Saturation behavior of superoxide dismutation catalyzed by the iron containing superoxide dismutase of E. coli B

SummaryThe iron containing superoxide dismutase from E. coli B is shown to catalyze superoxide dismutation by a mechanism which exhibits saturation kinetics. This behavior is quite different from that observed previously with bovine Zn/Cu- and iron-containing superoxide dismutase from P. leiognathi. Two parameters of catalysis were measured in the pH range 7.2 to 10.4: kcat was found to be independent of pH and Km varied with the function Km = Km(low pH) [1 + exp(pH -- 8.8)]. These results implicate a group in the catalytic mechanism which ionizes with pKa = 8.8.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24375/1/0000644.pd

Managing Injuries of the Neck Trial (MINT) : design of a randomised controlled trial of treatments for whiplash associated disorders

Background: A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods: Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion: This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Proyecto FEPES: Fase I. Identificación de destrezas y habilidades básicas para el mundo del trabajo

Un problema constatado en diversos países europeos es que un porcentaje elevado de los alumnos que concluyen la Educación Obligatoria no ha desarrollado suficientemente habilidades generales necesarias para el desarrollo de la vida personal y profesional, tales como la comunicación oral y escrita, la planificación y la solución de problemas. Estas carencias suelen venir marcadas por el énfasis que, en muchas ocasiones, pone el profesorado en la adquisición de los conocimientos necesarios para continuar estudios superiores como si, por si misma, dicha adquisición asegurara el desarrollo de habilidades transferibles a otros campos de actuación. En este contexto un grupo de profesores de distintas universidades europeas ha planteado la necesidad de que en la Educación Obligatoria se forme a los ciudadanos no solamente para continuar estudios superiores, sino en destrezas propias del desarrollo de cualquier profesión y también en aquellas destrezas que le permiten un mejor desarrollo de su vida personal. Por ello, si se desea modificar el tipo de formación que recibe el alumno es necesario actuar sobre la formación y orientación del profesorado de Educación Obligatoria. Como resultado aparece el proyecto FEPES (Formación Específica de Profesorado de Educación Secundaria): Destrezas y habilidades Básicas para el Mundo del Trabajo. Este proyecto fue presentado a la Comisión Europea y ha sido financiado dentro del programa SOCRATES, acción Comenius 3.2. En él participan las Universidades de Alcalá (Coordinación), Stirling (Escocia), Comenius de Bratislava (Eslovaquia), Coimbra (Portugal) y la Queen's University de Belfast (Irlanda del Norte). La temática del proyecto se enmarca en la categoría de mejora de los niveles de éxito escolar, aspectos transversales. El objetivo general va dirigido a desarrollar las habilidades personales para la vida y el futuro mundo del trabajo de los alumnos de Educación Obligatoria en los diferentes países participantes en el mismo y, por otra parte, trata de mejorar la formación inicial y continua del profesorado de dicho nivel para que los profesores incluyan en sus programas este tipo de objetivos. Dada la extensión de las posibles destrezas y habilidades básicas recomendables para el mejor desarrollo de la actividad laboral de estos jóvenes, en el presente trabajo se ha optado por incidir de manera concreta en el estudio de la destrezas correspondientes a la comprensión y expresión tanto en el ámbito oral como en el escrito en las áreas de Humanidades y Ciencias.Peer reviewe

Fifteen-Year Population Attributable Fractions and Causal Pies of Risk Factors for Newly Developed Hepatocellular Carcinomas in 11,801 Men in Taiwan

Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Taiwan, during which a total of 298 incident HCC cases were ascertained. The rate ratios adjusted by age were further modeled by an additive Poisson regression. Population attributable fractions (PAFs) and causal-pie weights (CPWs) were calculated. A PAF indicates the magnitude of case-load reduction under a particular intervention scenario, whereas a CPW for a particular class of causal pies represents the proportion of HCC cases attributable to that class. Using PAF we observed a chance to reduce around 60% HCC risk moving from no HBV-related intervention to the total elimination of the virus. An additional ∼15% (or ∼5%) reduction can be expected, if the HBV-related intervention is coupled with an HCV-related intervention (or an anti-drinking campaign). Eight classes of causal pies were found to be significant, including four dose-response classes of HBV (total CPW=52.7%), one independent-effect class of HCV (CPW=14.4%), one HBV-alcohol interaction class (CPW=4.2%), one HBV-HCV interaction class (CPW=1.7%), and one all-unknown class (CPW=27.0%). Causal-pie modeling for HCC helps clarify the relative importance of each viral and host factor, as well as their interactions

A systematic review of comorbidities and outcomes of adult patients with pleural infection

BACKGROUND: Pleural infection remains an important cause of mortality. This study aimed to investigate worldwide patterns of pre-existing comorbidities and clinical outcomes of patients with pleural infection. METHODS: Studies reporting on adults with pleural infection between 2000 and 2017 were identified from a search of Embase and Medline. Papers reporting exclusively on tuberculous, fungal or post pneumonectomy infection were excluded. Two reviewers assessed 20 980 records for eligibility. RESULTS: 211 studies met the inclusion criteria. 134 papers (227 898 patients, mean age 52.8 years) reported comorbidity and/or outcome data. The majority of studies were retrospective observational cohorts (n=104, 78%) and the most common region of reporting was East Asia (n=33, 24%) followed by North America (n=27, 20%).85 papers (50 756 patients) reported comorbidity. The median percentage prevalence of any comorbidity was 72% (IQR 58-83%), with respiratory illness (20%, 16-32%) and cardiac illness (19%, 15-27%) most commonly reported. 125 papers (192 298 patients) reported outcome data. The median length of stay was 19 days (IQR 13-27) and median in-hospital or 30-day mortality was 4% (IQR 1-11%).In regions with high-income economies (n=100, 74%) patients were older (mean 56.5 versus 42.5 years, p<0.0001), but there were no significant differences in prevalence of pre-existing comorbidity nor in length of hospital stay or mortality. CONCLUSION: Patients with pleural infection have high levels of comorbidity and long hospital stays. Most reported data are from high-income economy settings. Data from lower-income regions is needed to better understand regional trends and enable optimal resource provision going forward

Activity Increase Despite Arthritis (AÏDA): design of a Phase II randomised controlled trial evaluating an active management booklet for hip and knee osteoarthritis [ISRCTN24554946]

<p>Abstract</p> <p>Background</p> <p>Hip and knee osteoarthritis is a common cause of pain and disability, which can be improved by exercise interventions. However, regular exercise is uncommon in this group because the low physical activity level in the general population is probably reduced even further by pain related fear of movement. The best method of encouraging increased activity in this patient group is not known. A booklet has been developed for patients with hip or knee osteoarthritis. It focuses on changing disadvantageous beliefs and encouraging increased physical activity.</p> <p>Methods/Design</p> <p>This paper describes the design of a Phase II randomised controlled trial (RCT) to test the effectiveness of this new booklet for patients with hip and knee osteoarthritis in influencing illness and treatment beliefs, and to assess the feasibility of conducting a larger definitive RCT in terms of health status and exercise behaviour. A computerised search of four general medical practice patients' record databases will identify patients older than 50 years of age who have consulted with hip or knee pain in the previous twelve months. A random sample of 120 will be invited to participate in the RCT comparing the new booklet with a control booklet, and we expect 100 to return final questionnaires. This trial will assess the feasibility of recruitment and randomisation, the suitability of the control intervention and outcome measurement tools, and will provide an estimate of effect size. Outcomes will include beliefs about hip and knee pain, beliefs about exercise, fear avoidance, level of physical activity, health status and health service costs. They will be measured at baseline, one month and three months.</p> <p>Discussion</p> <p>We discuss the merits of testing effectiveness in a phase II trial, in terms of intermediate outcome measures, whilst testing the processes for a larger definitive trial. We also discuss the advantages and disadvantages of testing the psychometric properties of the primary outcome measures concurrently with the trial.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN24554946</p

Sequence- and Interactome-Based Prediction of Viral Protein Hotspots Targeting Host Proteins: A Case Study for HIV Nef

Virus proteins alter protein pathways of the host toward the synthesis of viral particles by breaking and making edges via binding to host proteins. In this study, we developed a computational approach to predict viral sequence hotspots for binding to host proteins based on sequences of viral and host proteins and literature-curated virus-host protein interactome data. We use a motif discovery algorithm repeatedly on collections of sequences of viral proteins and immediate binding partners of their host targets and choose only those motifs that are conserved on viral sequences and highly statistically enriched among binding partners of virus protein targeted host proteins. Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but is a poor predictor of Nef binding sites on highly flexible, hoop-like regions. Predicted hotspots recapture CD8 cell epitopes of HIV Nef highlighting their importance in modulating virus-host interactions. Host proteins potentially targeted or outcompeted by Nef appear crowding the T cell receptor, natural killer cell mediated cytotoxicity, and neurotrophin signaling pathways. Scanning of HIV Nef motifs on multiple alignments of hepatitis C protein NS5A produces results consistent with literature, indicating the potential value of the hotspot discovery in advancing our understanding of virus-host crosstalk