Apoptotic Elimination Of V beta 8.2+ Cells From The Central Nervous System During Recovery From Experimental Autoimmune Encephalomyelitis Induced By The Passive Transfer Of V beta 8.2+ Encephalitogenic T Cells

A CD4+ V beta 8.2+ T cell clone specific for the peptide 72-89 of guinea pig myelin basic protein (GMBP) was used to induce acute experimental autoimmune encephalomyelitis (EAE) in Lewis rats. To assess apoptosis in inflammatory cells infiltrating the central nervous system (CNS), we extracted cells from the spinal cord, enriched them for T cells and performed flow-cytometric analysis of their DNA stained with propidium iodide. The presence of apoptosis was confirmed by the demonstration of DNA fragmentation on gel electrophoresis. A gradual increase in the proportion of apoptotic cells was observed between 4 and 7 days after the transfer of the encephalitogenic T cells. The highest frequency of apoptotic cells (9.2 plus or minus 1.2%) was observed 7 days after cell transfer, when clinical recovery commenced. Passive transfer of ovalbumin-specific cells resulted in only a background level (0.8%) of apoptosis in the CNS. We conclude that the apoptotic process selectively eliminates autoreactive T cells from the CNS as: (a) there was a selective disappearance of disease-relevant CD5+ V beta 8.2+ cells from the CNS during the course of EAE; (b) there was a decrease in the frequency of CNS-infiltrating T cells reactive to the GMBP 72-89 peptide during the course of EAE, and in a standard proliferation assay there was a loss of in vitro reactivity of CNS-infiltrating cells to this peptide, but not to a non-CNS antigen (ovalbumin); (c) simultaneous surface labeling and DNA analysis of CNS-infiltrating cells revealed that the frequency of V beta 8.2+ cells was about sevenfold higher in the apoptotic T cell population than in the normal (non-apoptotic) T cell population; and (d) we were unable to detect recirculation of the V beta 8.2+ cells to lymphoid organs after their frequency decreased in the CNS. The selective apoptotic elimination of autoreactive T cells from the target organ of this spontaneously resolving autoimmune disease may have implications for the understanding of the mechanism by which an autoimmune attack is terminated and for the design of therapeutic strategies to facilitate this process

We need to talk about purpose : a critical interpretive synthesis of health and social care professionals’ approaches to self-management support for people with long-term conditions

Acknowledgements Many thanks to Cynthia Fraser, Information Specialist (Health Services Research Unit, University of Aberdeen), for leading the design and conduct of the literature searches, document retrieval and reference management. The Health Services Research Unit, University of Aberdeen is core funded by the Chief Scientist Office of the Scottish Government’s Health and Social Care Directorates. The authors accept full responsibility for this paper. Funding This research was funded by The Health Foundation (Project reference 7209).Peer reviewedPublisher PD

Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis

Background Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. Methods and Findings Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions—Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, the Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom—to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5–14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50–64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). Conclusions Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes

How the psychosocial context of clinical trials differs from usual care: a qualitative study of acupuncture patients

Background: qualitative studies of participants' experiences in randomised clinical trials (RCTs) suggest that the psychosocial context of treatment in RCTs may be quite different to the psychosocial context of treatment in usual practice. This is important, as the psychosocial context of treatment is known to influence patient outcomes in chronic illness. Few studies have directly compared the psychosocial context of treatment across RCTs and usual practice. In this study, we explored differences in psychosocial context between RCT and usual practice settings, using acupuncture as our model.Methods: we undertook a secondary analysis of existing qualitative interviews with 54 patients. 27 were drawn from a study of western and traditional acupuncture in usual practice (for a range of painful conditions). 27 were drawn from a qualitative study nested in an RCT of western acupuncture for osteoarthritis of the hip or knee. We used qualitative analysis software to facilitate an inductive thematic analysis in which we identified three main themes.Results: in usual practice, starting acupuncture was more likely to be embedded in an active and ongoing search for pain relief, whereas in the RCT starting acupuncture was opportunistic. Usual practice patients reported few uncertainties and these had minimal consequences for them. In the RCT, patients experienced considerable uncertainties about their treatment and its effectiveness, and were particularly concerned about whether they were receiving real (or fake) acupuncture. Patients stopped acupuncture only at the end of the fixed course of treatment in the RCT, which was similar to those receiving acupuncture in the public sector National Health Service (NHS). In comparison, private sector patients re-evaluated and re-negotiated treatments particularly when starting to use acupuncture.Conclusions: differences in psychosocial context between RCTs and usual practice could reduce the impact of acupuncture in RCT settings and/or lead to under-reporting of benefit by patients in trials. New trial designs that ensure participants' experiences are similar to usual practice should minimise differences in psychosocial context and help attenuate these potentially confounding effect