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Background: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk irrespective of conventional risk factors. The role of gut-liver interaction is implicated in its development. We investigated the effects of VSL#3® probiotic supplementation on biomarkers of cardiovascular risk and liver injury in patients with NAFLD.Methods: A randomised, double-blinded, placebo-controlled, proof-of-concept study was undertaken. Patients with NAFLD were randomly allocated to take 2 sachets VSL#3® probiotic or placebo twice daily for 10 weeks. Measurements of endothelial function (digital photoplethysmography, sVCAM-1 and cGMP), oxidative stress (glutathione ratio and LHP), inflammation (hsCRP), insulin resistance (HOMA-IR) and liver injury [transaminases, fibrosis risk score and acoustic structure quantification (ASQ)] were undertaken before and after intervention. Difference in baseline characteristics between the treatment groups was analysed using independent t-test or Mann Whitney U test for non-parametric data. Independent t-test was used to compare the outcomes at the end of the study between the two treatment groups. Wilcoxon Signed Rank test was used to determine the difference in fibrosis risk scores before and after treatment. Spearman's correlation was used to determine any association between cardiovascular and hepatic markers at baseline.Results: Thirty-five patients completed the study (28 males and 7 females) with a mean age of 57 ± 8 years, body mass index of 32.6 ± 5.0 kg/m2 and a relatively short duration of NAFLD (median duration 0.3 IQR 2.0 years). No significant difference was observed in biomarkers of cardiovascular risk and liver injury following VSL#3® supplementation. Significant correlations were noted between sVCAM-1 and hsCRP (rho = 0.392, p = 0.01), and HOMA-IR and AST (rho = 0.489, p < 0.01) at baseline.Conclusions: This is the first study to evaluate the effect of VSL#3® on ASQ in patients with NAFLD. VSL#3® did not significantly improve markers of cardiovascular risk and liver injury in patients with NAFLD. However, the study supports an association between endothelial dysfunction and inflammation in patients with NAFLD and suggests that NAFLD is linked with insulin resistance.Trial Registration: ISRCTN05474560 ( https://doi.org/10.1186/ISRCTN05474560 ) Registered 9 August 2012 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Advanced age is one indicator of likely immune dysfunction. As worldwide, the global population contains progressively more and more older individuals there is likelihood of an increased prevalence and incidence of infectious diseases due to common and emergent pathogens. The resultant increase in mortality and morbidity would be matched by the risk of functional decline and disability. Maintaining immune function at a plateau throughout life may therefore be associated with considerable cost savings. The aim of improving immune function in older individuals may be achieved through considering a therapeutic approach to rejuvenate, stimulate or support the indigenous immune systemto perform in a more optimal manner. In terms of cost effectiveness a therapeutic approach may prove difficult because of issues associated with; identifying those who would benefit the most from this treatment, identifying the type of treatment which would suit them and identifying whether the treatment was successful. The alternative of supporting or providing a stronger stimulus through vaccination, whilst more cost effective, may be a more valuable option in the short term. Both approaches will be addressed in this review. [ABSTRACT FROM AUTHOR]

Background: Monitoring health and care needs through the use of telehealthcare devices has been proposed to help alleviate funding concerns in a climate of limited budgets. As well as improving cost effectiveness, such an approach could be used to help individuals live at home for longer. In practice however, these devices often go unused. A qualitative study was carried out to determine the barriers to uptake of these devices from both the perspective of the end user and from key players in the healthcare supply chain.Methods: A qualitative approach was used involving focus groups and interviews. Two UK-based focus groups were held with users and potential users, to assess their views on the wide array of devices available. 27 individuals were involved in the groups, all over the age of 60. Additionally 27 telephone interviews were conducted with key supply chain players to ascertain their views on the barriers to uptake of these devices. A semi-structured interview guide was used. All data were audio-recorded, transcribed verbatim and analysed using a thematic approach.Results: Users were generally unaware of the wide array of devices available and when shown a selection, were often unclear as to their purpose. The interviews revealed extensive barriers to uptake due to lack of awareness, unfamiliar terminology, complex supply routes and costs, resistance from professionals to device usage and lack of expertise.Conclusions: Public and professional awareness campaigns are required with appropriate funding mechanisms for users to gain access to devices. The numerous barriers identified require systematically addressing, so that device usage is better promoted, enabling individuals to live at home successfully for longer. [ABSTRACT FROM AUTHOR]

Background: There are many telehealthcare devices currently available ranging from personal alarms, automated pill dispensers and fall detectors through to monitoring devices for blood sugar, blood pressure and heart rate. Many devices remain unused once acquired or shortly after a period of initial use.Methods: The study used a qualitative design involving focus groups and interviews. End users' opinions of telehealthcare devices were examined through focus groups along with the views of market experts and key supply chain players through telephone interviews to ascertain their views on the devices. The data were recorded, transcribed and analysed thematically.Results: Amongst the wide range of user issues associated with telehealthcare devices two themes merited particular attention: design characteristics and the lack of focus on end-user needs. Our findings suggested that few telehealthcare devices appear to be developed based on the principles of user-centred design. Consequently, many were non-intuitive to use, with the majority of the focus group participants not recognising the purpose of the devices from their appearance alone.Conclusions: Greater input from real end-users rather than "proxy" users such as carers, professional users or technologists is required when developing telehealthcare devices or systems. Design should be focussed on intuitive use to enable the user to successfully achieve what is required from the devices. This may require the existing supplier-driven market focus to be challenged, but could improve the contribution of technology to improving healthcare. [ABSTRACT FROM AUTHOR]

Transfusion of autologous leukocytes after prolonged storage has been proposed as a means of rejuvenating the immune system of older individuals. The rationale for this approach is that age related immune decline is associated with a diminished pool of naïve T cells following atrophy of the thymus and reduction in thymic output. The presence of high levels of naïve T cells within the blood of young individuals could provide a boost to the immune system of an older "self" through a rejuvenation of the naïve T cell pool. However what remains unresolved is whether the cells could be incorporated effectively into the T cell pool of the host and whether effectors could be generated. Using CD45 congenic mice in our experiments we show that the transfusion of young donor cells into older congenic host animals leads to their successful incorporation into the peripheral T cell pool. When the recipients were challenged with influenza virus, specific effector CD8 cells were generated which were of both host and donor origin. We found no relationship between the number of responder cells of donor origin at the time of assay and the number of cells injected. [ABSTRACT FROM AUTHOR]

The increased susceptibility of the elderly to infection presents a major challenge to public health services. An aging immune system is well documented as the cause of increased infection rates in elderly people. Such immunosenescence is multi-factorial and incompletely understood. Immunosenescent changes include malfunctioning of innate immune system cellular receptors; involution of the thymus, with consequent reduction of the naïve T cell population; alteration of the T cell population composition; modified phenotypes of individual T cells; and replicative senescence of memory cells expressing naïve markers. Unfortunately, immunosenescence also renders vaccination less effective in the elderly. It is therefore important that the vaccines used against common but preventable diseases, such as influenza, are specifically enhanced to overcome the reduced immune responsiveness of this vulnerable population. [ABSTRACT FROM AUTHOR]

The problems associated with the ageing immune system coupled with possible solutions were discussed recently at the British Society for Immunology Annual Congress in Harrogate in December 2004. The session "Ageing and the Immune System in vivo" dealt in details with the immune risk phenotype and the potential methods of reversing the problems of an ageing immune system. This is a commentary on that session. [ABSTRACT FROM AUTHOR]

Background: The study exploits a natural human experimental model of subsistence farmers experiencing chronic and seasonally modified food shortages and infectious burden. Two seasons existed, one of increased deprivation and infections (Jul-Dec), another of abundance and low infections (Jan-Jun); referred to as the hungry/high infection and harvest/low infection seasons respectively. Prior analysis showed a 10-fold excess in infectious disease associated mortality in young adults born in the hungry/high infection versus harvest/low infection season, and reduced thymic output and T cell counts in infancy. Here we report findings on the role of early life stressors as contributors to the onset of T cell immunological defects in later life., Methods: We hypothesised that season of birth effects on thymic function and T cell immunity would be detectable in young adults since Kaplan-Meier survival curves indicated this to be the time of greatest mortality divergence. T cell subset analyses by flow-cytometry, sjTRECs, TCRVβ repertoire and telomere length by PCR, were performed on samples from 60 males (18-23 y) selected to represent births in the hungry/high infection and harvest/low infection, Results: Total lymphocyte counts were normal and did not differ by birth season. CD3+ and CD4+ but not CD8+ counts were lower for those born during the hungry/high infection season. CD8+ telomere length also tended to be shorter. Overall, CD8+ TCRVβ repertoire skewing was observed with 'public' expressions and deletions seen in TCRVβ12/22 and TCRVβ24, respectively but no apparent effect of birth season., Conclusions: We conclude that, although thymic function was unchanged, the CD4+ and CD3+ counts, and CD8+ telomere length results suggested that aspects of adult T cell immunity were under the influence of early life stressors. The endemicity of CMV and HBV suggested that chronic infections may modulate immunity through T cell repertoire development. The overall implications being that, this population is at an elevated risk of premature immunosenescence possibly driven by a combination of nutritional and infectious burden.