Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

Evaluation of the Birmingham IBS symptom questionnaire

Abstract Background Irritable Bowel Syndrome (IBS) is a chronic/common condition that causes a significant effect on the individual (reduced quality of life), society (time lost off work) and health services. Comparison of studies evaluating the management of IBS has been hindered by the lack of a widely adopted validated symptom score. The aim of this study was to develop and validate a disease specific score to measure the symptoms of patients with IBS. Methods A self-administered 14-item symptom questionnaire (based on Rome II criteria) was mailed to 533 persons included in a prevalence study of IBS. The reliability of each underlying dimension identified was measured by Cronbach's α. Validity was assessed by comparing symptom scores with concurrent IBS specific quality of life (QoL) scores. Reproducibility was measured by the test-retest method and responsiveness measured by effect size. Results 379 (71%) questionnaires were returned. The underlying dimensions identified were pain, diarrhoea and constipation. Cronbach's α was 0.74 for pain, 0.90 for diarrhoea and 0.79 for constipation. Pain and diarrhoea dimensions had good external validity (r = -0.3 to -0.6), constipation dimension had moderate external validity (r = -0.2 to -0.3). All dimensions were reproducible (ICCs 0.75 to 0.81). Effect sizes of 0.27 to 0.53 were calculated for those with a reported improvement in symptoms. Conclusion The Birmingham IBS Symptom Questionnaire has been developed and tested. It has been shown to be suitable for self-completion and acceptable to patients. The questionnaire has 3 internal dimensions which have good reliability, external validity and are responsive to a change in health status.</p

European agricultural landscapes, common agricultural policy and ecosystem services: a review

Since the 1950s, intensification and scale enlargement of agriculture have changed agricultural landscapes across Europe. The intensification and scale enlargement of farming was initially driven by the large-scale application of synthetic fertilizers, mechanization and subsidies of the European Common Agricultural Policy (CAP). Then, after the 1990s, a further intensification and scale enlargement, and land abandonment in less favored areas was caused by globalization of commodity markets and CAP reforms. The landscape changes during the past six decades have changed the flows and values of ecosystem services. Here, we have reviewed the literature on agricultural policies and management, landscape structure and composition, and the contribution of ecosystem services to regional competitiveness. The objective was to define an analytical framework to determine and assess ecosystem services at the landscape scale. In contrast to natural ecosystems, ecosystem service flows and values in agricultural landscapes are often a result of interactions between agricultural management and ecological structures. We describe how land management by farmers and other land managers relates to landscape structure and composition. We also examine the influence of commodity markets and policies on the behavior of land managers. Additionally, we studied the influence of consumer demand on flows and values of the ecosystem services that originate from the agricultural landscape

Efficacy of Helicobacter pylori eradication therapies: a single centre observational study

Background: Many Helicobacter pylori eradication regimens have been described. There are little data reporting their efficacy or integration in routine clinical practice. The overall results of eradication therapy in a cohort of patients are described and an algorithm for management outlined. Methods: 469 patients receiving eradication therapy in routine clinical practice were evaluated. The successes of individual regimes as first, second and third line therapy were determined. Results: Overall success after one, two and three courses of therapy were 73% (95% confidence intervals 69–77%), 94% (91–96%) and 98% (97–99%) respectively. 10 different regimens, including many non-recommended ones were used as primary therapy. Ranitidine bismuth citrate-amoxicillin-clarithromycin triple therapy (94.8%, 90–99%) was significantly more effective than any other combination as primary therapy, including all proton pump inhibitor based triple therapies. Quadruple therapy with bismuth chelate-proton pump inhibitor-tetracycline and a nitroimidazole (70%, 52–88%) and ranitidine bismuth citrate-based triple therapy (73%, 56–90%) where more effective second line combinations than proton pump inhibitor-triple therapies (37.5%, 12–58%). Third line therapy directed by the results of sensitivity testing improved eradication compared to further empirical antibiotics. The use of a proton pump inhibitor with clarithromycin and a nitroimidazole as initial therapy was associated with a significantly worse overall eradication rate than other combinations. Conclusions: Helicobacter pylori eradication rates can be maximised by using ranitidine bismuth citrate-clarithromycin-amoxicillin containing triple therapy, followed by bismuth and nitroimidazle containing second-line therapy, with third line combinations directed by sensitivity testing. Proton pump inhibitor-clarithromycin-metronidazole combinations should be avoided