345 research outputs found

    Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta

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    Cytochrome P-450-dependent mixed function oxidase activity is present in vascular tissue; however, as far as we could determine, the distribution of monooxygenase activity across the blood vessel wall has not previously been assessed. The aryl-hydrocarbon hydroxylase activity was examined by metabolism of benzo[a]pyrene in microsomes prepared from intimal and smooth muscle cell scrapings of the hog thoracic aorta. Microsomes of intimal cells comprising 95% endothelial cells showed an approximately 2.5-fold increase in aryl-hydrocarbon hydroxylase activity compared with that in microsomes prepared from medial smooth muscle cells. Michaelis-Mentin kinetics for the intimal enzyme yielded an apparent Km value of 11.11 microM and an apparent Vmax of 3-OH benzo[a]pyrene of 40 pmol/mg protein/10 min. Aryl-hydrocarbon hydroxylase activity was dependent on nicotinamide adenine dinucleotide phosphate and was inhibited by 7,8 benzoflavone, SKF 525A, and carbon monoxide. The localization of cytochrome P-450-dependent mixed function oxidase primarily to the intimal surface of the aorta may indicate a role for this enzyme system in vasoregulation and the pathogenesis of atherosclerosis

    Contingent electric shock as a treatment for challenging behavior for people with intellectual and developmental disabilities : support for the IASSIDD policy statement opposing its use

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    Issues: The International Association for the Scientific Study of Intellectual and Developmental Disabilities (IASSIDD) is an international group of researchers, clinicians, students, parents, and self-advocates that promotes worldwide research and exchange of information on intellectual and developmental disabilities. IASSIDD recently developed a policy statement regarding their opposition to the use of contingent electric skin shock (CESS) with individuals with challenging behaviour and intellectual and developmental disabilities. To support the policy, the available literature was reviewed to evaluate the efficacy, side effects, generalization, and long-term effectiveness of the procedure as an intervention for challenging behaviour. Findings: The review provides a history that demonstrates that, although CESS can decrease the frequency of challenging behaviour, it comes at a cost in terms of physical and emotional side effects, and questions remain regarding the long-term effectiveness of the procedure. In addition, we raise several ethical and methodological issues that make the research on the use of CESS even more concerning. Conclusions: Although research continues in some countries, these studies are now rare. In fact, in the United States, the Food and Drug Administration has just banned the use of such devices with individuals with self-injury and aggression (Federal Register, 2020). It is hoped that, because there are many other forms of treatment that have shown to be effective for severe challenging behaviour, we can completely avoid the use of CESS

    In situ wavelength calibration of the edge CXS spectrometers on JET

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    A method for obtaining an accurate wavelength calibration over the entire focal plane of the JET edge CXS spectrometers is presented that uses a combination of the fringe pattern created with a Fabry–Pérot etalon and a neon lamp for cross calibration. The accuracy achieved is 0.03 Å, which is the same range of uncertainty as when neglecting population effects on the rest wavelength of the CX line. For the edge CXS diagnostic, this corresponds to a flow velocity of 4.5 km/s in the toroidal direction or 1.9 km/s in the poloidal direction.EURATOM 63305

    Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

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    Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

    Using Point-of-Choice Prompts to Reduce Sedentary Behavior in Sit-Stand Workstation Users

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    Introduction: Desk-based office workers are at occupational risk for poor health outcomes from excessive time spent sitting. Sit-stand workstations are used to mitigate sitting, but lack of workstation usage has been observed. Point-of-choice (PoC) prompts offer a complementary strategy for office workers to break up their sitting time.Study purpose: The purpose of this study was to examine the preliminary efficacy, preference, and acceptability of a theory-driven (i.e., 40 unique prompts encompassing social cognitive theory; TD-PoC) and an atheoretical basic reminder PoC prompt intervention (R-PoC) on reducing sedentary behavior in office workers with self-reported low sit-stand workstation usage (≤4 h per day).Methods: In a cross-over design, participants (N = 19, 78.9% female, 39.4 ± 10.7 years of age) completed a 5-days no-prompt control condition followed by a random and counterbalanced assignment to one of the TD-PoC and R-PoC active conditions with a 1-week washout period between. Preliminary efficacy was assessed during work hours with the activPAL micro accelerometer. Preference was assessed prior to each active condition and acceptability was assessed following each active condition via questionnaire.Results: The R-PoC prompt condition significantly decreased sitting time (b[se] = −49.0 [20.8], p = 0.03) and increased standing time (b[se] = 49.8 [19.7], p = 0.02) and displayed a significant increase in sit-stand transitions (b[se] = 2.3 [1.1], p = 0.04), relative to no-prompt control. Both the R-PoC and TD-PoC prompt conditions significantly decreased time spent in prolonged sitting bouts at b[se] = −68.1 [27.8], (p = 0.02), (b[se] = −76.7 [27.1], p = 0.008) relative to no-prompt control. Overall, the TD-PoC prompt condition displayed higher preference and acceptability ratings; however, these differences were not significant (p's > 0.05).Conclusion: While the R-PoC prompt condition was slightly more efficacious than the TD-PoC prompt condition, the TD-PoC prompt condition was rated with higher preference and acceptability scores. Large variations between participants in preference, acceptability, and intervention feedback may indicate need for tailored messaging which may facilitate sustained use in the long-term

    Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

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    <p>Abstract</p> <p>Background</p> <p>Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model.</p> <p>Methods</p> <p>In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis.</p> <p>Results</p> <p>ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data.</p> <p>Conclusions</p> <p>ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.</p

    Attenuation of ischemic liver injury by augmentation of endogenous adenosine

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    Hepatic grafts from non-heartbeating donors may alleviate the organ shortage, but they inherently suffer from warm ischemia. In the present study, we tested our hypothesis that augmentation of endogenous adenosine by inhibition of nucleoside transport with R75231 attenuates ischemic liver injury. Adult female beagle dogs underwent 2-hr hepatic vascular exclusion with venovenous bypass. R75231 was given to the animals by continuous intravenous infusion for 30 min before ischemia at a dose of 0.1 mg/kg (Group 2, n=6), 0.05 mg/kg (Group 3, n=6), or 0.025 mg/kg (Group 4, n=6). Nontreated animals were used as the control (Group 1, n= 10). Animal survival, hepatic tissue blood flow, liver function, and histopathology were analyzed. Two- week animal survival was 30% in Group 1, 83% in Group 2, 100% in Group 3, and 100% in Group 4. Postreperfusion hepatic tissue blood flow was markedly improved by the treatment. Treatment significantly attenuated liver enzyme release, lipid peroxidation, and changes in adenine nucleotides and purine catabolites. Structural abnormality of the liver after reperfusion was markedly improved by R75231 treatment, showing better architecture and less neutrophil infiltration. Preischemic administration of a nucleoside transport inhibitor ameliorated ischemic liver injury due to the positive effects of augmented endogenous adenosine, and is applicable clinically when the liver is procured from a controlled non-heartbeating donor
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