The MHV68 M2 Protein Drives IL-10 Dependent B Cell Proliferation and Differentiation

Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1α. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10−/− B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells—perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis—identifying a strategy that appears to be conserved between at least EBV and MHV68

Motor imagery training for children with developmental coordination disorder: Study protocol for a randomized controlled trial

Contains fulltext : 151535.pdf (publisher's version ) (Open Access)Background: Previous studies have shown that the predictive control of movements is impaired in children with Developmental Coordination Disorder (DCD), most likely due to a deficit in the internal modeling of movements. Motor imagery paradigms have been used to test this internal modeling deficit. The aim of the present study is to examine whether a training focused on the mental imagery of motor skills, can help to improve the motor abilities of children with DCD. Methods/Design: A pre-post design will be used to examine the motor performance, motor imagery and motor planning abilities before and after a training of 9 weeks. Two groups will be included in this study (1) one receiving motor imagery (MI) training focused on the forward modeling of purposive actions, (2) one receiving Cognitive Orientation to daily Occupational Performance (CO-OP) training focused on identifying effective cognitive strategies that will increase motor competence. MI training will be given with the use of instruction videos of the motor skill that will be trained. Both groups will participate in 9 individual sessions of 45 min (once a week) with a paediatric physical or occupational therapist, added with homework sessions. Inclusion criteria are: (1) aged 7–12 years, (2) meeting the DSM-V criteria for DCD (motor performance substantially low (score on the m-ABC ≤ 16th percentile) and motor problems that interfere with daily life (DCDQ, and request for help at a paediatric physical or occupational therapist)). Exclusion criteria are IQ < 70 and other medical conditions causing the motor impairment. Discussion: The results of this study will help to make treatment protocols for children with DCD more evidence-based. This study will increase our knowledge about the efficacy of both the MI training and CO-OP training, and both children with DCD and therapists will benefit from this knowledge.9 p

Medication Adherence Following Acute Coronary Syndrome: Does One Size Fit All?

© 2015, Springer International Publishing Switzerland.Guideline-based management of acute coronary syndrome (ACS) is well established, yet some may challenge that strict implementation of guideline recommendations can limit the individualization of therapy. The use of all recommended medications following ACS places a high burden of responsibility and cost on patients, particularly when these medications have not been previously prescribed. Without close attention to avoiding non-adherence to these medications, the full benefits of the guideline recommendations will not be realized in many patients. Using a case example, we discuss how the recognition of adherence barriers can be an effective and efficient process for identifying patients at risk of non-adherence following ACS. For those identified as at risk, the World Health Organization’s model of adherence barriers is explored as a potentially useful tool to assist with individualization of therapy and promotion of adherence