762 research outputs found

    Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates With Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice During Murine Neurocysticercosis

    Get PDF
    Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to absence of eosinophils correlates with attenuated tissue damage and longer survival of ΔdblGATA mice. Therefore, our study suggests that approaches to clear NCC will require strategies to tightly control the host immune response while eradicating the parasite with minimal damage to brain tissue

    A multicentre, pragmatic, cluster randomised, controlled feasibility trial of the POD system of care

    Get PDF
    Objective to provide a preliminary estimate of the effectiveness of the prevention of delirium (POD) system of care in reducing incident delirium in acute hospital wards and gather data for a future definitive randomised controlled trial. Design cluster randomised and controlled feasibility trial. Setting sixteen acute care of older people and orthopaedic trauma wards in eight hospitals in England and Wales. Participants patients 65 years and over admitted to participating wards during the trial period. Interventions participating wards were randomly assigned to either the POD programme or usual care, determined by existing local policies and practices. The POD programme is a manualised multicomponent delirium prevention intervention that targets 10 risk factors for delirium. The intervention wards underwent a 6-month implementation period before trial recruitment commenced. Main outcome measure incidence of new-onset delirium measured using the Confusion Assessment Method (CAM) measured daily for up to 10 days post consent. Results out of 4449, 3274 patients admitted to the wards were eligible. In total, 714 patients consented (713 registered) to the trial, thirty-three participants (4.6%) withdrew. Adherence to the intervention was classified as at least medium for seven wards. Rates of new-onset delirium were lower than expected and did not differ between groups (24 (7.0%) of participants in the intervention group versus 33 (8.9%) in the control group; odds ratio (95% confidence interval) 0.68 (0.37–1.26); P = 0.2225). Conclusions based on these findings, a definitive trial is achievable and would need to recruit 5220 patients in 26 two-ward hospital clusters. Trial registration: ISRCTN01187372. Registered 13 March 2014

    THERMAL DENATURATION OF MONOMERIC AND TRIMERIC PHYCOCYANINS STUDIED BY STATIC AND SPECTROSCOPY POLARIZED TIME-RESOLVED FLUORESCENCE

    Get PDF
    C-Phycocyanin (PC) and allophycocyanin (APC). as well as the a-subunit of PC. have been isolated from the blue-green alga (cyanobacterium). Spirulina platensis. The effects of partial thermal denaturation of PC and of its state of aggregation have been studied by ps time-resolved, polarized fluorescence spectroscopy. All measurements have been performed under low photon fluxes (< 10’ ’ photonsipulse x cm’) to minimize singlet-singlet annihilation processes. A complex decay is obtained under most conditions, which can be fitted satisfactorily with a bi-exponential (7’ = 70400 ps. T? = 1000-3000 ps) for both the isotropic and the polarized part, but with different intensities and time constants for the two decay curves. The data are interpreted in the frameworkof the model first developed by Teak and Dale (Biochern. J. 116, 161 (1970)], which divides the spectroscopically different chromophores in (predominantly) sensitizing (s) and fluorescing U, ones. If one assumes temperature dependent losses in the energy transfer from the s to the f and between f chromophores. both the biexponential nature of the isotropic fluorescence decay and the polarization data can be rationalized. In the isotropic emission (corresponding to the population of excited states) the short lifetime is related to the s-,f transfer. the longer one to the “free“ decay of the final acceptor(s) (= f). The polarized part is dominated by an extremely short decay time. which is related to s+f transfer, as well as to resonance transfer between the f-chromophores

    FÖRSTER TRANSFER CALCULATIONS BASED ON CRYSTAL STRUCTURE DATA FROM Agmenellum quadruplicatum C-PHYCOCYANIN

    Get PDF
    Excitation energy transfer in C-phycocyanin is modeled using the Forster inductive resonance mechanism. Detailed calculations are carried out using coordinates and orientations of the chromophores derived from X-ray crystallographic studies of C-phycocyanin from two different species (Schirmer et al, J. Mol. Biol. 184, 257–277 (1985) and ibid., 188, 651-677 (1986)). Spectral overlap integrals are estimated from absorption and fluorescence spectra of C-phycocyanin of Mastigocladus laminosus and its separated subunits. Calculations are carried out for the β-subunit, αβ-monomer, (αβ)3-trimer and (αβ)0-hexamer species with the following chromophore assignments: β155 = 's’(sensitizer), β84 =‘f (fluorescer) and α84 =‘m’(intermediate):]:. The calculations show that excitation transfer relaxation occurs to 3=98% within 200 ps in nearly every case; however, the rates increase as much as 10-fold for the higher aggregates. Comparison with experimental data on fluorescence decay and depolarization kinetics from the literature shows qualitative agreement with these calculations. We conclude that Forster transfer is sufficient to account for all of the observed fluorescence properties of C-phycocyanin in aggregation states up to the hexamer and in the absence of linker polypeptides

    Measuring and optimising the efficiency of community hospital inpatient care for older people: the MoCHA mixed-methods study

    Get PDF
    Background: Community hospitals are small hospitals providing local inpatient and outpatient services. National surveys report that inpatient rehabilitation for older people is a core function but there are large differences in key performance measures. We have investigated these variations in community hospital ward performance. Objectives: (1) To measure the relative performance of community hospital wards (studies 1 and 2); (2) to identify characteristics of community hospital wards that optimise performance (studies 1 and 3); (3) to develop a web-based interactive toolkit that supports operational changes to optimise ward performance (study 4); (4) to investigate the impact of community hospital wards on secondary care use (study 5); and (5) to investigate associations between short-term community (intermediate care) services and secondary care utilisation (study 5). Methods: Study 1 – we used national data to conduct econometric estimations using stochastic frontier analysis in which a cost function was modelled using significant predictors of community hospital ward costs. Study 2 – a national postal survey was developed to collect data from a larger sample of community hospitals. Study 3 – three ethnographic case studies were performed to provide insight into less tangible aspects of community hospital ward care. Study 4 – a web-based interactive toolkit was developed by integrating the econometrics (study 1) and case study (study 3) findings. Study 5 – regression analyses were conducted using data from the Atlas of Variation Map 61 (rate of emergency admissions to hospital for people aged ≥ 75 years with a length of stay of < 24 hours) and the National Audit of Intermediate Care. Results: Community hospital ward efficiency is comparable with the NHS acute hospital sector (mean cost efficiency 0.83, range 0.72–0.92). The rank order of community hospital ward efficiencies was distinguished to facilitate learning across the sector. On average, if all community hospital wards were operating in line with the highest cost efficiency, savings of 17% (or £47M per year) could be achieved (price year 2013/14) for our sample of 101 wards. Significant economies of scale were found: a 1% rise in output was associated with an average 0.85% increase in costs. We were unable to obtain a larger community hospital sample because of the low response rate to our national survey. The case studies identified how rehabilitation was delivered through collaborative, interdisciplinary working; interprofessional communication; and meaningful patient and family engagement. We also developed insight into patients’ recovery trajectories and care transitions. The web-based interactive toolkit was established [http://mocha. nhsbenchmarking.nhs.uk/ (accessed 9 September 2019)]. The crisis response team type of intermediate care, but not community hospitals, had a statistically significant negative association with emergency admissions. Limitations: The econometric analyses were based on cross-sectional data and were also limited by missing data. The low response rate to our national survey means that we cannot extrapolate reliably from our community hospital sample. Conclusions: The results suggest that significant community hospital ward savings may be realised by improving modifiable performance factors that might be augmented further by economies of scale. Future work: How less efficient hospitals might reduce costs and sustain quality requires further research

    Photoproduction of Long-Lived Holes and Electronic Processes in Intrinsic Electric Fields Seen through Photoinduced Absorption and Dichroism in Ca_3Ga_{2-x}Mn_xGe_3O_{12} Garnets

    Full text link
    Long-lived photoinduced absorption and dichroism in the Ca_3Ga_{2-x}Mn_xGe_3O_{12} garnets with x < 0.06 were examined versus temperature and pumping intensity. Unusual features of the kinetics of photoinduced phenomena are indicative of the underlying electronic processes. The comparison with the case of Ca_3Mn_2Ge_3O_{12}, explored earlier by the authors, permits one to finally establish the main common mechanisms of photoinduced absorption and dichroism caused by random electric fields of photoproduced charges (hole polarons). The rate of their diffusion and relaxation through recombination is strongly influenced by the same fields, whose large statistical straggling is responsible for a broad continuous set of relaxation components (observed in the relaxation time range from 1 to about 1000 min). For Ca_3Ga_{2-x}Mn_xGe_3O_{12}, the time and temperature dependences of photoinduced absorption and dichroism bear a strong imprint of structure imperfection increasing with x.Comment: 20 pages, 10 figure
    • …
    corecore