Murine B Cell Development and Antibody Responses to Model Antigens Are Not Impaired in the Absence of the TNF Receptor GITR

The Glucocorticoid-Induced Tumor necrosis factor Receptor GITR, a member of the tumor necrosis factor receptor superfamily, has been shown to be important in modulating immune responses in the context of T cell immunity. B lymphocytes also express GITR, but a role of GITR in humoral immunity has not been fully explored. To address this question, we performed studies to determine the kinetics of GITR expression on naïve and stimulated B cells and the capacity of B cells to develop and mount antibody responses in GITR−/− mice. Results of our studies indicate that all mature B cells express GITR on the cell surface, albeit at different levels. Expression of GITR on naïve mature B cells is upregulated by BCR signaling, but is counteracted by helper T cell-related factors and other inflammatory signals in vitro. In line with these findings, expression of GITR on germinal center and memory B cells is lower than that on naïve B cells. However, the expression of GITR is strongly upregulated in plasma cells. Despite these differences in GITR expression, the absence of GITR has no effect on T cell-dependent and T cell-independent antibody responses to model antigens in GITR−/− mice, or on B cell activation and proliferation in vitro. GITR deficiency manifests only with a slight reduction of mature B cell numbers and increased turnover of naïve B cells, suggesting that GITR slightly contributes to mature B cell homeostasis. Overall, our data indicate that GITR does not play a significant role in B cell development and antibody responses to T-dependent and independent model antigens within the context of a GITR-deficient genetic background

APRIL is overexpressed in cancer: link with tumor progression

<p>Abstract</p> <p>Background</p> <p>BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia.</p> <p>Methods</p> <p>We compared the expression of <it>BAFF, APRIL, TACI and BAFF-R </it>gene expression in 40 human tumor types – brain, epithelial, lymphoid, germ cells – to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.</p> <p>Results</p> <p>We found significant overexpression of <it>TACI </it>in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, <it>BAFF and APRIL </it>are overexpressed in many cancers and we show that <it>APRIL </it>expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans.</p> <p>Conclusion</p> <p>Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.</p

Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA): a systematic review update and individual participant data meta-analysis protocol.

Knee and hip osteoarthritis (OA) is a leading cause of disability worldwide. Therapeutic exercise is a recommended core treatment for people with knee and hip OA, however, the observed effect sizes for reducing pain and improving physical function are small to moderate. This may be due to insufficient targeting of exercise to subgroups of people who are most likely to respond and/or suboptimal content of exercise programmes. This study aims to identify: (1) subgroups of people with knee and hip OA that do/do not respond to therapeutic exercise and to different types of exercise and (2) mediators of the effect of therapeutic exercise for reducing pain and improving physical function. This will enable optimal targeting and refining the content of future exercise interventions.Systematic review and individual participant data meta-analyses. A previous comprehensive systematic review will be updated to identify randomised controlled trials that compare the effects of therapeutic exercise for people with knee and hip OA on pain and physical function to a non-exercise control. Lead authors of eligible trials will be invited to share individual participant data. Trial-level and participant-level characteristics (for baseline variables and outcomes) of included studies will be summarised. Meta-analyses will use a two-stage approach, where effect estimates are obtained for each trial and then synthesised using a random effects model (to account for heterogeneity). All analyses will be on an intention-to-treat principle and all summary meta-analysis estimates will be reported as standardised mean differences with 95% CI.Research ethical or governance approval is exempt as no new data are being collected and no identifiable participant information will be shared. Findings will be disseminated via national and international conferences, publication in peer-reviewed journals and summaries posted on websites accessed by the public and clinicians.CRD42017054049

Emerging roles for telemedicine and smart technologies in dementia care

Ann L Bossen,1 Heejung Kim,2,3 Kristine N Williams,1 Andreanna E Steinhoff,2 Molly Strieker1 1University of Iowa College of Nursing, Iowa City, IA, USA; 2University of Kansas School of Nursing, Kansas City, KS, USA; 3Yonsei University College of Nursing, Seoul, Republic of Korea Abstract: Demographic aging of the world population contributes to an increase in the number of persons diagnosed with dementia (PWD), with corresponding increases in health care expenditures. In addition, fewer family members are available to care for these individuals. Most care for PWD occurs in the home, and family members caring for PWD frequently suffer negative outcomes related to the stress and burden of observing their loved one&#39;s progressive memory and functional decline. Decreases in cognition and self-care also necessitate that the caregiver takes on new roles and responsibilities in care provision. Smart technologies are being developed to support family caregivers of PWD in a variety of ways, including provision of information and support resources online, wayfinding technology to support independent mobility of the PWD, monitoring systems to alert caregivers to changes in the PWD and their environment, navigation devices to track PWD experiencing wandering, and telemedicine and e-health services linking caregivers and PWD with health care providers. This paper will review current uses of these advancing technologies to support care of PWD. Challenges unique to widespread acceptance of technology will be addressed and future directions explored. Keywords: technology, dementia care, caregiver support&nbsp

Community-Based Technology Co-Design: Insights on Participation, and the Value of the “Co”

Evidence and analysis of Community-Based Participatory Design (PD) and Co-Design programs are not abundant. Filling this gap allows for better understanding of (1) the value programs offer from a quantitative standpoint, and (2) how to formalize participation within PD. In this paper, we present evidence from a series of International Development Design Summits (IDDS), a PD-oriented program focused on low-cost technology co-design and co-production, in collaboration with local communities. The purpose is to provide opportunities for learning and practicing community-based PD in an intercultural setting. We examine data from five summits in Colombia between 2015-2018.We discuss the value of this approach across multiple groups, and how it can be understood as a measure of participation. We present evidence of participant benefits, including an exploratory analysis of self-perception using sentiment analysis. Finally, we discuss the challenges and potential directions for this work. This paper contributes to further understand the value of participation (the “co”) in the context of community-based PD

Designing Multidimensional Assessment of ICTs for Elderly People: The UNCAP Clinical Study Protocol

The elder with mild or moderate cognitive impairment (MMCI) suffers from progressive cognitive decline with increasing difficulties in performing activities of daily living. Information and Communication Technology (ICT) for Healthcare can provide solutions to relief the caregivers’ burden and to support the elder in maintaining dignity and independence. The UNCAP European project aimed at developing and testing a bundle of hardware and software technologies able to fit the individual needs of the elder with MMCI and his/her formal and informal caregivers. A multicenter clinical investigation was designed for assessing improvements in the quality of life of all users (elderly with MMCI and their caregivers) and the impact on the use of resources for care. Six pilot sites in Italy were involved in this clinical investigation. A complex set of assessment tools allowed exploring a wide range of dimensions and to extract common indicators and outcomes in accordance to the assessment dimensions required by the Health Technology Assessment approach