P2 purinergic receptor modulation of cytokine production

Cytokines serve important functions in controlling host immunity. Cells involved in the synthesis of these polypeptide mediators have evolved highly regulated processes to ensure that production is carefully balanced. In inflammatory and immune disorders, however, mis-regulation of the production and/or activity of cytokines is recognized as a major contributor to the disease process, and therapeutics that target individual cytokines are providing very effective treatment options in the clinic. Leukocytes are the principle producers of a number of key cytokines, and these cells also express numerous members of the purinergic P2 receptor family. Studies in several cellular systems have provided evidence that P2 receptor modulation can affect cytokine production, and mechanistic features of this regulation have emerged. This review highlights three separate examples corresponding to (1) P2Y6 receptor mediated impact on interleukin (IL)-8 production, (2) P2Y11 receptor-mediated affects on IL-12/23 output, and (3) P2X7 receptor mediated IL-1β posttranslational processing. These examples demonstrate important roles of purinergic receptors in the modulation of cytokine production. Extension of these cellular observations to in vivo situations may lead to new therapeutic strategies for treating cytokine-mediated diseases

Transperineal ultrasound compared to evacuation proctography for diagnosing enteroceles and intussusceptions

Contains fulltext : 117882.pdf (publisher's version ) (Closed access)INTRODUCTION: This study concerns the level of agreement between transperineal ultrasound and evacuation proctography for diagnosing enteroceles and intussusceptions. METHOD: In a prospective observational study, 50 consecutive women who were planned to have an evacuation proctography underwent transperineal ultrasound too. Sensitivity, specificity, positive (PPV) and negative predictive value, as well as the positive and negative likelihood ratio of transperineal ultrasound were assessed in comparison to evacuation proctography. To determine the interobserver agreement of transperineal ultrasound, the quadratic weighted kappa was calculated. Furthermore, receiver operating characteristic curves were generated to show the diagnostic capability of transperineal ultrasound. RESULTS: For diagnosing intussusceptions (PPV 1.00), a positive finding on transperineal ultrasound was predictive of an abnormal evacuation proctography. Sensitivity of transperineal ultrasound was poor for intussusceptions (0.25). For diagnosing enteroceles, the positive likelihood ratio was 2.10 and the negative likelihood ratio, 0.85. There are many false-positive findings of enteroceles on ultrasonography (PPV 0.29). The interobserver agreement of the two ultrasonographers assessed as the quadratic weighted kappa of diagnosing enteroceles was 0.44 and that of diagnosing intussusceptions was 0.23. CONCLUSION: An intussusception on ultrasound is predictive of an abnormal evacuation proctography. For diagnosing enteroceles, the diagnostic quality of transperineal ultrasound was limited compared to evacuation proctography

The Oswestry Disability Index, confirmatory factor analysis in a sample of 35,263 verifies a one-factor structure but practicality issues remain

© 2017, Springer-Verlag GmbH Germany. Purpose: To analyze the factor structure of the Oswestry Disability Index (ODI) in a large symptomatic low back pain (LBP) population using exploratory (EFA) and confirmatory factor analysis (CFA). Methods: Analysis of pooled baseline ODI LBP patient data from the international Spine Tango registry of EUROSPINE, the Spine Society of Europe. The sample, with n = 35,263 (55.2% female; age 15–99, median 59 years), included 76.1% of patients with a degenerative disease, and 23.9% of the patients with various other spinal conditions. The initial EFA provided a hypothetical construct for consideration. Subsequent CFA was considered in three scenarios: the full sample and separate genders. Models were compared empirically for best fit. Results: The EFA indicated a one-factor solution accounting for 54% of the total variance. The CFA analysis based on the full sample confirmed this one-factor structure. Sub-group analyses by gender achieved good model fit for configural and partial metric invariance, but not scalar invariance. A possible two-construct model solution as outlined by previous researchers: dynamic-activities (personal care, lifting, walking, sex and social) and static-activities (pain, sleep, standing, travelling and sitting) was not preferred. Conclusions: The ODI demonstrated a one-factor structure in a large LBP sample. A potential two-factor model was considered, but not found appropriate for constructs of dynamic and static activity. The use of the single summary score for the ODI is psychometrically supported. However, practicality limitations were reported for use in the clinical and research settings. Researchers are encouraged to consider a shift towards newer, more sensitive and robustly developed instruments