 ± 4.78 kg/m 2 ; FEV 1 : 35.3 ± 13.4% pred) were evaluated for spirometry, TGlittre, 6-minute walk test (6 MWT), physical ADL, modified Medical Research Council scale (mMRC), BODE index, Saint George's Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). The receiver operating characteristic (ROC) curve was used to determine the cut-off point for TGlittre in order to discriminate patients with 6 MWT < 82% pred. The ROC curve indicated a cut-off point of 3.5 minutes for the TGlittre (sensitivity = 92%, specificity = 83%, and area under the ROC curve = 0.95 [95% CI: 0.89-0.99]). Patients with abnormal functional capacity had higher mMRC (median difference 1 point), CAT (mean difference: 4.5 points), SGRQ (mean difference: 12.1 points), and BODE (1.37 points) scores, longer time of physical activity <1.5 metabolic equivalent of task (mean difference: 47.9 minutes) and in sitting position (mean difference: 59.4 minutes) and smaller number of steps (mean difference: 1,549 minutes); p < 0.05 for all. In conclusion, the cut-off point of 3.5 minutes in the TGlittre is sensitive and specific to distinguish COPD patients with abnormal and normal functional capacity.

Cytotoxic outcomes of orthodontic bands with and without silver solder in different cell lineages.

PubMed

Jacoby, Letícia Spinelli; Rodrigues Junior, Valnês da Silva; Campos, Maria Martha; Macedo de Menezes, Luciane

2017-05-01

The safety of orthodontic materials is a matter of high interest. In this study, we aimed to assess the in-vitro cytotoxicity of orthodontic band extracts, with and without silver solder, by comparing the viability outcomes of the HaCat keratinocytes, the fibroblastic cell lineages HGF and MRC-5, and the kidney epithelial Vero cells. Sterilized orthodontic bands with and without silver solder joints were added to culture media (6 cm 2 /mL) and incubated for 24 hours at 37°C under continuous agitation. Subsequently, the cell cultures were exposed to the obtained extracts for 24 hours, and an assay was performed to evaluate the cell viability. Copper strip extracts were used as positive control devices. The extracts from orthodontic bands with silver solder joints significantly reduced the viability of the HaCat, MRC-5, and Vero cell lines, whereas the viability of HGF was not altered by this material. Conversely, the extracts of orthodontic bands without silver solder did not significantly modify the viability index of all evaluated cell lines. Except for HGF fibroblasts, all tested cell lines showed decreased viability percentages after exposure to extracts of orthodontic bands containing silver solder joints. These data show the relevance of testing the toxicity of orthodontic devices in different cell lines. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Extrinsic and Intrinsic Apoptotic Responses Induced by Shiitake Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) Aqueous Extract against a Larynx Carcinoma Cell Line.

PubMed

Finimundy, Tiane C; Scola, Gustavo; Scariot, Fernando J; Dillon, Aldo J P; Moura, Sidnei; Echeverrigaray, Sérgio; Henriques, João Pegas; Roesch-Ely, Mariana

2018-01-01

Cumulative evidence from research studies has shown that the shiitake culinary-medicinal mushroom, Lentinus edodes, is an excellent source of natural antitumor agents and is capable of inhibiting cancer cell growth. However, the cell signaling pathway that leads tumor cells to apoptosis is not well understood because many chemical compounds may be acting. This study investigated the chemopreventive effects of an L. edodes aqueous extract on human HEp-2 epithelial larynx carcinoma cells and normal human MRC-5 lung fibroblasts by identifying proliferative and apoptotic pathways. The chemical characterization of the dry powder was assessed by high-performance liquid chromatography. Antiproliferative and proapoptotic effects induced by the extract were evaluated by assessing proliferative markers, cell sorting through flow cytometry, and expression levels of apoptotic proteins with Western blotting. The results suggest that inhibition of cell proliferation was more prominent in HEp-2 than in MRC-5 cells. Cell death analysis showed the appearance of cell populations in the sub-G1 phase, with late apoptotic signal increased in a dose-dependent manner. In addition, the aqueous extract induced depolarization of mitochondria, activating the generation of intracellular reactive oxygen species in HEp-2 cells. These observations suggest that L. edodes extract may exert a chemopreventive effect, regulating mitotic induction of apoptogenic signals. These findings highlight the mushroom's pharmacological potential in cancer treatment.

Design considerations for a computer controlled multileaf collimator for the Harper Hospital fast neutron therapy facility.

PubMed

Maughan, Richard L; Yudelev, Mark; Aref, Amr; Chuba, Paul J; Forman, Jeffrey; Blosser, Emanuel J; Horste, Timothy

2002-04-01

The d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron is collimated using a unique multirod collimator (MRC). A computer controlled multileaf collimator (MLC) is being designed to improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. For the current study the use of focused or unfocused collimator leaves has been studied. Since the engineering effort associated with the leaf design and materials choice impacts significantly on cost, it was desirable to determine the clinical impact of using unfocused leaves in the MLC design. The MRC is a useful tool for studying the effects of using focused versus unfocused beams on beam penumbra. The effects of the penumbra for the different leaf designs on tumor and normal tissue DVHs in two selected sites (prostate and head and neck) was investigated. The increase in the penumbra resulting from using unfocused beams was small (approximately 1.5 mm for a 5 x 5 cm2 field and approximately 7.6 mm for a 25 x 25 cm2 field at 10 cm depth) compared to the contribution of phantom scatter to the penumbra width (5.4 and 20 mm for the small and large fields at 10 cm depth, respectively). Comparison of DVHs for tumor and critical normal tissue in a prostate and head and neck case showed that the dosimetric disadvantages of using an unfocused rather than focused beam were minimal and only significant at shallow depths. For the rare cases, where optimum penumbra conditions are required, a MLC incorporating tapered leaves and, thus, providing focused collimation in one plane is necessary.

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study.

PubMed

Prabhu, Sandeep; Taylor, Andrew J; Costello, Ben T; Kaye, David M; McLellan, Alex J A; Voskoboinik, Aleksandr; Sugumar, Hariharan; Lockwood, Siobhan M; Stokes, Michael B; Pathik, Bhupesh; Nalliah, Chrishan J; Wong, Geoff R; Azzopardi, Sonia M; Gutman, Sarah J; Lee, Geoffrey; Layland, Jamie; Mariani, Justin A; Ling, Liang-Han; Kalman, Jonathan M; Kistler, Peter M

2017-10-17

Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF. This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months. A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093). AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of

Coupling Poisson rectangular pulse and multiplicative microcanonical random cascade models to generate sub-daily precipitation timeseries

NASA Astrophysics Data System (ADS)

Pohle, Ina; Niebisch, Michael; Müller, Hannes; Schümberg, Sabine; Zha, Tingting; Maurer, Thomas; Hinz, Christoph

2018-07-01

To simulate the impacts of within-storm rainfall variabilities on fast hydrological processes, long precipitation time series with high temporal resolution are required. Due to limited availability of observed data such time series are typically obtained from stochastic models. However, most existing rainfall models are limited in their ability to conserve rainfall event statistics which are relevant for hydrological processes. Poisson rectangular pulse models are widely applied to generate long time series of alternating precipitation events durations and mean intensities as well as interstorm period durations. Multiplicative microcanonical random cascade (MRC) models are used to disaggregate precipitation time series from coarse to fine temporal resolution. To overcome the inconsistencies between the temporal structure of the Poisson rectangular pulse model and the MRC model, we developed a new coupling approach by introducing two modifications to the MRC model. These modifications comprise (a) a modified cascade model ("constrained cascade") which preserves the event durations generated by the Poisson rectangular model by constraining the first and last interval of a precipitation event to contain precipitation and (b) continuous sigmoid functions of the multiplicative weights to consider the scale-dependency in the disaggregation of precipitation events of different durations. The constrained cascade model was evaluated in its ability to disaggregate observed precipitation events in comparison to existing MRC models. For that, we used a 20-year record of hourly precipitation at six stations across Germany. The constrained cascade model showed a pronounced better agreement with the observed data in terms of both the temporal pattern of the precipitation time series (e.g. the dry and wet spell durations and autocorrelations) and event characteristics (e.g. intra-event intermittency and intensity fluctuation within events). The constrained cascade model also

Assessment of medical reserve corps volunteers' emergency response willingness using a threat- and efficacy-based model.

PubMed

Errett, Nicole A; Barnett, Daniel J; Thompson, Carol B; Tosatto, Rob; Austin, Brad; Schaffzin, Samuel; Ansari, Armin; Semon, Natalie L; Balicer, Ran D; Links, Jonathan M

2013-03-01

The goal of this study was to investigate the willingness of Medical Reserve Corps (MRC) volunteers to participate in public health emergency-related activities by assessing their attitudes and beliefs. MRC volunteers responded to an online survey organized around the Extended Parallel Process Model (EPPM). Respondents reported agreement with attitude/belief statements representing perceived threat, perceived efficacy, and personal/organizational preparedness in 4 scenarios: a weather-related disaster, a pandemic influenza emergency, a radiological ("dirty bomb") emergency, and an inhalational anthrax bioterrorism emergency. Logistic regression analyses were used to evaluate predictors of volunteer response willingness. In 2 response contexts (if asked and regardless of severity), self-reported willingness to respond was higher among those with a high perceived self-efficacy than among those with low perceived self-efficacy. Analyses of the association between attitude/belief statements and the EPPM profiles indicated that, under all 4 scenarios and with few exceptions, those with a perceived high threat/high efficacy EPPM profile had statistically higher odds of agreement with the attitude/belief statements than those with a perceived low threat/low efficacy EPPM profile. The radiological emergency consistently received the lowest agreement rates for the attitude/belief statements and response willingness across scenarios. The findings suggest that enrollment with an MRC unit is not automatically predictive of willingness to respond in these types of scenarios. While MRC volunteers' self-reported willingness to respond was found to differ across scenarios and among different attitude and belief statements, the identification of self-efficacy as the primary predictor of willingness to respond regardless of severity and if asked highlights the critical role of efficacy in an organized volunteer response context.

Assessment of Medical Reserve Corps Volunteers' Emergency Response Willingness Using a Threat- and Efficacy-Based Model

PubMed Central

Barnett, Daniel J.; Thompson, Carol B.; Tosatto, Rob; Austin, Brad; Schaffzin, Samuel; Ansari, Armin; Semon, Natalie L.; Balicer, Ran D.; Links, Jonathan M.

2013-01-01

The goal of this study was to investigate the willingness of Medical Reserve Corps (MRC) volunteers to participate in public health emergency–related activities by assessing their attitudes and beliefs. MRC volunteers responded to an online survey organized around the Extended Parallel Process Model (EPPM). Respondents reported agreement with attitude/belief statements representing perceived threat, perceived efficacy, and personal/organizational preparedness in 4 scenarios: a weather-related disaster, a pandemic influenza emergency, a radiological (“dirty bomb”) emergency, and an inhalational anthrax bioterrorism emergency. Logistic regression analyses were used to evaluate predictors of volunteer response willingness. In 2 response contexts (if asked and regardless of severity), self-reported willingness to respond was higher among those with a high perceived self-efficacy than among those with low perceived self-efficacy. Analyses of the association between attitude/belief statements and the EPPM profiles indicated that, under all 4 scenarios and with few exceptions, those with a perceived high threat/high efficacy EPPM profile had statistically higher odds of agreement with the attitude/belief statements than those with a perceived low threat/low efficacy EPPM profile. The radiological emergency consistently received the lowest agreement rates for the attitude/belief statements and response willingness across scenarios. The findings suggest that enrollment with an MRC unit is not automatically predictive of willingness to respond in these types of scenarios. While MRC volunteers' self-reported willingness to respond was found to differ across scenarios and among different attitude and belief statements, the identification of self-efficacy as the primary predictor of willingness to respond regardless of severity and if asked highlights the critical role of efficacy in an organized volunteer response context. PMID:23477632

Phylogeography and genetic structure of the oriental river prawn Macrobrachium nipponense (Crustacea: Decapoda: Palaemonidae) in East Asia

PubMed Central

Chu, Ta-Jen; Lee, Ying-Chou

2017-01-01

The oriental river prawn (Macrobrachium nipponense) is mainly distributed in East Asia. The phylogeography, population genetic structure and historical demography of this species in the East Asia were examined by using partial sequences of the cytochrome oxidase subunit I (COI) and 16S rRNA in mitochondrial DNA. Ten populations that included 239 individuals were collected from Taiwan (Shihmen Reservoir, SMR, Mingte Reservoir, MTR and Chengching Lake Reservoir, CLR), mainland China (Taihu Lake, TLC, Min River, MRC, Jiulong River, JRC and Shenzhen Reservoir, SRC), Japan (Biwa Lake, BLJ and Kasumigaura Lake, KLJ) and Korea (Han River, HRK). The nucleotide diversity (π) of all individuals was 0.01134, with values ranging from 0.0089 (BLJ, Japan) to 0.01425 (MTR, Taiwan). A total of 83 haplotypes were obtained, and the haplotypes were divided into 2 main lineages: lineage A included the specimens from BLJ, KLJ, CLR, MTR, TLC, MRC and JRC, and lineage B comprised the ones from HRK, SRC, SMR, MTR, TLC, MRC and JRC. Lineage A could be further divided two sub-lineages (A1 and A2). Individuals of lineage A2 were only from TLC. Demographic expansion was observed in each lineage, starting within the second-to-latest interglacial period for lineage A and within the last glacial period for lineage B. All FST values among the ten populations were significantly different, except for the values between MRC and JRC, and SMR and SRC. The phylogeography and genetic structure of M. nipponense in East Asia might be influenced by Pleistocene glacial cycles, lake isolation and human introduction. The possible dispersal routes of M. nipponense in the East Asia were also discussed. PMID:28267807

Relationship between lower limb muscle strength and 6-minute walk test performance in stroke patients.

PubMed

Pradon, Didier; Roche, Nicolas; Enette, Lievyn; Zory, Raphaël

2013-01-01

The aim of this study was to determine if lower limb muscle strength and/or spasticity are related to performance in the 6-min walk test (6MWT) in stroke patients. A total of 24 patients (12 males and 12 females) participated in the study. Muscle strength (Medical Research Council (MRC) scale) and spasticity (modified Ashworth scale) were assessed prior to the 6MWT. Heart rate was recorded at rest and during the 6MWT. Subjects were divided into two groups: (i) those with a high MRC sum score, and (ii) those with a low MRC sum score. The relationship between the 6MWT distance and the other parameters was analysed using a Spearman's rank correlation coefficient. There was a significant and positive relationship between 6MWT distance and lower limb muscle strength (p = 0.001), whereas no significant correlations were found between the 6MWT distance and spasticity, resting heart rate and heart rate during the 6MWT. The 6MWT distance may be a good indicator of lower limb muscle strength, and lower limb strengthening may improve gait capacity in stroke patients.

Eutectic Experiment Development for Space Processing

NASA Technical Reports Server (NTRS)

Hopkins, R. H.

1972-01-01

A ground base test plan and a specimen evaluation scheme have been developed for the aluminum-copper eutectic solidification experiment to be run in the M518 multipurpose electric furnace during the Skylab mission. Besides thermal and solidification studies a detailed description is given of the quantitative metallographic technique which is appropriate for characterizing eutectic structures. This method should prove a key tool for evaluating specimen microstructure which is the most sensitive indicator of changes produced during solidification. It has been recommended that single grain pre-frozen eutectic specimens be used to simplify microstructural evaluation and to eliminate any porosity in the as-cast eutectic specimens. High purity (99.999%) materials from one supplier should be employed for all experiments. Laboratory studies indicate that porosity occurs in the MRC as-cast eutectic ingots but that this porosity can be eliminated by directional freezing. Chemical analysis shows that the MRC ingots are slightly Al rich and contain about .03% impurity. Because of the impurity content the lower cooldown rate (1.2 C/min) should be used for eutectic freezing if MRC material is used in the M518 furnace.

Efficacy and safety of Iranian made Deferasirox (Osveral®) in Iranian major thalassemic patients with transfusional iron overload: A one year prospective multicentric open-label non-comparative study.

PubMed

Eshghi, P; Farahmandinia, Z; Molavi, M; Naderi, M; Jafroodi, M; Hoorfar, H; Davari, K; Azarkeivan, A; Keikhaie, B; Ansari, S; Arasteh, M

2011-01-01

to determine the efficacy, adverse effects and safety of a new Iranian generic product of deferasirox (Osveral®) in Iranian transfusion dependent major thalassemic (TD-MT) patients. In 9 main thalassemia treatment centers, all of TD-MT patients (aged ≥2 yrs) with serum ferritin (SF) levels≥1000 ng/ml, or >100 ml/kg of RBC transfusion,who could not tolerate parental iron chelating were recruited regardless of their previous iron chelation therapy. Periodical clinical and laboratory evaluations were conducted for adverse effects (AEs). Primary efficacy end point was Mean of Relative Change of Serum Ferritin (MRC-SF) from the baseline level during one year. Analysis of variance (ANOVA), t test, chi-square or Fisher exact test were used for statistic analysis appropriately (P values <0.05 were considered as statistical significant). In 407 cases the male/female ratio was 0.98. Mean age was 11.5±7.4 (2-58) years. The mean of initiating dose of Osveral® and mean usage dose during the study was 23.5±4.9 mg/kg and 24.9±4.9 mg/kg respectively. MRC-SF was -11.44% ±38.92 and it showed significant decline in SF (P value<0.001) one hundred and forty eight patients out of 407 patients experienced at least one. AE, the most common of them were transient increase in serum creatinin (97;24.1%) and>5 time increase in transaminases (24;5.89%).The causes of discontinuation of treatment were non-satisfactory treatment ( 24; 5.8%), poor or non-compliance of patients (21;5.1%), and adverse effects (13; 3.1%) A detailed comparison with similar studies on deferasirox (Exjade®) shows a promising efficacy and safety for its Iranian generic product (Osveral ®).

The phrenic nerve as a donor for brachial plexus injuries: is it safe and effective? Case series and literature analysis.

PubMed

Socolovsky, Mariano; di Masi, Gilda; Bonilla, Gonzalo; Domínguez Paez, Miguel; Robla, Javier; Calvache Cabrera, Camilo

2015-06-01

Controversy exists surrounding the use of the phrenic nerve for transfer in severe brachial plexus injuries. The objectives of this study are: (1) to present the experience of the authors using the phrenic nerve in a single institution; and (2) to thoroughly review the existing literature to date. Adult patients with C5-D1 and C5-C8 lesions and a phrenic nerve transfer were retrospectively included. Patients with follow-up shorter than 18 months were excluded. The MRC muscle strength grading system was used to rate the outcome. Clinical repercussions relating to sectioning of the phrenic nerve were studied. An intense rehabilitation program was started after surgery, and compliance to this program was monitored using a previously described scale. Statistical analysis was performed with the obtained data. Fifty-one patients were included. The mean time between trauma and surgery was 5.7 months. Three-quarters of the patients had C5-D1, with the remainder C5-C8. Mean post-operative follow-up was 32.5 months A MRC of M4 was achieved in 62.7% patients, M3 21.6%, M2 in 3.9%, and M1 in 11.8%. The only significant differences between the two groups were in graft length (9.8 vs. 15.1 cm, p = 0.01); and in the rehabilitation compliance score (2.86 vs. 2.00, p = 0.01). Results of phrenic nerve transfer are predictable and good, especially if the grafts are short and the rehabilitation is adequate. It may adversely affect respiratory function tests, but this rarely correlates clinically. Contraindications to the use of the phrenic nerve exist and should be respected.

In vitro antiplasmodial, antileishmanial and antitrypanosomal activities of selected medicinal plants used in the traditional Arabian Peninsular region

PubMed Central

2012-01-01

Background Worldwide particularly in developing countries, a large proportion of the population is at risk for tropical parasitic diseases. Several medicinal plants are still used traditionally against protozoal infections in Yemen and Saudi Arabia. Thus the present study investigated the in vitro antiprotozoal activity of twenty-five plants collected from the Arabian Peninsula. Methods Plant materials were extracted with methanol and screened in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. Cytotoxic activity was determined against MRC-5 cells to assess selectivity. The criterion for activity was an IC50 < 10 μg/ml (<5 μg/ml for T. brucei) and selectivity index of >4. Results Antiplasmodial activity was found in the extracts of Chrozophora oblongifolia, Ficus ingens, Lavandula dentata and Plectranthus barbatus. Amastigotes of T. cruzi were affected by Grewia erythraea, L. dentata, Tagetes minuta and Vernonia leopoldii. Activity against T. brucei was obtained in G. erythraea, L. dentata, P. barbatus and T. minuta. No relevant activity was found against L. infantum. High levels of cytotoxicity (MRC-5 IC50 < 10 μg/ml) and hence non-specific activities were noted in Cupressus sempervirens, Kanahia laniflora and Kniphofia sumarae. Conclusion The results endorse that medicinal plants can be promising sources of natural products with antiprotozoal activity potential. The results support to some extent the traditional uses of some plants for the treatment of parasitic protozoal diseases. PMID:22520595

Comparison of HELIX TWT Simulation Using 2-D PIC (Magic), 2-D Modal (Gator), and 1-D Modal (Christine) Methods

DTIC Science & Technology

1998-05-01

Mission Research Corporation MRC/WDC-R-424 COMPARISON OF HELIX TWT SIMULATION USING 2-D PIC ( MAGIC ), 2-D MODAL (GATOR), AND 1-D MODAL (CHRISTINE...BRILLOUIN RUN 9 3.4 OUTLIER ELECTRON EFFECT IN GATOR 12 3.5 EMISSION CONDITION AND NONLAMINAR FLOW IN MAGIC 12 3.6 RADIAL SHEAR 13 SECTION 4. PPM B...Simulation using 2-D PIC ( MAGIC ), 2-D Modal (GATOR) and 1-D Modal (CHRISTINE) methods * D.N. Smithe(a), H. Freund(b), T. M. Antonsen Jr.,(b)’(c), E

Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives.

PubMed

Djurendić, Evgenija A; Ajduković, Jovana J; Sakač, Marija N; Csanádi, János J; Kojić, Vesna V; Bogdanović, Gordana M; Penov Gaši, Katarina M

2012-08-01

New 17-picolyl and 17-picolinylidene androstane derivatives, 3-10, 15, 18, 19, 22 and 23, were synthesized starting from 17α-picolyl-androst-5-en-3β,17β-diol (1) and 17(Z)-picolinylidene-androst-5-en-3β-ol (2). Reaction of 1 with m-chloroperoxybenzoic acid gives 5α,6α-epoxy N-oxide derivative 3, or, with Jones reagent, 3,6-dione derivative 4; while 17α-picolyl-androst-5-en-3β,4α,17β-triol (5) or 3β,4β,17β-triol (6) derivatives are obtainable from 1 using SeO(2) in dioxane. Base-catalyzed tosyl group elimination from 7 or 9 affords AB conjugated derivatives 8 and 10. Oppenauer oxidation of 1 and 2 yields 4-en-3-one derivatives 11 and 12, which, with H(2)O(2) in 4 M NaOH, affords 4α,5α and 4β,5β-epoxides 13, 14, 16 and 17. New 4-methoxy-3-keto derivatives 15 and 18 were obtained from 13 and 14, or, with methanol in 4 M NaOH, from 16 and 17. Reduction of 11 with NaBH(4) gives 22, which was then acetylated to obtain 23. All new derivatives were screened for antitumor activity against human breast adenocarcinoma ER+, MCF-7; human breast adenocarcinoma ER-, MDA-MB-231; prostate cancer AR-, PC-3; human cervix carcinoma, HeLa; and colon cancer, HT-29 cells; as well as one human non-tumor cell line, MRC-5. Compounds 3, 5, 6, 8, 10, 18, 19 and 22 exhibited significant antitumor activity against MDA-MB-231 breast cancer cells; while 5, 6 and 10 also showed strong cytotoxicity against HT-29. Only compound 19 exhibited significant activity against MCF-7 breast cancer cells. No compounds displayed cytotoxicity against non-tumor MRC-5 cells. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

PubMed Central

Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J.; Schmidt, Kristina H.

2016-01-01

In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186–212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks. PMID:27923055

A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression.

PubMed

Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J; Schmidt, Kristina H

2016-12-01

In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks.

Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and Eastern Asian population.

PubMed

Wei, Hui; Wang, Ying; Zhou, Chunlin; Lin, Dong; Liu, Bingcheng; Liu, Kaiqi; Qiu, Shaowei; Gong, Benfa; Li, Yan; Zhang, Guangji; Wei, Shuning; Gong, Xiaoyuan; Liu, Yuntao; Zhao, Xingli; Gu, Runxia; Mi, Yingchang; Wang, Jianxiang

2018-02-10

Racial and ethnic disparities in malignancies attract extensive attention. To investigate whether there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population, data from several prospective AML trials were retrospectively analyzed in this study. We found that there were more patients with core binding factor (CBF) leukemia in Eastern Asian cohorts and there were different CBF leukemia constitutions between them. The ratios of CBF leukemia are 27.7, 22.1, 21.1, and 23.4%, respectively, in our (ChiCTR-TRC-10001202), another Chinese, Korean, and Japanese Eastern Asian cohorts, which are significantly higher than those in ECOG1900, MRC AML15, UK NCRI AML17, HOVON/SAKK AML-42, and German AML2003 (15.5, 12.5, 9.3, 10.2, and 12%, respectively). And CBFbeta-MYH11 occurred more prevalently in HOVON/SAKK AML- 42 and ECOG1900 trials (50.0 and 54.3% of CBF leukemia, respectively) than in Chinese and Japanese trials (20.1 and 20.8%, respectively). The proportion of FLT3-ITD mutation is 11.2% in our cohort, which is lower than that in MRC AML15 and UK NCRI AML17 (24.6 and 17.9%, respectively). Even after excluding the age bias, there are still different incidence rates of mutation between Caucasian and Eastern Asian population. These data suggest that there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population.

Altered protein expression profile associated with phenotypic changes in lung fibroblasts co-cultured with gold nanoparticle-treated small airway epithelial cells.

PubMed

Ng, Cheng-Teng; Yung, Lin-Yue Lanry; Swa, Hannah Lee-Foon; Poh, Rebecca Wan-Yan; Gunaratne, Jayantha; Bay, Boon-Huat

2015-01-01

Despite the availability of toxicity studies on cellular exposure to gold nanoparticles (AuNPs), there is scarcity of information with regard to the bystander effects induced by AuNPs on neighboring cells not exposed to the NPs. In this study, we showed that exposure of small airway epithelial cells (SAECs) to AuNPs induced changes in protein expression associated with functional effects in neighboring MRC5 lung fibroblasts in a co-culture system. Uptake of 20 nm size AuNPs by SAECs was first verified by focused ion beam scanning electron microscopy. Subsequently, pretreated SAECs were co-cultured with unexposed MRC5 lung fibroblasts, which then underwent proteome profiling using a quantitative proteomic approach. Stable-isotope labeling by amino acids in cell culture (SILAC)-based mass spectrometry identified 109 proteins (which included 47 up-regulated and 62 down-regulated proteins) that were differentially expressed in the lung fibroblasts co-cultured with AuNP pretreated SAECs. There was altered expression of proteins such as Paxillin, breast cancer anti-estrogen resistance 1 and Caveolin-1, which are known to be involved in the cell adhesion process. Morphological studies revealed that there was a concomitant increase in cell adhesion and altered F-actin stress fiber arrangement involving vinculin in the lung fibroblasts. It is likely that phenotypic changes observed in the underlying lung fibroblasts were mediated by AuNP-induced downstream signals in the pretreated SAECs and cell-cell cross talk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis

PubMed Central

YANG, ZHIZHOU; SUN, ZHAORUI; LIU, HONGMEI; REN, YI; SHAO, DANBING; ZHANG, WEI; LIN, JINFENG; WOLFRAM, JOY; WANG, FENG; NIE, SHINAN

2015-01-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson’s trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury. PMID:25815693

Azilsartan and its Zn(II) complex. Synthesis, anticancer mechanisms of action and binding to bovine serum albumin.

PubMed

Martínez, Valeria R; Aguirre, María V; Todaro, Juan S; Piro, Oscar E; Echeverría, Gustavo A; Ferrer, Evelina G; Williams, Patricia A M

2018-04-01

Azilsartan is the eighth approved member of angiotensin II receptor blockers for hypertension treatment. Considering that some drugs have additional effects when administered, we studied its effects and mechanisms of action on a human lung cancer cell line A549. We have also modified the structure of the drug by complexation with Zn(II) cation and assayed the anticancer effect. The crystal structure of the new binuclear Zn(II) complex, for short [Zn 2 (azil) 2 (H 2 O) 4 ]·2H 2 O (ZnAzil), was determined by X-ray diffraction methods. The zinc ions are bridged by azilsartan ligands through their carboxylate oxygen and oxadiazol nitrogen atoms. The compounds were examined for their cytotoxic effects against human lung fibroblast (MRC5) and human lung cancer (A549) cell lines. Azilsartan displayed low cytotoxic effects at 150 μM concentrations in A549 human lung cancer cells but the higher effect measured for the Zn complex suggested that this compound may act as an anticancer agent. An apoptotic oxidative stress mechanism of action via the mitochondrial-dependent intrinsic pathway has been determined. Besides, the compounds exerted weak cytotoxic effects in the normal lung related cell line MRC5. Binding constants of the complex formed between each compound and bovine serum albumin (BSA) are in the intermediate range, hence suggesting that azilsartan and ZnAzil could be bonded and transported by BSA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

PubMed

Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

2015-07-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

Validation of Rules to Predict Emergent Surgical Intervention in Pediatric Trauma Patients

PubMed Central

Boatright, Dowin H; Byyny, Richard L; Hopkins, Emily; Bakes, Katherine; Hissett, Jennifer; Tunson, Java; Easter, Joshua S; Vogel, Jody A; Bensard, Denis; Haukoos, Jason S

2014-01-01

Background Trauma centers use guidelines to determine when a trauma surgeon is needed in the emergency department (ED) on patient arrival. A decision rule from Loma Linda University identified patients with penetrating injury and tachycardia as requiring emergent surgical intervention. Our goal was to validate this rule and to compare it to the American College of Surgeons’ Major Resuscitation Criteria (MRC). Study Design We used data from 1993 through 2010 from two Level 1 trauma centers in Denver, Colorado. Patient demographics, injury severity, times of ED arrival and surgical intervention, and all variables of the Loma Linda Rule and the MRC were obtained. The outcome, emergent intervention (defined as requiring operative intervention by a trauma surgeon within one hour of arrival to the ED or performance of cricothyroidotomy or thoracotomy in the ED) was confirmed using standardized abstraction. Sensitivities, specificities, and 95% confidence intervals (CIs) were calculated. Results 8,078 patients were included and 47 (0.6%) required emergent intervention. Of the 47 patients, the median age was 11 years (IQR: 7–14), 70% were male, 30% had penetrating mechanisms, and the median ISS was 25 (IQR: 9–41). At the two institutions, the Loma Linda Rule had a sensitivity and specificity of 69% (95% CI: 45%–94%) and 76% (95% CI: 69%–83%), respectively, and the MRC had a sensitivity and specificity of 80% (95% CI: 70%–92%) and 81% (95% CI: 77%–85%), respectively. Conclusions Emergent surgical intervention is rare in the pediatric trauma population. Although precision of predictive accuracies of the Loma Linda Rule and MRC were limited by small numbers of outcomes, neither set of criteria appears to be sufficiently accurate to recommend their routine use. PMID:23623222

Long-term effects of oxygen-enriched high-flow nasal cannula treatment in COPD patients with chronic hypoxemic respiratory failure.

PubMed

Storgaard, Line Hust; Hockey, Hans-Ulrich; Laursen, Birgitte Schantz; Weinreich, Ulla Møller

This study investigated the long-term effects of humidified high-flow nasal cannula (HFNC) in COPD patients with chronic hypoxemic respiratory failure treated with long-term oxygen therapy (LTOT). A total of 200 patients were randomized into usual care ± HFNC. At inclusion, acute exacerbation of COPD (AECOPD) and hospital admissions 1 year before inclusion, modified Medical Research Council (mMRC) score, St George's Respiratory Questionnaire (SGRQ), forced expiratory volume in 1 second (FEV 1 ), 6-minute walk test (6MWT) and arterial carbon dioxide (PaCO 2 ) were recorded. Patients completed phone interviews at 1, 3 and 9 months assessing mMRC score and AECOPD since the last contact. At on-site visits (6 and 12 months), mMRC, number of AECOPD since last contact and SGRQ were registered and FEV 1 , FEV 1 %, PaCO 2 and, at 12 months, 6MWT were reassessed. Hospital admissions during the study period were obtained from hospital records. Hours of the use of HFNC were retrieved from the high-flow device. The average daily use of HFNC was 6 hours/day. The HFNC group had a lower AECOPD rate (3.12 versus 4.95/patient/year, p <0.001). Modeled hospital admission rates were 0.79 versus 1.39/patient/year for 12- versus 1-month use of HFNC, respectively ( p <0.001). The HFNC group had improved mMRC scores from 3 months onward ( p <0.001) and improved SGRQ at 6 and 12 months ( p =0.002, p =0.033) and PaCO 2 ( p =0.005) and 6MWT ( p =0.005) at 12 months. There was no difference in all-cause mortality. HFNC treatment reduced AECOPD, hospital admissions and symptoms in COPD patients with hypoxic failure.

Comparison of intermittent positive pressure breathing and temporary positive expiratory pressure in patients with severe chronic obstructive pulmonary disease.

PubMed

Nicolini, Antonello; Mollar, Elena; Grecchi, Bruna; Landucci, Norma

2014-01-01

Results supporting the use and the effectiveness of positive expiratory, pressure devices in chronic obstructive pulmonary disease (COPD) patients are still controversial, We have tested the hypothesis that adding TPEP or IPPB to standard pharmacological therapy may provide additional clinical benefit over, pharmacological therapy only in patients with severe COPD. Fourty-five patients were randomized in three groups: a group was treated; with IPPB,a group was treated with TPEP and a group with pharmacological; therapy alone (control group). Primary outcome measures included the measurement of scale or, questionnaire concerning dyspnea (MRC scale),dyspnea,cough, and, sputum (BCSS) and quality of life (COPD assessment test) (CAT). Secondary, outcome measures were respiratory function testing,arterial blood gas,analysis,and hematological examinations. Both patients in the IPPB group and in the TPEP group showed a significant, improvement in two of three tests (MRC,CAT) compared to the control, group.However,in the group comparison analysis for, the same variables between IPPB group and TPEP group we observed a, significant improvement in the IPPB group (P≤.05 for MRC and P≤.01 for, CAT). The difference of action of the two techniques are evident in the results of, pulmonary function testing: IPPB increases FVC, FEV1, and MIP; this reflects, its capacity to increase lung volume. Also TPEP increases FVC and FEV1 (less, than IPPB), but increases MEP, while decreasing total lung capacity and, residual volume. The two techniques (IPPB and TPEP) improves significantly dyspnea; quality of; life tools and lung function in patients with severe COPD. IPPB demonstrated a greater effectiveness to improve dyspnea and quality of life tools (MRC, CAT) than TPEP. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Quality of life in smokers: focus on functional limitations rather than on lung function?

PubMed Central

Geijer, Roeland MM; Sachs, Alfred PE; Verheij, Theo JM; Kerstjens, Huib AM; Kuyvenhoven, Marijke M; Hoes, Arno W

2007-01-01

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of severity of chronic obstructive pulmonary disease (COPD) is based solely on obstruction and does not capture physical functioning. The hypothesis that the Medical Research Council (MRC) dyspnoea scale would correlate better with quality of life than the level of airflow limitation was examined. Aim To study the associations between quality of life in smokers and limitations in physical functioning (MRC dyspnoea scale) and, quality of life and airflow limitation (GOLD COPD stages). Design Cross-sectional study. Setting The city of IJsselstein, a small town in the centre of The Netherlands. Method Male smokers aged 40–65 years without a prior diagnosis of COPD and enlisted with a general practice, participated in this study. Quality of life was assessed by means of a generic (SF–36) and a disease-specific, questionnaire (QOLRIQ). Results A total of 395 subjects (mean age 55.4 years, pack years 27.1) performed adequate spirometry and completed the questionnaires. Limitations of physical functioning according to the MRC dyspnoea scale were found in 25.1 % (99/395) of the participants and airflow limitation in 40.2% (159/395). The correlations of limitations of physical functioning with all quality-of-life components were stronger than the correlations of all quality-of-life subscales with the severity of airflow limitation. Conclusion In middle-aged smokers the correlation of limitations of physical functioning (MRC dyspnoea scale) with quality of life was stronger than the correlation of the severity of airflow limitation with quality of life. Future staging systems of severity of COPD should capture this and not rely on forced expiratory volume in one second (FEV1) alone. PMID:17550673

Magic User’s Manual 2006

DTIC Science & Technology

2006-12-01

K (M) M issioin Research MRC/WDC-R-556 MAGIC USER’S MANUAL 2006 Author(s): Larry Ludeking ATK Mission Research Contract No.: F49620-03-C-0030 L¾[iJiD... Magic Tool Suite for Windows. It uses the standard Windows Help so it is pretty self-explanatory. You can use the panel to the left to scan through... MAGIC Go to Part 2. MCL Commands Go to Part 3. Tirnc and Space Go to Part 4. Spatial Extensions Go to Part 5. Properties Go to Part 6. Algorithms Go

Microsurgical reconstruction of large nerve defects using autologous nerve grafts.

PubMed

Daoutis, N K; Gerostathopoulos, N E; Efstathopoulos, D G; Misitizis, D P; Bouchlis, G N; Anagnostou, S K

1994-01-01

Between 1986 and 1993, 643 patients with peripheral nerve trauma were treated in our clinic. Primary neurorraphy was performed in 431 of these patients and nerve grafting in 212 patients. We present the functional results after nerve grafting in 93 patients with large nerve defects who were followed for more than 2 years. Evaluation of function was based on the Medical Research Council (MRC) classification for motor and sensory recovery. Factors affecting functional outcome, such as age of the patient, denervation time, length of the defect, and level of the injury were noted. Good results according to the MRC classification were obtained in the majority of cases, although function remained less than that of the uninjured side.

Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study.

PubMed

Kitchener, H; Swart, A M C; Qian, Q; Amos, C; Parmar, M K B

2009-01-10

Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14). Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early

Heteropentanuclear Oxalato-Bridged nd–4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity

PubMed Central

Kuhn, Paul-Steffen; Cremer, Laura; Gavriluta, Anatolie; Jovanović, Katarina K; Filipović, Lana; Hummer, Alfred A; Büchel, Gabriel E; Dojčinović, Biljana P; Meier, Samuel M; Rompel, Annette; Radulović, Siniša; Tommasino, Jean Bernard; Luneau, Dominique; Arion, Vladimir B

2015-01-01

A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d–4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(μ-ox)(NO)}4], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by 13C NMR spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)]2− are coordinated to YIII and DyIII, respectively, with formation of [Ln{RuCl3(μ-ox)(NO)}4]5− (Ln=Y, Dy). While YIII is eight-coordinate in 2, DyIII is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu4N+ ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2–5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d–4f) analogues (nBu4N)5[Ln{OsCl3(ox)(NO)}4] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2–5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d–4f metal complexes 6–9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4 μM was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells. PMID:26260662

Design and development of a film-based intervention about teenage men and unintended pregnancy: applying the Medical Research Council framework in practice.

PubMed

Aventin, Áine; Lohan, Maria; O'Halloran, Peter; Henderson, Marion

2015-04-01

Following the UK Medical Research Council's (MRC) guidelines for the development and evaluation of complex interventions, this study aimed to design, develop and optimise an educational intervention about young men and unintended teenage pregnancy based around an interactive film. The process involved identification of the relevant evidence base, development of a theoretical understanding of the phenomenon of unintended teenage pregnancy in relation to young men, and exploratory mixed methods research. The result was an evidence-based, theory-informed, user-endorsed intervention designed to meet the much neglected pregnancy education needs of teenage men and intended to increase both boys' and girls' intentions to avoid an unplanned pregnancy during adolescence. In prioritising the development phase, this paper addresses a gap in the literature on the processes of research-informed intervention design. It illustrates the application of the MRC guidelines in practice while offering a critique and additional guidance to programme developers on the MRC prescribed processes of developing interventions. Key lessons learned were: (1) know and engage the target population and engage gatekeepers in addressing contextual complexities; (2) know the targeted behaviours and model a process of change; and (3) look beyond development to evaluation and implementation. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Activity matters: a web-based resource to enable people with multiple sclerosis to become more active.

PubMed

Casey, Blathin; Coote, Susan; Byrne, Molly

2018-03-27

Increasing physical activity (PA) through exercise is associated with improvements in many of the symptoms associated with multiple sclerosis (MS) such as fatigue, strength, balance, and mobility. Despite this, people with MS remain largely inactive. Interventions that are grounded in theory and that aim to change PA behavior need to be developed. The purpose of this study was to describe the development process of a web-based resource, namely, "Activity Matters," to enable people with MS to become more active. Development of the "Activity Matters" online intervention was guided by the UK's Medical Research Council (MRC) framework for the development and evaluation of complex interventions and the behavior change wheel (BCW). Seven sources of data were used to inform the process and were mapped on to both the MRC and BCW frameworks. The intervention is theoretically based, and constructs including knowledge, memory, attention and decision processes, skills, social influences, environmental context and resources, beliefs about capabilities, beliefs about consequences, goals, and emotions were recognized as important. "Activity Matters" is the first MS PA intervention to be developed using the theoretical approach outlined by the BCW and MRC complex interventions frameworks. The next phase of this work is to test the usability, acceptability, and preliminary effectiveness of "Activity Matters" among people with MS.

Implementing psychological first-aid training for medical reserve corps volunteers.

PubMed

Chandra, Anita; Kim, Jee; Pieters, Huibrie C; Tang, Jennifer; McCreary, Michael; Schreiber, Merritt; Wells, Kenneth

2014-02-01

We assessed the feasibility and impact on knowledge, attitudes, and reported practices of psychological first-aid (PFA) training in a sample of Medical Reserve Corps (MRC) members. Data have been limited on the uptake of PFA training in surge responders (eg, MRC) who are critical to community response. Our mixed-methods approach involved self-administered pre- and post-training surveys and within-training focus group discussions of 76 MRC members attending a PFA training and train-the-trainer workshop. Listen, protect, connect (a PFA model for lay persons) focuses on listening and understanding both verbal and nonverbal cues; protecting the individual by determining realistic ways to help while providing reassurance; and connecting the individual with resources in the community. From pre- to post-training, perceived confidence and capability in using PFA after an emergency or disaster increased from 71% to 90% (P < .01), but no significant increase was found in PFA-related knowledge. Qualitative analyses suggest that knowledge and intentions to use PFA increased with training. Brief training was feasible, and while results were modest, the PFA training resulted in greater reported confidence and perceived capability in addressing psychological distress of persons affected by public health threats. PFA training is a promising approach to improve surge responder confidence and competency in addressing postdisaster needs.

Muscle MRI STIR signal intensity and atrophy are correlated to focal lower limb neuropathy severity.

PubMed

Deroide, N; Bousson, V; Mambre, L; Vicaut, E; Laredo, J D; Kubis, Nathalie

2015-03-01

The objective is to determine if muscle MRI is useful for assessing neuropathy severity. Clinical, MRI and electromyography (EMG) examinations were performed in 17 patients with focal lower limb neuropathies. MRI Short Tau Inversion Recovery (STIR) signal intensity, amyotrophy, and muscle fatty infiltration measured after T1-weighted image acquisition, EMG spontaneous activity (SA), and maximal voluntary contraction (MVC) were graded using semiquantitative scores and quantitative scores for STIR signal intensity and were correlated to the Medical Research Council (MRC) score for testing muscle strength. Within this population, subgroups were selected according to severity (mild versus severe), duration (subacute versus chronic), and topography (distal versus proximal) of the neuropathy. EMG SA and MVC MRI amyotrophy and quantitative scoring of muscle STIR intensity were correlated with the MRC score. Moreover, MRI amyotrophy was significantly increased in severe, chronic, and proximal neuropathies along with fatty infiltration in chronic lesions. Muscle MRI atrophy and quantitative evaluation of signal intensity were correlated to MRC score in our study. Semiquantitative evaluation of muscle STIR signal was sensitive enough for detection of topography of the nerve lesion but was not suitable to assess severity. Muscle MRI could support EMG in chronic and proximal neuropathy, which showed poor sensitivity in these patients.

Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study

PubMed Central

2009-01-01

Summary Background Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. Methods From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. Findings After a median follow-up of 37 months (IQR 24–58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1·16 (95% CI 0·87–1·54; p=0·31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI −4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1·35 (1·06–1·73; p=0·017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1–12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1·04 (0·74–1·45; p=0·83) and for recurrence-free survival was 1·25 (0·93–1·66; p=0·14). Interpretation Our results show no evidence of benefit in terms of overall

Time course for measuring endolymphatic size in healthy volunteers following intravenous administration of gadoteridol.

PubMed

Naganawa, Shinji; Suzuki, Kojiro; Yamazaki, Masahiro; Sakurai, Yasuo; Ikeda, Mitsuru

2014-01-01

We developed semi-quantitative methods to measure endolymphatic size on images obtained 4 hours after intravenous administration of single-dose gadolinium-based contrast medium (IV-SD-GBCM) and found little variation in results between observers. We used the methods to measure the size of the endolymph in healthy volunteers at various times after IV-SD-GBCM and attempted to determine the optimal timing for the evaluation. In 8 healthy male volunteers, we obtained heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery (hT2W-3D-FLAIR) images 1.5, 3, 4.5, and 6 hours after IV-SD-GBCM as positive perilymph images (PPI) as well as acquiring positive endolymph images (PEI) and magnetic resonance cisternography (MRC). To evaluate the endolymph, we generated 2 kinds of processed images (HYDROPS-Mi2 and HYDROPS2-Mi2) by subtracting PEI or MRC from PPI as previously proposed. We semi-quantitatively measured the ratio of the area of the endolymph (%EL) to that of total lymph on the 2 kinds of generated images for the cochlea and vestibule according to the previously proposed method. We analyzed statistics to evaluate the change in %EL over time and used analysis of variance (ANOVA) for a 2 × 4 repeated-measures design to assess difference in image type. We adopted 5% as a significance level. The %EL was significantly larger at 1.5 hours after IV-SD-GBCM than at 3, 4.5, and 6 hours in both the cochlea and vestibule for both kinds of generated images. Between 4.5 and 6 hours, the %EL plateaued for both the cochlea and vestibule, and the 2 kinds of generated images did not differ significantly. A delay of 1.5 hours after IV-SD-GBCM is not sufficient to evaluate endolymphatic size. The %EL plateaus between 4.5 and 6 hours. These data might be valuable for further clinical studies.

Interleukin-1 or tumor necrosis factor-alpha augmented the cytotoxic effect of mycobacteria on human fibroblasts: application to evaluation of pathogenesis of clinical isolates of Mycobacterium tuberculosis and M. avium complex.

PubMed

Takii, T; Abe, C; Tamura, A; Ramayah, S; Belisle, J T; Brennan, P J; Onozaki, K

2001-03-01

Mycobacteria-induced in vitro events reflecting human tuberculosis can contribute to the evaluation of the pathogenesis of Mycobacterium tuberculosis (MTB). In this study, we propose such an in vitro method based on live mycobacteria-induced cytotoxicity to human cell lines. When human lung-derived normal fibroblast cell line MRC-5 was infected with various strains of mycobacteria (M. tuberculosis H(37)Rv and H(37) Ra, Mycobacterium avium 427S and 2151SmO, and Mycobacterium bovis BCG Pasteur and Tokyo), the fibroblasts were killed by mycobacteria according to the degree of virulence. Other human originated macrophage (U-937, THP-1), myeloid (HL-60), and epithelial carcinoma (A549) cell lines exhibited a similar cytotoxic response to virulent mycobacteria. MRC-5 was most susceptible to virulent mycobacteria among various human cell lines examined. The cytotoxicity was enhanced by the proinflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-alpha), which in the absence of mycobacteria stimulate the growth of normal human fibroblasts. This in vitro evaluation system was applied to clinical isolates of drug-sensitive MTB (DS-MTB), drug-resistant MTB (DR-MTB) including multidrug-resistant (MDR-MTB), and M. avium complex (MAC). MTB strains (n = 24) exhibited strong cytotoxic activity, but MAC strains (n = 5) had only weak activity. Furthermore, there was no significant difference in cytotoxicity between DS-MTB (n = 11) and DR-MTB (n = 13). Collectively, these results suggest that this new in vitro system is useful for evaluating the pathogenesis of mycobacteria and that there was no difference in the pathogenesis between drug-susceptible and drug-resistant clinical isolates.

Electrical characterization of single cells using polysilicon wire ion sensor in an isolation window.

PubMed

Wu, You-Lin; Hsu, Po-Yen; Hsu, Chung-Ping; Wang, Chih-Cheng; Lee, Li-Wen; Lin, Jing-Jenn

2011-10-01

A polysilicon wire (PSW) sensor can detect the H(+) ion density (pH value) of the medium coated on its surface, and different cells produce different extracellular acidification and hence different H(+) ion densities. Based on this, we used a PSW sensor in combination with a mold-cast polydimethylsiloxane (PDMS) isolation window to detect the adhesion, apoptosis and extracellular acidification of single normal cells and single cancer cells. Single living human normal cells WI38, MRC5, and BEAS-2B as well as non-small-cell lung cancer (NSCLC) cells A549, H1299, and CH27 were cultivated separately inside the isolation window. The current flowing through the PSW channel was measured. From the PSW channel current change as a function of time, we determined the cell adhesion time by observing the time required for the current change to saturate, since a stable extracellular ion density was established after the cells were completely adhered to the PSW surface. The apoptosis of cells can also be determined when the channel current change drops to zero. We found that all the NSCLC cells had a higher channel current change and hence a lower pH value than the normal cells anytime after they were seeded. The corresponding average pH values were 5.86 for A549, 6.00 for H1299, 6.20 for CH27, 6.90 for BEAS-2B, 6.96for MRC5, and 7.02 for WI38, respectively, after the cells were completely adhered to the PSW surface. Our results show that NSCLC cells have a stronger cell-substrate adhesion and a higher extracellular acidification rate than normal cells.

Up-regulation of Survivin during Immortalization of Human Myofibroblasts Is Linked to Repression of Tumor Suppressor p16INK4a Protein and Confers Resistance to Oxidative Stress*

PubMed Central

Kan, Chin-Yi; Petti, Carlotta; Bracken, Lauryn; Maritz, Michelle; Xu, Ning; O'Brien, Rosemary; Yang, Chen; Liu, Tao; Yuan, Jun; Lock, Richard B.; MacKenzie, Karen L.

2013-01-01

Survivin is an essential component of the chromosomal passenger complex and a member of the inhibitor of apoptosis family. It is expressed at high levels in a large variety of malignancies, where it has been implicated in drug resistance. It was also shown previously that survivin is up-regulated during telomerase-mediated immortalization, which occurs at a relatively early stage during carcinogenesis. This study shows that up-regulation of survivin during immortalization of human myofibroblasts is an indirect consequence of the repression of p16INK4a. Survivin and p16INK4a were functionally linked by assays that showed that either the up-regulation of survivin or repression of p16INK4a rendered telomerase-transduced MRC-5 myofibroblasts resistant to oxidative stress. Conversely, siRNA-mediated down-regulation of survivin activated caspases and enhanced the sensitivity of immortal MRC-5 cells to oxidative stress. The E2F1 transcription factor, which is negatively regulated by the pRB/p16INK4a tumor suppressor pathway, was implicated in the up-regulation of survivin. Using the ChIP assay, it was shown that E2F1 directly interacted with the survivin gene (BIRC5) promoter in cells that spontaneously silenced p16INK4a during telomerase-mediated immortalization. E2F1 binding to the BIRC5 was also enhanced in telomerase-transduced cells subjected to shRNA-mediated repression of p16INK4a. Together, these data show that repression of p16INK4a contributes to the up-regulation of survivin and thereby provides a survival advantage to cells exposed to oxidative stress during immortalization. The up-regulation of survivin during immortalization likely contributes to the vulnerability of immortal cells to transformation by oncogenes that alter intracellular redox state. PMID:23449974

PubMed

Scotta, Ana Verónica; Bongiovanni, Guillermina Azucena; Soria, Elio Andrés

2018-03-21

Antecedentes: Clorpirifos es un pesticida altamente tóxico, que puede producir inmunotoxicidad con efectos deletéreos sobre la salud a nivel mundial. Por otro lado, las plantas americanas pueden tener derivados con actividad protectora e inmunoestimulante. Por lo tanto, debe evaluarse el potencial de estas plantas frente a clorpirifos. Objetivo: Identificar extractos acuosos bioactivos de Lantana grisebachii (LG), Aspidosperma quebracho-blanco (AQ), Peumus boldus (PB), e Ilex paraguariensis (IP), contra la toxicidad de clorpirifos sobre esplenocitos de hembras Balb/c. Materiales y Métodos: Esplenocitos fueron tratados in vitro por 72 horas con 0-35 µg/mL de clorpirifos, 0-100 µg/mL de cada extracto (LG, AQ, PB, IP) y 0-5 µg/mL de concanavalina A. Luego, se midió y analizó estadísticamente viabilidad y muerte celular (tinciones de resazurina y yoduro de propidio), hidroperóxidos, lipoperóxidos (ensayos basados en naranja de xilenol), actividad de la ?-glutamiltranspeptidasa (método de Szasz). Resultados: Clorpirifos redujo la viabilidad celular de forma dosis dependiente, lo que fue contrarrestado por AQ e IP, los que fueron menos activos en las células inducibles por concanavalina A (p<0,05). La toxicidad por clorpirifos implicó la inducción de la ?-glutamiltranspeptidasa con la consecuente reducción de los peróxidos, mientras que AQ y principalmente IP antagonizaron dichas respuestas (p<0,05). Conclusiones: Los extractos de Ilex paraguariensis y Aspidosperma quebracho-blanco protegieron in vitro a los esplenocitos frente a clorpirifos. Este efecto dependió del tipo celular, dado que las células inducibles por concanavalina A fueron más susceptibles a este tóxico.

Hydrograph monitoring and analysis for sustainable karst water management in Nyadeng Spring, East Borneo

NASA Astrophysics Data System (ADS)

Widyastuti, M.; Fatchurohman, H.; Fathoni, W. A.; Hakim, A. A.; Haryono, E.

2018-04-01

Karst aquifer stores abundant water resources within its matrix, conduits, and intergranular pores. Karst aquifer plays an important role in providing water supply, especially in the areas nearby that commonly dry and lack of surface water resources. Karst spring hydrograph analysis is very fundamental step to–assess and determines the condition of the catchment area in karst terrain. Recession curve is believed to be the most stable part in single flood hydrograph that represents the aquifer characteristics. Nyadeng is one of the most significant karst springs that located in Merabu Karst Area, East Borneo. Villagers in Merabu highly depend on Nyadeng Spring for fulfilled their freshwater need. Hydrograph monitoring has been initiated for one year in Nyadeng Spring as a preliminary action for karst water management in Merabu. Water level data series obtained using automatic water level data logger and then correlated with manual discharge measurement to generate stage-discharge rating curve. The stage-discharge rating curve formula for Nyadeng Spring calculated as y = 0,0102e5,8547x with r2 value = 0.8759. From the combination of several single flood events, Master Recession Curve (MRC) was generated to determine flow regime as the main consideration for karstification degree calculation. From the MRC result, flow regimes formula determined as Qt = 3.2-0.001t + 1.2(1-0.012t)+1.6(1-0.035t) indicated that one sub-regime with laminar flow and two sub-regimes with turbulent flow existed. From the MRC formula, the degree of karstification in Nyadeng Spring classified at seventh scale (developed karstification of the aquifer) based on Malik’s karstification degree (2012). The degree of karstification in Nyadeng Spring indicates that the aquifer formed by large conduit channels, fissures, and macro fissures which are able to provide significant water sources that can be utilized for multi purposes. Therefore, it is concluded that spring hydrograph monitoring provide

Mars Rover Curriculum: Teacher Self Reporting of Increased Frequency and Confidence in their Science and Language Arts Instruction

NASA Astrophysics Data System (ADS)

Bering, E. A.; Carlson, C.; Nieser, K.; Slagle, E.

2013-12-01

The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 65 Mars Rover teachers from the 2012-2013 cohort were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. In total, 29 teachers participated in the survey. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. In addition, they were asked to rate the degree to which they felt their confidence increased in the past year as a result of their participation in the MRC program. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching 'Earth and the solar system and universe' increased 'Quite a bit' as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. In addition, the vast majority reported believing that their confidence increased somewhat to quite a bit as a result of their

Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells

PubMed Central

Invernizzi, F.; D'Amato, I.; Jensen, P.B.; Ravaglia, S.; Zeviani, M.; Tiranti, V.

2012-01-01

Given the complexity of the respiratory chain structure, assembly and regulation, the diagnostic workout for the identification of defects of oxidative phosphorylation (OXPHOS) is a major challenge. Spectrophotometric assays, that measure the activity of individual respiratory complexes in tissue and cell homogenates or isolated mitochondria, are highly specific, but their utilization is limited by the availability of sufficient biological material and intrinsic sensitivity. A further limitation is tissue specificity, which usually determines attenuation, or disappearance, in cultured fibroblasts, of defects detected in muscle or liver. We used numerous fibroblast cell lines derived from patients with OXPHOS deficiencies to set up experimental protocols required for the direct readout of cellular respiration using the Seahorse XF96 apparatus, which measures oxygen consumption rate (OCR) and extra-cellular acidification rate (ECAR) in 96 well plates. Results demonstrate that first level screening based on microscale oxygraphy is more sensitive, cheaper and rapid than spectrophotometry for the biochemical evaluation of cells from patients with suspected mitochondrial disorders. PMID:22310368

The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.

PubMed

Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony

2012-01-05

Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Miyoung; Jeong, Sang Young; Ha, Jueun

2014-04-18

Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challengemore » in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.« less

Potential gastroprotective effect of novel cyperenoic acid/quinone derivatives in human cell cultures.

PubMed

Theoduloz, Cristina; Carrión, Ivanna Bravo; Pertino, Mariano Walter; Valenzuela, Daniela; Schmeda-Hirschmann, Guillermo

2012-11-01

The stem bark of Tabebuia species and the rhizomes of Jatropha isabelii are used in Paraguayan traditional medicine to treat gastric lesions and as anti-inflammatory agents. The sesquiterpene cyperenoic acid obtained from J. isabelii has been shown to display a gastroprotective effect in animal models of induced gastric ulcers while the quinone lapachol shows several biological effects associated with the use of the crude drug. The aim of this work was to prepare hybrid molecules presenting a terpene and a quinone moiety and to obtain an assessment of the gastroprotective activity of the new compounds using human cell cultures (MRC-5 fibroblasts and AGS epithelial gastric cells). Eight compounds, including the natural products and semisynthetic derivatives were assessed for proliferation of MRC-5 fibroblasts, protection against sodium taurocholate-induced damage, prostaglandin E2 content, and stimulation of cellular-reduced glutathione synthesis in AGS cells. The following antioxidant assays were performed: DPPH discoloration, scavenging of the superoxide anion, and inhibition of induced lipoperoxidation in erythrocyte membranes. 3-Hydroxy-β-lapachone (3) and cyperenoic acid (4) stimulated fibroblast proliferation. Lapachol (1), dihydroprenyl lapachol (2), 3-hydroxy-β-lapachone (3), and lapachoyl cyperenate (6) protected against sodium taurocholate-induced damage in AGS cells. Lapachol (1) and dihydroprenyl lapachoyl cyperenate (7) significantly stimulated prostaglandin E2 synthesis in AGS cells. Compounds 3, 4, and 7 raised reduced glutathione levels in AGS cells. The hybrid compounds presented activities different than those of the starting sesquiterpene or quinones. Georg Thieme Verlag KG Stuttgart · New York.

[Development of an activity of daily living scale for patients with COPD: the Activity of Daily Living Dyspnea scale].

PubMed

Yoza, Yoshiyasu; Ariyoshi, Koya; Honda, Sumihisa; Taniguchi, Hiroyuki; Senjyu, Hideaki

2009-10-01

Patients with COPD often experience restriction in their activities of daily living (ADL) due to dyspnea. This type of restriction is unique to patients with COPD and cannot be adequately evaluated by the generic ADL scales. This study developed an ADL scale (the Activity of Daily Living Dyspnea scale [ADL-D scale]) for patients with COPD and investigated its validity and internal consistency. Patients with stable COPD were recruited and completed a pilot 26-item questionnaire. Patients also performed the Incremental Shuttle Walk Test (ISWT), and completed the St George's Respiratory Questionnaire (SGRQ), and Medical Research Council (MRC) dyspnea grade. There were 83 male participants who completed the pilot questionnaire. Following the pilot, 8 items that were not undertaken by the majority of subjects, and 3 items judged to be of low clinical importance by physical therapists were removed from the pilot questionnaire. The final ADL-D scale contained 15 items. Scores obtained with the ADL-D scale were significantly correlated with the MRC dyspnea grades, distance walked on the ISWT and SGRQ scores. The ADL-D scores were significantly different across the five grades of the MRC dyspnea grade. The ADL-D scale showed high consistency (Chronbach's alpha coefficient of 0.96). The ADL-D scale is a useful scale for assessing impairments in ADL in Japanese male patients with COPD.

Syndromes associated with mitochondrial DNA depletion

PubMed Central

2014-01-01

Mitochondrial dysfunction accounts for a large group of inherited metabolic disorders most of which are due to a dysfunctional mitochondrial respiratory chain (MRC) and, consequently, deficient energy production. MRC function depends on the coordinated expression of both nuclear (nDNA) and mitochondrial (mtDNA) genomes. Thus, mitochondrial diseases can be caused by genetic defects in either the mitochondrial or the nuclear genome, or in the cross-talk between the two. This impaired cross-talk gives rise to so-called nuclear-mitochondrial intergenomic communication disorders, which result in loss or instability of the mitochondrial genome and, in turn, impaired maintenance of qualitative and quantitative mtDNA integrity. In children, most MRC disorders are associated with nuclear gene defects rather than alterations in the mtDNA itself. The mitochondrial DNA depletion syndromes (MDSs) are a clinically heterogeneous group of disorders with an autosomal recessive pattern of transmission that have onset in infancy or early childhood and are characterized by a reduced number of copies of mtDNA in affected tissues and organs. The MDSs can be divided into least four clinical presentations: hepatocerebral, myopathic, encephalomyopathic and neurogastrointestinal. The focus of this review is to offer an overview of these syndromes, listing the clinical phenotypes, together with their relative frequency, mutational spectrum, and possible insights for improving diagnostic strategies. PMID:24708634

Effect of neuromuscular stimulation and individualized rehabilitation on muscle strength in Intensive Care Unit survivors: A randomized trial.

PubMed

Patsaki, Irini; Gerovasili, Vasiliki; Sidiras, Georgios; Karatzanos, Eleftherios; Mitsiou, Georgios; Papadopoulos, Emmanuel; Christakou, Anna; Routsi, Christina; Kotanidou, Anastasia; Nanas, Serafim

2017-08-01

Intensive Care Unit (ICU) survivors experience muscle weakness leading to restrictions in functional ability. Neuromuscular electrical stimulation (NMES) has been an alternative to exercise in critically ill patients. The aim of our study was to investigate its effects along with individualized rehabilitation on muscle strength of ICU survivors. Following ICU discharge, 128 patients (age: 53±16years) were randomly assigned to daily NMES sessions and individualized rehabilitation (NMES group) or to control group. Muscle strength was assessed by the Medical Research Council (MRC) score and hand grip at hospital discharge. Secondary outcomes were functional ability and hospital length of stay. MRC, handgrip, functional status and hospital length of stay did not differ at hospital discharge between groups (p>0.05). ΔMRC% one and two weeks after ICU discharge tended to be higher in NMES group, while it was significant higher in NMES group of patients with ICU-acquired weakness at two weeks (p=0.05). NMES and personalized physiotherapy in ICU survivors did not result in greater improvement of muscle strength and functional status at hospital discharge. However, in patients with ICU-aw NMES may be effective. The potential benefits of rehabilitation strategies should be explored in larger number of patients in future studies. www.Clinicaltrials.gov: NCT01717833. Copyright © 2017. Published by Elsevier Inc.

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.

PubMed

Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida

2012-12-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer

PubMed Central

Wojcieszek, Piotr; Białas, Brygida

2012-01-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years. PMID:23378855

Synthesis, characterization and biological activities of copper(II) complex of 2-Benzimidazolyl-urea and the nitrate salt of 2-Benzimidazolyl-urea

NASA Astrophysics Data System (ADS)

Poyraz, Mehmet; Sari, Musa; Banti, Christina N.; Hadjikakou, Sotiris K.

2017-10-01

The synthesis of the complex {[Cu(BZIMU)2](NO3)2} (1) (BZIMU = 2-Benzimidazolyl-urea) is reported here. The complex 1 was characterized by elemental analysis, FT-IR, magnetic susceptibility and molar conductance measurements. The crystal structures of 1 and of the nitrate salt of [(BZIMUH+)(NO3)-] (2) were determined by X-ray diffraction analysis. The copper complex 1 and [(BZIMUH+)(NO3)-] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cervix adenocarcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cell line and normal human fetal lung fibroblast cells (MRC-5) with SRB assay.

Building for the future

PubMed Central

2013-01-01

As the staff of the MRC Laboratory of Molecular Biology settle into their new building in Cambridge, its director Hugh Pelham explains the challenges of living up to its prestigious past. PMID:23741620

ALMA finds dew drops in the dusty spider's web

NASA Astrophysics Data System (ADS)

Gullberg, Bitten; Lehnert, Matthew D.; De Breuck, Carlos; Branchu, Steve; Dannerbauer, Helmut; Drouart, Guillaume; Emonts, Bjorn; Guillard, Pierre; Hatch, Nina; Nesvadba, Nicole P. H.; Omont, Alain; Seymour, Nick; Vernet, Joël

2016-06-01

We present 0.̋5 resolution ALMA detections of the observed 246 GHz continuum, [CI] 3P2→3P1 fine structure line ([CI]2-1), CO(7-6), and H2O lines in the z = 2.161 radio galaxy MRC1138-262, the so-called Spiderweb galaxy. We detect strong [CI]2-1 emission both at the position of the radio core, and in a second component ~4 kpc away from it. The 1100 km s-1 broad [CI]2-1 line in this latter component, combined with its H2 mass of 1.6 × 1010 M⊙, implies that this emission must come from a compact region <60 pc, possibly containing a second active galactic nucleus (AGN). The combined H2 mass derived for both objects, using the [CI]2-1 emission, is 3.3 × 1010 M⊙. The total CO(7-6)/[CI]2-1 line flux ratio of 0.2 suggests a low excitation molecular gas reservoir and/or enhanced atomic carbon in cosmic ray dominated regions. We detect spatially-resolved H2O 211-202 emission - for the first time in a high-z unlensed galaxy - near the outer radio lobe to the east, and near the bend of the radio jet to the west of the radio galaxy. No underlying 246 GHz continuum emission is seen at either position. We suggest that the H2O emission is excited in the cooling region behind slow (10-40 km s-1) shocks in dense molecular gas (103-5 cm-3). The extended water emission is likely evidence of the radio jet's impact on cooling and forming molecules in the post-shocked gas in the halo and inter-cluster gas, similar to what is seen in low-z clusters and other high-z radio galaxies. These observations imply that the passage of the radio jet in the interstellar and inter-cluster medium not only heats gas to high temperatures, as is commonly assumed or found in simulations, but also induces cooling and dissipation, which can lead to substantial amounts of cold dense molecular gas. The formation of molecules and strong dissipation in the halo gas of MRC1138-262 may explain both the extended diffuse molecular gas and the young stars observed around MRC1138-262. The reduced data cubes

Using the Medical Research Council framework to develop a complex intervention to improve delivery of care for young people with type 1 diabetes.

PubMed

Eiser, C; Johnson, B; Brierley, S; Ayling, K; Young, V; Bottrell, K; Whitehead, V; Elliott, J; Scott, A; Heller, S

2013-06-01

We describe how we have used the development phase of the Medical Research Council (MRC) Guidelines to construct a complex intervention to improve physical and psychological health among young people (16-21 years) with Type 1 diabetes. We consulted previous reviews where available and conducted systematic searches of electronic databases to determine physical and mental health among the population, audited medical records, surveyed self-reported psychological health among our clinic population; and interviewed staff (n = 13), young people (n = 27) and parents (n = 18) about their views of current care. Our audit (n = 96) confirmed a high HbA1c [86 mmol/mol (10.0%)] and one third (36.1%) reported significant eating problems. Young people did not attend 12% of their clinic appointments. Staff described difficulties communicating with young people who wanted staff to take account of their individual lifestyle when giving information. Based on the findings of the systematic reviews and our audit, we concluded that there was sufficient evidence to justify development of a model of care specific to this age group. The components of the complex intervention include changes to standard care, an optional 5-day self-management course directed at young people and a separate family communication programme. The MRC Guidelines provided a valuable structure to guide development and evaluation of this intervention. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity.

PubMed

Kuhn, Paul-Steffen; Cremer, Laura; Gavriluta, Anatolie; Jovanović, Katarina K; Filipović, Lana; Hummer, Alfred A; Büchel, Gabriel E; Dojčinović, Biljana P; Meier, Samuel M; Rompel, Annette; Radulović, Siniša; Tommasino, Jean Bernard; Luneau, Dominique; Arion, Vladimir B

2015-09-21

A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(μ-ox)(NO)}4], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (13)C NMR spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y(III) and Dy(III), respectively, with formation of [Ln{RuCl3(μ-ox)(NO)}4](5-) (Ln=Y, Dy). While Y(III) is eight-coordinate in 2, Dy(III) is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu4N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu4N)5[Ln{OsCl3(ox)(NO)}4] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4 μM was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells. © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open

Bactericidal impact of Ag, ZnO and mixed AgZnO colloidal nanoparticles on H37Rv Mycobacterium tuberculosis phagocytized by THP-1 cell lines.

PubMed

Jafari, Alireza; Mosavari, Nader; Movahedzadeh, Farahnaz; Nodooshan, Saeedeh Jafari; Safarkar, Roya; Moro, Rossella; Kamalzadeh, Morteza; Majidpour, Ali; Boustanshenas, Mina; Mosavi, Tahereh

2017-09-01

The purpose of this research project was to infection of human macrophages (THP-1) cell lines by H 37 Rv strain of Mycobacterium tuberculosis (H 37 RvMTB) and find out the ratio/dilution of mixture silver (Ag NPs) and zinc oxide nanoparticles (ZnO NPs) whose ability to eliminate phagocytized bacteria compared to rifampicin. The colloidal Ag NPs and ZnO NPs were synthesized and their characteristics were evaluated. The THP-1 cell lines were infected with different concentration of H 37 RvMTB. Next, the infected cells were treated with different ratios/dilutions of Ag NPs, ZnO NPs and rifampicin. The THP-1 were lysed and were cultured in Lowenstein-Jensen agar medium, for eight weeks. The TEM and AFM images of NPs and H 37 RvMTB were supplied. It is observed that Ag NPs, 2 Ag :8 ZnO and 8 Ag :2 ZnO did not have any anti-tubercular effects on phagocytized H 37 RvMTB. Conversely, ZnO NPs somehow eliminated 18.7 × 10 4  CFU ml -1 of H 37 RvMTB in concentration of ∼ 0.468 ppm. To compare with 40 ppm of rifampicin, ∼ 0.663 ppm of 5 Ag :5 ZnO had the ability to kill of H 37 RvMTB, too. Based on previous research, ZnO NPs had strong anti-tubercular impact against H 37 RvMTB to in-vitro condition, but it was toxic in concentration of ∼ 0.468 ppm to both of THP-1 and normal lung (MRC-5) cell lines. It also seems that 5 Ag :5 ZnO is justified because in concentration of ∼ 0.663 ppm of 5 Ag :5 ZnO , phagocytized H 37 RvMTB into the THP-1 had died without any toxicity effects against THP-1 and also MRC-5 cell lines. It is obvious that the mixture of colloidal silver and zinc oxide NPs with ratio of 5 Ag :5 ZnO would be trustworthy options as anti-tubercular nano-drugs in future researches. Copyright © 2017. Published by Elsevier Ltd.

Enhancing the versatility of wireless biopotential acquisition for myoelectric prosthetic control

NASA Astrophysics Data System (ADS)

Bercich, Rebecca A.; Wang, Zhi; Mei, Henry; Hammer, Lauren H.; Seburn, Kevin L.; Hargrove, Levi J.; Irazoqui, Pedro P.

2016-08-01

Objective. A significant challenge in rehabilitating upper-limb amputees with sophisticated, electric-powered prostheses is sourcing reliable and independent channels of motor control information sufficient to precisely direct multiple degrees of freedom simultaneously. Approach. In response to the expressed needs of clinicians, we have developed a miniature, batteryless recording device that utilizes emerging integrated circuit technology and optimal impedance matching for magnetic resonantly coupled (MRC) wireless power transfer to improve the performance and versatility of wireless electrode interfaces with muscle. Main results. In this work we describe the fabrication and performance of a fully wireless and batteryless EMG recording system and use of this system to direct virtual and electric-powered limbs in real-time. The advantage of using MRC to optimize power transfer to a network of wireless devices is exhibited by EMG collected from an array of eight devices placed circumferentially around a human subject’s forearm. Significance. This is a comprehensive, low-cost, and non-proprietary solution that provides unprecedented versatility of configuration to direct myoelectric prostheses without wired connections to the body. The amenability of MRC to varied coil geometries and arrangements has the potential to improve the efficiency and robustness of wireless power transfer links at all levels of upper-limb amputation. Additionally, the wireless recording device’s programmable flash memory and selectable features will grant clinicians the unique ability to adapt and personalize the recording system’s functional protocol for patient- or algorithm-specific needs.

Enhancing the versatility of wireless biopotential acquisition for myoelectric prosthetic control.

PubMed

Bercich, Rebecca A; Wang, Zhi; Mei, Henry; Hammer, Lauren H; Seburn, Kevin L; Hargrove, Levi J; Irazoqui, Pedro P

2016-08-01

A significant challenge in rehabilitating upper-limb amputees with sophisticated, electric-powered prostheses is sourcing reliable and independent channels of motor control information sufficient to precisely direct multiple degrees of freedom simultaneously. In response to the expressed needs of clinicians, we have developed a miniature, batteryless recording device that utilizes emerging integrated circuit technology and optimal impedance matching for magnetic resonantly coupled (MRC) wireless power transfer to improve the performance and versatility of wireless electrode interfaces with muscle. In this work we describe the fabrication and performance of a fully wireless and batteryless EMG recording system and use of this system to direct virtual and electric-powered limbs in real-time. The advantage of using MRC to optimize power transfer to a network of wireless devices is exhibited by EMG collected from an array of eight devices placed circumferentially around a human subject's forearm. This is a comprehensive, low-cost, and non-proprietary solution that provides unprecedented versatility of configuration to direct myoelectric prostheses without wired connections to the body. The amenability of MRC to varied coil geometries and arrangements has the potential to improve the efficiency and robustness of wireless power transfer links at all levels of upper-limb amputation. Additionally, the wireless recording device's programmable flash memory and selectable features will grant clinicians the unique ability to adapt and personalize the recording system's functional protocol for patient- or algorithm-specific needs.

The Hydractinia echinata test-system. III: Structure-toxicity relationship study of some azo-, azo-anilide, and diazonium salt derivatives.

PubMed

Chicu, Sergiu Adrian; Munteanu, Melania; Cîtu, Ioana; Soica, Codruta; Dehelean, Cristina; Trandafirescu, Cristina; Funar-Timofei, Simona; Ionescu, Daniela; Simu, Georgeta Maria

2014-07-08

Structure-toxicity relationships for a series of 75 azo and azo-anilide dyes and five diazonium salts were developed using Hydractinia echinata (H. echinata) as model species. In addition, based on these relationships, predictions for 58 other azo-dyes were made. The experimental results showed that the measured effectiveness Mlog(1/MRC50) does not depend on the number of azo groups or the ones corresponding to metobolites, but it is influenced by the number of anilide groups, as well as by the substituents' positions within molecules. The conformational analysis pointed out the intramolecular hydrogen bonds, especially the simple tautomerization of quinoidic (STOH) or aminoidic (STNH2) type. The effectiveness is strongly influenced by the "push-pull" electronic effect, specific to two hydroxy or amino groups separated by an azo moiety (double alternate tautomery, (DAT), to the -COOH or -SO3H groups which are located in ortho or para position with respect to the azo group. The levels of the lipophylic/hydrophilic, electronic and steric equilibriums, pointed out by the Mlog(1/MRC50) values, enabled the calculation of their average values Clog(1/MRC50) ("Köln model"), characteristic to one derivative class (class isotoxicity). The azo group reduction and the hydrolysis of the amido/peptidic group are two concurrent enzymatic reactions, which occur with different reaction rates and mechanisms. The products of the partial biodegradation are aromatic amines. No additive or synergic effects are noticed among them.

Field test of a motorcycle safety education course for novice riders

DOT National Transportation Integrated Search

1982-07-01

The purpose of this study was to subject the Motorcycle Safety Foundation's Motorcycle Rider Course (MRC) to a large-scale field test designed to evaluate the following aspects of the course: (1) Instructional Effectiveness, (2) User Acceptance, and ...

Protein-Phospholipid Interactions in Nonclassical Protein Secretion: Problem and Methods of Study

PubMed Central

Prudovsky, Igor; Kumar, Thallapuranam Krishnaswamy Suresh; Sterling, Sarah; Neivandt, David

2013-01-01

Extracellular proteins devoid of signal peptides use nonclassical secretion mechanisms for their export. These mechanisms are independent of the endoplasmic reticulum and Golgi. Some nonclassically released proteins, particularly fibroblast growth factors (FGF) 1 and 2, are exported as a result of their direct translocation through the cell membrane. This process requires specific interactions of released proteins with membrane phospholipids. In this review written by a cell biologist, a structural biologist and two membrane engineers, we discuss the following subjects: (i) Phenomenon of nonclassical protein release and its biological significance; (ii) Composition of the FGF1 multiprotein release complex (MRC); (iii) The relationship between FGF1 export and acidic phospholipid externalization; (iv) Interactions of FGF1 MRC components with acidic phospholipids; (v) Methods to study the transmembrane translocation of proteins; (vi) Membrane models to study nonclassical protein release. PMID:23396106

Binding of hnRNP H and U2AF65 to Respective G-codes and a Poly-Uridine Tract Collaborate in the N50-5'ss Selection of the REST N Exon in H69 Cells

PubMed Central

Ortuño-Pineda, Carlos; Galindo-Rosales, José Manuel; Calderón-Salinas, José Victor; Villegas-Sepúlveda, Nicolás; Saucedo-Cárdenas, Odila; De Nova-Ocampo, Mónica; Valdés, Jesús

2012-01-01

The splicing of the N exon in the pre-mRNA coding for the RE1-silencing transcription factor (REST) results in a truncated protein that modifies the expression pattern of some of its target genes. A weak 3'ss, three alternative 5'ss (N4-, N50-, and N62-5'ss) and a variety of putative target sites for splicing regulatory proteins are found around the N exon; two GGGG codes (G2-G3) and a poly-Uridine tract (N-PU) are found in front of the N50-5'ss. In this work we analyzed some of the regulatory factors and elements involved in the preferred selection of the N50-5'ss (N50 activation) in the small cell lung cancer cell line H69. Wild type and mutant N exon/β-globin minigenes recapitulated N50 exon splicing in H69 cells, and showed that the N-PU and the G2-G3 elements are required for N50 exon splicing. Biochemical and knockdown experiments identified these elements as U2AF65 and hnRNP H targets, respectively, and that they are also required for N50 exon activation. Compared to normal MRC5 cells, and in keeping with N50 exon activation, U2AF65, hnRNP H and other splicing factors were highly expressed in H69 cells. CLIP experiments revealed that hnRNP H RNA-binding occurs first and is a prerequisite for U2AF65 RNA binding, and EMSA and CLIP experiments suggest that U2AF65-RNA recognition displaces hnRNP H and helps to recruit other splicing factors (at least U1 70K) to the N50-5'ss. Our results evidenced novel hnRNP H and U2AF65 functions: respectively, U2AF65-recruiting to a 5'ss in humans and the hnRNP H-displacing function from two juxtaposed GGGG codes. PMID:22792276

Asymmetric Radical Cyclopropanation of Alkenes with In Situ-Generated Donor-Substituted Diazo Reagents via Co(II)-Based Metalloradical Catalysis.

PubMed

Wang, Yong; Wen, Xin; Cui, Xin; Wojtas, Lukasz; Zhang, X Peter

2017-01-25

Donor-substituted diazo reagents, generated in situ from sulfonyl hydrazones in the presence of base, can serve as suitable radical precursors for Co(II)-based metalloradical catalysis (MRC). The cobalt(II) complex of D 2 -symmetric chiral porphyrin [Co(3,5-Di t Bu-Xu(2'-Naph)Phyrin)] is an efficient metalloradical catalyst that is capable of activating different N-arylsulfonyl hydrazones for asymmetric radical cyclopropanation of a broad range of alkenes, affording the corresponding cyclopropanes in high yields with effective control of both diastereo- and enantioselectivity. This Co(II)-based metalloradical system represents the first catalytic protocol that can effectively utilize donor-type diazo reagents for asymmetric olefin cyclopropanation.

76 FR 56254 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

...''); the Education Finance Council (``EFC''); Fi360; Lewis Young Robertson & Burningham, Inc. (``Lewis... (``MRC''); the National Association of Independent Public Finance Advisors (``NAIPFA''); Not for Profit... banking services (relating to corporate trust and mutual funds), such as shareholder servicing fees and...

In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles

PubMed Central

Štarha, Pavel; Trávníček, Zdeněk; Drahoš, Bohuslav; Dvořák, Zdeněk

2016-01-01

A series of gold(I) complexes of the general composition [Au(naza)(PPh3)] (1–8) was prepared and thoroughly characterized (e.g., electrospray ionization (ESI) mass spectrometry and multinuclear nuclear magnetic resonance (NMR) spectroscopy). The N1-deprotonated anions of 7-azaindole or its derivatives (naza) are coordinated to the metal centre through the N1 atom of their pyrrole ring, as proved by a single crystal X-ray analysis of the complexes [Au(3I5Braza)(PPh3)] (7) and [Au(2Me4Claza)(PPh3)]·½H2O (8′). The in vitro cytotoxicity of the complexes 1–8 was studied against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the MRC-5 human normal fibroblast cell line. The complexes 4, 5, and 8, containing deprotonated 3-iodo-7-azaindole, 5-bromo-7-azaindole, and 2-methyl-4-chloro-7-azaindole (2Me4Claza), respectively, showed significantly higher potency (IC50 = 2.8–3.5 µM) than cisplatin (IC50 = 20.3 µM) against the A2780 cells and markedly lower effect towards the MRC-5 non-cancerous cells (IC50 = 26.0–29.2 µM), as compared with the mentioned A2780 cancer cells. The results of the flow cytometric studies of the A2780 cell cycle perturbations revealed a G2-cell cycle phase arrest of the cells treated by the representative complexes 1 and 5, which is indicative of a different mechanism of action from cisplatin (induced S-cell cycle phase arrest). The stability of the representative complex 8 in the water-containing solution as well as its ability to interact with the reduced glutathione, cysteine and bovine serum albumin was also studied using 1H and 31P-NMR spectroscopy (studied in the 50% DMF-d7/50% D2O mixture) and ESI+ mass spectrometry (studied in the 50% DMF/50% H2O mixture); DMF = dimethylformamide. The obtained results are indicative for the release of the N-donor azaindole-based ligand in the presence of the used biomolecules. PMID:27973440

Expression of the rat CD26 antigen (dipeptidyl peptidase IV) on subpopulations of rat lymphocytes.

PubMed

Gorrell, M D; Wickson, J; McCaughan, G W

1991-04-15

The T cell activation antigen CD26 has been recently identified as the cell surface ectopeptidase dipeptidyl peptidase IV (DPP-IV). DPP-IV is found on many cell types, including lymphocytes, epithelial cells, and certain endothelial cells. The MRC OX61 monoclonal antibody (MAb) which specifically recognises rat DPP-IV was used to examine the expression of CD26/DPP-IV on rat lymphocytes. The molecular nature of the antigen was examined by immunoprecipitation from thymocytes, splenocytes, and hepatocytes. Analysis by one- and two-dimensional gel electrophoresis indicated that the native form of CD26 includes a 220-kDa homodimer. On tissue sections MRC OX61 MAb stained nearly all thymocytes and in the spleen and lymph nodes predominantly stained the T cell areas. However, in immunofluorescence experiments OX61 stained 80 to 87% of lymph node cells and 78 to 85% of spleen cells. Furthermore, two-colour immunofluorescence analysis of the CD4+, CD8+, and Ig+ lymphocyte subsets indicated that only 2 to 5% of each of these subsets lacked OX61 staining. Spleen cells and thymocytes of both CD4+ and CD8+ subsets stained much more intensely with OX61 after these cells were stimulated with phytohemagglutinin. These findings indicate that rat CD26 antigen expression is not confined to the T cell population as has been suggested, but also occurs on B cells, and is increased on T cells following their activation.

Morphological and ultrastructural characterization of ionoregulatory cells in the teleost Oreochromis niloticus following salinity challenge combining complementary confocal scanning laser microscopy and transmission electron microscopy using a novel prefixation immunogold labeling technique.

PubMed

Fridman, Sophie; Rana, Krishen J; Bron, James E

2013-10-01

Aspects of ionoregulatory or mitochondria-rich cell (MRC) differentiation and adaptation in Nile tilapia yolk-sac larvae following transfer from freshwater to elevated salinities, that is, 12.5 and 20 ppt are described. Investigations using immunohistochemistry on whole-mount Nile tilapia larvae using anti- Na⁺/K⁺-ATPase as a primary antibody and Fluoronanogold™ (Nanoprobes) as a secondary immunoprobe allowed fluorescent labeling with the high resolution of confocal scanning laser microscopy combined with the detection of immunolabeled target molecules at an ultrastructural level using transmission electron microscopy (TEM). It reports, for the first time, various developmental stages of MRCs within the epithelial layer of the tail of yolk-sac larvae, corresponding to immature, developing, and mature MRCs, identifiable by their own characteristic ultrastructure and form. Following transfer to hyperosmotic salinities the density of immunogold particles and well as the intricacy of the tubular system appeared to increase. In addition, complementary confocal scanning laser microscopy allowed identification of immunopositive ramifying extensions that appeared to emanate from the basolateral portion of the cell that appeared to be correlated with the localization of subsurface tubular areas displaying immunogold labeled Na⁺/K⁺-ATPase. This integrated approach describes a reliable and repeatable prefixation immunogold labeling technique allowing precise visualization of NaK within target cells combined with a 3D imaging that offers valuable insights into MRC dynamics at an ultrastructural level. Copyright © 2013 Wiley Periodicals, Inc.

Theory of Change: a theory-driven approach to enhance the Medical Research Council's framework for complex interventions

PubMed Central

2014-01-01

Background The Medical Research Councils’ framework for complex interventions has been criticized for not including theory-driven approaches to evaluation. Although the framework does include broad guidance on the use of theory, it contains little practical guidance for implementers and there have been calls to develop a more comprehensive approach. A prospective, theory-driven process of intervention design and evaluation is required to develop complex healthcare interventions which are more likely to be effective, sustainable and scalable. Methods We propose a theory-driven approach to the design and evaluation of complex interventions by adapting and integrating a programmatic design and evaluation tool, Theory of Change (ToC), into the MRC framework for complex interventions. We provide a guide to what ToC is, how to construct one, and how to integrate its use into research projects seeking to design, implement and evaluate complex interventions using the MRC framework. We test this approach by using ToC within two randomized controlled trials and one non-randomized evaluation of complex interventions. Results Our application of ToC in three research projects has shown that ToC can strengthen key stages of the MRC framework. It can aid the development of interventions by providing a framework for enhanced stakeholder engagement and by explicitly designing an intervention that is embedded in the local context. For the feasibility and piloting stage, ToC enables the systematic identification of knowledge gaps to generate research questions that strengthen intervention design. ToC may improve the evaluation of interventions by providing a comprehensive set of indicators to evaluate all stages of the causal pathway through which an intervention achieves impact, combining evaluations of intervention effectiveness with detailed process evaluations into one theoretical framework. Conclusions Incorporating a ToC approach into the MRC framework holds promise for

Consultation performance of general practitioners when supported by an asthma/COPDC-service

PubMed Central

2012-01-01

Background General practitioners (GPs) can refer patients to an asthma/COPD service (AC-service) for diagnostic assessment of spirometry and medical history and for asthma or COPD monitoring. The AC-service reports diagnostic results and additional information about disease burden (BORG-score for complaints, MRC-dyspnoea score, exacerbation rate), life style, medication and compliance, to the patient’s GP. This study explores how GPs use this additional information when discussing the patient’s disease burden and how this influences GPs’ information and education provision during consultations with asthma/COPD patients. Method Patients with (a suspicion of) asthma or COPD were referred to an AC-service and consulted their GPs after they had received a report from the AC-service. Retrospectively patients answered questions about their GPs’ performance during these consultations. Performances were compared with performances of the same GPs during consultations without support of the AC-service (usual care), earlier that year. Results Of consultations not initiated by an AC-service check-up, 91% focussed on complaints, the initial reason for the consultation. In AC-service supported follow-up consultations, GPs explored disease burden when the (BORG-)score for complaints was high - as reported by the AC-service - even when patients themselves thought it was irrelevant. GPs put significantly less effort in exploring disease burden when the Borg-score was low (BORG 3–4: 69%; BORG1-2: 51%, p = 0,01). GPs mostly ignored MRC-dyspnoea scores: attention to dyspnoea was 18% for MRC-score <3 and 25% for MRC-score ≥3 (p = 0,63). GPs encouraged physical fitness in 13% of patients. Smoking behaviour was discussed with 66% of the actual smokers but only 14% remembered a stop smoking advice. Furthermore, pharmacotherapeutic management education in AC-service supported consultations did not differ from performance in usual care according to patient evaluations

Theory of Change: a theory-driven approach to enhance the Medical Research Council's framework for complex interventions.

PubMed

De Silva, Mary J; Breuer, Erica; Lee, Lucy; Asher, Laura; Chowdhary, Neerja; Lund, Crick; Patel, Vikram

2014-07-05

The Medical Research Councils' framework for complex interventions has been criticized for not including theory-driven approaches to evaluation. Although the framework does include broad guidance on the use of theory, it contains little practical guidance for implementers and there have been calls to develop a more comprehensive approach. A prospective, theory-driven process of intervention design and evaluation is required to develop complex healthcare interventions which are more likely to be effective, sustainable and scalable. We propose a theory-driven approach to the design and evaluation of complex interventions by adapting and integrating a programmatic design and evaluation tool, Theory of Change (ToC), into the MRC framework for complex interventions. We provide a guide to what ToC is, how to construct one, and how to integrate its use into research projects seeking to design, implement and evaluate complex interventions using the MRC framework. We test this approach by using ToC within two randomized controlled trials and one non-randomized evaluation of complex interventions. Our application of ToC in three research projects has shown that ToC can strengthen key stages of the MRC framework. It can aid the development of interventions by providing a framework for enhanced stakeholder engagement and by explicitly designing an intervention that is embedded in the local context. For the feasibility and piloting stage, ToC enables the systematic identification of knowledge gaps to generate research questions that strengthen intervention design. ToC may improve the evaluation of interventions by providing a comprehensive set of indicators to evaluate all stages of the causal pathway through which an intervention achieves impact, combining evaluations of intervention effectiveness with detailed process evaluations into one theoretical framework. Incorporating a ToC approach into the MRC framework holds promise for improving the design and evaluation of complex

Transcription of the herpes simplex virus 1 genome during productive and quiescent infection of neuronal and nonneuronal cells.

PubMed

Harkness, Justine M; Kader, Muhamuda; DeLuca, Neal A

2014-06-01

Herpes simplex virus 1 (HSV-1) can undergo a productive infection in nonneuronal and neuronal cells such that the genes of the virus are transcribed in an ordered cascade. HSV-1 can also establish a more quiescent or latent infection in peripheral neurons, where gene expression is substantially reduced relative to that in productive infection. HSV mutants defective in multiple immediate early (IE) gene functions are highly defective for later gene expression and model some aspects of latency in vivo. We compared the expression of wild-type (wt) virus and IE gene mutants in nonneuronal cells (MRC5) and adult murine trigeminal ganglion (TG) neurons using the Illumina platform for cDNA sequencing (RNA-seq). RNA-seq analysis of wild-type virus revealed that expression of the genome mostly followed the previously established kinetics, validating the method, while highlighting variations in gene expression within individual kinetic classes. The accumulation of immediate early transcripts differed between MRC5 cells and neurons, with a greater abundance in neurons. Analysis of a mutant defective in all five IE genes (d109) showed dysregulated genome-wide low-level transcription that was more highly attenuated in MRC5 cells than in TG neurons. Furthermore, a subset of genes in d109 was more abundantly expressed over time in neurons. While the majority of the viral genome became relatively quiescent, the latency-associated transcript was specifically upregulated. Unexpectedly, other genes within repeat regions of the genome, as well as the unique genes just adjacent the repeat regions, also remained relatively active in neurons. The relative permissiveness of TG neurons to viral gene expression near the joint region is likely significant during the establishment and reactivation of latency. During productive infection, the genes of HSV-1 are transcribed in an ordered cascade. HSV can also establish a more quiescent or latent infection in peripheral neurons. HSV mutants

Two Simulated-Smog Atmospheres with Different Chemical Compositions Produce Contrasting Mutagenicity in Salmonella**

EPA Science Inventory

Ozone (O3), particulate matter (PM), and nitrogen dioxide (NO2) are criteria pollutants used to evaluate air quality. Using EPA’s Mobile Reaction Chamber (MRC), we generated 2 simulated-smog atmospheres (SSA-1 & SSA-2) with different concentrations of these criteria pol...

[Interventional effects of different management programs on the outcomes of stable chronic obstructive pulmonary disease patients].

PubMed

Zhang, Rong-bao; Tan, Xing-yu; He, Quan-ying; Chen, Qing; Gai, Jun; Wei, Jing-an; Wang, Yan

2012-11-27

To evaluate the interventional effects of different management programs on the outcomes of stable chronic obstructive pulmonary disease (COPD) patients. Systemic education, follow-up and control groups were divided according to the frequency of follow-ups and the profile of participating in education. A total of 157 patients were enrolled into the COPD database from May 2002 to May 2010. They were interviewed face-to-face at our department. The investigation contained general conditions, the frequency of acute exacerbations (AE) the previous year, COPD Assessment Test (CAT), Modified British Medical Research Council Dyspnea Scale (mMRC) and spirometric classification. A combined assessment was conducted. The frequency of AE and rate of AE < once the previous year in systemic education group was 0.9 ± 1.1 and 71.2%, 1.0 ± 0.8 and 68.6% in follow-up group and 1.4 ± 1.1 and 44.4% in control group. And the frequency of AE in systemic education and follow-up groups was significantly less than that in control group (P < 0.05). Rate of AE < once in systemic education and follow-up groups was significantly higher than that in control group (P < 0.01). CAT and rate of CAT ≤ 20 in systemic education, follow-up and control groups were 10.0 ± 5.0 and 96.2%, 11.1 ± 6.0 and 88.2%, 15.3 ± 6.8 and 64.8% respectively. CAT in systemic education and follow-up groups was significantly lower than that in control group (P < 0.01). Rate of CAT ≤ 20 in systemic education and follow-up groups was significantly higher than that in control group (P < 0.01). mMRC in systemic education, follow-up and control groups was 1.5 ± 0.8, 1.6 ± 0.9 and 2.1 ± 1.0 respectively. mMRC in systemic education and follow-up groups was significantly lower than that in control group (P < 0.05). Combined assessment showed that no significant difference existed in Types A and B among three groups (P > 0.05). Type C in the systemic education group was significantly higher than that of the control (P

Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies.

PubMed

Milošev, Milorad Z; Jakovljević, Katarina; Joksović, Milan D; Stanojković, Tatjana; Matić, Ivana Z; Perović, Milka; Tešić, Vesna; Kanazir, Selma; Mladenović, Milan; Rodić, Marko V; Leovac, Vukadin M; Trifunović, Snežana; Marković, Violeta

2017-06-01

A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b, 5e, and 5j on the cell cycle were investigated by flow cytometric analysis. It was found that these compounds cause the accumulation of cells in the subG1 and G1 phases of the cell cycle and induce caspase-dependent apoptosis, while the anti-angiogenic effects of 5b, 5e, and 5j have been confirmed in EA.hy926 cells using a tube formation assay. Further, the interaction of Bax protein with compound 5b was investigated by means of molecular modeling, applying the combined molecular docking/molecular dynamics approach. © 2016 John Wiley & Sons A/S.

Outcomes of sudden cardiac arrest in a state-wide integrated resuscitation program: Results from the Minnesota Resuscitation Consortium.

PubMed

Adabag, Selcuk; Hodgson, Lucinda; Garcia, Santiago; Anand, Vidhu; Frascone, Ralph; Conterato, Marc; Lick, Charles; Wesley, Keith; Mahoney, Brian; Yannopoulos, Demetris

2017-01-01

Despite many advances in resuscitation science the outcomes of sudden cardiac arrest (SCA) remain poor. The Minnesota Resuscitation Consortium (MRC) is a statewide integrated resuscitation program, established in 2011, to provide standardized, evidence-based resuscitation and post-resuscitation care. The objective of this study is to assess the outcomes of a state-wide integrated resuscitation program. We examined the trends in resuscitation metrics and outcomes in Minnesota since 2011 and compared these to the results from the national Cardiac Arrest Registry to Enhance Survival (CARES) program. Since 2011 MRC has expanded significantly providing service to >75% of Minnesota's population. A total of 5192 SCA occurred in counties covered by MRC from 2011 to 2014. In this period, bystander cardiopulmonary resuscitation (CPR) and use of hypothermia, automatic CPR device and impedance threshold device increased significantly (p<0.0001 for all). Compared to CARES, SCA cases in Minnesota were more likely to be ventricular fibrillation (31% vs. 23%, p<0.0001) but less likely to receive bystander CPR (33% vs. 39%, p<0.0001). Survival to hospital discharge with good or moderate cerebral performance (12% vs. 8%, p<0.0001), survival in SCA with a shockable rhythm (Utstein survival) (38% vs. 33%, p=0.0003) and Utstein survival with bystander CPR (44% vs. 37%, p=0.003) were greater in Minnesota than CARES. State-wide integration of resuscitation services in Minnesota was feasible. Survival rate after cardiac arrest is greater in Minnesota compared to the mean survival rate in CARES. Published by Elsevier Ireland Ltd.

Ozone affects leaf physiology and causes injury to foliage of native tree species from the tropical Atlantic Forest of southern Brazil.

PubMed

Moura, Bárbara Baêsso; Alves, Edenise Segala; Marabesi, Mauro Alexandre; de Souza, Silvia Ribeiro; Schaub, Marcus; Vollenweider, Pierre

2018-01-01

In southern Brazil, the recent increase in tropospheric ozone (O 3 ) concentrations poses an additional threat to the biodiverse but endangered and fragmented remnants of the Atlantic Forest. Given the mostly unknown sensitivity of tropical species to oxidative stress, the principal objective of this study was to determine whether the current O 3 levels in the Metropolitan Region of Campinas (MRC), downwind of São Paulo, affect the native vegetation of forest remnants. Foliar responses to O 3 of three tree species typical of the MRC forests were investigated using indoor chamber exposure experiments under controlled conditions and a field survey. Exposure to 70ppb O 3 reduced assimilation and leaf conductance but increased respiration in Astronium graveolens while gas exchange in Croton floribundus was little affected. Both A. graveolens and Piptadenia gonoacantha developed characteristic O 3 -induced injury in the foliage, similar to visible symptoms observed in >30% of trees assessed in the MRC, while C. floribundus remained asymptomatic. The underlying structural symptoms in both O 3 -exposed and field samples were indicative of oxidative burst, hypersensitive responses, accelerated cell senescence and, primarily in field samples, interaction with photo-oxidative stress. The markers of O 3 stress were thus mostly similar to those observed in other regions of the world. Further research is needed, to estimate the proportion of sensitive forest species, the O 3 impact on tree growth and stand stability and to detect O 3 hot spots where woody species in the Atlantic Forest are mostly affected. Copyright © 2017 Elsevier B.V. All rights reserved.

A computer program for predicting recharge with a master recession curve

USGS Publications Warehouse

Heppner, Christopher S.; Nimmo, John R.

2005-01-01

Water-table fluctuations occur in unconfined aquifers owing to ground-water recharge following precipitation and infiltration, and ground-water discharge to streams between storm events. Ground-water recharge can be estimated from well hydrograph data using the water-table fluctuation (WTF) principle, which states that recharge is equal to the product of the water-table rise and the specific yield of the subsurface porous medium. The water-table rise, however, must be expressed relative to the water level that would have occurred in the absence of recharge. This requires a means for estimating the recession pattern of the water-table at the site. For a given site there is often a characteristic relation between the water-table elevation and the water-table decline rate following a recharge event. A computer program was written which extracts the relation between decline rate and water-table elevation from well hydrograph data and uses it to construct a master recession curve (MRC). The MRC is a characteristic water-table recession hydrograph, representing the average behavior for a declining water-table at that site. The program then calculates recharge using the WTF method by comparing the measured well hydrograph with the hydrograph predicted by the MRC and multiplying the difference at each time step by the specific yield. This approach can be used to estimate recharge in a continuous fashion from long-term well records. Presented here is a description of the code including the WTF theory and instructions for running it to estimate recharge with continuous well hydrograph data.

Cascade rainfall disaggregation application in U.S. Central Plains

USDA-ARS?s Scientific Manuscript database

Hourly rainfall are increasingly used in complex, process-based simulations of the environment. Long records of daily rainfall are common, but long continuous records of hourly rainfall are rare and must be developed. A Multiplicative Random Cascade (MRC) model is proposed to disaggregate observed d...

Students' Big Three Personality Traits, Perceptions of Teacher Interpersonal Behavior, and Mathematics Achievement: An Application of the Model of Reciprocal Causation

ERIC Educational Resources Information Center

Charalampous, Kyriakos; Kokkinos, Constantinos M.

2014-01-01

The purpose of the present study was to investigate the application of the Model of Reciprocal Causation (MRC) in examining the relationship between student personality (personal factors), student-perceived teacher interpersonal behavior (environment), and Mathematics achievement (behavior), with the simultaneous investigation of mediating effects…

The overall impact of COPD (CAT) and BODE index on COPD male patients: correlation?

PubMed

Ladeira, I; Gomes, T; Castro, A; Ribeiro, C; Guimarães, M; Taveira, N

2015-01-01

Chronic Obstructive Pulmonary Disease (COPD) will be the 5th leading cause of disability (DALYs) and the 4th leading cause of death by 2030. Measuring the real impact of COPD using CAT ("COPD Assessment Test") can complement BODE index, an indicator of mortality. To assess correlation between CAT and BODE index in COPD patients. A retrospective study was conducted in a population of patients with COPD in a Respiratory Rehabilitation program. We analyzed demographic variables, variables in respiratory function--6 min walking test (6 MWT), post-BD forced expiratory volume in 1st second (FEV1%); dyspnea by mMRC scale; BODE Index and CAT. The study included 50 patients--GOLD stage I (7), II (25), III (14) and IV (4), 48 men; mean age 62.6 years (± 9.5), average BMI 25.8 kg/m(2) (± 4.8) and FEV1 57.1% (± 19.6); 6 MWT of 443.3m (± 61.6); 46% patients in classes 2 and 3 of mMRC scale; 84% were class 2 in BODE Index. About 80% reported slight to medium impact in CAT. CAT score and impact were correlated with BODE index score: R=0.475, p<0.01, and R=0.377, p=0.004, and BODE index class: R=0.357, p=0.011, and R=0.326, p=0.021. As pre-existent data in the literature (exacerbations and benefit of rehabilitation in COPD), the positive correlations found with BODE index reinforce the discriminative validity of CAT as a complement in the evaluation of what the true impact of COPD is on a patient's daily life. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Glycogen synthase kinase-3 (GSK-3) regulates TGF-β1-induced differentiation of pulmonary fibroblasts

PubMed Central

Baarsma, Hoeke A; Engelbertink, Lilian HJM; van Hees, Lonneke J; Menzen, Mark H; Meurs, Herman; Timens, Wim; Postma, Dirkje S; Kerstjens, Huib AM; Gosens, Reinoud

2013-01-01

Background Chronic lung diseases such as asthma, COPD and pulmonary fibrosis are characterized by abnormal extracellular matrix (ECM) turnover. TGF-β is a key mediator stimulating ECM production by recruiting and activating lung fibroblasts and initiating their differentiation process into more active myofibroblasts. Glycogen synthase kinase-3 (GSK-3) regulates various intracellular signalling pathways; its role in TGF-β1-induced myofibroblast differentiation is currently largely unknown. Purpose To determine the contribution of GSK-3 signalling in TGF-β1-induced myofibroblast differentiation. Experimental Approach We used MRC5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD. Protein and mRNA expression were determined by immunoblotting and RT-PCR analysis respectively. Results Stimulation of MRC5 and primary human lung fibroblasts with TGF-β1 resulted in time- and dose-dependent increases of α-sm-actin and fibronectin expression, indicative of myofibroblast differentiation. Pharmacological inhibition of GSK-3 by SB216763 dose-dependently attenuated TGF-β1-induced expression of these myofibroblasts markers. Moreover, silencing of GSK-3 by siRNA or pharmacological inhibition by CT/CHIR99021 fully inhibited the TGF-β1-induced expression of α-sm-actin and fibronectin. The effect of GSK-3 inhibition on α-sm-actin expression was similar in fibroblasts from individuals with and without COPD. Neither smad, NF-κB nor ERK1/2 were involved in the inhibitory actions of GSK-3 inhibition by SB126763 on myofibroblast differentiation. Rather, SB216763 increased the phosphorylation of CREB, which in its phosphorylated form acts as a functional antagonist of TGF-β/smad signalling. Conclusion and Implication We demonstrate that GSK-3 signalling regulates TGF-β1-induced myofibroblast differentiation by regulating CREB phosphorylation. GSK-3 may constitute a useful target for treatment of chronic lung diseases. PMID:23297769

Polydimethylsiloxane SlipChip for mammalian cell culture applications.

PubMed

Chang, Chia-Wen; Peng, Chien-Chung; Liao, Wei-Hao; Tung, Yi-Chung

2015-11-07

This paper reports a polydimethylsiloxane (PDMS) SlipChip for in vitro cell culture applications, multiple-treatment assays, cell co-cultures, and cytokine detection assays. The PDMS SlipChip is composed of two PDMS layers with microfluidic channels on each surface that are separated by a thin silicone fluid (Si-fluid) layer. The integration of Si-fluid enables the two PDMS layers to be slid to different positions; therefore, the channel patterns can be re-arranged for various applications. The SlipChip design significantly reduces the complexity of sample handling, transportation, and treatment processes. To apply the developed SlipChip for cell culture applications, human lung adenocarcinoma epithelial cells (A549) and lung fibroblasts (MRC-5) were cultured to examine the biocompatibility of the developed PDMS SlipChip. Moreover, embryonic pluripotent stem cells (ES-D3) were also cultured in the device to evaluate the retention of their stemness in the device. The experimental results show that cell morphology, viability and proliferation are not affected when the cells are cultured in the SlipChip, indicating that the device is highly compatible with mammalian cell culture. In addition, the stemness of the ES-D3 cells was highly retained after they were cultured in the device, suggesting the feasibility of using the SlipChip for stem cell research. Various cell experiments, such as simultaneous triple staining of cells and co-culture of MRC-5 with A549 cells, were also performed to demonstrate the functionalities of the PDMS SlipChip. Furthermore, we used a cytokine detection assay to evaluate the effect of endotoxin (lipopolysaccharides, LPS) treatment on the cytokine secretion of A549 cells using the SlipChip. The developed PDMS SlipChip provides a straightforward and effective platform for various on-chip in vitro cell cultures and consequent analysis, which is promising for a number of cell biology studies and biomedical applications.

Feature long axis size and local luminance contrast determine ship target acquisition performance: strong evidence for the TOD case

NASA Astrophysics Data System (ADS)

Bijl, Piet; Toet, Alexander; Kooi, Frank L.

2016-10-01

Visual images of a civilian target ship on a sea background were produced using a CAD model. The total set consisted of 264 images and included 3 different color schemes, 2 ship viewing aspects, 5 sun illumination conditions, 2 sea reflection values, 2 ship positions with respect to the horizon and 3 values of atmospheric contrast reduction. In a perception experiment, the images were presented on a display in a long darkened corridor. Observers were asked to indicate the range at which they were able to detect the ship and classify the following 5 ship elements: accommodation, funnel, hull, mast, and hat above the bridge. This resulted in a total of 1584 Target Acquisition (TA) range estimates for two observers. Next, the ship contour, ship elements and corresponding TA ranges were analyzed applying several feature size and contrast measures. Most data coincide on a contrast versus angular size plot using (1) the long axis as characteristic ship/ship feature size and (2) local Weber contrast as characteristic ship/ship feature contrast. Finally, the data were compared with a variety of visual performance functions assumed to be representative for Target Acquisition: the TOD (Triangle Orientation Discrimination), MRC (Minimum Resolvable Contrast), CTF (Contrast Threshold Function), TTP (Targeting Task Performance) metric and circular disc detection data for the unaided eye (Blackwell). The results provide strong evidence for the TOD case: both position and slope of the TOD curve match the ship detection and classification data without any free parameter. In contrast, the MRC and CTF are too steep, the TTP and disc detection curves are too shallow and all these curves need an overall scaling factor in order to coincide with the ship and ship feature recognition data.

Synthesis, biological evaluation and structure-activity relationship studies of isoflavene based Mannich bases with potent anti-cancer activity.

PubMed

Chen, Yilin; Cass, Shelley L; Kutty, Samuel K; Yee, Eugene M H; Chan, Daniel S H; Gardner, Christopher R; Vittorio, Orazio; Pasquier, Eddy; Black, David StC; Kumar, Naresh

2015-11-15

Phenoxodiol, an analogue of the isoflavone natural product daidzein, is a potent anti-cancer agent that has been investigated for the treatment of hormone dependent cancers. This molecular scaffold was reacted with different primary amines and secondary amines under different Mannich conditions to yield either benzoxazine or aminomethyl substituted analogues. These processes enabled the generation of a diverse range of analogues that were required for structure-activity relationship (SAR) studies. The resulting Mannich bases exhibited prominent anti-proliferative effects against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. Further cytotoxicity studies against MRC-5 normal lung fibroblast cells showed that the isoflavene analogues were selective towards cancer cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identifying Mechanisms of Change in a Conversation Therapy for Aphasia Using Behaviour Change Theory and Qualitative Methods

ERIC Educational Resources Information Center

Johnson, Fiona M.; Best, Wendy; Beckley, Firle Christina; Maxim, Jane; Beeke, Suzanne

2017-01-01

Background: Conversation therapy for aphasia is a complex intervention comprising multiple components and targeting multiple outcomes. UK Medical Research Council (MRC) guidelines published in 2008 recommend that in addition to measuring the outcomes of complex interventions, evaluation should seek to clarify how such outcomes are produced,…

One-step electrochemical deposition of Schiff base cobalt complex as effective water oxidation catalyst

NASA Astrophysics Data System (ADS)

Huang, Binbin; Wang, Yan; Zhan, Shuzhong; Ye, Jianshan

2017-02-01

Schiff base metal complexes have been applied in many fields, especially, a potential homogeneous catalyst for water splitting. However, the high overpotential, time consumed synthesis process and complicated working condition largely limit their application. In the present work, a one-step approach to fabricate Schiff base cobalt complex modified electrode is developed. Microrod clusters (MRC) and rough spherical particles (RSP) can be obtained on the ITO electrode through different electrochemical deposition condition. Both of the MRC and RSP present favorable activity for oxygen evolution reaction (OER) compared to the commercial Co3O4, taking an overpotential of 650 mV and 450 mV to drive appreciable catalytic current respectively. The highly active and stable RSP shows a Tafel plot of 84 mV dec-1 and negligible decrease of the current density for 12 h bulk electrolysis. The synthesis strategy of effective and stable catalyst in this work provide a simple method to fabricate heterogeneous OER catalyst with Schiff base metal complex.

Application of powder metallurgy techniques to produce improved bearing elements for liquid rocket engines

NASA Technical Reports Server (NTRS)

Moracz, D. J.; Shipley, R. J.; Moxson, V. S.; Killman, R. J.; Munson, H. E.

1992-01-01

The objective was to apply powder metallurgy techniques for the production of improved bearing elements, specifically balls and races, for advanced cryogenic turbopump bearings. The materials and fabrication techniques evaluated were judged on the basis of their ability to improve fatigue life, wear resistance, and corrosion resistance of Space Shuttle Main Engine (SSME) propellant bearings over the currently used 440C. An extensive list of candidate bearing alloys in five different categories was considered: tool/die steels, through hardened stainless steels, cobalt-base alloys, and gear steels. Testing of alloys for final consideration included hardness, rolling contact fatigue, cross cylinder wear, elevated temperature wear, room and cryogenic fracture toughness, stress corrosion cracking, and five-ball (rolling-sliding element) testing. Results of the program indicated two alloys that showed promise for improved bearing elements. These alloys were MRC-2001 and X-405. 57mm bearings were fabricated from the MRC-2001 alloy for further actual hardware rig testing by NASA-MSFC.

Discharge rates in electromyography distinguish early between peripheral and central paresis.

PubMed

Jürgens, Tim P; Puchner, Christoph; Schulte-Mattler, Wilhelm J

2012-10-01

Abnormally increased discharge rates (DRs) of motor unit potentials on concentric needle electromyography (CNEMG) indicate a loss of motor units in peripheral neurogenic lesions. To determine when increased DRs occur during the course of a peripheral nerve lesion, we retrospectively analyzed CNEMG recordings of 19 patients with acute weakness of peripheral origin. The initial CNEMG studies took place from 3.7 hours to 10 days after the onset of the lesion. Abnormally increased DRs (≥20/s) were found in all but 1 of the muscles in which MRC grade was <4. Peripheral neurogenic damage was confirmed in all patients thereafter. The DRs depended on neither the kind of lesion nor the time between onset and CNEMG examination. The measurement of DRs of motor unit potentials is helpful immediately after a sudden paresis of MRC grade 3 or worse to differentiate between a central and a peripheral lesion. Copyright © 2012 Wiley Periodicals, Inc.

Toward an objective measure of functional disability in dysferlinopathy.

PubMed

Woudt, Lisanne; Di Capua, Gabriella A; Krahn, Martin; Castiglioni, Claudia; Hughes, Ricardo; Campero, Mario; Trangulao, Alejandra; González-Hormazábal, Patricio; Godoy-Herrera, Raúl; Lévy, Nicolas; Urtizberea, Jon Andoni; Jara, Lilian; Bevilacqua, Jorge A

2016-01-01

Understanding the natural history of dysferlinopathy is essential to design and quantify novel therapeutic protocols. Our aim in this study was to assess, clinically and functionally, a cohort of patients with dysferlinopathy, using validated scales. Thirty-one patients with genetically confirmed dysferlinopathy were assessed using the motor function measure (MFM), Modified Rankin Scale (MRS), Muscle Research Council (MRC) scale, serum creatine kinase (CK) assessment, baseline spirometry data, and echocardiographic and electrophysiologic studies. MFM and MRC scores showed a significant negative correlation with disease duration and inverse correlation with MRS, but not with onset age, clinical phenotype, or CK levels. Percent forced vital capacity (%FVC) correlated negatively with disease duration and onset age. Eight known pathogenic mutations were identified recurrently, 4 of which accounted for 79% of the total. The results suggest that MFM is a reliable outcome measure that may be useful for longitudinal follow-up in dysferlinopathy. Recurrent mutations suggest a founder effect in the Chilean population. © 2015 Wiley Periodicals, Inc.

Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models.

PubMed

Lew, D Betty; Michael, Christie F; Overbeck, Tracie; Robinson, W Scout; Rohman, Erin L; Lehman, Jeffrey M; Patel, Jennifer K; Eiseman, Brandi; LeMessurier, Kim S; Samarasinghe, Amali E; Gaber, M Waleed

2017-01-01

One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM) remodeling effects. The mannose receptor (MR) family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR) and that mannan derived from Saccharomyces cerevisiae (SC-MN) inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2) expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

Hand Robotics Rehabilitation: Feasibility and Preliminary Results of a Robotic Treatment in Patients with Hemiparesis

PubMed Central

Sale, Patrizio; Lombardi, Valentina; Franceschini, Marco

2012-01-01

Background. No strongly clinical evidence about the use of hand robot-assisted therapy in stroke patients was demonstrated. This preliminary observer study was aimed at evaluating the efficacy of intensive robot-assisted therapy in hand function recovery, in the early phase after a stroke onset. Methods. Seven acute ischemic stroke patients at their first-ever stroke were enrolled. Treatment was performed using Amadeo robotic system (Tyromotion GmbH Graz, Austria). Each participant received, in addition to inpatients standard rehabilitative treatment, 20 sessions of robotic treatment for 4 consecutive weeks (5 days/week). Each session lasted for 40 minutes. The exercises were carried out as follows: passive modality (5 minutes), passive/plus modality (5 minutes), assisted therapy (10 minutes), and balloon (10 minutes). The following impairment and functional evaluations, Fugl-Meyer Scale (FM), Medical Research Council Scale for Muscle Strength (hand flexor and extensor muscles) (MRC), Motricity Index (MI), and modified Ashworth Scale for wrist and hand muscles (AS), were performed at the beginning (T0), after 10 sessions (T1), and at the end of the treatment (T2). The strength hand flexion and extension performed by Robot were assessed at T0 and T2. The Barthel Index and COMP (performance and satisfaction subscale) were assessed at T0 and T2. Results. Clinical improvements were found in all patients. No dropouts were recorded during the treatment and all subjects fulfilled the protocol. Evidence of a significant improvement was demonstrated by the Friedman test for the MRC (P < 0.0123). Evidence of an improvement was demonstrated for AS, FM, and MI. Conclusions. This original rehabilitation treatment could contribute to increase the hand motor recovery in acute stroke patients. The simplicity of the treatment, the lack of side effects, and the first positive results in acute stroke patients support the recommendations to extend the clinical trial of this treatment

Reciprocal Neural Pathways and Associative Networks.

DTIC Science & Technology

1982-12-15

with present experimental methods. 0.00 We thank Drs. Kathleen Rockland and Jennifer Lund for sending us o0o6 their paper in advance of publication. We...92037 * Present address: MRC Laboratory of Molecular Biology and the Kenneth Craik Laboratory, Cambridge, England. 2 SUMMARY We propose that the

Method and Excel VBA Algorithm for Modeling Master Recession Curve Using Trigonometry Approach.

PubMed

Posavec, Kristijan; Giacopetti, Marco; Materazzi, Marco; Birk, Steffen

2017-11-01

A new method was developed and implemented into an Excel Visual Basic for Applications (VBAs) algorithm utilizing trigonometry laws in an innovative way to overlap recession segments of time series and create master recession curves (MRCs). Based on a trigonometry approach, the algorithm horizontally translates succeeding recession segments of time series, placing their vertex, that is, the highest recorded value of each recession segment, directly onto the appropriate connection line defined by measurement points of a preceding recession segment. The new method and algorithm continues the development of methods and algorithms for the generation of MRC, where the first published method was based on a multiple linear/nonlinear regression model approach (Posavec et al. 2006). The newly developed trigonometry-based method was tested on real case study examples and compared with the previously published multiple linear/nonlinear regression model-based method. The results show that in some cases, that is, for some time series, the trigonometry-based method creates narrower overlaps of the recession segments, resulting in higher coefficients of determination R 2 , while in other cases the multiple linear/nonlinear regression model-based method remains superior. The Excel VBA algorithm for modeling MRC using the trigonometry approach is implemented into a spreadsheet tool (MRCTools v3.0 written by and available from Kristijan Posavec, Zagreb, Croatia) containing the previously published VBA algorithms for MRC generation and separation. All algorithms within the MRCTools v3.0 are open access and available free of charge, supporting the idea of running science on available, open, and free of charge software. © 2017, National Ground Water Association.

Formoterol attenuates increased oxidative stress and myosin protein loss in respiratory and limb muscles of cancer cachectic rats

PubMed Central

Salazar-Degracia, Anna; Busquets, Sílvia; Argilés, Josep M.; López-Soriano, Francisco J.

2017-01-01

Muscle mass loss and wasting are characteristic features of patients with chronic conditions including cancer. Therapeutic options are still scarce. We hypothesized that cachexia-induced muscle oxidative stress may be attenuated in response to treatment with beta2-adrenoceptor-selective agonist formoterol in rats. In diaphragm and gastrocnemius of tumor-bearing rats (108 AH-130 Yoshida ascites hepatoma cells inoculated intraperitoneally) with and without treatment with formoterol (0.3 mg/kg body weight/day for seven days, daily subcutaneous injection), redox balance (protein oxidation and nitration and antioxidants) and muscle proteins (1-dimensional immunoblots), carbonylated proteins (2-dimensional immunoblots), inflammatory cells (immunohistochemistry), and mitochondrial respiratory chain (MRC) complex activities were explored. In the gastrocnemius, but not the diaphragm, of cancer cachectic rats compared to the controls, protein oxidation and nitration levels were increased, several functional and structural proteins were carbonylated, and in both study muscles, myosin content was reduced, inflammatory cell counts were greater, while no significant differences were seen in MRC complex activities (I, II, and IV). Treatment of cachectic rats with formoterol attenuated all the events in both respiratory and limb muscles. In this in vivo model of cancer-cachectic rats, the diaphragm is more resistant to oxidative stress. Formoterol treatment attenuated the rise in oxidative stress in the limb muscles, inflammatory cell infiltration, and the loss of myosin content seen in both study muscles, whereas no effects were observed in the MRC complex activities. These findings have therapeutic implications as they demonstrate beneficial effects of the beta2 agonist through decreased protein oxidation and inflammation in cachectic muscles, especially the gastrocnemius. PMID:29255650

Modular Research-Based Composably Trustworthy Mission-Oriented Resilient Clouds (MRC2)

DTIC Science & Technology

2016-02-01

obtain in this way, encapsulation is a very promising technique to apply to larger cloud components. For example, ‘ big data ’ processing systems, such...UNITED STATES AIR FORCE  ROME, NY 13441 AIR FORCE MATERIEL COMMAND NOTICE AND SIGNATURE PAGE Using Government drawings, specifications, or other data ...Government formulated or supplied the drawings, specifications, or other data does not license the holder or any other person or corporation; or convey

Impact Assessment on Teachers of Student-led, Inquiry-based Planetary Science Instruction in Grades 3-8

NASA Astrophysics Data System (ADS)

Bering, E. A., III; Slagle, E. M.; Carlson, C.; Nieser, K.

2015-12-01

The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on Mars. A total of 195 Mars Rover teachers from the 2012-2013, 2013-2014, and 2014-2015 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. A total of 1300 students from the 2013-2014 and 2014-2015 cohort wereinvited to submit self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching "Earth and the solar system and universe" increased "Quite a bit" as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. The most striking increases were the percentage of teachers who felt their confidence increased "Quite a bit" as a result of their participation in the MRC program in the following areas: "Getting

Mars Rover Curriculum: Impact Assessment and Evaluation

NASA Astrophysics Data System (ADS)

Bering, E. A., III; Carlson, C.; Nieser, K.; Slagle, E. M.; Jacobs, L. T.; Kapral, A. J.

2014-12-01

The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover: the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 140 Mars Rover teachers from the 2012-2013 and 2013-2014 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. So far ~40 teachers have participated with responses still coming in. A total of 675 students from the 2013-2014 cohort were invited to submit brief self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching "Earth and the solar system and universe" increased "Quite a bit" as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. The most striking increases were the percentage of teachers who felt their confidence increased "Quite a bit" as a result of their participation

Cytotoxic components of Pereskia bleo (Kunth) DC. (Cactaceae) leaves.

PubMed

Malek, Sri Nurestri Abdul; Shin, Sim Kae; Wahab, Norhanom Abdul; Yaacob, Hashim

2009-05-06

Dihydroactinidiolide (1) and a mixture of sterols [campesterol (2), stigmasterol (3) and beta-sitosterol (4)], together with the previously isolated individual compounds beta-sitosterol (4), 2,4-di-tert-butylphenol (5), alpha-tocopherol (6), phytol (7) were isolated from the active ethyl acetate fraction of Pereskia bleo (Kunth) DC. (Cactaceae) leaves. Cytotoxic activities of the above mentioned compounds against five human carcinoma cell lines, namely the human nasopharyngeal epidermoid carcinoma cell line (KB), human cervical carcinoma cell line (CasKi), human colon carcinoma cell line (HCT 116), human hormone-dependent breast carcinoma cell line (MCF7) and human lung carcinoma cell line (A549); and non-cancer human fibroblast cell line (MRC-5) were investigated. Compound 5 possessed very remarkable cytotoxic activity against KB cells, with an IC(50 )value of 0.81microg/mL. This is the first report on the cytotoxic activities of the compounds isolated from Pereskia bleo.

Analysis and Interpretation of Findings Using Multiple Regression Techniques

ERIC Educational Resources Information Center

Hoyt, William T.; Leierer, Stephen; Millington, Michael J.

2006-01-01

Multiple regression and correlation (MRC) methods form a flexible family of statistical techniques that can address a wide variety of different types of research questions of interest to rehabilitation professionals. In this article, we review basic concepts and terms, with an emphasis on interpretation of findings relevant to research questions…

Effects of a Preschool Intervention on Cognitive Development among East-African Preschool Children: A Flexibly Time-Coded Growth Model

ERIC Educational Resources Information Center

Malmberg, Lars-Erik; Mwaura, Peter; Sylva, Kathy

2011-01-01

The aim of the study is to investigate the effects of the Madrasa Resource Center (MRC), a child-centered intervention program, on East-African (Kenya, Zanzibar, and Uganda) preschool children's cognitive development. Altogether 321 children (153 non-intervention and 168 intervention) participated in a cross-sequential study over three time-points…

78 FR 17763 - Housatonic Railroad Company, Inc., Maybrook Railroad Company, and Housatonic Transportation...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-22

... Family Transaction Exemption Housatonic Railroad Company, Inc. (HRRC), Maybrook Railroad Company (MRC... notice of exemption under 49 CFR 1180.2(d)(3) and 1180.2(d)(6) for an intra-corporate family transaction... ownership and common control and are members of the Housatonic corporate family. \\1\\ The Berkshire Line is...

Structure of the vault, a ubiquitous celular component.

PubMed

Kong, L B; Siva, A C; Rome, L H; Stewart, P L

1999-04-15

The vault is a ubiquitous and highly conserved ribonucleoprotein particle of approximately 13 MDa. This particle has been shown to be upregulated in certain multidrug-resistant cancer cell lines and to share a protein component with the telomerase complex. Determination of the structure of the vault was undertaken to provide a first step towards understanding the role of this cellular component in normal metabolism and perhaps to shed some light on its role in mediating drug resistance. Over 1300 particle images were combined to calculate an approximately 31 A resolution structure of the vault. Rotational power spectra did not yield a clear symmetry peak, either because of the thin, smooth walls or inherent flexibility of the vault. Although cyclic eightfold (C8) symmetry was imposed, the resulting reconstruction may be partially cylindrically averaged about the eightfold axis. Our results reveal the vault to be a hollow, barrel-like structure with two protruding caps and an invaginated waist. Although the normal cellular function of the vault is as yet undetermined, the structure of the vault is consistent with either a role in subcellular transport, as previously suggested, or in sequestering macromolecular assemblies.

"Fuzziness" in the celular interactome: a historical perspective.

PubMed

Welch, G Rickey

2012-01-01

Some historical background is given for appreciating the impact of the empirical construct known as the cellular protein-protein interactome, which is a seemingly de novo entity that has arisen of late within the context of postgenomic systems biology. The approach here builds on a generalized principle of "fuzziness" in protein behavior, proposed by Tompa and Fuxreiter.(1) Recent controversies in the analysis and interpretation of the interactome studies are rationalized historically under the auspices of this concept. There is an extensive literature on protein-protein interactions, dating to the mid-1900s, which may help clarify the "fuzziness" in the interactome picture and, also, provide a basis for understanding the physiological importance of protein-protein interactions in vivo.

AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC's 9th AML trial.

PubMed

Hoyle, C F; de Bastos, M; Wheatley, K; Sherrington, P D; Fischer, P J; Rees, J K; Gray, R; Hayhoe, F G

1989-05-01

The outcome of treatment with standard first line therapy of 66 patients with acute myeloid leukaemia (AML) secondary to preceding chemotherapy (Group 1), a myelodysplastic state (Group 2) or a myeloproliferative disorder (Group 3) was analysed in relation to the preceding disorder, the cytogenetic pattern where available, and the cytology and cytochemistry of blood and bone marrow. The complete remission (CR) rate for the secondary AMLs was 36% (24/66), with 24% (16/66) dying in the induction period and 39% (26/66) having resistant disease. The CR rate was 25% (5/20) for Group 1, 42% (15/36) for Group 2, and 40% (4/10) for Group 3. Even after allowance for the generally older age of the secondary AML patients, they still had a significantly poorer CR rate than the de novo AMLs (P = 0.0004). The lower CR rate was chiefly due to resistant disease. Despite this, overall survival was not significantly worse for the secondary AML patients (P = 0.15). For the 36% that achieved remission, remission duration appeared similar to that of de novo cases. Of 62 cases with adequate cytology, 38 (61%) had evidence of erythroid and/or megakaryocytic dysplasia with a CR rate of 32% (12/38). The CR rate of these multineage leukaemias was not significantly different from that of the 24 (39%) who showed granulocyte/monocyte precursor involvement only, 42% (10) of whom achieved CR. The presence of features of differentiation within blast cells such as Auer rods or sudanophilia (greater than 50% positive blasts) was associated with a higher remission rate 47% (18/38) than that of poorly differentiated cases 17% (3/18) (P = 0.04) and thus appeared to be a more important determinant of CR achievement than was lineage involvement. Cases with a normal karyotype had a 33% (7/21) CR rate, while those with chromosomal abnormalities had a 37% (9/24) CR rate. Only 12 of the 45 cases with adequate cytogenetic analysis showed deletions or monosomies involving chromosomes 5 or 7, and seven of

Cognitive function and dementia in six areas of England and Wales: the distribution of MMSE and prevalence of GMS organicity level in the MRC CFA Study. The Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).

PubMed

1998-03-01

This two-stage prevalence survey involved geographically delimited areas, four urban (Liverpool, Newcastle, Nottingham and Oxford) and two rural (Cambridgeshire and Gwynedd), including institutions. Stratified random population samples of people in their 65th year and above, from Family Health Service Authorities were studied. The sample was stratified (65-74 years and > or = 75) to provide equal numbers. In Liverpool equal numbers in 5 year age groups were taken. After an initial screening interview, approximately 20% were selected on the basis of age, AGECAT organicity confidence level and MMSE score to proceed to a detailed assessment interview from which the full AGECAT organicity confidence level could be derived. Major influences on MMSE were confirmed as age, sex, social class and educational level. Estimates of prevalence of AGECAT O3 and above for each centre and the entire sample according to age are given, based on 1991 Census population structure, and suggest that around half a million (543,400) people in England and Wales would be defined as case level by this method. The five centres employing the same methodology showed no heterogeneity in prevalence. Prevalence of cognitive impairment and dementia appear not to vary widely across the centres examined in this study, which provides stable estimates by age and sex for AGECAT O3 and above, and norms for MMSE. Using these estimates as an indication of the size of the population affected, around 550,000 individuals in England and Wales would be expected to be suffering from dementia of mild or greater severity.

"Safe Schools within Safe Communities: A Regional Summit in the Heartland." Policy Briefs Special Report.

ERIC Educational Resources Information Center

Huertas, Aurelio, Jr.; Sullivan, Carol

This report documents the proceedings of a regional policy seminar hosted by the Iowa Department of Education with support from the North Central Regional Educational Laboratory (NCREL) and the Midwest Regional Center for Drug-Free Schools and Communities (MRC). The seminar, "Safe Schools Within Safe Communities," was held on September 19-20,…

Improving the Representational Strategies of Children in a Music-Listening and Playing Task: An Intervention-Based Study

ERIC Educational Resources Information Center

Gil, Vicent; Reybrouck, Mark; Tejada, Jesús; Verschaffel, Lieven

2015-01-01

This intervention-based study focuses on the relation between music and its graphic representation from a meta-representational point of view. It aims to determine whether middle school students show an increase in meta-representational competence (MRC) after an educational intervention. Three classes of 11 to 14-year-old students participated in…

[The role of transforming growth factor-β1/connective tissue growth factor signaling pathway in paraquat-induced pulmonary fibrosis].

PubMed

Li, H H; Cai, Q; Wang, Y P; Liu, H R; Huang, M

2016-07-20

Objective: To investigate the effects of Paraquat on human embryonic lung fibroblasts (MRC5) and explore the role of transforming growth factor-β 1 /connective tissue growth factor signaling pathway in paraquat-induced pulmonary fibrosis. Methods: MRC5 cells were cultured with different concentration of PQ (0, 12.5, 25, 50, 100, 200, 400 μmol/L) for 24 h. The viability of cells was measured by MTT. The protein level of TGF-β 1 were analyzed by ELISA after PQ treatment (0, 25, 50, 100 μmol/L) . To examine whether TGF-β 1 /CTGF signaling pathway was involved in paraquat-induced cytotoxicity, cells was divided into 6 groups: (1) control; (2) 25 μmol/L PQ group; (3) 50 μmol/L PQ group; (4) 100 μmol/L PQ group; (5) TGF-β 1 positive control group (50 μmol/L rhTGF-β 1 ) ; (6) stimulate group (100 μmol/L PQ+50 μmol/L TGF-β 1 ) . The protein levels of p-Smad2, p-Smad3 and CTGF were assayed by western blot. The mRNA level of CTGF was assayed by real time RT-PCR. Results: MTT showed that cell viability decreased with increasing PQ concentration ( P <0.05) . The protein expression of TGF-β 1 treated with PQ (25, 50, 100 μmol/L) significantly increased compared with control in a dose-independent manner ( P <0.05) . Exposure to PQ (25, 50, 100 μmol/L) induced increase of protein levels of p-Smad2 and p-Smad3. Noteworthy, the expression of p-Smad2 and p-Smad3 were dramatically increased following PQ plus TGF-β 1 stimulation ( P <0.05) . Exposure to PQ (50, 100μmol/L) induced increase of CTGF protein expression and similar greatly increase following PQ plus TGF-β 1 stimulation ( P <0.05) . Real time RT-PCR showed CTGF mRNA in all groups also significantly up-regulated compared with control ( P <0.05) . Conclusion: TGF-β 1 regulates the expression of target gene CTGF to exhibit its pro-fibrogenic effects by activating TGF-β 1 /Smad signaling pathway in PQ-induced pulmonary fibrosis.

In-patient rehabilitation in haemophilic subjects with total knee arthroplasty.

PubMed

Viliani, T; Zambelan, G; Pandolfi, C; Martini, C; Morfini, M; Pasquetti, P; Innocenti, M

2011-09-01

Total knee arthroplasty (TKA) is a major orthopaedic surgery intervention, indicated for severe haemophilic arthropathy. The aim of our study was to analyse rehabilitation outcome in haemophilic patients after TKA. A consecutive series of 21 patients (23 knees) was retrospectively evaluated. The mean age was 37 ± 8 years (range 22-55). Physiotherapy treatment was performed twice a day for 5 days week⁻¹, for 3 h day⁻¹. Assessment included knee range of motion (ROM), Visual Analogue Scale (VAS) for pain evaluation, Western Ontario and McMaster University (WOMAC) Score for functional outcome, Medical Research Council Scale (MRC) for quadriceps muscle strength evaluation, incidence of adverse events and a self-reported questionnaire. The patients'data were recorded before surgery (t0), at Rehabilitation Unit admission (t1), before discharge (t2) and at follow-up (t3), 11-48 months after rehabilitation. Western Ontario and McMaster University Score (ref. score: 0-96) was 56.7 ± 12 at t0 and 6.2 ± 6 at t3 (t3 vs. t0: P < 0.001). Visual Analogue Scale (ref. score: 0-10) decreased from 5.0 ± 2 at t1 to 2.1 ± 2 at t2 (t2 vs. t1: P < 0.05) and to 0.1 ± 0 at t3 (t3 vs. t2: P < 0.05). Flexion degrees increased from 43.4 ± 21° at t1 to 80.2 ± 15° at t2 (t2 vs. t1: P < 0.001) and to 95.0 ± 15° at t3 (t3 vs t2: P < 0.05). According to MRC (ref. score: 0-5), quadriceps muscle strength increased from 2.3 ± 0.6 at t1 to 3.6 ± 0.5 at t2 (t2 vs. t1: P < 0.05). Adverse events were found in four patients. Patients' satisfaction on their outcome at follow-up was referred as good by 72% of patients or excellent by 28% of patients. Postsurgical intensive rehabilitation in haemophilic patients resulted effective, safe and feasible. © 2011 Blackwell Publishing Ltd.

Involvement of consumers in studies run by the Medical Research Council Clinical Trials Unit: Results of a survey

PubMed Central

2012-01-01

Background We aimed to establish levels of consumer involvement in randomised controlled trials (RCTs), meta-analyses and other studies carried out by the UK Medical Research Council (MRC) Clinical Trials Unit across the range of research programs, predominantly in cancer and HIV. Methods Staff responsible for studies that were included in a Unit Progress Report (MRC CTU, April 2009) were asked to complete a semi-structured questionnaire survey regarding consumer involvement. This was defined as active involvement of consumers as partners in the research process and not as subjects of that research. The electronic questionnaires combined open and closed questions, intended to capture quantitative and qualitative information on whether studies had involved consumers; types of activities undertaken; recruitment and support; advantages and disadvantages of involvement and its perceived impact on aspects of the research. Results Between October 2009 and April 2010, 138 completed questionnaires (86%) were returned. Studies had been conducted over a 20 year period from 1989, and around half were in cancer; 30% in HIV and 20% were in other disease areas including arthritis, tuberculosis and blood transfusion medicine. Forty-three studies (31%) had some consumer involvement, most commonly as members of trial management groups (TMG) [88%]. A number of positive impacts on both the research and the researcher were identified. Researchers generally felt involvement was worthwhile and some felt that consumer involvement had improved the credibility of the research. Benefits in design and quality, trial recruitment, dissemination and decision making were also perceived. Researchers felt they learned from consumer involvement, albeit that there were some barriers. Conclusions Whilst most researchers identified benefits of involving consumers, most of studies included in the survey had no involvement. Information from this survey will inform the development of a unit policy on

Away-from-home family dinner sources and associations with weight status, body composition and related biomarkers of chronic disease among adolescents and their parents

PubMed Central

Farbakhsh, Kian; Lytle, Leslie; Hearst, Mary O.; Dengel, Donald R.; Pasch, Keryn E.; Kubik, Martha Y.

2011-01-01

Information regarding associations between types of away-from-home family meal sources and obesity and other chronic diseases could help guide dietitians. The present study describes the purchase frequency of away-from-home food sources for family dinner (fast food, other restaurant purchases, home delivery, and take-out foods) and associations with weight status and percent body fat among adolescents (n=723) and parents (n=723) and related biomarkers of chronic disease among adolescents (n=367). A cross-sectional study design was used with baseline parent surveys and anthropometry/fasting blood samples from two community-based obesity studies (2006–2008) in Minnesota. Logistic regression and general linear modeling assessed associations between frequency of family dinner sources (weekly versus none in past week) and outcomes (parent and adolescent overweight/obesity and percent body fat; adolescent metabolic risk cluster z-score (MRC), cholesterol, HDL-C, LDL, triglycerides, fasting glucose, insulin and systolic blood pressure. Models accounted for clustering and adjusted for study allocation, baseline meal frequency and demographic characteristics. The odds of overweight/obesity were significantly greater when families reported at least one away-from-home dinner purchase in the past week (OR=1.2–2.6). Mean percent body fat, MRC z-scores and insulin levels were significantly greater with weekly purchases of family dinner from fast food restaurants (p’s < .05). Mean percent body fat, MRC z-scores and HDL levels were significantly higher for families who purchased weekly family dinner from take-out sources (p’s < .05). Although frequent family dinners may be beneficial for adolescents, the source of dinners is likely as important in maintaining a healthy weight. Interventions should focus on encouragement of healthful family meals. PMID:22117665

Comparative study of phrenic and intercostal nerve transfers for elbow flexion after global brachial plexus injury.

PubMed

Liu, Yuzhou; Lao, Jie; Zhao, Xin

2015-04-01

Global brachial plexus injuries (BPIs) are devastating events frequently resulting in severe functional impairment. The widely used nerve transfer sources for elbow flexion in patients with global BPIs include intercostal and phrenic nerves. The aim of this study was to compare phrenic and intercostal nerve transfers for elbow flexion after global BPI. A retrospective review of 33 patients treated with phrenic and intercostal nerve transfer for elbow flexion in posttraumatic global root avulsion BPI was carried out. In the phrenic nerve transfer group, the phrenic nerve was transferred to the anterolateral bundle of the anterior division of the upper trunk (23 patients); in the intercostal nerve transfer group, three intercostal nerves were coapted to the anterolateral bundles of the musculocutaneous nerve. The British Medical Research Council (MRC) grading system, angle of elbow flexion, and electromyography (EMG) were used to evaluate the recovery of elbow flexion at least 3 years postoperatively. The efficiency of motor function in the phrenic nerve transfer group was 83%, while it was 70% in the intercostal nerve transfer group. The two groups were not statistically different in terms of the MRC grade (p=0.646) and EMG results (p=0.646). The outstanding rates of angle of elbow flexion were 48% and 40% in the phrenic and intercostal nerve transfer groups, respectively. There was no significant difference of outstanding rates in the angle of elbow flexion between the two groups. Phrenic nerve transfer had a higher proportion of good prognosis for elbow flexion than intercostal nerve transfer, but the effective and outstanding rate had no significant difference for biceps reinnervation between the two groups according to MRC grading, angle of elbow flexion, and EMG. Copyright © 2014 Elsevier Ltd. All rights reserved.

Magnetic MIMO Signal Processing and Optimization for Wireless Power Transfer

NASA Astrophysics Data System (ADS)

Yang, Gang; Moghadam, Mohammad R. Vedady; Zhang, Rui

2017-06-01

In magnetic resonant coupling (MRC) enabled multiple-input multiple-output (MIMO) wireless power transfer (WPT) systems, multiple transmitters (TXs) each with one single coil are used to enhance the efficiency of simultaneous power transfer to multiple single-coil receivers (RXs) by constructively combining their induced magnetic fields at the RXs, a technique termed "magnetic beamforming". In this paper, we study the optimal magnetic beamforming design in a multi-user MIMO MRC-WPT system. We introduce the multi-user power region that constitutes all the achievable power tuples for all RXs, subject to the given total power constraint over all TXs as well as their individual peak voltage and current constraints. We characterize each boundary point of the power region by maximizing the sum-power deliverable to all RXs subject to their minimum harvested power constraints. For the special case without the TX peak voltage and current constraints, we derive the optimal TX current allocation for the single-RX setup in closed-form as well as that for the multi-RX setup. In general, the problem is a non-convex quadratically constrained quadratic programming (QCQP), which is difficult to solve. For the case of one single RX, we show that the semidefinite relaxation (SDR) of the problem is tight. For the general case with multiple RXs, based on SDR we obtain two approximate solutions by applying time-sharing and randomization, respectively. Moreover, for practical implementation of magnetic beamforming, we propose a novel signal processing method to estimate the magnetic MIMO channel due to the mutual inductances between TXs and RXs. Numerical results show that our proposed magnetic channel estimation and adaptive beamforming schemes are practically effective, and can significantly improve the power transfer efficiency and multi-user performance trade-off in MIMO MRC-WPT systems.

Involvement of consumers in studies run by the Medical Research Council Clinical Trials Unit: results of a survey.

PubMed

Vale, Claire L; Thompson, Lindsay C; Murphy, Claire; Forcat, Silvia; Hanley, Bec

2012-01-13

We aimed to establish levels of consumer involvement in randomised controlled trials (RCTs), meta-analyses and other studies carried out by the UK Medical Research Council (MRC) Clinical Trials Unit across the range of research programs, predominantly in cancer and HIV. Staff responsible for studies that were included in a Unit Progress Report (MRC CTU, April 2009) were asked to complete a semi-structured questionnaire survey regarding consumer involvement. This was defined as active involvement of consumers as partners in the research process and not as subjects of that research. The electronic questionnaires combined open and closed questions, intended to capture quantitative and qualitative information on whether studies had involved consumers; types of activities undertaken; recruitment and support; advantages and disadvantages of involvement and its perceived impact on aspects of the research. Between October 2009 and April 2010, 138 completed questionnaires (86%) were returned. Studies had been conducted over a 20 year period from 1989, and around half were in cancer; 30% in HIV and 20% were in other disease areas including arthritis, tuberculosis and blood transfusion medicine. Forty-three studies (31%) had some consumer involvement, most commonly as members of trial management groups (TMG) [88%]. A number of positive impacts on both the research and the researcher were identified. Researchers generally felt involvement was worthwhile and some felt that consumer involvement had improved the credibility of the research. Benefits in design and quality, trial recruitment, dissemination and decision making were also perceived. Researchers felt they learned from consumer involvement, albeit that there were some barriers. Whilst most researchers identified benefits of involving consumers, most of studies included in the survey had no involvement. Information from this survey will inform the development of a unit policy on consumer involvement, to guide future

The Diagnosis and Management of Auditory Processing Disorder

ERIC Educational Resources Information Center

Moore, David R.

2011-01-01

Purpose: To provide a personal perspective on auditory processing disorder (APD), with reference to the recent clinical forum on APD and the needs of clinical speech-language pathologists and audiologists. Method: The Medical Research Council-Institute of Hearing Research (MRC-IHR) has been engaged in research into APD and auditory learning for 8…

China on the Mekong: Legitimacy Imperatives and Policy Case Studies

DTIC Science & Technology

2013-12-01

1  B.  IMPORTANCE ................................................................................................1  C.  PROBLEMS...gross domestic product GMS Greater Mekong Subregion HDI human development indicators MRC Mekong River Commission MOU memoranda of understanding MPS...home affect China’s policies along the Mekong River? B. IMPORTANCE A careful investigation of PRC policies on the Mekong River will contribute to a

Should sensory function after median nerve injury and repair be quantified using two-point discrimination as the critical measure?

PubMed

Jerosch-Herold, C

2000-12-01

Two-point discrimination (2PD) is widely used for evaluating outcome from peripheral nerve injury and repair. It is the only quantifiable measure used in the British Medical Research Council (MRC) classification that was developed by Highet in 1954. This paper reports the results of a study of 41 patients with complete median nerve lacerations to the wrist or forearm. Two-point discrimination thresholds were assessed together with locognosia (locognosia is the ability to localise a sensory stimulus on the body's surface), tactile gnosis, and touch threshold. Using the MRC classification 29 (71%) patients had a result of S2 or below, 11 (27%) were S3, and only one scored S3+. Patients scored much better on the other tests and showed progressive recovery. It remains too difficult for patients to obtain a measurable threshold value on 2PD and the test therefore lacks responsiveness. The rating of outcome from peripheral nerve repair should not be based solely on 2PD testing and must include other tests of tactile sensibility.

Frequency, location, and association with dental pathology of mucous retention cysts in the maxillary sinus. A radiographic study using cone beam computed tomography (CBCT).

PubMed

Yeung, Andy Wai Kan; Tanaka, Ray; Khong, Pek-Lan; von Arx, Thomas; Bornstein, Michael M

2018-04-01

The purpose of the present study was to evaluate the frequency, locations, and dimensions of mucous retention cysts of the maxillary sinus and analyze potential associated dental pathology. A total of 156 cone beam computed tomography (CBCT) scans were included in the analysis, resulting in an evaluation of 310 maxillary sinuses. The presence of mucous retention cysts (MRC) manifesting as dome-shaped radiopacities in the sinus was diagnosed. Their locations were recorded, and dimensions (mm) were measured in coronal and sagittal/axial slices. The patients were grouped into (a) patients/sinuses with MRCs (test), and (b) patients/sinuses with healthy or any other changes (control) for further comparison and evaluation. There were 40 sinuses (12.9%) with a presence of a total of 56 MRCs. The mean age of involved patients was 29.0 years. The analysis showed that gender, age, sinus side, status of dentition, endodontic status, and periodontal status did not have a significant influence on the presence of MRCs when compared between test and control groups. Age and endodontic status exhibited a significant association with cyst location. Most of the sinuses analyzed (79.5%) did not present any MRC, and only 28.6% of the cysts diagnosed were found on the floor of the maxillary sinus. The mean dimension of the MRCs measured 6.28 ± 2.93 mm. No influencing factors on the presence or absence of MRCs were found in the present study. Most MRCs were not located on the floor of maxillary sinus. Future studies should assess their impact on surgical interventions in the sinus.

Comparative analyses of gene copy number and mRNA expression in GBM tumors and GBM xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodgson, J. Graeme; Yeh, Ru-Fang; Ray, Amrita

2009-04-03

Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors,more » genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.« less

Medical Reserve Corps Volunteers’ Ability and Willingness to Report to Work for the Department of Health During Catastrophic Disasters

DTIC Science & Technology

2007-03-01

National Security Affairs iv THIS PAGE INTENTIONALLY LEFT BLANK v ABSTRACT Local public health systems ...assist in fulfilling their MRC role. As key enablers and modifiers of risk perception, these two manageable characteristics of potential emergency...Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188

Nonparametric Estimation of the Probability of Ruin.

DTIC Science & Technology

1985-02-01

MATHEMATICS RESEARCH CENTER I E N FREES FEB 85 MRC/TSR...in NONPARAMETRIC ESTIMATION OF THE PROBABILITY OF RUIN Lf Edward W. Frees * Mathematics Research Center University of Wisconsin-Madison 610 Walnut...34 - .. --- - • ’. - -:- - - ..- . . .- -- .-.-. . -. . .- •. . - . . - . . .’ . ’- - .. -’vi . .-" "-- -" ,’- UNIVERSITY OF WISCONSIN-MADISON MATHEMATICS RESEARCH CENTER NONPARAMETRIC ESTIMATION OF THE PROBABILITY

Multi-cellular human bronchial models exposed to diesel exhaust particles: assessment of inflammation, oxidative stress and macrophage polarization.

PubMed

Ji, Jie; Upadhyay, Swapna; Xiong, Xiaomiao; Malmlöf, Maria; Sandström, Thomas; Gerde, Per; Palmberg, Lena

2018-05-02

Diesel exhaust particles (DEP) are a major component of outdoor air pollution. DEP mediated pulmonary effects are plausibly linked to inflammatory and oxidative stress response in which macrophages (MQ), epithelial cells and their cell-cell interaction plays a crucial role. Therefore, in this study we aimed at studying the cellular crosstalk between airway epithelial cells with MQ and MQ polarization following exposure to aerosolized DEP by assessing inflammation, oxidative stress, and MQ polarization response markers. Lung mucosa models including primary bronchial epithelial cells (PBEC) cultured at air-liquid interface (ALI) were co-cultured without (PBEC-ALI) and with MQ (PBEC-ALI/MQ). Cells were exposed to 12.7 μg/cm 2 aerosolized DEP using XposeALI ® . Control (sham) models were exposed to clean air. Cell viability was assessed. CXCL8 and IL-6 were measured in the basal medium by ELISA. The mRNA expression of inflammatory markers (CXCL8, IL6, TNFα), oxidative stress (NFKB, HMOX1, GPx) and MQ polarization markers (IL10, IL4, IL13, MRC1, MRC2 RETNLA, IL12 andIL23) were measured by qRT-PCR. The surface/mRNA expression of TLR2/TLR4 was detected by FACS and qRT-PCR. In PBEC-ALI exposure to DEP significantly increased the secretion of CXCL8, mRNA expression of inflammatory markers (CXCL8, TNFα) and oxidative stress markers (NFKB, HMOX1, GPx). However, mRNA expressions of these markers (CXCL8, IL6, NFKB, and HMOX1) were reduced in PBEC-ALI/MQ models after DEP exposure. TLR2 and TLR4 mRNA expression increased after DEP exposure in PBEC-ALI. The surface expression of TLR2 and TLR4 on PBEC was significantly reduced in sham-exposed PBEC-ALI/MQ compared to PBEC-ALI. After DEP exposure surface expression of TLR2 was increased on PBEC of PBEC-ALI/MQ, while TLR4 was decreased in both models. DEP exposure resulted in similar expression pattern of TLR2/TLR4 on MQ as in PBEC. In PBEC-ALI/MQ, DEP exposure increased the mRNA expression of anti-inflammatory M2 macrophage

The possibility of using remote sensing technology of lidar for monitoring ecosystem health by detecting habitat condition

NASA Astrophysics Data System (ADS)

Huseyinoglu, M. F.; Salaeva, Z.; Secgin, A.; Allakhverdiev, S. R.; Allakhverdiev, K. R.

2012-01-01

Since the emergence of laser and henceforth laser remote sensing in the 1960's, lidar (light detecting and ranging) technology has became a significant tool for the detection of various phenomena like wind direction and intensity, atmospheric temperature, urban and rural topography, forest fires, ocean planktonic development, and detection of various constituants such as tropospheric aerosols, stratospheric ozone, trace chemicals and etc. In 2009, a homemade multiwavelength Raman aerosol lidar (named MRC K09) was designed, developed and installed in the Scientific and Technological Research Council of Turkey (TUBITAK) Marmara Research Center (MRC), and since 21 February 2011, it has been accepted to EARLINET (European Aerosol Research Lidar Network). Since 2009, aerosol spatio-temporal distribution and microphysical properties have been investigated in the extremely industrialized vicinity [1,2]. MRC K09 lidar uses a Quantel Brilliant B Nd:YAG laser (1064 nm) with the second and third optical harmonics at 532 and 355 nm, and a homemade Newtonian 40 cm aperture 120 cm focal length telescope. It has 7 channel spectrum analyzer detecting: parallel and perpendicular polarizations at 355 nm, elastic signals at 532 and 1064 nm, Raman signal of molecular nitrogen at 387 nm and Raman signal of water vapor at 408 nm (excited with 355 laser line), and Raman signal for molecular nitrogen at 608 nm (excited with 532 nm laser line). In Spring 2010, preliminary applications for the determination of forest tree species and of forest health in the Black Sea Area using an aeroborne lidar in collaboration with Bartin University, Bartin, Turkey have been made. In early 2011, a fluorescence module utilizing a Princeton Instruments PI-MAX3 1024x256 resolution CCD camera with a Princeton Instruments Acton SP 2500 0.500 m Imaging Triple Grating Monochromator/Spectograph was connected to the MRC K09 lidar system, and the first remote measurements of chlorophyll from different types of

Effect of the anti-neoplastic drug doxorubicin on XPD-mutated DNA repair-deficient human cells.

PubMed

Saffi, Jenifer; Agnoletto, Mateus H; Guecheva, Temenouga N; Batista, Luís F Z; Carvalho, Helotonio; Henriques, João A P; Stary, Anne; Menck, Carlos F M; Sarasin, Alain

2010-01-02

Doxorubicin (DOX), a member of the anthracycline group, is a widely used drug in cancer therapy. The mechanisms of DOX action include topoisomerase II-poisoning, free radical release, DNA adducts and interstrand cross-link (ICL) formation. Nucleotide excision repair (NER) is involved in the removal of helix-distorting lesions and chemical adducts, however, little is known about the response of NER-deficient cell lines to anti-tumoral drugs like DOX. Wild type and XPD-mutated cells, harbouring mutations in different regions of this gene and leading to XP-D, XP/CS or TTD diseases, were treated with this drug and analyzed for cell cycle arrest and DNA damage by comet assay. The formation of DSBs was also investigated by determination of gammaH2AX foci. Our results indicate that all three NER-deficient cell lines tested are more sensitive to DOX treatment, when compared to wild type cells or XP cells complemented by the wild type XPD cDNA, suggesting that NER is involved in the removal of DOX-induced lesions. The cell cycle analysis showed the characteristic G2 arrest in repair-proficient MRC5 cell line after DOX treatment, whereas the repair-deficient cell lines presented significant increase in sub-G1 fraction. The NER-deficient cell lines do not show different patterns of DNA damage formation as assayed by comet assay and phosphorylated H2AX foci formation. Knock-down of topoisomerase IIalpha with siRNA leads to increased survival in both MRC5 and XP cells, however, XP cell line still remained significantly more sensitive to the treatment by DOX. Our study suggests that the enhanced sensitivity is due to DOX-induced DNA damage that is subject to NER, as we observed decreased unscheduled DNA synthesis in XP-deficient cells upon DOX treatment. Furthermore, the complementation of the XPD-function abolished the observed sensitivity at lower DOX concentrations, suggesting that the XPD helicase activity is involved in the repair of DOX-induced lesions. Copyright (c) 2009

The International Cytokine Conference (11th) Held in Dublin (Ireland) on September 20-24 2003 (European Cytokine Network, Volume 14, Number 3, September 2003)

DTIC Science & Technology

2003-09-01

Fisiologia Celular UNAM, Mexico City/ Mexico specific marker of bacterial sepsis. Despite the increasing clinical importance of PCT the knowledge about its...about their function or scription factor NF-kappaB. Likewise, Varicella -zoster virus strongly mechanism of action. activates the AP- 1 components Jun and

Respiratory symptoms and pulmonary function impairment among detergent plant workers in Jos, Northern Nigeria.

PubMed

Babashani, M; Iliyasu, Z; Ukoli, C O

2008-01-01

The industrial process of detergent production could be deleterious to lung function. This study describes respiratory symptoms and ventilatory function impairment among detergent workers in Jos, Northern Nigeria. Two hundred detergent plant workers and controls were studied for the presence of respiratory symptoms and ventilatory function impairment using the MRC questionnaire and Spirometry. A significantly higher proportion of exposed detergent workers 178 (87.0%) reported respiratory symptoms compared to 52 (26.0%) controls [OR=23; 95% CI=12.9-41.3] (P<0.001). Commonest symptoms include rhinitis (57.5% versus 11.0%) and cough (48.5% versus 15%). Symptoms were most prevalent in the packaging section. FEV1, FVC and PEFR were significantly reduced among exposed detergent workers. Similarly, the predicted values of PEFR, FVC and FEV1, were significantly reduced among smokers (P<0. 001). Respiratory symptoms are highly prevalent among detergent workers. This was associated with impaired pulmonary function. Protective equipment and periodic lung function tests could reduce these effects.

N,N'-disubstituted cinnamamide derivatives potentiate ciprofloxacin activity against overexpressing NorA efflux pump Staphylococcus aureus 1199B strains.

PubMed

Radix, Sylvie; Jordheim, Anne Doléans; Rocheblave, Luc; N'Digo, Serge; Prignon, Anne-Laure; Commun, Carine; Michalet, Serge; Dijoux-Franca, Marie-Geneviève; Mularoni, Angélique; Walchshofer, Nadia

2018-04-25

A multi-step procedure has been described which afforded satisfactory yields of N,N'-disubstituted cinnamamides derived from N-Boc-protected amino acids (Boc-Gly, Boc-Val, Boc-Phe). The key step of this synthesis was a regioselective RedAl reduction of an amide function in presence of a carbamate group. Next, these cinnamamides were evaluated in co-admnistration with ciprofloxacin as efflux pump inhibitors against two S. aureus strains, NorA overexpressing SA1199B and wild type SA1199. In parallel, their intrinsic toxicity was appreciated on human lung fibroblast MRC5 cells. Therefore, the cinnamamide combining both carbamate and indol-3-yl groups, was found to be the most active and one of the less toxic EPI and constituted a promising hit. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cytotoxic Withanolide Constituents of Physalis longifolia

PubMed Central

Zhang, Huaping; Samadi, Abbas K.; Gallagher, Robert J.; Araya, Juan J.; Tong, Xiaoqin; Day, Victor W.; Cohen, Mark S.; Kindscher, Kelly; Gollapudi, Rao; Timmermann, Barbara N.

2011-01-01

Fourteen new withanolides 1-14, named withalongolides A-N, respectively, were isolated from the aerial parts of Physalis longifolia together with eight known compounds (15-22). The structures of compounds 1-14 were elucidated through spectroscopic techniques and chemical methods. In addition, the structures of withanolides 1, 2, 3, and 6 were confirmed by X-ray crystallographic analysis. Using a MTS viability assays, eight withanolides (1, 2, 3, 7, 8, 15, 16, and 19) and four acetylated derivatives (1a, 1b, 2a, and 2b) showed potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal fibroblast (MRC-5) cells with IC50 values in the range between 0.067 and 9.3 μM. PMID:22098611

Clinical variables impacting on the estimation of utilities in chronic obstructive pulmonary disease

PubMed Central

Miravitlles, Marc; Huerta, Alicia; Valle, Manuel; García-Sidro, Patricia; Forné, Carles; Crespo, Carlos; López-Campos, José Luis

2015-01-01

Purpose Health utilities are widely used in health economics as a measurement of an individual’s preference and show the value placed on different health states over a specific period. Thus, health utilities are used as a measure of the benefits of health interventions in terms of quality-adjusted life years. This study aimed to determine the demographic and clinical variables significantly associated with health utilities for chronic obstructive pulmonary disease (COPD) patients. Patients and methods This was a multicenter, observational, cross-sectional study conducted between October 2012 and April 2013. Patients were aged ≥40 years, with spirometrically confirmed COPD. Utility values were derived from the preference-based generic questionnaire EQ-5D-3L applying weighted Spanish societal preferences. Demographic and clinical variables associated with utilities were assessed by univariate and multivariate linear regression models. Results Three hundred and forty-six patients were included, of whom 85.5% were male. The mean age was 67.9 (standard deviation [SD] =9.7) years and the mean forced expiratory volume in 1 second (%) was 46.2% (SD =15.5%); 80.3% were former smokers, and the mean smoking history was 54.2 (SD =33.2) pack-years. Median utilities (interquartile range) were 0.81 (0.26) with a mean value of 0.73 (SD =0.29); 22% of patients had a utility value of 1 (ceiling effect) and 3.2% had a utility value lower than 0. The factors associated with utilities in the multivariate analysis were sex (beta =-0.084, 95% confidence interval [CI]: −0.154; -0.013 for females), number of exacerbations the previous year (−0.027, 95% CI: −0.044; -0.010), and modified Medical Research Council Dyspnea Scale (mMRC) score (−0.123 [95% CI: −0.185; −0.061], −0.231 [95% CI: −0.301; −0.161], and −0.559 [95% CI: −0.660; −0.458] for mMRC scores 2, 3, and 4 versus 1), all P<0.05. Conclusion Multivariate analysis showed that female sex, frequent

Home-based Computer Assisted Arm Rehabilitation (hCAAR) robotic device for upper limb exercise after stroke: results of a feasibility study in home setting.

PubMed

Sivan, Manoj; Gallagher, Justin; Makower, Sophie; Keeling, David; Bhakta, Bipin; O'Connor, Rory J; Levesley, Martin

2014-12-12

Home-based robotic technologies may offer the possibility of self-directed upper limb exercise after stroke as a means of increasing the intensity of rehabilitation treatment. The current literature has a paucity of robotic devices that have been tested in a home environment. The aim of this research project was to evaluate a robotic device Home-based Computer Assisted Arm Rehabilitation (hCAAR) that can be used independently at home by stroke survivors with upper limb weakness. hCAAR device comprises of a joystick handle moved by the weak upper limb to perform tasks on the computer screen. The device provides assistance to the movements depending on users ability. Nineteen participants (stroke survivors with upper limb weakness) were recruited. Outcome measures performed at baseline (A0), at end of 8-weeks of hCAAR use (A1) and 1 month after end of hCAAR use (A2) were: Optotrak kinematic variables, Fugl Meyer Upper Extremity motor subscale (FM-UE), Action Research Arm Test (ARAT), Medical Research Council (MRC) and Modified Ashworth Scale (MAS), Chedoke Arm and Hand Activity Inventory (CAHAI) and ABILHAND. Two participants were unable to use hCAAR: one due to severe paresis and the other due to personal problems. The remaining 17 participants were able to use the device independently in their home setting. No serious adverse events were reported. The median usage time was 433 minutes (IQR 250 - 791 min). A statistically significant improvement was observed in the kinematic and clinical outcomes at A1. The median gain in the scores at A1 were by: movement time 19%, path length 15% and jerk 19%, FM-UE 1 point, total MAS 1.5 point, total MRC 2 points, ARAT 3 points, CAHAI 5.5 points and ABILHAND 3 points. Three participants showed clinically significant improvement in all the clinical outcomes. The hCAAR feasibility study is the first clinical study of its kind reported in the current literature; in this study, 17 participants used the robotic device independently

Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation.

PubMed

Yang, Lina; Liu, Yuanyuan; Sun, Chao; Yang, Xinrui; Yang, Zhen; Ran, Juntao; Zhang, Qiuning; Zhang, Hong; Wang, Xinyu; Wang, Xiaohu

2015-11-01

Non-small cell lung cancer (NSCLC) exhibits radioresistance to conventional rays, due to its DNA damage repair systems. NSCLC may potentially be sensitized to radiation treatment by reducing those factors that continuously enhance the repair of damaged DNA. In the present study, normal lung fibroblast MRC-5 and lung cancer A549 cells were treated with NU7026 and CGK733, which are inhibitors of the DNA-dependent protein kinase catalytic subunit (PKcs) and ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR), respectively, followed by exposure to X-rays and carbon ion irradiation. The cytotoxic activity, cell survival rate, DNA damage repair ability, cell cycle arrest and apoptosis rate of the treated cells were analyzed with MTT assay, colony formation assay, immunofluorescence and flow cytometry, respectively. The transcription and translation levels of the ATM, ATR and DNA-PKcs genes were detected by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The results indicated that the radiosensitivity and DNA repair ability of A549 cells were reduced, and the percentages of apoptotic cells and those arrested at the G 2 /M phase of the cell cycle were significantly increased, following ionizing radiation with inhibitor-pretreatment. The expression levels of ATM, ATR, DNA-PKcs and phosphorylated histone H2AX, a biomarker for DNA double-strand breaks, were all upregulated at the transcriptional or translational level in A549 cells treated with carbon ion irradiation, compared with the control and X-rays-treated cells. In addition, the treatment with 5-50 µM NU7026 or CGK733 did not produce any obvious cytotoxicity in MRC-5 cells, and the effect of the DNA-PKcs-inhibitor on enhancing the radiosensitivity of A549 cells was stronger than that observed for the ATM and ATR-inhibitor. These findings demonstrated a minor role for ATM and ATR in radiation-induced cell death, since the upregulation of

A User Oriented Review of the Literature on the Effects of Sleep Loss, Work-Rest Schedules, and Recovery on Performance

DTIC Science & Technology

1974-12-01

Martin , 0. E. and Alluisi, E. A., "Human Performance as a Function of the Work-Rest Cycle: A Review of Selected Studies," National Academy.of Sciences...WilKinson, R. T., "One Stress on Top of Another," New So0eety, 12 JOly 1972, 72-75 52. Wilkinson, R. T., "Sleep Deprivation-Eight Questions," MRC

Mass Vertical Envelopment (Airborne) Operations: A Critical Capability in the Army After Next?

DTIC Science & Technology

2002-06-01

purpose of this thesis is to review the viability of mass airborne operations in the context of today’s modern war environment, specifically in a Major...context of today’s modern war environment, specifically in a Major Regional Contingency (MRC) scenario as outlined in the most current Quadrennial...8 1. World War II........................................................................................8 a. Invasion of Sicily (Operation Husky

Watershed Analysis Results for Mendocino Redwood Company Lands in Coastal Mendocino and Sonoma Counties

Treesearch

Christopher G. Surfleet

2007-01-01

To assess the needs for conservation, restoration and condition of aquatic habitat within its land Mendocino Redwood Company (MRC) has been conducting watershed analysis. From watershed analysis completed to date, we estimate 73percent of the total sediment inputs over the last 30 to 40 years are road and skid trail associated. Of that percentage 30 percent is road and...

Inviability of a DNA2 deletion mutant is due to the DNA damage checkpoint.

PubMed

Budd, Martin E; Antoshechkin, Igor A; Reis, Clara; Wold, Barbara J; Campbell, Judith L

2011-05-15

Dna2 is a dual polarity exo/endonuclease, and 5' to 3' DNA helicase involved in Okazaki Fragment Processing (OFP) and Double-Strand Break (DSB) Repair. In yeast, DNA2 is an essential gene, as expected for a DNA replication protein. Suppression of the lethality of dna2Δ mutants has been found to occur by two mechanisms: overexpression of RAD27 (scFEN1) , encoding a 5' to 3' exo/endo nuclease that processes Okazaki fragments (OFs) for ligation, or deletion of PIF1, a 5' to 3' helicase involved in mitochondrial recombination, telomerase inhibition and OFP. Mapping of a novel, spontaneously arising suppressor of dna2Δ now reveals that mutation of rad9 and double mutation of rad9 mrc1 can also suppress the lethality of dna2Δ mutants. Interaction of dna2Δ and DNA damage checkpoint mutations provides insight as to why dna2Δ is lethal but rad27Δ is not, even though evidence shows that Rad27 (ScFEN1) processes most of the Okazaki fragments, while Dna2 processes only a subset.

Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial

PubMed Central

Sebag-Montefiore, David; Stephens, Richard J; Steele, Robert; Monson, John; Grieve, Robert; Khanna, Subhash; Quirke, Phil; Couture, Jean; de Metz, Catherine; Myint, Arthur Sun; Bessell, Eric; Griffiths, Gareth; Thompson, Lindsay C; Parmar, Mahesh

2009-01-01

Summary Background Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy. Methods We undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842. Findings At the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0·39, 95% CI 0·27–0·58, p<0·0001), and an absolute difference at 3 years of 6·2% (95% CI 5·3–7·1) (4·4% preoperative radiotherapy vs 10·6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0·76, 95% CI 0·62–0·94, p=0·013), and an absolute difference at 3 years of 6·0% (95% CI 5·3–6·8) (77·5% vs 71·5%). Overall survival did not differ between the groups (HR 0·91, 95% CI

Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

PubMed

Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

2015-07-02

Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

The nature and ethics of natural experiments.

PubMed

Dawson, Angus; Sim, Julius

2015-10-01

Natural experiments are an important methodology often used to answer research questions that would, otherwise, be impossible to address, or employed because of ethical concerns about the use of randomisation to interventions that carry known risks. The UK Medical Research Council (MRC) recently produced an extremely useful document discussing the nature and significance of natural experiments within medical and public health research. In this paper, however, we suggest that the MRC document's definition of the term 'natural experiment' is insufficiently precise. In response, we offer a taxonomy of different types of natural experiments and related methods, and explore the ethical implications of these different types. We argue that while the ethical issues that may arise within natural experiments in relation to risks of harm or informed consent may differ from those within the randomised controlled trial, they are not thereby less pressing. The implications of the argument are explored and recommendations made for those involved in research governance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Multiple-methods investigation of recharge at a humid-region fractured rock site, Pennsylvania, USA

USGS Publications Warehouse

Heppner, C.S.; Nimmo, J.R.; Folmar, G.J.; Gburek, W.J.; Risser, D.W.

2007-01-01

Lysimeter-percolate and well-hydrograph analyses were combined to evaluate recharge for the Masser Recharge Site (central Pennsylvania, USA). In humid regions, aquifer recharge through an unconfined low-porosity fractured-rock aquifer can cause large magnitude water-table fluctuations over short time scales. The unsaturated hydraulic characteristics of the subsurface porous media control the magnitude and timing of these fluctuations. Data from multiple sets of lysimeters at the site show a highly seasonal pattern of percolate and exhibit variability due to both installation factors and hydraulic property heterogeneity. Individual event analysis of well hydrograph data reveals the primary influences on water-table response, namely rainfall depth, rainfall intensity, and initial water-table depth. Spatial and seasonal variability in well response is also evident. A new approach for calculating recharge from continuous water-table elevation records using a master recession curve (MRC) is demonstrated. The recharge estimated by the MRC approach when assuming a constant specific yield is seasonal to a lesser degree than the recharge estimate resulting from the lysimeter analysis. Partial reconciliation of the two recharge estimates is achieved by considering a conceptual model of flow processes in the highly-heterogeneous underlying fractured porous medium. ?? Springer-Verlag 2007.

M2-like macrophages are responsible for collagen degradation through a mannose receptor–mediated pathway

PubMed Central

Madsen, Daniel H.; Leonard, Daniel; Masedunskas, Andrius; Moyer, Amanda; Jürgensen, Henrik Jessen; Peters, Diane E.; Amornphimoltham, Panomwat; Selvaraj, Arul; Yamada, Susan S.; Brenner, David A.; Burgdorf, Sven; Engelholm, Lars H.; Behrendt, Niels; Holmbeck, Kenn; Weigert, Roberto

2013-01-01

Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase–dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor–associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process. PMID:24019537

The impairment of HCCS leads to MLS syndrome by activating a non-canonical cell death pathway in the brain and eyes

PubMed Central

Indrieri, Alessia; Conte, Ivan; Chesi, Giancarlo; Romano, Alessia; Quartararo, Jade; Tatè, Rosarita; Ghezzi, Daniele; Zeviani, Massimo; Goffrini, Paola; Ferrero, Ileana; Bovolenta, Paola; Franco, Brunella

2013-01-01

Mitochondrial-dependent (intrinsic) programmed cell death (PCD) is an essential homoeostatic mechanism that selects bioenergetically proficient cells suitable for tissue/organ development. However, the link between mitochondrial dysfunction, intrinsic apoptosis and developmental anomalies has not been demonstrated to date. Now we provide the evidence that non-canonical mitochondrial-dependent apoptosis explains the phenotype of microphthalmia with linear skin lesions (MLS), an X-linked developmental disorder caused by mutations in the holo-cytochrome c-type synthase (HCCS) gene. By taking advantage of a medaka model that recapitulates the MLS phenotype we demonstrate that downregulation of hccs, an essential player of the mitochondrial respiratory chain (MRC), causes increased cell death via an apoptosome-independent caspase-9 activation in brain and eyes. We also show that the unconventional activation of caspase-9 occurs in the mitochondria and is triggered by MRC impairment and overproduction of reactive oxygen species (ROS). We thus propose that HCCS plays a key role in central nervous system (CNS) development by modulating a novel non-canonical start-up of cell death and provide the first experimental evidence for a mechanistic link between mitochondrial dysfunction, intrinsic apoptosis and developmental disorders. PMID:23239471

Evaluation of the visit frequency and the use of questionnaires and indices for COPD: a national survey from the On-Sint study.

PubMed

López Ramírez, Cecilia; Calero Acuña, Carmen; Represas Represas, Cristina; Aballe Santos, Luz; Casamor, Ricard; Fernández-Villar, Alberto; López-Campos, José Luis

2017-05-01

Despite widespread recommendations to use standardized questionnaires and multidimensional indices for the assessment of patients with chronic obstructive pulmonary disease (COPD), few data are available on the application of these tools in clinical practice. This study evaluates the attitude of physicians participating in the On-Sint cohort toward the use of health status questionnaires and multidimensional indices, as well as toward the frequency of visits and spirometry in primary care and specialized care. During the constitution of the On-Sint cohort, the participating physicians were surveyed about their clinical practice. They were questioned on the frequency of spirometry and visits and on the use of various questionnaires and indices. The health status questionnaires assessed were St. George's respiratory questionnaire, chronic respiratory questionnaire, airways questionnaire 20 and COPD assessment test (CAT). Physicians were also asked about the use of the medical research council (MRC) dyspnea scale and multidimensional indices such as body mass index, airflow obstruction, dyspnea, exercise capacity (BODE). Of the 356 physicians who participated in the study, 258 (72.5 %) completed the investigator's questionnaire (185 primary care, 73 specialized care). Nonscheduled visits were inversely proportional to the severity of COPD. Overall, 34.1% reported using health status questionnaires, mainly CAT (20.9%). We found differences between primary and specialized care in the use of multidimensional indices (84.9% vs 47.6%; P < 0.001). Of all the participants, 33.3% reported using the MRC scale and 28.7% the BODE index. Multidimensional indices and questionnaires are not commonly used with some differences between primary care and specialized care physicians. There is a considerable variability in the frequency of follow-up visits and spirometry. © 2015 John Wiley & Sons Ltd.

Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Dan; Wu, Chun-qi; Li, Ze-jun

Objective: To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Methods: Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50 μM) for 48 h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrialmore » respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p < 0.05. Results: Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alterations of mitochondrial structure. Conclusion: All investigated TZDs show a certain degree of mitochondrial toxicity, with troglitazone exhibiting the highest potency. The underlying mechanism of TZD-induced hepatotoxicity may be associated with alterations in mitochondrial respiratory function disorders, oxidative stress, and changes in membrane permeability. These parameters may be used early in drug development to further optimize risk:benefit profiles. - Highlights: • We compared three TZD mitochondrial toxicity characteristics in HepaRG cells. • TZD induced respiratory disorders and mitochondrial structural damage. • Mitochondrial toxicity evaluation presents guidance value for

Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy.

PubMed

Markvardsen, L H; Harbo, T; Sindrup, S H; Christiansen, I; Andersen, H; Jakobsen, J

2014-12-01

Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year in an open-label follow-up study. Seventeen responders to intravenous immunoglobulin (IVIG) who had participated in the previous study of SCIG versus placebo in CIDP were included. After one IVIG infusion 2 weeks prior to baseline, all continued on SCIG treatment at weekly equal dosage and were evaluated after 3, 6 and 12 months. Primary end-points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40-m walking test (40-MWT) and nine-hole peg test (9-HPT). Secondary end-points were changes of each of the listed parameters at each time point as well as an overall disability sum score (ODSS). The dose of SCIG was significantly unaltered during the follow-up period. Overall the isokinetic dynamometry value increased by 7.2% (P = 0.033) and after 3, 6 and 12 months by 5.7%, 8.2% and 6.8% (ns). The overall composite score at all time intervals and for each interval remained unchanged. Amongst the secondary parameters the MRC score increased significantly by 1.7% (P = 0.007), whereas grip strength, 40-MWT, 9-HPT and ODSS remained unchanged. SCIG preserves muscle strength and functional ability in patients with CIDP who previously responded to IVIG. SCIG should be considered as an alternative in long-term treatment of CIDP patients. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort

PubMed Central

2016-01-01

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies. PMID:27051239

Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease.

PubMed

Paulin, Laura M; Diette, Gregory B; Blanc, Paul D; Putcha, Nirupama; Eisner, Mark D; Kanner, Richard E; Belli, Andrew J; Christenson, Stephanie; Tashkin, Donald P; Han, MeiLan; Barr, R Graham; Hansel, Nadia N

2015-03-01

Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. To determine the impact of occupational exposures on COPD morbidity. A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

Characterisation of fatigue and its substantial impact on health status in a large cohort of patients with chronic pulmonary aspergillosis (CPA).

PubMed

Al-Shair, Khaled; Muldoon, Eavan G; Morris, Julie; Atherton, Graham T; Kosmidis, Chris; Denning, David W

2016-05-01

Fatigue is a prominent disabling symptom in several pulmonary diseases. Its impact on health status in patients with chronic pulmonary aspergillosis (CPA) has not been investigated. A total of 151 CPA patients attending the National Aspergillosis Centre completed Manchester COPD Fatigue Scale (MCFS), St. George's Respiratory Questionnaire (SGRQ) and Medical Research Council (MRC) dyspnoea score. Lung function and BMI were measured. Univariate, multivariate linear and binary analyses, and principal component analysis (PCA) were used. Female patients accounted for 44%. The mean (range) of age was 59.6 (31-83) years, FEV1% was 64 (14-140), BMI was 23.6 (16.3-43.4), SGRQ total score was 56 (4-96.2) and MCFS total score was 30.6 (0-54). PCA showed that 27 items of MCFS loaded on three components; physical, psychosocial and cognitive fatigue, explaining 78.4% of fatigue variance. MCFS score correlated strongly with total SGRQ score (r = 0.83, p < 0.001). Using linear multivariate analysis, fatigue was the strongest factor (beta = 0.7 p < 0.0001) associated with impaired health status, after adjusting for age, BMI, FEV1%, and MRC dyspnoea score. Using patients' 5 self-assessment grades of their health, one-way ANOVA showed that those with "very poor" health status had the highest fatigue scores (45 (±6) (p < 0.001)). Logistic regression analysis showed that fatigue score (OR = 0.9, 95% CI 0.84-0.97; p = 0.005) and FEV1% (OR = 1.03, 95% CI 1.01-1.07, p = 0.02) are significantly associated with self-assessed impaired health status after correcting for age, gender and DLCO%. Fatigue is a major component of impaired health status of CPA patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial.

PubMed

Kuwabara, Satoshi; Misawa, Sonoko; Mori, Masahiro; Iwai, Yuta; Ochi, Kazuhide; Suzuki, Hidekazu; Nodera, Hiroyuki; Tamaoka, Akira; Iijima, Masahiro; Toda, Tatsushi; Yoshikawa, Hiroo; Kanda, Takashi; Sakamoto, Ko; Kusunoki, Susumu; Sobue, Gen; Kaji, Ryuji

2018-06-01

Intravenous immunoglobulin (IVIg) therapy is currently the only established treatment in patients with multifocal motor neuropathy (MMN), and many patients have an IVIg-dependent fluctuation. We aimed to investigate the efficacy and safety of every 3 week IVIg (1.0 g/kg) for 52 weeks. This study was an open-label phase 3 clinical trial, enrolling 13 MMN patients. After an induction IVIg therapy (0.4 g/kg/d for 5 consecutive days), maintenance dose (1.0 g/kg) was given every 3 weeks for 52 weeks. The major outcome measures were the Medical Research Council (MRC) sum score and hand-grip strength at week 52. This trial is registered with ClinicalTrials.gov, number NCT01827072. At week 52, 11 of the 13 patients completed the study, and all 11 had a sustained improvement. The mean (SD) MRC sum score was 85.6 (8.7) at the baseline, and 90.6 (12.8) at week 52. The mean grip strength was 39.2 (30.0) kPa at the baseline and 45.2 (32.8) kPa at week 52. Two patients dropped out because of adverse event (dysphagia) and decision of an investigator, respectively. Three patients developed coronary spasm, dysphagia, or inguinal herniation, reported as the serious adverse events, but considered not related with the study drug. The other adverse effects were mild and resolved by the end of the study period. Our results show that maintenance treatment with 1.0 g/kg IVIg every 3 week is safe and efficacious for MMN patients up to 52 weeks. Further studies are required to investigate optimal dose and duration of maintenance IVIg for MMN. © 2018 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.

Feasibility and safety of early lower limb robot-assisted training in sub-acute stroke patients: a pilot study.

PubMed

Gandolfi, Marialuisa; Geroin, Christian; Tomelleri, Christopher; Maddalena, Isacco; Kirilova Dimitrova, Eleonora; Picelli, Alessandro; Smania, Nicola; Waldner, Andreas

2017-12-01

So far, the development of robotic devices for the early lower limb mobilization in the sub-acute phase after stroke has received limited attention. To explore the feasibility of a newly robotic-stationary gait training in sub-acute stroke patients. To report the training effects on lower limb function and muscle activation. A pilot study. Rehabilitation ward. Two sub-acute stroke inpatients and ten age-matched healthy controls were enrolled. Healthy controls served as normative data. Patients underwent 10 robot-assisted training sessions (20 minutes, 5 days/week) in alternating stepping movements (500 repetitions/session) on a hospital bed in addition to conventional rehabilitation. Feasibility outcome measures were compliance, physiotherapist time, and responses to self-report questionnaires. Efficacy outcomes were bilateral lower limb muscle activation pattern as measured by surface electromyography (sEMG), Motricity Index (MI), Medical Research Council (MRC) grade, and Ashworth Scale (AS) scores before and after training. No adverse events occurred. No significant differences in sEMG activity between patients and healthy controls were observed. Post-training improvement in MI and MRC scores, but no significant changes in AS scores, were recorded. Post-treatment sEMG analysis of muscle activation patterns showed a significant delay in rectus femoris offset (P=0.02) and prolonged duration of biceps femoris (P=0.04) compared to pretreatment. The robot-assisted training with our device was feasible and safe. It induced physiological muscle activations pattern in both stroke patients and healthy controls. Full-scale studies are needed to explore its potential role in post-stroke recovery. This robotic device may enrich early rehabilitation in subacute stroke patients by inducing physiological muscle activation patterns. Future studies are warranted to evaluate its effects on promoting restorative mechanisms involved in lower limb recovery after stroke.

Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy.

PubMed

Maddur, Mohan S; Stephen-Victor, Emmanuel; Das, Mrinmoy; Prakhar, Praveen; Sharma, Varun K; Singh, Vikas; Rabin, Magalie; Trinath, Jamma; Balaji, Kithiganahalli N; Bolgert, Francis; Vallat, Jean-Michel; Magy, Laurent; Kaveri, Srini V; Bayry, Jagadeesh

2017-03-20

Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (T reg ) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4-5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA. The fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with T reg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and T reg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. T reg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α. T reg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. T reg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort.

PubMed

Lee, Jung Yeon; Chon, Gyu Rak; Rhee, Chin Kook; Kim, Deog Kyeom; Yoon, Hyoung Kyu; Lee, Jin Hwa; Yoo, Kwang Ha; Lee, Sang Haak; Lee, Sang Yeub; Kim, Tae-Eun; Kim, Tae-Hyung; Park, Yong Bum; Hwang, Yong Il; Kim, Young Sam; Jung, Ki Suck

2016-04-01

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies.

Occupational Exposures Are Associated with Worse Morbidity in Patients with Chronic Obstructive Pulmonary Disease

PubMed Central

Paulin, Laura M.; Diette, Gregory B.; Blanc, Paul D.; Putcha, Nirupama; Eisner, Mark D.; Kanner, Richard E.; Belli, Andrew J.; Christenson, Stephanie; Tashkin, Donald P.; Han, MeiLan; Barr, R. Graham

2015-01-01

Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. Objectives: To determine the impact of occupational exposures on COPD morbidity. Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04–1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (−26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (−3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may

A physical function test for use in the intensive care unit: validity, responsiveness, and predictive utility of the physical function ICU test (scored).

PubMed

Denehy, Linda; de Morton, Natalie A; Skinner, Elizabeth H; Edbrooke, Lara; Haines, Kimberley; Warrillow, Stephen; Berney, Sue

2013-12-01

Several tests have recently been developed to measure changes in patient strength and functional outcomes in the intensive care unit (ICU). The original Physical Function ICU Test (PFIT) demonstrates reliability and sensitivity. The aims of this study were to further develop the original PFIT, to derive an interval score (the PFIT-s), and to test the clinimetric properties of the PFIT-s. A nested cohort study was conducted. One hundred forty-four and 116 participants performed the PFIT at ICU admission and discharge, respectively. Original test components were modified using principal component analysis. Rasch analysis examined the unidimensionality of the PFIT, and an interval score was derived. Correlations tested validity, and multiple regression analyses investigated predictive ability. Responsiveness was assessed using the effect size index (ESI), and the minimal clinically important difference (MCID) was calculated. The shoulder lift component was removed. Unidimensionality of combined admission and discharge PFIT-s scores was confirmed. The PFIT-s displayed moderate convergent validity with the Timed "Up & Go" Test (r=-.60), the Six-Minute Walk Test (r=.41), and the Medical Research Council (MRC) sum score (rho=.49). The ESI of the PFIT-s was 0.82, and the MCID was 1.5 points (interval scale range=0-10). A higher admission PFIT-s score was predictive of: an MRC score of ≥48, increased likelihood of discharge home, reduced likelihood of discharge to inpatient rehabilitation, and reduced acute care hospital length of stay. Scoring of sit-to-stand assistance required is subjective, and cadence cutpoints used may not be generalizable. The PFIT-s is a safe and inexpensive test of physical function with high clinical utility. It is valid, responsive to change, and predictive of key outcomes. It is recommended that the PFIT-s be adopted to test physical function in the ICU.

Biophysical and Biochemical Mechanisms in Synaptic Transmitter Release.

DTIC Science & Technology

1992-01-31

vesicle is normally released per active zone Sci USA 83. 3032 (1986) pared (15, 19, 20). In fact, in squid, the quantum 8 0 Shimomura 8 Musicki. V Kisni...8217, AND R. LLINAS• *Instituto de Biologia Celular Facultad de Medicina. Universidad de Buenos Aires. Paraguay 2155. Buenos Aires 1121. Argentina: and

[Photodrugtherapy of psoriasis with oral psoralen and black light therapy].

PubMed

Corrales Padilla, H

1975-01-01

Oral 4, 5', 8 trimethoxypsoralen (TMP) or 8-M-methoxypsoralen (8 MP) plus black light therapy of psoriasis produced disappearing of lesions in 6 out of 8 pacients treated with TMP and in 6 out of 7 treated with 8 MP. In three patients treated with the first drug, a paired comparision demonstrated that the ingestion of it, when followed of black exposure, is more effective than the exposure to conventional ultraviolet light. Parrish et al. have shown this for oral methoxalen and long wave ultraviolet light. Combined TMP or 8-MP and black light therapy inhibits epidermal DNA synthesis and this is the scientific base of its application in the therapy of psoriasis, disease in which an accelerated celular cicle and DNA synthesis has been postulated.

Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial.

PubMed

Seymour, Matthew T; Thompson, Lindsay C; Wasan, Harpreet S; Middleton, Gary; Brewster, Alison E; Shepherd, Stephen F; O'Mahony, M Sinead; Maughan, Timothy S; Parmar, Mahesh; Langley, Ruth E

2011-05-21

Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials. We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer. We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy. After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D). Treatment allocation was not masked. Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks. The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL). Analysis was by intention to treat. Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU). This study is registered, number ISRCTN21221452. 459 patients were randomly assigned (115 to each of groups A-C, 114 to group D). Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3-7·5] vs 4·5 months [2·8-6·4]; hazard ratio 0·84, 95% CI 0·69-1·01, p=0·07). Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine. The risk of having any grade 3 or worse toxic effect was not significantly increased

Plasmoid Propagation.

DTIC Science & Technology

1988-02-12

experimentally , a pulsed power system com- prising separate anode and cathode pulsers was designed and assembled. A double diode was developed to produce...be closed. To initiate this assessment, Mission Research Corporation (MRC) performed a two-year primarily experimental investigation of non - neutral...through from the cathode nad to be designed . Experimentation with several materials and setups produced a workable design , using nylon stocking hose

JPRS Report Science & Technology Europe Twenty-Fourth Isata International Symposium on Automotive Technology and Automation.

DTIC Science & Technology

1991-09-05

34 Learning from Learning : Principles for Supporting Drivers" J A Groeger, MRC Applied Psychology Unit, UK "Argos: A Driver Behaviour Analysis System...Technology (CEST), UK MISCELLANEOUS "Modular Sensor System for Guiding Handling Machines " J Geit and J 423 Heinrich, TZN Forshcungs, FRG "Flexible...PUBLIC TRANSP . MANAa RESEARCH Arrrtympe PARTI "Implementation Strategl»» Systems engineering \\ PART III / Validation through Pilot

dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.

PubMed

Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J

2015-05-12

Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.

[Analysis of clinical features in patients with pneumoconiosis complicated with pulmonary emphysema].

PubMed

Li, X; Dai, W R; Li, L; Liu, W F; Yang, Z X; Xie, L

2017-11-20

Objective: To investigate the clinical features of pneumoconiosis complicated with pulmo-nary emphysema. Methods: selected 868 patients with pneumoconiosis were selected from December 2015 to December 2016 in Hunan occupational disease prevention and treatment hospital. Collected the results of high-resolution spiral CT, arterial blood gas, ECG, pulmonary function and MRC score. The subjects were divided into pneumoconiosis complicated with pulmonary emphysema group and simple pneumoconiosis group accord-ing to the results of HRCT. The smoking, MRC score, pulmonary function, blood gas and complications were compared. Results: A total of 868 patients were enrolled in the study. Emphysema 232 people, accounting for 26.73%. The incidence of emphysema in the first phase of pneumoconiosis was 12.69%, and the incidence rate of emphysema in pneumoconiosis was 17.03%, The incidence of three Stage pneumoconiosis was highest, up to 60.76%, the incidence of emphysema increased with the increase of stages of pneumoconiosis ( P =0.000) .The smoking index of pneumoconiosis combined with emphysema group was significantly higher than that of simple pneumoconiosis group ( P <0.01) . The MRC score of pneumoconiosis complicated with pulmonary em-physema group was higher than that of simple pneumoconiosis group ( P =0.000) . In pneumoconiosis complicat-ed with pulmonary emphysema group the FEV(1.0)%, FVC%, FEV(1.0)/FVC, DLCO%, oxygen partial pressure were significantly lower than that of simple pneumoconiosis group ( P ≤0.05) . The combined rate of Bullae of lung in pneumoconiosis complicated with pulmonary emphysema group was higher than that of simple pneumo-coniosis group ( P <0.01) . Conclusion: pneumoconiosis stage and smoking. Patients with pneumoconiosis com-plicated with pulmonary emphysema had heavier breathing difficulties, more serious pulmonary function and active endurance, the degree of hypoxia is more serious, and had a higher incidence of complications. The pul

Mapping wetlands in the Lower Mekong Basin for wetland resource and conservation management using Landsat ETM images and field survey data.

PubMed

MacAlister, Charlotte; Mahaxay, Manithaphone

2009-05-01

The Mekong River Basin is considered to be the second most species rich river basin in the world. The 795,000 km(2) catchment encompasses several ecoregions, incorporating biodiverse and productive wetland systems. Eighty percent of the rapidly expanding population of the Lower Mekong Basin (LMB), made up in part by Lao PDR, Thailand, Cambodia and Viet Nam, live in rural areas and are heavily reliant on wetland resources. As the populations of Cambodia and Lao PDR will double in the next 20 years, pressure on natural resources and particularly wetlands can only increase. For development planning, resource and conservation management to incorporate wetland issues, information on the distribution and character of Mekong wetlands is essential. The existing but outdated wetland maps were compiled from secondary landuse-landcover data, have limited coverage, poor thematic accuracy and no meta-data. Therefore the Mekong River Commission (MRC) undertook to produce new wetland coverage for the LMB. As resources, funding and regional capacity are limited, it was determined that the method applied should use existing facilities, be easily adaptable, and replicable locally. For the product to be useful it must be accepted by local governments and decision makers. The results must be of acceptable accuracy (>75%) and the methodology should be relatively understandable to non-experts. In the first stage of this exercise, field survey was conducted at five pilot sites covering a range of typical wetland habitats (MRC wetland classification) to supply data for a supervised classification of Landsat ETM images from the existing MRC archive. Images were analysed using ERDAS IMAGINE and applying Maximum Likelihood Classification. Field data were reserved to apply formal accuracy assessment to the final wetland habitat maps, with resulting accuracy ranging from 77 to 94%. The maps produced are now in use at a Provincial and National level in three countries for resource and

Evaluation of Laser Stabilization and Imaging Systems for LCLS-II - Final Paper

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barry, Matthew

2015-08-20

By combining the top performing commercial laser beam stabilization system with the most ideal optical imaging configuration, the beamline for the Linear Accelerator Coherent Light Source II (LCLS-II) will deliver the highest quality and most stable beam to the cathode. To determine the optimal combination, LCLS-II beamline conditions were replicated and the systems tested with a He-Ne laser. The Guidestar-II and MRC active laser beam stabilization systems were evaluated for their ideal positioning and stability. Both a two and four lens optical imaging configuration was then evaluated for beam imaging quality, magnification properties, and natural stability. In their best performancesmore » when tested over fifteen hours, Guidestar-II kept the beam stable over approximately 70-110um while the MRC system kept it stable over approximately 90-100um. During short periods of time, Guidestar-II kept the beam stable between 10-20um, but was more susceptible to drift over time, while the MRC system maintained the beam between 30-50um with less overall drift. The best optical imaging configuration proved to be a four lens system that images to the iris located in the cathode room and from there, imaged to the cathode. The magnification from the iris to the cathode was 2:1, within an acceptable tolerance to the expected 2.1:1 magnification. The two lens configuration was slightly more stable in small periods of time (less than 10 minutes) without the assistance of a stability system, approximately 55um compared to approximately 70um, but the four lens configurations beam image had a significantly flatter intensity distribution compared to the two lens configuration which had a Gaussian distribution. A final test still needs to be run with both stability systems running at the same time through the four lens system. With this data, the optimal laser beam stabilization system can be determined for the beamline of LCLS-II.« less

Exploring the role and function of trial steering committees: results of an expert panel meeting.

PubMed

Harman, Nicola L; Conroy, Elizabeth J; Lewis, Steff C; Murray, Gordon; Norrie, John; Sydes, Matt R; Lane, J Athene; Altman, Douglas G; Baigent, Colin; Bliss, Judith M; Campbell, Marion K; Elbourne, Diana; Evans, Stephen; Sandercock, Peter; Gamble, Carrol

2015-12-30

The independent oversight of clinical trials, which is recommended by the Medical Research Council (MRC) Guidelines for Good Clinical Practice, is typically provided by an independent advisory Data Monitoring Committee (DMC) and an independent executive committee, to whom the DMC makes recommendations. The detailed roles and function of this executive committee, known as the Trial Steering Committee (TSC), have not previously been studied or reviewed since those originally proposed by the MRC in 1998. An expert panel (n = 7) was convened comprising statisticians, clinicians and trial methodologists with prior TSC experience. Twelve questions about the role and responsibilities of the TSC were discussed by the panel at two full-day meetings. Each meeting was transcribed in full and the discussions were summarised. The expert panel reached agreement on the role of the TSC, to which it was accountable, the membership, the definition of independence, and the experience and training needed. The management of ethical issues, difficult/complex situations and issues the TSC should not ask the DMC to make recommendations on were more difficult to discuss without specific examples, but support existed for further work to help share issues and to provide appropriate training for TSC members. Additional topics discussed, which had not been identified by previous work relating to the DMCs but were pertinent to the role of the TSC, included the following: review of data sharing requests, indemnity, lifespan of the TSC, general TSC administration, and the roles of both the Funder and the Sponsor. This paper presents recommendations that will contribute to the revision and update of the MRC TSC terms of reference. Uncertainty remains in some areas due to the absence of real-life examples; future guidance on these issues would benefit from a repository of case studies. Notably, the role of a patient and public involvement (PPI) contributor was not discussed, and further work is

Cytotoxic and Antimicrobial Activity of Dehydrozingerone based Cyclopropyl Derivatives.

PubMed

Burmudžija, Adrijana Z; Muškinja, Jovana M; Kosanić, Marijana M; Ranković, Branislav R; Novaković, Slađana B; Đorđević, Snežana B; Stanojković, Tatjana P; Baskić, Dejan D; Ratković, Zoran R

2017-08-01

A small series of 1-acetyl-2-(4-alkoxy-3-methoxyphenyl)cyclopropanes was prepared, starting from dehydrozingerone (4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one) and its O-alkyl derivatives. Their microbiological activities toward some strains of bacteria and fungi were tested, as well as their in vitro cytotoxic activity against some cancer cell lines (HeLa, LS174 and A549). All synthesized compounds showed significant antimicrobial activity and expressed cytotoxic activity against tested carcinoma cell lines, but they showed no significant influence on normal cell line (MRC5). Butyl derivative is the most active on HeLa cells (IC 50 = 8.63 μm), while benzyl one is active against LS174 and A549 cell lines (IC 50 = 10.17 and 12.15 μm, respectively). © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Observation of a cytopathogenic effect on cell lines used for routine viral cultures led to the diagnosis of lymphogranuloma venereum.

PubMed

Busson, Laurent; Crucitti, Tania; De Foor, Marc; Van den Wijngaert, Sigi; Vandenberg, Olivier

2013-08-01

This article reports the fortuitous recovery of nine Chlamydia trachomatis serovar L strains in cell cultures (Vero and LLC-MK(2) cell line) designed for viral culture. Nine ano-genital swabs were inoculated on confluent Vero, MRC5 and LLC-MK(2) cell cultures. They were collected from HIV-positive patients who were primarily men who have sex with men (MSM) presenting ulcerations that mimicked herpes simplex infections. A cytopathogenic effect was observed on Vero and LLC-MK(2) cells on day 14. The presence of C trachomatis serovar L in the cell lines was confirmed by Real Time-PCR. C trachomatis serovar L can grow on Vero and LLC-MK(2) cell lines designed for viral cultures. Lymphogranuloma venereum must be considered as a differential diagnosis for herpes-like lesions, particularly in MSM with high-risk behaviours.

Possibilities of vaccine manufacture in human diploid cell strains with a serum replacement factor.

PubMed

Candal, F J; George, V G; Ades, E W

1991-07-01

Cell lines MDCK (canine kidney), BGM (Buffalo green monkey kidney) and human embryonic lung fibroblast will support viral growth efficiently in medium without serum. Both MRC-5 and WI-38 cell strains have been approved by the Food and Drug Administration for manufacturing viral vaccines against cytomegalovirus and varicella-zoster virus. In this study we examine these two cell lines and viruses for their ability to grow in medium containing a serum replacement. The serum substitute used is LPSR-1 (low protein serum replacement). Using LPSR-1 in defined medium, we demonstrate multipassage cell growth and viral cultivation and replication equivalent to those obtained in medium containing fetal bovine serum (FBS). Viral growth after complete elimination of FBS varies and depends on cell line and virus. Serum substitutes can eliminate FBS in the viral growth phase of vaccine production and reduce costs.

Oxidized C5-methyl cytosine bases in DNA: 5-Hydroxymethylcytosine; 5-formylcytosine; and 5-carboxycytosine.

PubMed

Klungland, Arne; Robertson, Adam B

2017-06-01

Recent reports suggest that the Tet enzyme family catalytically oxidize 5-methylcytosine in mammalian cells. The oxidation of 5-methylcytosine can result in three chemically distinct species - 5-hydroxymethylcytsine, 5-formylcytosine, and 5-carboxycytosine. While the base excision repair machinery processes 5-formylcytosine and 5-carboxycytosine rapidly, 5-hydroxymethylcytosine is stable under physiological conditions. As a stable modification 5-hydroxymethylcytosine has a broad range of functions, from stem cell pluriopotency to tumorigenesis. The subsequent oxidation products, 5-formylcytosine and 5-carboxycytosine, are suggested to be involved in an active DNA demethylation pathway. This review provides an overview of the biochemistry and biology of 5-methylcytosine oxidation products. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Platform for High-Assurance Cloud Computing

DTIC Science & Technology

2016-06-01

to create today’s standard cloud computing applications and services. Additionally , our SuperCloud (a related but distinct project under the same... Additionally , our SuperCloud (a related but distinct project under the same MRC funding) reduces vendor lock-in and permits application to migrate, to follow...managing key- value storage with strong assurance properties. This first accomplishment allows us to climb the cloud technical stack, by offering

Destroyer Engineered Operating Cycle (DDEOC), System Maintenance Analysis DDG-37 Class, Salt Water Circulating System SMA 37-106-256, Review of Experience

DTIC Science & Technology

1978-07-01

horizontally mounted, single-end suction, single- stage centrifugal pumps. The rotating elements are mounted on the shaft of the driving motor, and the pump...annual open-and-inspect requirement for MIP E-17/296-21, MRC 21 A14V A. Industrial Facility Improvements -- None IMA Improvements -- None Intergrated ...Circulating Pump, Warren Pumps, Inc., NAVSHIPS 347-3146, January 1959. 4. Technical Manual - Horizontal Close-Co!;pled Pumps Sea (Salt) Water

Modelling short pulse, high intensity laser plasma interactions

NASA Astrophysics Data System (ADS)

Evans, R. G.

2006-06-01

Modelling the interaction of ultra-intense laser pulses with solid targets is made difficult through the large range of length and time scales involved in the transport of relativistic electrons. An implicit hybrid PIC-fluid model using the commercial code LSP (LSP is marketed by MRC (Albuquerque), New Mexico, USA) reveals a variety of complex phenomena which seem to be borne out in experiments and some existing theories.

Powder-Metallurgical Bearings For Turbopumps

NASA Technical Reports Server (NTRS)

Bhat, B. N.; Humphries, T. S.; Thom, R. L.; Moxson, V.; Friedman, G. I.; Dolan, F. J.; Shipley, R. J.

1993-01-01

Bearings fabricated by powder metallurgy developed for use in machines subjected to extremes of temperature, rolling-contact cyclic stresses, and oxidizing or otherwise corrosive fluids. Bearings also extend operating lives of other machines in which bearings required to resist extreme thermal, mechanical, and chemical stresses. One alloy exhibiting outstanding properties was MRC-2001. Resistance to fatigue, stress corrosion cracking, and wear found superior to that of 440C stainless steel.

Recovery of motor deficit accompanying sciatica--subgroup analysis of a randomized controlled trial.

PubMed

Overdevest, Gijsbert M; Vleggeert-Lankamp, Carmen L A M; Jacobs, Wilco C H; Brand, Ronald; Koes, Bart W; Peul, Wilco C

2014-09-01

In patients with sciatica due to a lumbar disc herniation, it is generally recommended to reserve surgical treatment for those who suffer from intolerable pain or those who demonstrate persistent symptoms after conservative management. Controversy exists about the necessity of early surgical intervention for those patients that have an additional motor deficit. The aim of this study was to compare the recovery of motor deficit among patients receiving early surgery to those receiving prolonged conservative treatment. Subgroup analysis of a randomized controlled trial. This subgroup analysis focuses on 150 (53%) of 283 patients with sciatica due to a lumbar disc herniation and whose symptoms at baseline (before randomization) were accompanied by a motor deficit. Motor deficit was assessed through manual muscle testing and graded according to the Medical Research Council (MRC) scale. In total, 150 patients with 6 to 12 weeks of sciatica due to a lumbar disc herniation and whose symptoms were accompanied by a moderate (MRC Grade 4) or severe (MRC Grade 3) motor deficit were randomly allocated to early surgery or prolonged conservative treatment. Repeated standardized neurologic examinations were performed at baseline and at 8, 26, and 52 weeks after randomization. This study was supported by a grant from the Netherlands Organization for Health Research and Development (ZonMW) and the Hoelen Foundation The Hague. Sciatica recovered among seven (10%) of the 70 patients assigned to early surgery before surgery could be performed, and of the 80 patients assigned to conservative treatment, 32 patients (40%) were treated surgically because of intolerable pain. Baseline severity of motor deficit was graded moderate in 84% of patients and severe in 16% of patients. Motor deficit recovered significantly faster among patients allocated to early surgery (p=.01), but the difference was no longer significant at 26 (p=.21) or 52 weeks (p=.92). At 1 year, complete recovery of motor

A fast combination method in DSmT and its application to recommender system

PubMed Central

Liu, Yihai

2018-01-01

In many applications involving epistemic uncertainties usually modeled by belief functions, it is often necessary to approximate general (non-Bayesian) basic belief assignments (BBAs) to subjective probabilities (called Bayesian BBAs). This necessity occurs if one needs to embed the fusion result in a system based on the probabilistic framework and Bayesian inference (e.g. tracking systems), or if one needs to make a decision in the decision making problems. In this paper, we present a new fast combination method, called modified rigid coarsening (MRC), to obtain the final Bayesian BBAs based on hierarchical decomposition (coarsening) of the frame of discernment. Regarding this method, focal elements with probabilities are coarsened efficiently to reduce computational complexity in the process of combination by using disagreement vector and a simple dichotomous approach. In order to prove the practicality of our approach, this new approach is applied to combine users’ soft preferences in recommender systems (RSs). Additionally, in order to make a comprehensive performance comparison, the proportional conflict redistribution rule #6 (PCR6) is regarded as a baseline in a range of experiments. According to the results of experiments, MRC is more effective in accuracy of recommendations compared to original Rigid Coarsening (RC) method and comparable in computational time. PMID:29351297

Comparative genomics and mutagenesis analyses of choline metabolism in the marine R oseobacter clade

PubMed Central

Lidbury, Ian; Kimberley, George; Scanlan, David J.; Murrell, J. Colin

2015-01-01

Summary Choline is ubiquitous in marine eukaryotes and appears to be widely distributed in surface marine waters; however, its metabolism by marine bacteria is poorly understood. Here, using comparative genomics and molecular genetic approaches, we reveal that the capacity for choline catabolism is widespread in marine heterotrophs of the marine Roseobacter clade (MRC). Using the model bacterium R uegeria pomeroyi, we confirm that the bet A, bet B and bet C genes, encoding choline dehydrogenase, betaine aldehyde dehydrogenase and choline sulfatase, respectively, are involved in choline metabolism. The bet T gene, encoding an organic solute transporter, was essential for the rapid uptake of choline but not glycine betaine (GBT). Growth of choline and GBT as a sole carbon source resulted in the re‐mineralization of these nitrogen‐rich compounds into ammonium. Oxidation of the methyl groups from choline requires formyltetrahydrofolate synthetase encoded by fhs in R . pomeroyi, deletion of which resulted in incomplete degradation of GBT. We demonstrate that this was due to an imbalance in the supply of reducing equivalents required for choline catabolism, which can be alleviated by the addition of formate. Together, our results demonstrate that choline metabolism is ubiquitous in the MRC and reveal the role of Fhs in methyl group oxidation in R . pomeroyi. PMID:26058574

Heterogeneous fluorescence intermittency in single layer reduced graphene oxide

NASA Astrophysics Data System (ADS)

Si, Jixin; Volkan-Kacso, Sandor; Eltom, Ahmed; Morozov, Yurii; McDonald, Matthew P.; Ruth, Anthony; Kuno, Masaru; Janko, Boldizsar

Fluorescence intermittency, or blinking, has been observed in a wide range of systems, including quantum dots, nanorods, and nanowires. Striking similarities have been documented in the optical response of these nanoscale emitters. However, the mechanism behind blinking still remains elusive. For the first time, blinking has been observed in a two-dimensional system in recent experiments on reduced graphene oxide (rGO). Here we reveal the power spectral density (PSD) of the blinking in rGO shares the same 1/f-like behavior of previously known blinking systems; meanwhile, the heterogeneous dynamic evolution and spatial correlation make rGO a unique blinking system. To investigate the origin of blinking, we self-consistently explain the evolution of rGO blinking using the phenomenological multiple recombination center (MRC) model that captures common features of nanoscale blinking. Furthermore, tight binding method and ab-initio method calculations of carbon nanodots are utilized to look for the microscopic structure corresponding to the RCs in the MRC model. M. K. thanks the American Chemical Society Petroleum Research Fund, the Army Research Office (W911NF-12-1-0578) for support. B.J. was supported in part by the U. S. DOE, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38.

Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome.

PubMed

Lee, Jin Sook; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Chae, Jong Hee

2016-04-01

Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome. Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included. Their medical records, neuroimaging findings, and histological/biochemical findings of skeletal muscle specimens were reviewed. Targeted sequencing of mitochondrial DNA was performed based on mitochondrial respiratory chain (MRC) enzyme defects. Isolated complex I deficiency was the most frequently observed MRC defect (in 42% of 38 investigated patients). Mitochondrial DNA mutations were identified in 11 patients, of which 81.8% were MT-ND genes. The clinical outcome varied widely, from independent daily activity to severe disability. Poor functional outcomes and neurological deterioration were significantly associated with early onset (before an age of 1 year) and the presence of other lesions additional to basal ganglia involvement in the initial neuroimaging. The neurological severity and outcome of LS may vary widely and be better than those predicted based on previous studies. We suggest that age at onset and initial neuroimaging findings are prognostic indicators in LS.

Antiproliferative activity and induction of apoptotic by ethanolic extract of Alpinia galanga rhizhome in human breast carcinoma cell line.

PubMed

Samarghandian, Saeed; Hadjzadeh, Mousa-Al-Reza; Afshari, Jalil Tavakkol; Hosseini, Mohadeseh

2014-06-17

We investigated the potential of galangal rhizomes to induce cytotoxic and apoptotic effects in the cultured human breast carcinoma cell line, (MCF-7) in compare with the non-malignant (MRC-5) cells. Both cells were cultured in DMEM medium and treated with galangal rhizomes for three consecutive days. The percentage of apoptotic cells was determined by flow cytometry using Annexin-V fluorescein isothiocyanate. The results showed that the ethanolic extract of galangal rhizomes decreased cell viability in the malignant cells as a concentration- and time- dependent manner. The IC50 values against MCF-7 were determined at 400.0 ± 11.7 and 170.0 ± 5.9 μg/ml after 48 and 72 h respectively. The morphology of MCF-7 cells treated with the ethanolic extract confirmed the cell proliferation assay results. Alpinia galanga induced apoptosis in MCF-7 cells, as determined by flow cytometry. We concluded that the extract of Alpinia galanga exerts pro-apoptotic effects in a breast cancer-derived cell line and could be considered as a potential chemotherapeutic agent in breast cancer.

Sulforaphane homologues: Enantiodivergent synthesis of both enantiomers, activation of the Nrf2 transcription factor and selective cytotoxic activity.

PubMed

Elhalem, Eleonora; Recio, Rocío; Werner, Sabine; Lieder, Franziska; Calderón-Montaño, José Manuel; López-Lázaro, Miguel; Fernández, Inmaculada; Khiar, Noureddine

2014-11-24

Reported is an enantiodivergent approach for the synthesis of both enantiomers of sulforaphane (SFN) homologues with different chain lengths between the sulfinyl sulfur and the isothiocyanate groups and different substituents on the sulfinyl sulfur. The homologues were designed in order to unravel the effect of all the diversity elements included in sulforaphane's structure. The key step of the approach is the diastereoselective synthesis of both sulfinate ester epimers at sulfur, using as single chiral auxiliary the sugar derived diacetone-d-glucose. The approach allows the first synthesis of both enantiomers of 5-methylsulfinylpentyl isothiocyanate, and the biologically important 6-methylsulfinylhexyl isothiocyanate (6-HITC) found in Japanese horseradish, wasabi (Wasabia japonica). The ability of the synthesized compounds as inductors of phase II detoxifying enzymes has been studied by determining their ability to activate the cytoprotective transcription factor Nrf2. The cytotoxic activity of all the synthesized compounds against human lung adenocarcinoma (A549) and foetal lung fibroblasts (MRC-5) is also reported. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Assessment of the in vitro antiprotozoal and cytotoxic potential of 20 selected medicinal plants from the island of Soqotra.

PubMed

Mothana, Ramzi A; Al-Musayeib, Nawal M; Matheeussen, An; Cos, Paul; Maes, Louis

2012-12-03

Malaria, leishmaniasis and human African trypanosomiasis continue to be major public health problems in need of new and more effective drugs. The aim of this study was to evaluate in vitro antiprotozoal activity of twenty endemic medicinal plants collected from the island of Soqotra in the Indian Ocean. The plant materials were extracted with methanol and tested for antiplasmodial activity against erythrocytic schizonts of Plasmodium falciparum, for antileishmanial activity against intracellular amastigotes of Leishmania infantum and for antitrypanosomal activity against intracellular amastigotes of Trypanosoma cruzi and free trypomastigotes of T. brucei. To assess selectivity, cytotoxicity was determined against MRC-5 fibroblasts. Selective activity was obtained for Punica protopunica against Plasmodium (IC₅₀ 2.2 µg/mL) while Eureiandra balfourii and Hypoestes pubescens displayed activity against the three kinetoplastid parasites (IC₅₀ < 10 µg/mL). Acridocarpus socotranus showed activity against T. brucei and T. cruzi (IC₅₀ 3.5 and 8.4 µg/mL). Ballochia atrovirgata, Dendrosicycos socotrana, Dracaena cinnabari and Euphorbia socotrana displayed non-specific inhibition of the parasites related to high cytotoxicity.

Antituberculosis nanodelivery system with controlled-release properties based on para-amino salicylate–zinc aluminum-layered double-hydroxide nanocomposites

PubMed Central

Saifullah, Bullo; Hussein, Mohd Zobir; Hussein-Al-Ali, Samer Hasan; Arulselvan, Palanisamy; Fakurazi, Sharida

2013-01-01

We report the intercalation and characterization of para-amino salicylic acid (PASA) into zinc/aluminum-layered double hydroxides (ZLDHs) by two methods, direct and indirect, to form nanocomposites: PASA nanocomposite prepared by a direct method (PASA-D) and PASA nanocomposite prepared by an indirect method (PASA-I). Powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis revealed that the PASA drugs were accommodated within the ZLDH interlayers. The anions of the drug were accommodated as an alternate monolayer (along the long-axis orientation) between ZLDH interlayers. Drug loading was estimated to be 22.8% and 16.6% for PASA-D and PASA-I, respectively. The in vitro release properties of the drug were investigated in physiological simulated phosphate-buffered saline solution of pH 7.4 and 4.8. The release followed the pseudo-second-order model for both nanocomposites. Cell viability (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assays) was assessed against normal human lung fibroblast MRC-5 and 3T3 mouse fibroblast cells at 24, 48, and 72 hours. The results showed that the nanocomposite formulations did not possess any cytotoxicity, at least up to 72 hours. PMID:24255593

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster

PubMed Central

Ng, Cheng Teng; Yong, Liang Qing; Hande, Manoor Prakash; Ong, Choon Nam; Yu, Liya E; Bay, Boon Huat; Baeg, Gyeong Hun

2017-01-01

Background Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. Methods In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs. Results For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript (DDIT3) and endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production. Conclusion The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster.

PubMed

Ng, Cheng Teng; Yong, Liang Qing; Hande, Manoor Prakash; Ong, Choon Nam; Yu, Liya E; Bay, Boon Huat; Baeg, Gyeong Hun

2017-01-01

Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster . A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs. For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript ( DDIT3 ) and endoplasmic reticulum (ER) to nucleus signaling 1 ( ERN1 ) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production. The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. More extensive studies would

Essential Oil of Cymbopogon nardus (L.) Rendle: A Strategy to Combat Fungal Infections Caused by Candida Species

PubMed Central

De Toledo, Luciani Gaspar; Ramos, Matheus Aparecido Dos Santos; Spósito, Larissa; Castilho, Elza Maria; Pavan, Fernando Rogério; Lopes, Érica De Oliveira; Zocolo, Guilherme Julião; Silva, Francisca Aliny Nunes; Soares, Tigressa Helena; dos Santos, André Gonzaga; Bauab, Taís Maria; De Almeida, Margarete Teresa Gottardo

2016-01-01

Background: The incidence of fungal infections, especially those caused by Candida yeasts, has increased over the last two decades. However, the indicated therapy for fungal control has limitations. Hence, medicinal plants have emerged as an alternative in the search for new antifungal agents as they present compounds, such as essential oils, with important biological effects. Published data demonstrate important pharmacological properties of the essential oil of Cymbopogon nardus (L.) Rendle; these include anti-tumor, anti-nociceptive, and antibacterial activities, and so an investigation of this compound against pathogenic fungi is interesting. Objective: The aim of this study was to evaluate the chemical composition and biological potential of essential oil (EO) obtained from the leaves of C. nardus focusing on its antifungal profile against Candida species. Methods: The EO was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Testing of the antifungal potential against standard and clinical strains was performed by determining the minimal inhibitory concentration (MIC), time-kill, inhibition of Candida albicans hyphae growth, and inhibition of mature biofilms. Additionally, the cytotoxicity was investigated by the IC50 against HepG-2 (hepatic) and MRC-5 (fibroblast) cell lines. Results: According to the chemical analysis, the main compounds of the EO were the oxygen-containing monoterpenes: citronellal, geranial, geraniol, citronellol, and neral. The results showed important antifungal potential for all strains tested with MIC values ranging from 250 to 1000 μg/mL, except for two clinical isolates of C. tropicalis (MIC > 1000 μg/mL). The time-kill assay showed that the EO inhibited the growth of the yeast and inhibited hyphal formation of C. albicans strains at concentrations ranging from 15.8 to 1000 μg/mL. Inhibition of mature biofilms of strains of C. albicans, C. krusei and C. parapsilosis occurred at a

Essential Oil of Cymbopogon nardus (L.) Rendle: A Strategy to Combat Fungal Infections Caused by Candida Species.

PubMed

De Toledo, Luciani Gaspar; Ramos, Matheus Aparecido Dos Santos; Spósito, Larissa; Castilho, Elza Maria; Pavan, Fernando Rogério; Lopes, Érica De Oliveira; Zocolo, Guilherme Julião; Silva, Francisca Aliny Nunes; Soares, Tigressa Helena; Dos Santos, André Gonzaga; Bauab, Taís Maria; De Almeida, Margarete Teresa Gottardo

2016-08-09

The incidence of fungal infections, especially those caused by Candida yeasts, has increased over the last two decades. However, the indicated therapy for fungal control has limitations. Hence, medicinal plants have emerged as an alternative in the search for new antifungal agents as they present compounds, such as essential oils, with important biological effects. Published data demonstrate important pharmacological properties of the essential oil of Cymbopogon nardus (L.) Rendle; these include anti-tumor, anti-nociceptive, and antibacterial activities, and so an investigation of this compound against pathogenic fungi is interesting. The aim of this study was to evaluate the chemical composition and biological potential of essential oil (EO) obtained from the leaves of C. nardus focusing on its antifungal profile against Candida species. The EO was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Testing of the antifungal potential against standard and clinical strains was performed by determining the minimal inhibitory concentration (MIC), time-kill, inhibition of Candida albicans hyphae growth, and inhibition of mature biofilms. Additionally, the cytotoxicity was investigated by the IC50 against HepG-2 (hepatic) and MRC-5 (fibroblast) cell lines. According to the chemical analysis, the main compounds of the EO were the oxygen-containing monoterpenes: citronellal, geranial, geraniol, citronellol, and neral. The results showed important antifungal potential for all strains tested with MIC values ranging from 250 to 1000 μg/mL, except for two clinical isolates of C. tropicalis (MIC > 1000 μg/mL). The time-kill assay showed that the EO inhibited the growth of the yeast and inhibited hyphal formation of C. albicans strains at concentrations ranging from 15.8 to 1000 μg/mL. Inhibition of mature biofilms of strains of C. albicans, C. krusei and C. parapsilosis occurred at a concentration of 10× MIC. The values of the IC50

Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway)

NASA Astrophysics Data System (ADS)

Ganesh Kumar, C.; Poornachandra, Y.; Chandrasekhar, Cheemalamarri

2015-11-01

The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2/M phase and also inhibited the microtubule assembly in DU145 cells. Mechanistic studies, such as ROS, MMP, Cyt-c, GSH, caspases 9, 8 and 3 activation and the Annexin V-FITC staining, along with the above parameters tested provided sufficient evidence that the b-Au NPs induced apoptosis through the intrinsic pathway. The results supported the use of b-Au NPs for future therapeutic application in cancer therapy and other biomedical applications.The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2

Doxycycline Compliance at Bagram Air Field

DTIC Science & Technology

2014-05-01

doxycycline absorption. In 2008, the Institute of Medicine issued a report entitled ·’Use of Dietary Supplements by Military Personnel" that reported 34...absorption by tetracycline. Br J Clin Pharmacal. 1975 February; 2(1): 94- 96. 19. 0. M. e. Greenwood MRC, "Use of Dietary Supplements by Military...Personnel.Institute of Medicine (US) Committee on Dietary Supplement Use by Military Personnel," National Academies Press, Washington (DC), 2008. 20

Multiple functions of the S-phase checkpoint mediator.

PubMed

Tanaka, Katsunori

2010-01-01

There is mounting evidence that replication defects are the major source of spontaneous genomic instability in cells, and that S-phase checkpoints are the principal defense against such instability. The S-phase checkpoint mediator protein Mrc1/Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of effector kinase by a sensor kinase. In this review, the multiple functions and the regulation of the S-phase checkpoint mediator are discussed.

Further Studies of the NRL Collective Particle Accelerator VIA Numerical Modeling with the MAGIC Code.

DTIC Science & Technology

1984-08-01

COLLFCTIVF PAPTTCLE ACCELERATOR VIA NUMERICAL MODFLINC WITH THF MAGIC CODE Robert 1. Darker Auqust 19F4 Final Report for Period I April. qI84 - 30...NUMERICAL MODELING WITH THE MAGIC CODE Robert 3. Barker August 1984 Final Report for Period 1 April 1984 - 30 September 1984 Prepared for: Scientific...Collective Final Report Particle Accelerator VIA Numerical Modeling with April 1 - September-30, 1984 MAGIC Code. 6. PERFORMING ORG. REPORT NUMBER MRC/WDC-R

Lower Mississippi River Environmental Program. Report 13. Preliminary Environmental Design Considerations Associated with Articulated Concrete Mattress Revetments along the Lower Mississippi River

DTIC Science & Technology

1988-05-01

Engineer Water Resources Support Center, Fort Belvoir, Va. Conner, J. W., Pennington, C. H., and Bosley, T. R. 1983. "Larval Fish of Selected Aquatic ...Mississippi River Environmental Program; Report 13 6a NAME OF PERFORMING ORGANIZATION 6b OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Aquatic Ecosystem...Jenkins, Aquatic Ecosystem Analysts, PO Box 4188, Fayetteville, Ark. Mr. Stephen P. Cobb, MRC, Vicksburg, Miss., was the project officer and program manager

Focused Application Software for Ferrite Patch Antennas

DTIC Science & Technology

1999-10-01

Trott Mr. Rene D. Guidry Mr. Christopher G. Repesh 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Mission Research Corporation 147 John Sims...July 99 Contract Number: F49620-97-C-0022 SBIR Topic: AF96-003 MRC Project: 97054 Prepared by: Dr. Keith D. Trott , Mr. Rene D. Guidry, and Mr...application of recent innovations in the finite element (FE) method to the problem of modeling conformal antennas embedded in or on (substrate or

Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

PubMed Central

Saifullah, Bullo; El Zowalaty, Mohamed E; Arulselvan, Palanisamy; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin M; Hussein, Mohd Zobir

2014-01-01

The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis. PMID:25114509

Acute closed radial nerve injury

PubMed Central

Tuncel, Umut; Turan, Aydin; Kostakoglu, Naci

2011-01-01

We present a 45-year-old patient who had acute radial nerve palsy following a blunt trauma without any fracture or dislocation. He was injured by strucking in a combat three months ago. The patient has been followed by application of a long-arm plaster cast before referred to our clinic. Preoperative electromyoneurography and magnetic resonance imaging (MRI) indicated that there was a radial nerve injury on humeral groove. The British Medical Research Council (MRC) grade was 2/5 on his wrist preoperatively. The patient underwent an operation under general anesthesia. It was seen to be a second-degree nerve injury. The patient has subsequently regained full movement on his wrist and finger extension in six months. We suggest that a detailed clinical and electrodiagnostical evaluation is necessary in patients who have radial nerve injury when deciding the treatment, conservative or surgical. PMID:22347334

Degradation of chitosan hydrogel dispersed in dilute carboxylic acids by solution plasma and evaluation of anticancer activity of degraded products

NASA Astrophysics Data System (ADS)

Chokradjaroen, Chayanaphat; Rujiravanit, Ratana; Theeramunkong, Sewan; Saito, Nagahiro

2018-01-01

Chitosan is a polysaccharide that has been extensively studied in the field of biomedicine, especially its water-soluble degraded products called chitooligosaccharides (COS). In this study, COS were produced by the degradation of chitosan hydrogel dispersed in a dilute solution (i.e., 1.55 mM) of various kinds of carboxylic acids using a non-thermal plasma technology called solution plasma (SP). The degradation rates of chitosan were influenced by the type of carboxylic acids, depending on the interaction between chitosan and each carboxylic acid. After SP treatment, the water-soluble degraded products containing COS could be easily separated from the water-insoluble residue of chitosan hydrogel by centrifugation. The production yields of the COS were mostly higher than 55%. Furthermore, the obtained COS products were evaluated for their inhibitory effect as well as their selectivity against human lung cancer cells (H460) and human lung normal cells (MRC-5).

Asthma in Black African, Black Caribbean and South Asian adolescents in the MRC DASH study: a cross sectional analysis

PubMed Central

2010-01-01

Background Ethnic differences in the prevalence of asthma among children in the UK are under-researched. We aimed to determine the ethnic differences in the prevalence of asthma and atopic asthma in children from the main UK ethnic groups, and whether differences are associated with differential distributions in social and psychosocial risk factors. Methods 6,643 pupils aged 11-13 years, 80% ethnic minorities. Outcomes were asthma/wheeze with (atopic) and without hay fever/eczema. Risk factors examined were family history of asthma, length of residence in the UK, socioeconomic disadvantage, tobacco exposure, psychological well-being, and body mass index (BMI). Results There was a pattern of lower prevalence of asthma in Black African boys and girls, and Indian and Bangladeshi girls compared to White UK. The overall prevalence was higher in Mixed Black Caribbean/White boys, with more atopic asthma in Black Caribbean boys and Mixed Black Caribbean/White boys due to more hayfever. Poor psychological well-being and family history of asthma were associated with an increased risk of asthma within each ethnic group. UK residence for ≤ 5 years was protective for Black Caribbeans and Black Africans. Increased BMI was associated with an increased reporting of asthma for Black Africans. Adjustments for all variables did not remove the excess asthma reported by Black Caribbean boys (atopic) or Mixed Black Caribbean/White boys. Conclusion The protective effect of being born abroad accounted for ethnic differences in some groups, signalling a role for socio-environmental factors in patterning ethnic differences in asthma in adolescence. PMID:20334698

Asthma in Black African, Black Caribbean and South Asian adolescents in the MRC DASH study: a cross sectional analysis.

PubMed

Whitrow, Melissa J; Harding, Seeromanie

2010-03-25

Ethnic differences in the prevalence of asthma among children in the UK are under-researched. We aimed to determine the ethnic differences in the prevalence of asthma and atopic asthma in children from the main UK ethnic groups, and whether differences are associated with differential distributions in social and psychosocial risk factors. 6,643 pupils aged 11-13 years, 80% ethnic minorities. Outcomes were asthma/wheeze with (atopic) and without hay fever/eczema. Risk factors examined were family history of asthma, length of residence in the UK, socioeconomic disadvantage, tobacco exposure, psychological well-being, and body mass index (BMI). There was a pattern of lower prevalence of asthma in Black African boys and girls, and Indian and Bangladeshi girls compared to White UK. The overall prevalence was higher in Mixed Black Caribbean/White boys, with more atopic asthma in Black Caribbean boys and Mixed Black Caribbean/White boys due to more hayfever. Poor psychological well-being and family history of asthma were associated with an increased risk of asthma within each ethnic group. UK residence for 5 years was protective for Black Caribbeans and Black Africans. Increased BMI was associated with an increased reporting of asthma for Black Africans. Adjustments for all variables did not remove the excess asthma reported by Black Caribbean boys (atopic) or Mixed Black Caribbean/White boys. The protective effect of being born abroad accounted for ethnic differences in some groups, signalling a role for socio-environmental factors in patterning ethnic differences in asthma in adolescence.

5 CFR 1215.5 - Hearing.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

5 CFR 1215.5 - Hearing.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

5 CFR 1215.5 - Hearing.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

5 CFR 1215.5 - Hearing.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

5 CFR 1215.5 - Hearing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Hearing. 1215.5 Section 1215.5... § 1215.5 Hearing. (a) Request for hearing. (1) An employee must file a petition for a hearing in accordance with the instructions outlined in the agency's notice to offset. (2) A hearing may be requested by...

Effect of the inclusion of mobile phone interviews to Vigitel.

PubMed

Bernal, Regina Tomie Ivata; Malta, Deborah Carvalho; Claro, Rafael Moreira; Monteiro, Carlos Augusto

2017-06-01

To evaluate the impact on the prevalence changes of risk factors for chronic diseases, published in the Surveillance System of Risk and Protection Factors for Chronic Diseases by Telephone Survey (Vigitel), after the inclusion of data from the population only with mobile phone. Our study used data from the 26 State capitals and Federal District of Brazil obtained by the National Survey on Health (PNS) and Vigitel, both held in 2013. In each capital, we added a subsample of 200 adults living in households with only mobile phones, extracted from PNS, to the Vigitel 2013 database, with approximately 1,900 households, named Vigitel dual frame. Vigitel results showed absolute relative biases between 0.18% and 14.85%. The system underestimated the frequency of adult smokers (10.77%), whole milk consumption (52.82%), and soft drink consumption (22.22%). Additionally, it overestimated the prevalence of hypertension (25.46%). In the simulations using Vigitel dual frame, with inclusion of the sample of adults living in households with only mobile phones, the bias of estimates was reduced in five out of eight analyzed indicators, with greater effects in regions with lower rates of landline coverage. In comparing regions, we observed negative correlation (ρ = -0.91) between the percentage of indicators with presence of bias and the percentage of households with only mobile phone. The results of this study indicate the benefits of including a subsample of 200 adults with only mobile phone on the Vigitel sample, especially in the capitals of the North and Northeast regions. Avaliar o impacto nas mudanças das prevalências de fatores de risco de doenças crônicas, divulgadas no Vigitel, após a inclusão de dados provenientes da população com somente telefone celular. O estudo utilizou os dados das capitais obtidos da Pesquisa Nacional de Saúde e do Vigitel, que foram realizados em 2013. Em cada capital, acrescentou-se uma subamostra de 200 adultos residentes em domic

43 CFR 1610.5-5 - Amendment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Amendment. 1610.5-5 Section 1610.5-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING Resource Management Planning § 1610.5-5 Amendment. A resource...

43 CFR 1610.5-5 - Amendment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Amendment. 1610.5-5 Section 1610.5-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING Resource Management Planning § 1610.5-5 Amendment. A resource...

43 CFR 1610.5-5 - Amendment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Amendment. 1610.5-5 Section 1610.5-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING Resource Management Planning § 1610.5-5 Amendment. A resource...

43 CFR 1610.5-5 - Amendment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Amendment. 1610.5-5 Section 1610.5-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING Resource Management Planning § 1610.5-5 Amendment. A resource...

36 CFR 5.5 - Commercial photography.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Commercial photography. 5.5 Section 5.5 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR COMMERCIAL AND PRIVATE OPERATIONS § 5.5 Commercial photography. (a) Motion pictures, television. Before any motion picture may be filmed or any...

Cytotoxic effect of Alpinia scabra (Blume) Náves extracts on human breast and ovarian cancer cells

PubMed Central

2013-01-01

Background Alpinia scabra, locally known as 'Lengkuas raya’, is an aromatic, perennial and rhizomatous herb from the family Zingiberaceae. It is a wild species which grows largely on mountains at moderate elevations in Peninsular Malaysia, but it can also survive in the lowlands like in the states of Terengganu and Northern Johor. The present study reports the cytotoxic potential of A. scabra extracts from different parts of the plant. Methods The experimental approach in the present study was based on a bioassay-guided fractionation. The crude methanol and fractionated extracts (hexane, chloroform and water) from different parts of A. scabra (leaves, rhizomes, roots and pseudo stems) were prepared prior to the cytotoxicity evaluation against human ovarian (SKOV-3) and hormone-dependent breast (MCF7) carcinoma cells. The identified cytotoxic extracts were then subjected to chemical investigations in order to identify the active ingredients. A normal human lung fibroblast cell line (MRC-5) was used to determine the specificity for cancerous cells. The cytotoxic extracts and fractions were also subjected to morphological assessment, DNA fragmentation analysis and DAPI nuclear staining. Results The leaf (hexane and chloroform) and rhizome (chloroform) extracts showed high inhibitory effect against the tested cells. Ten fractions (LC1-LC10) were yielded after purification of the leaf chloroform extract. Fraction LC4 which showed excellent cytotoxic activity was further purified and resulted in 17 sub-fractions (VLC1-VLC17). Sub-fraction VLC9 showed excellent cytotoxicity against MCF7 and SKOV-3 cells but not toxic against normal MRC-5 cells. Meanwhile, eighteen fractions (RC1-RC18) were obtained after purification of the rhizome chloroform extract, of which fraction RC5 showed cytotoxicity against SKOV-3 cells with high selectivity index. There were marked morphological changes when observed using phase-contrast inverted microscope, DAPI nuclear staining and also DNA

Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

USGS Publications Warehouse

Monette, M.Y.; Yada, T.; Matey, V.; McCormick, S.D.

2010-01-01

We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4??gl-1 Al), acid and low Al (LAl: pH 5.4, 11??gl-1 Al), acid and moderate Al (MAl: pH 5.3, 42??gl-1 Al), and acid and high Al (HAl: pH 5.4, 56??gl-1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na+/K+-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl- channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose that when smolts are

Developing Land Use Land Cover Maps for the Lower Mekong Basin to Aid SWAT Hydrologic Modeling

NASA Astrophysics Data System (ADS)

Spruce, J.; Bolten, J. D.; Srinivasan, R.

2017-12-01

This presentation discusses research to develop Land Use Land Cover (LULC) maps for the Lower Mekong Basin (LMB). Funded by a NASA ROSES Disasters grant, the main objective was to produce updated LULC maps to aid the Mekong River Commission's (MRC's) Soil and Water Assessment Tool (SWAT) hydrologic model. In producing needed LULC maps, temporally processed MODIS monthly NDVI data for 2010 were used as the primary data source for classifying regionally prominent forest and agricultural types. The MODIS NDVI data was derived from processing MOD09 and MYD09 8-day reflectance data with the Time Series Product Tool, a custom software package. Circa 2010 Landsat multispectral data from the dry season were processed into top of atmosphere reflectance mosaics and then classified to derive certain locally common LULC types, such as urban areas and industrial forest plantations. Unsupervised ISODATA clustering was used to derive most LULC classifications. GIS techniques were used to merge MODIS and Landsat classifications into final LULC maps for Sub-Basins (SBs) 1-8 of the LMB. The final LULC maps were produced at 250-meter resolution and delivered to the MRC for use in SWAT modeling for the LMB. A map accuracy assessment was performed for the SB 7 LULC map with 14 classes. This assessment was performed by comparing random locations for sampled LULC types to geospatial reference data such as Landsat RGBs, MODIS NDVI phenologic profiles, high resolution satellite data from Google Map/Earth, and other reference data from the MRC (e.g., crop calendars). LULC accuracy assessment results for SB 7 indicated an overall agreement to reference data of 81% at full scheme specificity. However, by grouping 3 deciduous forest classes into 1 class, the overall agreement improved to 87%. The project enabled updated LULC maps, plus more specific rice types were classified compared to the previous LULC maps. The LULC maps from this project should improve the use of SWAT for modeling

Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia.

PubMed

Naganawa, Shinji; Nakane, Toshiki; Kawai, Hisashi; Taoka, Toshiaki

2017-01-10

In textbooks, the perivascular space (PVS) is described as non-enhancing after the intravenous administration of gadolinium-based contrast agent (IV-GBCA). We noticed that the PVS sometimes has high signal intensity (SI) on heavily T 2 -weighted 3D-FLAIR (hT 2 -FL) images obtained 4 h after IV-GBCA. The purpose of this study was to retrospectively evaluate the contrast enhancement of the PVS. In 8 healthy subjects and 19 patients with suspected endolymphatic hydrops, magnetic resonance cisternography (MRC) and hT 2 -FL images were obtained before and 4 h after a single dose of IV-GBCA. No subjects had renal insufficiency. On axial MRC at the level of the anterior commissure (AC)-posterior commissure (PC) line, 1 cm circular regions of interest (ROIs) were drawn centering on the PVS in the bilateral basal ganglia and thalami. Three-millimeter diameter ROIs were set in the cerebrospinal fluid (CSF) of the bilateral ambient cistern. The ROIs on MRC were copied onto the hT 2 -FL images and the SI was measured. The SI ratio (SIR) was defined as SIR PVS = SI of PVS/SI of the thalami, and SIR CSF = SI of CSF/SI of the thalami. The average of the bilateral values was used for the calculation. The SIR CSF , SIR PVS , and SI of the thalami were compared between before and 4 h after IV-GBCA. The SIR was increased significantly from 1.02 ± 0.37 to 2.65 ± 0.82 in the CSF (P < 0.01) and from 1.20 ± 0.35 to 2.13 ± 1.23 in the PVS at 4 h after IV-GBCA (P < 0.01). The SI of the thalami showed no significant difference. The enhancement of the PVS at 4 h after IV-GBCA was confirmed even in subjects without renal insufficiency. It is possible that the GBCA in the blood vessels might have permeated into the cerebrospinal fluid (CSF) space and the PVS. This might be a first step in the imaging evaluation of the glymphatic system (waste clearance system) of the brain.

Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia

PubMed Central

Naganawa, Shinji; Nakane, Toshiki; Kawai, Hisashi; Taoka, Toshiaki

2017-01-01

Purpose: In textbooks, the perivascular space (PVS) is described as non-enhancing after the intravenous administration of gadolinium-based contrast agent (IV-GBCA). We noticed that the PVS sometimes has high signal intensity (SI) on heavily T2-weighted 3D-FLAIR (hT2-FL) images obtained 4 h after IV-GBCA. The purpose of this study was to retrospectively evaluate the contrast enhancement of the PVS. Materials and Methods: In 8 healthy subjects and 19 patients with suspected endolymphatic hydrops, magnetic resonance cisternography (MRC) and hT2-FL images were obtained before and 4 h after a single dose of IV-GBCA. No subjects had renal insufficiency. On axial MRC at the level of the anterior commissure (AC)-posterior commissure (PC) line, 1 cm circular regions of interest (ROIs) were drawn centering on the PVS in the bilateral basal ganglia and thalami. Three-millimeter diameter ROIs were set in the cerebrospinal fluid (CSF) of the bilateral ambient cistern. The ROIs on MRC were copied onto the hT2-FL images and the SI was measured. The SI ratio (SIR) was defined as SIRPVS = SI of PVS/SI of the thalami, and SIRCSF = SI of CSF/SI of the thalami. The average of the bilateral values was used for the calculation. The SIRCSF, SIRPVS, and SI of the thalami were compared between before and 4 h after IV-GBCA. Results: The SIR was increased significantly from 1.02 ± 0.37 to 2.65 ± 0.82 in the CSF (P < 0.01) and from 1.20 ± 0.35 to 2.13 ± 1.23 in the PVS at 4 h after IV-GBCA (P < 0.01). The SI of the thalami showed no significant difference. Conclusion: The enhancement of the PVS at 4 h after IV-GBCA was confirmed even in subjects without renal insufficiency. It is possible that the GBCA in the blood vessels might have permeated into the cerebrospinal fluid (CSF) space and the PVS. This might be a first step in the imaging evaluation of the glymphatic system (waste clearance system) of the brain. PMID:27430361

Assessment of Impact on Students and Teachers of Student-led, inquiry-based planetary science instruction in Grades 3-8

NASA Astrophysics Data System (ADS)

Bering, Edgar Andrew; Carlson, Coleen; Nieser, Kenneth; Slagle, Elana

2015-11-01

The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 195 Mars Rover teachers from the 2012-2013, 2013-2014, and 2014-2015 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. So far ~90 teachers have participated with responses still coming in. A total of 1300 students from the 2013-2014 and 2014-2015 cohort were invited to submit brief self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching “Earth and the solar system and universe” increased “Quite a bit” as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. The most striking increases were the percentage of teachers who felt their confidence increased “Quite a bit” as a result of their participation in the MRC program in the following areas: “Getting students interested in and curious about science” (63%); “Teaching science as a co-inquirer with students” (56%); and “Continually find better ways to teach science” (59%). Student outcome analysis is pending correlation with

COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members

PubMed Central

Pasquale, Margaret K; Xu, Yihua; Baker, Christine L; Zou, Kelly H; Teeter, John G; Renda, Andrew M; Davis, Cralen C; Lee, Theodore C; Bobula, Joel

2016-01-01

Background The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs. Methods The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs. Results Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P<0.001 for all). The odds ratio for high vs low symptoms using CAT was 2.51 (P<0.001). Similarly, exacerbation-related costs were 73% higher with each incremental pre-index exacerbation, and over four fold higher for high-vs low-symptom patients using CAT (each P<0.001). The symptoms using mMRC were not

41 CFR 51-5.5 - Prices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Prices. 51-5.5 Section 51... FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED 5-CONTRACTING REQUIREMENTS § 51-5.5 Prices. (a) The prices for items on the Procurement List are fair market prices established by the Committee...

Lifetimes and oscillator strengths for the 5s5p6s, 5s5p5d and 5p3 levels in single-ionized tin

NASA Astrophysics Data System (ADS)

Colón, C.; Alonso-Medina, A.

2004-08-01

Radiative oscillator strengths for 103 lines arising from 5s5p6s, 5s5p5d and 5p3 configurations of Sn II and lifetimes corresponding to several levels of these configurations have been calculated. These values were obtained in intermediate coupling (IC) and using ab initio relativistic Hartree-Fock (HFR) calculations. We use the standard method of least square fitting of experimental energy levels for the IC calculations by means of computer codes from Cowan. Tables 1 and 2 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/422/1109

Association between religiousness and blood donation among Brazilian postgraduate students from health-related areas.

PubMed

Zangiacomi Martinez, Edson; Dos Santos Almeida, Rodrigo Guimarães; Garcia Braz, Ana Carolina; Duarte de Carvalho, Antonio Carlos

2014-01-01

The aim of this study was to examine the association between religiousness and blood donation among postgraduate students. The Portuguese-language version of the Duke University Religion Index was administered to a sample of 226 Brazilian students with ages ranging from 22 to 55 years. All study participants had completed undergraduate courses in health-related areas. In the present study, 23.5% of the students were regular donors. Organizational religiousness was found to be associated with attitudes related to blood donation. This study also shows evidence that regular blood donors have a higher intrinsic religiousness than subjects who donate only once and do not return. This study shows that the attitudes concerning blood donation may have some association with religiosity. Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

5 CFR 2500.5 - Derivative classification.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Derivative classification. 2500.5 Section 2500.5 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF THE PRESIDENT INFORMATION SECURITY REGULATION § 2500.5 Derivative classification. The Office of Administration serves only as the...

5 CFR 2500.5 - Derivative classification.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Derivative classification. 2500.5 Section 2500.5 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF THE PRESIDENT INFORMATION SECURITY REGULATION § 2500.5 Derivative classification. The Office of Administration serves only as the...

5 CFR 2500.5 - Derivative classification.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Derivative classification. 2500.5 Section 2500.5 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF THE PRESIDENT INFORMATION SECURITY REGULATION § 2500.5 Derivative classification. The Office of Administration serves only as the...

5 CFR 2500.5 - Derivative classification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Derivative classification. 2500.5 Section 2500.5 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF THE PRESIDENT INFORMATION SECURITY REGULATION § 2500.5 Derivative classification. The Office of Administration serves only as the...

Is the COPD assessment test (CAT) effective in demonstrating the systemic inflammation and other components in COPD?

PubMed

Sarioglu, N; Hismiogullari, A A; Bilen, C; Erel, F

2016-01-01

Chronic obstructive pulmonary disease (COPD) is currently a complex, multicomponent disorder. The COPD Assessment Test (CAT) has been increasingly used to assess COPD patients. This study aims to investigate the relationship between CAT and inflammation markers and other COPD components. We enrolled 110 stable COPD patients and 65 control subjects in this study. All patients completed the CAT questionnaire and the modified Medical Research Council (mMRC) dispnea scale. The quality of life of these patients was measured with St. George's Respiratory Questionnaire (SGRQ). Levels of TNFα, IL-6, CRP were determined in blood samples. In COPD patients, serum levels of TNFα (109.5 ± 58 pg/ml), IL-6 (10.3 ± 18 pg/ml), and C-reactive protein (CRP) (1.6 ± 1.7 mg/L) were found to be significantly higher compared to controls (TNF-α: 14.6 ± 18 pg/ml, IL-6: 2.14 ± 1.9 pg/ml, CRP: 0.4 ± 0.3mg/L, p<0.001). These markers were correlated with smoking (r from 0.27 to 0.35, p<0.001), FEV1 (r from -0.39 to -0.57, p<0.001), FVC (r from -0.32 to -0.37, p<0.001) and FEV1/FVC (r from -0.31 to -0.66, p<0.001). The CAT score correlated with GOLD spirometric stages, mMRC dyspnea score, number of exacerbations in the previous year and FEV1 (p<0.001). There was a significant correlation between levels of CRP and the CAT score (r=0.43, p<0.001) but no similar relationship between levels of TNFα and IL-6 and the CAT was observed. Systemic inflammation persists in the stable period of COPD. CRP, one of the inflammation markers, was correlated with the CAT. Further studies are required to confirm the relationship between CAT and biomarkers. Copyright © 2015 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012–2013

PubMed Central

Landis, Sarah H; Muellerova, Hana; Mannino, David M; Menezes, Ana M; Han, MeiLan K; van der Molen, Thys; Ichinose, Masakazu; Aisanov, Zaurbek; Oh, Yeon-Mok; Davis, Kourtney J

2014-01-01

Purpose The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999–2000. Materials and methods Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples. Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments. Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale. Results Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey. COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%–9%. In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%–14%) than among women (range 5%–11%). A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries. Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment. Conclusion This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey. A significant burden of COPD was

Identifying Patients at Higher Risk of Prolonged Air Leak After Lung Resection.

PubMed

Gilbert, Sebastien; Maghera, Sonam; Seely, Andrew J; Maziak, Donna E; Shamji, Farid M; Sundaresan, Sudhir R; Villeneuve, Patrick J

2016-11-01

Predictive models of prolonged air leak have relied on information not always available preoperatively (eg, extent of resection, pleural adhesions). Our objective was to construct a model to identify patients at increased risk of prolonged air leak using preoperative factors exclusively. From 2012 to 2014, data on consecutive patients undergoing pulmonary resection were collected prospectively. Prolonged air leak was defined as lasting longer than 7 days and requiring hospitalization. Factors associated with the primary outcome (p < 0.2) were included in a multivariate model. Regression coefficients were used to develop a weighted risk score for prolonged air leak. Of 225 patients, 8% (18/225) experienced a prolonged air leak. Male gender (p = 0.08), smoking history (p = 0.03), body mass index (BMI) 25 or below (p < 0.01), Medical Research Council (MRC) dyspnea score above 1 (p = 0.06), and diffusion capacity for carbon monoxide below 80% (Dlco) (p = 0.01) were selected for inclusion in the final model. Weighted scores were male gender (1 point), BMI 25 or below (0.5 point), smoker (2 points), Dlco% below 80% (2 points), and MRC dyspnea score above 1 (1 point). The area under the receiver operating characteristic curve was 0.8 (95% confidence interval [CI] = 0.7 to 0.9]. An air leak score above 4 points offered the best combination of sensitivity (83% [95% CI = 58 to 96]) and specificity (65% [95% CI = 58 to 71]). A subgroup of lung resection patients at higher risk for a prolonged air leak can be effectively identified with the use of widely available, preoperative factors. The proposed scoring system is simple, is clinically relevant to the informed consent, and allows preoperative patient selection for interventions to reduce the risk of prolonged air leak. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

36 CFR 5.5 - Commercial photography.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Commercial photography. 5.5... COMMERCIAL AND PRIVATE OPERATIONS § 5.5 Commercial photography. (a) Motion pictures, television. Before any... Federal Regulations. (b) Still photography. The taking of photographs of any vehicle, or other articles of...

36 CFR 5.5 - Commercial photography.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Commercial photography. 5.5... COMMERCIAL AND PRIVATE OPERATIONS § 5.5 Commercial photography. (a) Motion pictures, television. Before any... Federal Regulations. (b) Still photography. The taking of photographs of any vehicle, or other articles of...

36 CFR 5.5 - Commercial photography.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Commercial photography. 5.5... COMMERCIAL AND PRIVATE OPERATIONS § 5.5 Commercial photography. (a) Motion pictures, television. Before any... Federal Regulations. (b) Still photography. The taking of photographs of any vehicle, or other articles of...

.beta.-glucosidase 5 (BGL5) compositions

DOEpatents

Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

2010-06-01

The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl5, and the corresponding BGL5 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL5, recombinant BGL5 proteins and methods for producing the same.

5 CFR 1650.5 - Returned funds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Returned funds. 1650.5 Section 1650.5 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN General § 1650.5 Returned funds. If a withdrawal is returned as undeliverable, the TSP record...

5 CFR 1650.5 - Returned funds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Returned funds. 1650.5 Section 1650.5 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN General § 1650.5 Returned funds. If a withdrawal is returned as undeliverable, the TSP record...

5 CFR 2422.5 - Filing petitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Filing petitions. 2422.5 Section 2422.5... FEDERAL LABOR RELATIONS AUTHORITY REPRESENTATION PROCEEDINGS § 2422.5 Filing petitions. (a) Where to file. Petitions must be filed with the Regional Director for the region in which the unit or employee(s) affected...

Spiritual Well-Being and Correlated Factors in Subjects With Advanced COPD or Lung Cancer.

PubMed

Hasegawa, Takaaki; Kawai, Momoko; Kuzuya, Nanori; Futamura, Yohei; Horiba, Akane; Ishiguro, Takashi; Yoshida, Tsutomu; Sawa, Toshiyuki; Sugiyama, Yasuyuki

2017-05-01

Spiritual care for patients with COPD has rarely been discussed, and thus much remains unknown about their needs. The aims of this study were to identify the factors associated with spiritual well-being and to compare the levels of spiritual well-being between subjects with advanced COPD and those with inoperable lung cancer. A total of 96 subjects with COPD or lung cancer participated in this study, which was conducted between December 2014 and April 2016. Measures included the Japanese version of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, the McGill Quality of Life Questionnaire (MQOL), the modified Medical Research Council (mMRC) dyspnea scale, and various other medico-social factors. No significant differences were found between subjects with COPD and those with lung cancer in median FACIT-Sp-12 scores (COPD, 27; lung cancer, 26; P = .81). However, significant differences were found in the 2 MQOL domains, suggesting that subjects with COPD had a better psychological state ( P = .01) and that subjects with lung cancer had a better support state ( P = .002). Multiple regression analysis revealed that mMRC was significantly associated with FACIT-Sp-12 scores in subjects with COPD. These results suggest that subjects with advanced COPD experience spiritual well-being similar to that of subjects with inoperable lung cancer. Copyright © 2017 by Daedalus Enterprises.

Effects of N-acetyl-L-cysteine on the membrane vesicle release and growth of respiratory pathogens.

PubMed

Volgers, Charlotte; Benedikter, Birke J; Grauls, Gert E; Hellebrand, Pauline H M; Savelkoul, Paul H M; Stassen, Frank R M

2017-05-01

Bacterial infections contribute to the disease progression of chronic obstructive pulmonary disease by stimulating mucus production in the airways. This increased mucus production and other symptoms are often alleviated when patients are treated with mucolytics such as N-acetyl-L-cysteine (NAC). Moreover, NAC has been suggested to inhibit bacterial growth. Bacteria can release membrane vesicles (MVs) in response to stress, and recent studies report a role for these proinflammatory MVs in the pathogenesis of airways disease. Yet, until now it is not clear whether NAC also affects the release of these MVs. This study set out to determine whether NAC, at concentrations reached during high-dose nebulization, affects bacterial growth and MV release of the respiratory pathogens non-typeable Haemophilus influenzae (NTHi), Moraxella catarrhalis (Mrc), Streptococcus pneumoniae (Spn) and Pseudomonas aeruginosa (Psa). We observed that NAC exerted a strong bacteriostatic effect, but also induced the release of proinflammatory MVs by NTHi, Mrc and Psa, but not by Spn. Interestingly, NAC also markedly blunted the release of TNF-α by naive macrophages in response to MVs. This suggests that the application of NAC by nebulization at a high dosage may be beneficial for patients with airway conditions associated with bacterial infections. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PBP1a/LpoA but Not PBP1b/LpoB Are Involved in Regulation of the Major β-Lactamase Gene blaA in Shewanella oneidensis

PubMed Central

Yin, Jianhua; Sun, Yiyang; Mao, Yinting; Jin, Miao

2015-01-01

β-Lactamase production is one of the most important strategies for Gram-negative bacteria to combat β-lactam antibiotics. Studies of the regulation of β-lactamase expression have largely been focused on the class C β-lactamase AmpC, whose induction by β-lactams requires LysR-type regulator AmpR and permease AmpG-dependent peptidoglycan recycling intermediates. In Shewanella, which is ubiquitous in aquatic environments and is a reservoir for antibiotic resistance, production of the class D β-lactamase BlaA confers bacteria with natural resistance to many β-lactams. Expression of the blaA gene in the genus representative Shewanella oneidensis is distinct from the AmpC paradigm because of the lack of an AmpR homologue and the presence of an additional AmpG-independent regulatory pathway. In this study, using transposon mutagenesis, we identify proteins that are involved in blaA regulation. Inactivation of mrcA and lpoA, which encode penicillin binding protein 1a (PBP1a) and its lipoprotein cofactor, LpoA, respectively, drastically enhances blaA expression in the absence of β-lactams. Although PBP1b and its cognate, LpoB, also exist in S. oneidensis, their roles in blaA induction are dispensable. We further show that the mrcA-mediated blaA expression is independent of AmpG. PMID:25824223

Pixel-based OPC optimization based on conjugate gradients.

PubMed

Ma, Xu; Arce, Gonzalo R

2011-01-31

Optical proximity correction (OPC) methods are resolution enhancement techniques (RET) used extensively in the semiconductor industry to improve the resolution and pattern fidelity of optical lithography. In pixel-based OPC (PBOPC), the mask is divided into small pixels, each of which is modified during the optimization process. Two critical issues in PBOPC are the required computational complexity of the optimization process, and the manufacturability of the optimized mask. Most current OPC optimization methods apply the steepest descent (SD) algorithm to improve image fidelity augmented by regularization penalties to reduce the complexity of the mask. Although simple to implement, the SD algorithm converges slowly. The existing regularization penalties, however, fall short in meeting the mask rule check (MRC) requirements often used in semiconductor manufacturing. This paper focuses on developing OPC optimization algorithms based on the conjugate gradient (CG) method which exhibits much faster convergence than the SD algorithm. The imaging formation process is represented by the Fourier series expansion model which approximates the partially coherent system as a sum of coherent systems. In order to obtain more desirable manufacturability properties of the mask pattern, a MRC penalty is proposed to enlarge the linear size of the sub-resolution assistant features (SRAFs), as well as the distances between the SRAFs and the main body of the mask. Finally, a projection method is developed to further reduce the complexity of the optimized mask pattern.

Early prediction of intensive care unit-acquired weakness using easily available parameters: a prospective observational study.

PubMed

Wieske, Luuk; Witteveen, Esther; Verhamme, Camiel; Dettling-Ihnenfeldt, Daniela S; van der Schaaf, Marike; Schultz, Marcus J; van Schaik, Ivo N; Horn, Janneke

2014-01-01

An early diagnosis of Intensive Care Unit-acquired weakness (ICU-AW) using muscle strength assessment is not possible in most critically ill patients. We hypothesized that development of ICU-AW can be predicted reliably two days after ICU admission, using patient characteristics, early available clinical parameters, laboratory results and use of medication as parameters. Newly admitted ICU patients mechanically ventilated ≥2 days were included in this prospective observational cohort study. Manual muscle strength was measured according to the Medical Research Council (MRC) scale, when patients were awake and attentive. ICU-AW was defined as an average MRC score <4. A prediction model was developed by selecting predictors from an a-priori defined set of candidate predictors, based on known risk factors. Discriminative performance of the prediction model was evaluated, validated internally and compared to the APACHE IV and SOFA score. Of 212 included patients, 103 developed ICU-AW. Highest lactate levels, treatment with any aminoglycoside in the first two days after admission and age were selected as predictors. The area under the receiver operating characteristic curve of the prediction model was 0.71 after internal validation. The new prediction model improved discrimination compared to the APACHE IV and the SOFA score. The new early prediction model for ICU-AW using a set of 3 easily available parameters has fair discriminative performance. This model needs external validation.

MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.

PubMed

Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

2013-11-01

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.

Does an isolated benign choledochal stricture hide a PSC?

PubMed

De Angelis, Paola; Tambucci, Renato; Romeo, Erminia; Rea, Francesca; Caloisi, Claudia; Caldaro, Tamara; di Abriola, Giovanni Federici; Foschia, Francesca; Torroni, Filippo; Monti, L; Dall'Oglio, Luigi

2013-05-01

Strictures of the extra-hepatic biliary tree are rare in children and have a benign non-traumatic inflammatory origin or are related to idiopathic fibrosing pancreatitis. Primary sclerosing cholangitis (PSC) can manifest as multiple biliary strictures or as a single dominant stricture. We describe the presentation, treatment, and outcome of six cases of isolated benign choledochal stricture (IBCS). All patients underwent magnetic resonance cholangiography (MRC). Five patients underwent diagnostic and therapeutic ERCP, and 4 patients underwent intra-choledochal mini-probe EUS and biopsy. Colonoscopy was performed in suspected ulcerative colitis (UC). We report 6 patients (mean age at diagnosis: four males, 12.1 years; two females, 14.2 years) with IBCS. Clinical onset included 3 cases of acute biliary pancreatitis and obstructive jaundice, one obstructive jaundice, one cholestasis, and one pancreatitis. At diagnosis, MRC confirmed IBCS in all patients. Biliary sphincterotomy, stricture dilation, and stenting were performed in 4 patients. One child underwent hepaticojejunostomy for a type I choledocal cyst. During follow-up (mean: 21 months; range: 1-3 years), all patients were asymptomatic. Four patients developed UC (three pancolitis, one descending colitis). One child developed PSC. IBCS can be successfully treated by therapeutic ERCP. The occurrence of UC could suggest that IBCS is a form of PSC. Copyright © 2013 Elsevier Inc. All rights reserved.

Data sharing in international transboundary contexts: The Vietnamese perspective on data sharing in the Lower Mekong Basin

NASA Astrophysics Data System (ADS)

Thu, Hang Ngo; Wehn, Uta

2016-05-01

Transboundary data sharing is widely recognised as a necessary element in the successful handling of water-related climate change issues, as it is a means towards integrated water resources management (IWRM). However, in practice it is often a challenge to achieve it. The Mekong River Commission (MRC), an inter-governmental agency established by Cambodia, Lao PDR, Thailand and Vietnam, has adopted IWRM in its water strategy plan in order to properly manage the transboundary waters of the Mekong River. In this context, data sharing procedures were institutionalised and have been officially implemented by the four member countries since 2001. This paper uses a systematic approach to identify the extent of data sharing and the factors influencing the willingness of key individuals in the Vietnam National Mekong Committee and its Primary Custodians to share data. We find that the initial objectives of the Procedures for Data and Information Exchange and Sharing (PDIES) have not been fully achieved and, further, that Vietnam has much to gain and little to lose by engaging in data sharing in the MRC context. The primary motivation for data sharing stems from the desire to protect national benefits and to prevent upstream countries from overexploiting the shared water resources. However, data sharing is hindered by a lack of national regulations in the Vietnam context concerning data sharing between state agencies and outdated information management systems.

The MRC CRASH trial--a large, simple randomised trial of steroids in head injury.

PubMed

Wasserberg, J

2004-01-01

CRASH (Corticosteroid randomisation after significant head injury) is a prospective multi-centre randomised double blind study of methylprednisolone versus placebo in mild, moderate and severe head injury. Patients are eligible up to 8 hours from injury. To date the CRASH trial has recruited 9000 patients. The trial is recruiting from 200 hospitals in 50 countries with another 100 centres planning to join the trial. The target for recruitment is 20,000 patients by 2006. The trial is wholly funded by the Medical Research Council of Great Britain and is multidisciplinary, involving doctors and nurses from a range of specialities. A recent systematic review of corticosteroids in head injury demonstrated a risk of death in the corticosteroid treated group 2% lower than in the control group. The 95% confidence interval ranges from a 60%, lower mortality to a 2% higher mortality. This result is compatible with there being no real benefit, but it is also compatible with there being a small benefit of a few percent. An improvement in mortality of 2% would theoretically save 10,000 lives per 500,000 patients treated. The global impact of such a treatment effect would be significant as the number of head injuries world-wide continues to rise.

15 CFR 5.5 - Vending machines.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Vending machines. 5.5 Section 5.5... machines. (a) The income from any vending machines which are located within reasonable proximity to and are... shall be assigned to the operator of such stand. (b) If a vending machine vends articles of a type...

15 CFR 5.5 - Vending machines.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Vending machines. 5.5 Section 5.5... machines. (a) The income from any vending machines which are located within reasonable proximity to and are... shall be assigned to the operator of such stand. (b) If a vending machine vends articles of a type...

Fabrication of Fe3O4@mSiO2 Core-Shell Composite Nanoparticles for Drug Delivery Applications

NASA Astrophysics Data System (ADS)

Uribe Madrid, Sergio I.; Pal, Umapada; Kang, Young Soo; Kim, Junghoon; Kwon, Hyungjin; Kim, Jungho

2015-05-01

We report the synthesis of Fe3O4@mSiO2 nanostructures of different meso-silica (mSiO2) shell thickness, their biocompatibility and behaviors for loading and release of a model drug ibuprofen. The composite nanostructures have superparamagnetic magnetite cores of 208 nm average size and meso-silica shells of 15 to 40 nm thickness. A modified Stöber method was used to grow the meso-silica shells over the hydrothermally grown monodispersed magnetite particles. The composite nanoparticles show very promising drug holding and releasing behaviors, which depend on the thickness of meso-silica shell. The biocompatibility of the meso-silica-coated and uncoated magnetite nanoparticles was tested through cytotoxicity assay on breast cancer (MCF-7), ovarian cancer (SKOV3), normal human lung fibroblasts MRC-5, and IMR-90 cells. The high drug holding capacity and reasonable biocompatibility of the nanostructures make them ideal agents for targeted drug delivery applications in human body.

3D confocal reconstruction of gene expression in mouse.

PubMed

Hecksher-Sørensen, J; Sharpe, J

2001-01-01

Three-dimensional computer reconstructions of gene expression data will become a valuable tool in biomedical research in the near future. However, at present the process of converting in situ expression data into 3D models is a highly specialized and time-consuming procedure. Here we present a method which allows rapid reconstruction of whole-mount in situ data from mouse embryos. Mid-gestation embryos were stained with the alkaline phosphotase substrate Fast Red, which can be detected using confocal laser scanning microscopy (CLSM), and cut into 70 microm sections. Each section was then scanned and digitally reconstructed. Using this method it took two days to section, digitize and reconstruct the full expression pattern of Shh in an E9.5 embryo (a 3D model of this embryo can be seen at genex.hgu.mrc.ac.uk). Additionally we demonstrate that this technique allows gene expression to be studied at the single cell level in intact tissue.

Discovery of Potent, Orally Bioavailable Inhibitors of Human Cytomegalovirus

PubMed Central

2016-01-01

A high-throughput screen based on a viral replication assay was used to identify inhibitors of the human cytomegalovirus. Using this approach, hit compound 1 was identified as a 4 μM inhibitor of HCMV that was specific and selective over other herpes viruses. Time of addition studies indicated compound 1 exerted its antiviral effect early in the viral life cycle. Mechanism of action studies also revealed that this series inhibited infection of MRC-5 and ARPE19 cells by free virus and via direct cell-to-cell spread from infected to uninfected cells. Preliminary structure–activity relationships demonstrated that the potency of compound 1 could be improved to a low nanomolar level, but metabolic stability was a key optimization parameter for this series. A strategy focused on minimizing metabolic hydrolysis of the N1-amide led to an alternative scaffold in this series with improved metabolic stability and good pharmacokinetic parameters in rat. PMID:27190604

Tula hantavirus isolate with the full-length ORF for nonstructural protein NSs survives for more consequent passages in interferon-competent cells than the isolate having truncated NSs ORF.

PubMed

Jääskeläinen, Kirsi M; Plyusnina, Angelina; Lundkvist, Ake; Vaheri, Antti; Plyusnin, Alexander

2008-01-11

The competitiveness of two Tula hantavirus (TULV) isolates, TULV/Lodz and TULV/Moravia, was evaluated in interferon (IFN) -competent and IFN-deficient cells. The two isolates differ in the length of the open reading frame (ORF) encoding the nonstructural protein NSs, which has previously been shown to inhibit IFN response in infected cells. In IFN-deficient Vero E6 cells both TULV isolates survived equally well. In contrast, in IFN-competent MRC5 cells TULV/Lodz isolate, that possesses the NSs ORF for the full-length protein of 90 aa, survived for more consequent passages than TULV/Moravia isolate, which contains the ORF for truncated NSs protein (66-67 aa). Our data show that expression of a full-length NSs protein is beneficial for the virus survival and competitiveness in IFN-competent cells and not essential in IFN-deficient cells. These results suggest that the N-terminal aa residues are important for the full activity of the NSs protein.

Overview of measles and mumps vaccine: origin, present, and future of vaccine production.

PubMed

Betáková, T; Svetlíková, D; Gocník, M

2013-01-01

Measles and mumps are common viral childhood diseases that can cause serious complications. Vaccination remains the most efficient way to control the spread of these viruses. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblast or primary dog kidney cell substrates, is no longer sufficient. This limitation can be overcome by utilizing other recognized cell substrates such as Madin Darby Canine Kidney (MDCK), Chinese Hamster Ovary (CHO), Vero (monkey origin) cells, MRC-5 (human diploid) or as an alternative, introducing new cell substrates of human or avian origin. A very important factor in vaccine production is the safety and immunogenicity of the final vaccine, where the proper choice of cell substrate used for virus propagation is made. All substrates used in vaccine production must be fully characterized to avoid the contamination of hidden unknown pathogens which is difficult to achieve in primary cell substrates.

Trametes versicolor ethanol extract, a promising candidate for health-promoting food supplement.

PubMed

Janjušević, Ljiljana; Pejin, Boris; Kaišarević, Sonja; Gorjanović, Stanislava; Pastor, Ferenc; Tešanović, Kristina; Karaman, Maja

2018-04-01

This study aimed to estimate antiradical, antioxidant (AO) and cytotoxic activities of the fungus Trametes versicolor ethanol fruiting body extract. The extract was found to effectively scavenge both O 2 •- and NO • (29.62 and 52.48 μg/mL, respectively). It also showed a good AO activity in the polarographic HPMC assay (950%/mL). p-Hydroxybenzoic acid may be one of the responsible compounds for the afore-mentioned activities. The same extract also exhibited a concentration-dependent cytotoxicity against MCF-7 and HepG2 tumour cell lines reaching IC 50 values of 123.51 and 134.29 μg/mL, respectively with no cytotoxic activity against normal MRC-5 cells. Gentisic, syringic and protocatechuic acids may be among the bioactive principles for the observed cytotoxicity. Taken all together, T. versicolor ethanol extract can be considered as a promising candidate for development of health promoting food supplement.

Functional diversity for biomass deconstruction in family 5 subfamily 5 (GH5_5) of fungal endo-β1,4-glucanases.

PubMed

Li, Bingyao; Walton, Jonathan D

2017-05-01

Endo-β1,4-glucanases in glycosyl hydrolase family 5 (GH5) are ubiquitous enzymes in the multicellular fungi and are common components of enzyme cocktails for biomass conversion. We recently showed that an endo-glucanase of subfamily 5 of GH5 (GH5_5) from Sporotrichum thermophile (StCel5A) was more effective at releasing glucose from pretreated corn stover, when part of an eight-component synthetic enzyme mixture, compared to its closely related counterpart from Trichoderma reesei, TrCel5A. StCel5A and TrCel5A belong to different clades of GH5_5 (GH5_5_1 and GH5_5_2, respectively). To test whether the superior activity of StCel5A was a general property of all enzymes in the GH5_5_2 clade, StCel5A, TrCel5A, and two additional members of each subfamily were expressed in a common host that had been engineered to suppress its native cellulases (T. reesei Δxyr1) and compared against each other alone on pure substrates, in synthetic mixtures on pure substrates, and against each other in synthetic mixtures on real biomass. The results indicated that superiority is a unique property of StCel5A and not of GH5_5_2 generally. The six Cel5A enzymes had significant differences in relative activities on different substrates, in specific activities, and in sensitivities to mannan inhibition. Importantly, the behavior of the six endo-glucanases on pure cellulose substrates did not predict their behavior in combination with other cellulolytic enzymes on a real lignocellulosic biomass substrate.

High-level ab initio predictions for the ionization energy, electron affinity, and heats of formation of cyclopentadienyl radical, cation, and anion, C5H5/C5H5+/C5H5-.

PubMed

Lo, Po-Kam; Lau, Kai-Chung

2014-04-03

The ionization energy (IE), electron affinity (EA), and heats of formation (ΔH°f0/ΔH°f298) for cyclopentadienyl radical, cation, and anion, C5H5/C5H5(+)/C5H5(-), have been calculated by wave function-based ab initio CCSDT/CBS approach, which involves approximation to complete basis set (CBS) limit at coupled-cluster level with up to full triple excitations (CCSDT). The zero-point vibrational energy correction, core-valence electronic correction, scalar relativistic effect, and higher-order corrections beyond the CCSD(T) wave function are included in these calculations. The allylic [C5H5((2)A2)] and dienylic [C5H5((2)B1)] forms of cyclopentadienyl radical are considered: the ground state structure exists in the dienyl form and it is about 30 meV more stable than the allylic structure. Both structures are lying closely and are interconvertible along the normal mode of b2 in-plane vibration. The CCSDT/CBS predictions (in eV) for IE[C5H5(+)((3)A1')←C5H5((2)B1)] = 8.443, IE[C5H5(+)((1)A1)←C5H5((2)B1)] = 8.634 and EA[C5H5(-)((1)A1')←C5H5((2)B1)] = 1.785 are consistent with the respective experimental values of 8.4268 ± 0.0005, 8.6170 ± 0.0005, and 1.808 ± 0.006, obtained from photoelectron spectroscopic measurements. The ΔH°f0/ΔH°f298's (in kJ/mol) for C5H5/C5H5(+)/C5H5(-) have also been predicted by the CCSDT/CBS method: ΔH°f0/ΔH°f298[C5H5((2)B1)] = 283.6/272.0, ΔH°f0/ΔH°f298[C5H5(+)((3)A1')] = 1098.2/1086.9, ΔH°f0/ΔH°f298[C5H5(+)((1)A1)] = 1116.6/1106.0, and ΔH°f0/ΔH°f298[C5H5(-)((1)A1')] = 111.4/100.0. The comparisons between the CCSDT/CBS predictions and the experimental values suggest that the CCSDT/CBS procedure is capable of predicting reliable IE(C5H5)'s and EA(C5H5) with uncertainties of ± 17 and ± 23 meV, respectively.

Chronic respiratory disease in adults treated for tuberculosis in Khartoum, Sudan.

PubMed

Osman, R K; Mortimer, K; Bjune, G; El Sony, A I

2016-09-01

Background: Chronic respiratory disease (CRD) causes substantial morbidity and mortality. Although the global CRD epidemic collides with the tuberculosis (TB) epidemic in many low- and middle-income country settings, the risk of TB-associated CRD is not well described in countries with a high burden of TB. Methods: We recruited 136 patients with a history of sputum smear-positive pulmonary TB (PTB) from the TB clinic at Omdurman Teaching Hospital in Khartoum, Sudan, and 136 age- and sex-matched community controls, between 28 July 2013 and 30 December 2013. Data were collected using standardised questionnaires and spirometry was performed before and after bronchodilator. Results: The mean age of the subjects with previous PTB and controls was respectively 44.0 years (SD 8.5) and 44.5 years (SD 8.6), with 27.2% females in both groups. Chronic respiratory symptoms such as chronic cough (OR 6.67, 95%CI 2.98-14.90, P < 0.001) and the presence of chronic airflow obstruction (OR 12.4, 95%CI 1.56-98.40, P = 0.02) were both strongly associated with a past history of PTB after adjusting for potential confounders. Conclusion: The clinical features of CRDs are strongly associated with past history of PTB. An integrated approach to improve the management of these common conditions should be considered. Contexte : Les maladies respiratoires chroniques (MRC) sont à l'origine d'une morbidité et d'une mortalité considérables dans le monde. Bien que l'épidémie mondiale des MRC entre en conflit avec l'épidémie de tuberculose (TB) dans de nombreux pays à revenu faible ou moyen, le risque de MRC associée à la TB n'est pas bien décrit dans les pays durement frappés par la TB. Méthodes : Nous avons recruté 136 patients ayant des antécédents de tuberculose pulmonaire (TBP) à frottis positif dans le service de pneumologie du Centre Hospitalier Universitaire Omdurman à Khartoum, Soudan, et 136 témoins de la communauté, appariés sur l'âge et le sexe, entre le 28

Why are SiX5(-) and GeX5(-) (X = F, Cl) stable but not CF5(-) and CCl5(-)?

PubMed

Marchaj, Marzena; Freza, Sylwia; Skurski, Piotr

2012-03-01

The possible existence of the CF(5)(-), CCl(5)(-), SiF(5)(-), SiCl(5)(-), GeF(5)(-), and GeCl(5)(-) anions has been investigated using ab initio methods. The species containing Si and Ge as central atoms were found to adopt the D(3h)-symmetry trigonal bipyramidal equilibrium structures whose thermodynamic stabilities were confirmed by examining the most probable fragmentation channels. The ab initio re-examination of the electronic stabilities of the SiF(5)(-), SiCl(5)(-), GeF(5)(-), and GeCl(5)(-) anions [using the OVGF(full) method with the 6-311+G(3df) basis set] led to the very large vertical electron detachment (VDE) energies of 9.316 eV (SiF(5)(-)) and 9.742 eV (GeF(5)(-)), whereas smaller VDEs of 6.196 and 6.452 eV were predicted for the SiCl(5)(-) and GeCl(5)(-) species, respectively. By contrast, the high-symmetry and structurally compact anionic CF(5)(-) and CCl(5)(-) systems cannot exist due to the strongly repulsive potential predicted for the X(-) (F(-) or Cl(-)) approaching the CX(4) (CF(4) or CCl(4)). The formation of weakly bound CX(4)···X(-) (CF(4)···F(-) and CCl(4)···Cl(-)) anionic complexes (consisting of pseudotetrahedral neutral CX(4) with the weakly tethered X(-)) might be expected at low temperatures (approaching 0 K), whereas neither CX(5)(-) (CF(5)(-), CCl(5)(-)) systems nor CX(4)···X(-) (CF(4)···F(-) and CCl(4)···Cl(-)) complexes can exist in the elevated temperatures (above 0K) due to their susceptibility to the fragmentation (leading to the X(-) loss). © 2012 American Chemical Society

5 CFR 2414.5 - Communications prohibited.

Code of Federal Regulations, 2010 CFR

2010-01-01

...; and (b) Such communications, when oral, unless advance notice thereof is given by the communicator to... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Communications prohibited. 2414.5 Section... RELATIONS AUTHORITY AND FEDERAL SERVICE IMPASSES PANEL GENERAL PROVISIONS EX PARTE COMMUNICATIONS § 2414.5...

Antiproliferative activity and induction of apoptotic by ethanolic extract of Alpinia galanga rhizhome in human breast carcinoma cell line

PubMed Central

2014-01-01

Background We investigated the potential of galangal rhizomes to induce cytotoxic and apoptotic effects in the cultured human breast carcinoma cell line, (MCF-7) in compare with the non-malignant (MRC-5) cells. Methods Both cells were cultured in DMEM medium and treated with galangal rhizomes for three consecutive days. The percentage of apoptotic cells was determined by flow cytometry using Annexin-V fluorescein isothiocyanate. Results The results showed that the ethanolic extract of galangal rhizomes decreased cell viability in the malignant cells as a concentration- and time- dependent manner. The IC50 values against MCF-7 were determined at 400.0 ± 11.7 and 170.0 ± 5.9 μg/ml after 48 and 72 h respectively. The morphology of MCF-7 cells treated with the ethanolic extract confirmed the cell proliferation assay results. Alpinia galanga induced apoptosis in MCF-7 cells, as determined by flow cytometry. Conclusions We concluded that the extract of Alpinia galanga exerts pro-apoptotic effects in a breast cancer-derived cell line and could be considered as a potential chemotherapeutic agent in breast cancer. PMID:24935101

Development of a new live attenuated mumps virus vaccine in human diploid cells.

PubMed

Sassani, A; Mirchamsy, H; Shafyi, A; Ahourai, P; Razavi, J; Gholami, M R; Mohammadi, A; Ezzi, A; Rahmani, M; Fateh, G

1991-07-01

A new live attenuated mumps vaccine was developed in human diploid cells. The S-12 virus was isolated from a 10-year-old girl showing typical symptoms of mumps infection, the diagnosis was confirmed by a pediatrician. The virus was isolated in green monkey kidney cells, without passage in chick embryo cavity or chick embryo fibroblasts. Attenuation of the wild virus was performed by serial passages in human diploid cells (MRC-5). The attenuated virus was characterized by identity tests, as well as by a reduction in plaque size, as marker tests. The virus was free from adventitious agents and safe for laboratory animals as well as for monkeys. The reactogenicity and immunogenicity of the S-12 virus for man was investigated by administration of a monovalent vaccine to 20 seronegative adult male volunteers and 30 children aged 1 to 5 years without history of mumps infection or vaccination. Seroconversion was obtained in 95% of the vaccinees. The new vaccine has the advantage of not requiring specific pathogen-free eggs, and being free from avian proteins and therefore can be used in sensitized patients.

4 CFR 5.5 - Travel, transportation, and subsistence.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 4 Accounts 1 2010-01-01 2010-01-01 false Travel, transportation, and subsistence. 5.5 Section 5.5 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.5 Travel, transportation, and subsistence. The provisions of chapter 57 of title 5, U.S. Code and the implementing regulations for the...

4 CFR 5.5 - Travel, transportation, and subsistence.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 4 Accounts 1 2011-01-01 2011-01-01 false Travel, transportation, and subsistence. 5.5 Section 5.5 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.5 Travel, transportation, and subsistence. The provisions of chapter 57 of title 5, U.S. Code and the implementing regulations for the...

4 CFR 5.5 - Travel, transportation, and subsistence.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 4 Accounts 1 2012-01-01 2012-01-01 false Travel, transportation, and subsistence. 5.5 Section 5.5 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.5 Travel, transportation, and subsistence. The provisions of chapter 57 of title 5, U.S. Code and the implementing regulations for the...

4 CFR 5.5 - Travel, transportation, and subsistence.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 4 Accounts 1 2014-01-01 2013-01-01 true Travel, transportation, and subsistence. 5.5 Section 5.5 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.5 Travel, transportation, and subsistence. The provisions of chapter 57 of title 5, U.S. Code and the implementing regulations for the...

4 CFR 5.5 - Travel, transportation, and subsistence.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 4 Accounts 1 2013-01-01 2013-01-01 false Travel, transportation, and subsistence. 5.5 Section 5.5 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.5 Travel, transportation, and subsistence. The provisions of chapter 57 of title 5, U.S. Code and the implementing regulations for the...

Synthesis of monomethyl 5,5'-dehydrodiferulic acid

USDA-ARS?s Scientific Manuscript database

Synthesis of the internal reference compound, monomethyl 5,5’-dehydrodiferulic acid, is described. The synthetic scheme relies on a selective monomethylation of the known compound 5,5-dehydrodivanillin, followed by elaboration into the dehydrodiferulic framework through a dual Horner-Emmons-Wadswort...

5 CFR 5.1 - Civil Service regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Civil Service regulations. 5.1 Section 5.1 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE RULES REGULATIONS, INVESTIGATION, AND ENFORCEMENT (RULE V) § 5.1 Civil Service regulations. The Director, Office of Personnel...

5 CFR 5.1 - Civil Service regulations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Civil Service regulations. 5.1 Section 5.1 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE RULES REGULATIONS, INVESTIGATION, AND ENFORCEMENT (RULE V) § 5.1 Civil Service regulations. The Director, Office of Personnel...

5 CFR 1209.5 - Time of filing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Time of filing. 1209.5 Section 1209.5 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION AND PROCEDURES PRACTICES AND PROCEDURES FOR APPEALS AND STAY REQUESTS OF PERSONNEL ACTIONS ALLEGEDLY BASED ON WHISTLEBLOWING Appeals § 1209.5 Time of...

5 CFR 1315.5 - Accelerated payment methods.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Accelerated payment methods. 1315.5 Section 1315.5 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES PROMPT PAYMENT § 1315.5 Accelerated payment methods. (a) A single invoice under $2,500. Payments may be made as soon as...

5 CFR 1315.5 - Accelerated payment methods.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Accelerated payment methods. 1315.5 Section 1315.5 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES PROMPT PAYMENT § 1315.5 Accelerated payment methods. (a) A single invoice under $2,500. Payments may be made as soon as...

5 CFR 1315.5 - Accelerated payment methods.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Accelerated payment methods. 1315.5 Section 1315.5 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES PROMPT PAYMENT § 1315.5 Accelerated payment methods. (a) A single invoice under $2,500. Payments may be made as soon as...

The GEOS-5 Data Assimilation System-Documentation of Versions 5.0.1, 5.1.0, and 5.2.0

NASA Technical Reports Server (NTRS)

Suarez, Max J.; Rienecker, M. M.; Todling, R.; Bacmeister, J.; Takacs, L.; Liu, H. C.; Gu, W.; Sienkiewicz, M.; Koster, R. D.; Gelaro, R.;

5 CFR 9800.5 - Public reading room.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Public reading room. 9800.5 Section 9800.5 Administrative Personnel COUNCIL OF THE INSPECTORS GENERAL ON INTEGRITY AND EFFICIENCY FREEDOM OF INFORMATION ACT REGULATIONS § 9800.5 Public reading room. CIGIE maintains an electronic public reading room on its Web site, http://www.ignet.gov,...

5 CFR 9800.5 - Public reading room.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Public reading room. 9800.5 Section 9800.5 Administrative Personnel COUNCIL OF THE INSPECTORS GENERAL ON INTEGRITY AND EFFICIENCY FREEDOM OF INFORMATION ACT REGULATIONS § 9800.5 Public reading room. CIGIE maintains an electronic public reading room on its Web site, http://www.ignet.gov,...

Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes.

PubMed

Gul, Halise Inci; Yamali, Cem; Bulbuller, Merve; Kirmizibayrak, Petek Ballar; Gul, Mustafa; Angeli, Andrea; Bua, Silvia; Supuran, Claudiu T

2018-08-01

In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5-aryl-3,4-dihydro-1'H,H-[3,4'-bipyrazole]-1',2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by 1 H NMR, 13 C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory effects of the dibenzensulfonamides 7-9 were also evaluated on the cytosolic human (h) hCA I and II and the tumor-associated hCA IX and XII isoenzymes. Results indicate that both 7 and 8 induced cleavage of poly (ADP ribose) polymerase (PARP), activation of caspases -3, -7 and -9 which are the hallmarks of apoptosis. Meanwhile both compounds induced autophagy in HCC1937 cells which is shown by enhanced expression of LC3 and decreased level of p62 protein. The compounds tested were also effectively inhibited tumor-associated hCA IX and hCA XII isoenzymes in the range of 20.7-28.1 nM and 4.5-9.3 nM, respectively. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of lymphopoietic stem cells with a monoclonal antibody to the rat transferrin receptor.

PubMed Central

Jefferies, W A; Brandon, M R; Williams, A F; Hunt, S V

1985-01-01

A mouse monoclonal IgG2a antibody, designated MRC OX-26, is shown to be specific for the rat transferrin receptor, but does not block transferrin binding. The antibody labelled a myeloma, three leukaemia cell lines and normal dividing cells of various types, but also bound to a number of nondividing normal tissues. No labelling of lymphopoietic stem cells could be detected, even though approximately 25% of bone marrow and over 95% of fetal liver cells were clearly labelled. Images Figure 1 Figure 3 PMID:2981766

[Cardiac efficiency in patients with Cheyne-Stokes respiration as a result of heart insufficiency during long-term nasal respiratory treatment with adaptive servo ventilation (AutoSet CS)].

PubMed

Schädlich, S; Königs, I; Kalbitz, F; Blankenburg, T; Busse, H-J; Schütte, W

2004-06-01

Cheyne-Stokes respiration (CSR) is known to be an important negative predictor of outcome in patients with congestive heart failure. The goal of this study was to investigate whether the use of adaptive servo ventilation (AutoSet CS) would permit sufficient suppression of this pathological breathing pattern and improve cardiac function in longterm use over 1 year. Inclusion criteria for the study were congestive heart failure (left ventricular ejection fraction 20-50%), proven CSR with a central apnea-hypopnea index (AHI) > 15/h and stable clinical status with standard medical therapy. Patients with obstructive sleep apnea and COPD were excluded. Twenty consecutive patients (16 male) age 65.5 years (range 48-77) were followed with full blood counts, blood gas analysis, lung function tests and questionnaires for cardiopulmonary capacities (Minnesota, MRC Scale) and sleepiness (Epworth Sleepiness Scale). In addition, we performed 6-min walk distance (6MWD), echocardiography and polysomnography just before and after adjusting to adaptive servo ventilation and 3 and 12 months later. Mean usage of adaptive servo ventilation was sufficient (4.3 +/- 2.1 h/day at 12 months). No significant changes in blood gas analysis, blood counts and pulmonary function were detectable. CSR disappeared almost completely in all patients (AHI pre-study 44.3 +/- 13.4/h vs 3.4 +/- 8.0/h at 12 months; p < 0.0001). Saturation normalized steadily over the course of the study. The desaturation index decreased from 45.3 +/- 17.8/h to 5.2 +/- 11.5/h at 12 months (p < 0.0001). Mean saturation increased with the first night of sleep with adaptive servo ventilation from 92.0 +/- 2.5% to 93.0 +/- 1.6% (p < 0.05) and then to 94.1 +/- 1.9% at 3, and 94.2 +/- 1.9% at 12 months (p < 0.001). Quality of sleep was significantly improved with an increase of slow-wave sleep from 4.5 +/- 4.6% to 13.7 +/- 6.9% at 12 months (p < 0.0001). The arousal index concomitantly decreased from 29.8 +/- 17.9/h pre-study to

The third spectrum of rhenium (Re III): Analysis of the (5d5 + 5d46s)-(5d46p + 5d36s6p) transition array

NASA Astrophysics Data System (ADS)

Azarov, Vladimir I.; Gayasov, Robert R.

2018-05-01

The spectrum of rhenium was observed in the (1017-2074) Å wavelength region. The (5d5 + 5d46s)-(5d46p + 5d36s6p) transition array of two times ionized rhenium, Re III, has been investigated and 1305 spectral lines have been classified in the region. The analysis has led to the determination of the 5d5, 5d46s, 5d46p and 5d36s6p configurations. Seventy levels of the 5d5 and 5d46s configurations in the even system and 161 levels of the 5d46p and 5d36s6p configurations in the odd system have been established. The orthogonal operators technique was used to calculate the level structure and transition probabilities. The energy parameters have been determined by the least squares fit to the observed levels. Calculated transition probability and energy values, as well as LS-compositions obtained from the fitted parameters are presented.

Fidelity of DNA Replication in Normal and Malignant Human Breast Cells.

DTIC Science & Technology

1997-08-01

enzyme) into the multiple cloning site (MCS). This template will not only replicate inside a mammalian cell (utilizing the E-B virus origin), and...Maniatis, T. Commonly used techniques in molecular cloning . In: Molecular cloning : REFERENCES a laboratory manual, 2nd edition. Cold Spring Harbor...A vatit"Y Of DNA synthesis and the typt of DNA replica~tion Products " celular prca including DNA rsplicatlon. DNA repsair. R~NA formed in experiments

Maintaining a Class M 5.5 environment in a Class M 6.5 cleanroom

NASA Astrophysics Data System (ADS)

Hughes, David W.; Hedgeland, Randy J.; Geer, Wayne C.; Greenberg, Barry N.

1994-10-01

During Kennedy Space Center processing of the Hubble Space Telescope First Servicing Mission, critical optical components were integrated in a Class 100,000 (M 6.5 at 0.5 micrometers and 5.0 micrometers , per Fed-Std 209E) cleanroom. A Class 10,000 (M 5.5) environment was mandated by the 400B (per Mil-Std 1246B) surface cleanliness requirement of the Scientific Instruments. To maintain a Class M 5.5 environment, a contamination control plan was implemented which addressed personnel constraints, operations, and site management. This plan limited personnel access, imposed strict gowning requirements, and increased cleanroom janitorial operations, prohibited operations known to generate contamination while sensitive hardware was exposed to the environment, and controlled roadwork, insecticide spraying, and similar activities. Facility preparations included a ceiling to floor cleaning, sealing of vents and doors, and revising the garment change room entry patterns. The cleanroom was successfully run below Class 5000 while the instruments were present; certain operations, however, were observed to cause local contamination levels to increase above Class M 5.5.

Mobile phone use among Medical Reserve Corps coordinators and volunteers: an exploratory study.

PubMed

Scheller, Amy; Peck, Megan; Olson, Debra K

2014-01-01

To better understand how mobile phones can be used during emergency response, this study identifies a) current mobile phone use among Medical Reserve Corps (MRC) volunteers and coordinators in their daily lives and during response; b) challenges for mobile phone use during response; and c) areas for capacity building. In 2012, 459 MRC volunteers and coordinators responded to a 35-question survey conducted online through SurveyMonkey. Respondents were asked how they use their mobile phones in their daily lives and during response, and how they would like to use them during response. Frequencies were calculated using SurveyMonkey and Excel. Respondents reported frequent and varied mobile phone use in their daily lives, with 99 percent of respondents owning a phone, 82 percent texting, and 87 percent of smartphone owners using apps. Although 80 percent of respondents who had been deployed used mobile phones during response, use of sophisticated mobile phone features was low; only 10 percent accessed emergency preparedness apps and 23 percent browsed the Internet for emergency response information. Respondents indicated a desire to use more features during response, such as emergency preparedness apps (72 percent) and e-mail to send or receive response instructions (80 percent). Results indicate that given access to mobile technology and training, emergency responders would like to increase their mobile phone use during response. Implications of these findings show a need for organizations to improve their support of mobile phone use.

[Effects of organic-inorganic mixed fertilizers on rice yield and nitrogen use efficiency].

PubMed

Zhang, Xiao-li; Meng, Lin; Wang, Qiu-jun; Luo, Jia; Huang, Qi-wei; Xu, Yang-chun; Yang, Xing-ming; Shen, Qi-rong

2009-03-01

A field experiment was carried to study the effects of organic-inorganic mixed fertilizers on rice yield, nitrogen (N) use efficiency, soil N supply, and soil microbial diversity. Rapeseed cake compost (RCC), pig manure compost (PMC), and Chinese medicine residue compost (MRC) were mixed with chemical N, P and K fertilizers. All the treatments except CK received the same rate of N. The results showed that all N fertilizer application treatments had higher rice yield (7918.8-9449.2 kg x hm(-2)) than the control (6947.9 kg x hm(-2)). Compared with that of chemical fertilizers (CF) treatment (7918.8 kg x hm(-2)), the yield of the three organic-inorganic mixed fertilizers treatments ranged in 8532.0-9449.2 kg x hm(-2), and the increment was 7.7%-19.3%. Compared with treatment CF, the treatments of organic-inorganic mixed fertilizers were significantly higher in N accumulation, N transportation efficiency, N recovery rate, agronomic N use efficiency, and physiological N use efficiency. These mixed fertilizers treatments promoted rice N uptake and improved soil N supply, and thus, increased N use efficiency, compared with treatments CF and CK. Neighbor joining analysis indicated that soil bacterial communities in the five treatments could be classified into three categories, i.e., CF and CK, PMC and MRC, and RCC, implying that the application of exogenous organic materials could affect soil bacterial communities, while applying chemical fertilizers had little effect on them.

RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis

PubMed Central

Craciun, Florin L.; Bijol, Vanesa; Ajay, Amrendra K.; Rao, Poornima; Kumar, Ramya K.; Hutchinson, John; Hofmann, Oliver; Joshi, Nikita; Luyendyk, James P.; Kusebauch, Ulrike; Moss, Christopher L.; Srivastava, Anand; Himmelfarb, Jonathan; Waikar, Sushrut S.; Moritz, Robert L.

2016-01-01

CKD is the gradual, asymptomatic loss of kidney function, but current tests only identify CKD when significant loss has already happened. Several potential biomarkers of CKD have been reported, but none have been approved for preclinical or clinical use. Using RNA sequencing in a mouse model of folic acid-induced nephropathy, we identified ten genes that track kidney fibrosis development, the common pathologic finding in patients with CKD. The gene expression of all ten candidates was confirmed to be significantly higher (approximately ten- to 150-fold) in three well established, mechanistically distinct mouse models of kidney fibrosis than in models of nonfibrotic AKI. Protein expression of these genes was also high in the folic acid model and in patients with biopsy-proven kidney fibrosis. mRNA expression of the ten genes increased with increasing severity of kidney fibrosis, decreased in response to therapeutic intervention, and increased only modestly (approximately two- to five-fold) with liver fibrosis in mice and humans, demonstrating specificity for kidney fibrosis. Using targeted selected reaction monitoring mass spectrometry, we detected three of the ten candidates in human urine: cadherin 11 (CDH11), macrophage mannose receptor C1 (MRC1), and phospholipid transfer protein (PLTP). Furthermore, urinary levels of each of these three proteins distinguished patients with CKD (n=53) from healthy individuals (n=53; P<0.05). In summary, we report the identification of urinary CDH11, MRC1, and PLTP as novel noninvasive biomarkers of CKD. PMID:26449608