Exploring the impact of cultural beliefs in the self-management of type 2 diabetes among Black sub-Saharan Africans in the UK – a qualitative study informed by the PEN-3 cultural model

Objective The purpose of this study was to examine cultural beliefs, attitudes, and practices of Black sub-Saharan Africans (BsSAs) in the UK regarding their type 2 diabetes (T2D) self-management using the concepts of the PEN-3 cultural model. Method A qualitative study involved 36 semi-structured interviews with BsSAs living with T2D in the UK to examine relevant cultural practices and beliefs that have contributed to the uneven burden of self-management behaviours. A narrative thematic analysis of the data was then conducted for the study using NVivo software and guided by the PEN-3 cultural model, which moves beyond individualistic health behaviour models of diabetes but centralises culture in understanding health behaviours. Results Cultural perceptions and self-management behaviours of T2D varied among the BsSAs. Systems of self-management and treatment practices that were congruent with their cultural beliefs and personal priorities were seen as essential in the positive response to self-managing T2D. Knowledge and perceptions of non-conventional and alternative remedies linked to cultural beliefs reflected the existential health-seeking behaviours, and the significance attached to BsSAs negotiated cultural identities and collective practices within the communities. Social network supports were seen as enablers while advice and regimens from healthcare professionals (HCPs) were presented as medicalised and devoid of cultural sensitivities to respondents. Conclusion The study findings highlight the need to be not only aware of the negative impact of diabetes perceptions and health behaviours among the BsSA communities, but also be aware of the enabling factors and collective practices within the communities that are equally critical in influencing the self-management and health-seeking decisions of BsSAs living with T2D. PEN-3 model was significant with exploring not only how cultural context shapes health beliefs and practices, but also how social networks and systems play a critical role in enabling or nurturing positive health behaviours and health outcomes

Transformation induced by Ewing's sarcoma associated EWS/FLI-1 is suppressed by KRAB/FLI-1

Ewing's sarcoma is a childhood bone tumour with poor prognosis, most commonly associated with a t(11;22)(q24;q12) reciprocal translocation that fuses the EWS and FLI-1 genes, resulting in the production of an aberrant chimeric transcription factor EWS/FLI-1. To erucidate the mechanisms by which EWS/FLI-1 mediates transformation in mouse models, we have generated a murine Ews/Fli-1 fusion protein. We demonstrate that this protein transforms fibroblast celrs in vitro similar to human EWS/FLI-1 as demonstrated by serum and anchorage-independent growth, the formation of tumours in nude mice and elevation of the oncogenic marker c-myc. Furthermore, transformation of these cells was inhibited by a specific represser, KRAB/FLI-1. The KRAB/FLI-1 repressor also suppressed the tumorigenic phenotype of a human Ewing's sarcoma cell line. These findings suggest that the transformed phenotype of Ewing's sarcoma cells can be reversed by using the sequence-specific FLI-1-DNA-binding domain to target a gone repressor domain. The inhibition of EWS/FLI-1 is the first demonstration of the KRAB domain suppressing the action of an ETS factor. This approach provides potential avenues for the elucidation of the biological mechanisms of EWS/FLI-1 oncogenesis and the development of novel therapeutic strategies. © 2003 Cancer Research UK.link_to_subscribed_fulltex

Systemic Treatment with CpG-B after Sublethal Rickettsial Infection Induces Mouse Death through Indoleamine 2,3-Dioxygenase (IDO)

Due to its strong immune stimulatory effects through TLR9, CpG-containing oligodeoxynucleotides (CpG ODN) have been tested in multiple clinical trials as vaccine adjuvant for infectious diseases and cancer. However, immune suppression induced by systemic administration of CpGs has been reported recently. In this study, we evaluated the impact of CpGs in an acute rickettsiosis model. We found that systemic treatment with type B CpG (CpG-B), but not type A CpG (CpG-A), at 2 days after sublethal R. australis infection induced mouse death. Although wild-type (WT) B6 and IDO−/− mice showed similar survival rates with three different doses of R. australis infection, treatment with CpG-B after sublethal infection consistently induced higher mortality with greater tissue bacterial loads in WT but not IDO−/− mice. Also, CpG-B treatment promoted the development of higher serum concentrations of proinflammatory cytokines/chemokines through IDO. Furthermore, while T cell-mediated immune responses enhanced by CpG-B were independent of IDO, treatment with CpG-B promoted T cell activation, PD-1 expression and cell apoptosis partially through IDO. A depletion study using anti-mPDCA-1 mAb indicated that plasmacytoid dendritic cells (pDC) were not required for CpG-B-induced death of R. australis-infected mice. Additionally, the results in iNOS−/− mice suggested that nitric oxide (NO) was partially involved in CpG-B-induced death of R. australis-infected mice. Surprisingly, pre-treatment with CpG-B before administration of a lethal dose of R. australis provided effective immunity in WT, IDO−/− and iNOS−/− mice. Taken together, our study provides evidence that CpGs exert complex immunological effects by both IDO-dependent and -independent mechanisms, and that systemic treatment with CpGs before or after infection has a significant and distinct impact on disease outcomes

Beyond ecosystem modeling: a roadmap to community cyberinfrastructure for ecological data‐model integration

In an era of rapid global change, our ability to understand and predict Earth's natural systems is lagging behind our ability to monitor and measure changes in the biosphere. Bottlenecks to informing models with observations have reduced our capacity to fully exploit the growing volume and variety of available data. Here, we take a critical look at the information infrastructure that connects ecosystem modeling and measurement efforts, and propose a roadmap to community cyberinfrastructure development that can reduce the divisions between empirical research and modeling and accelerate the pace of discovery. A new era of data‐model integration requires investment in accessible, scalable, transparent tools that integrate the expertise of the whole community, including both modelers and empiricists. This roadmap focuses on five key opportunities for community tools: the underlying foundationsof community cyberinfrastructure; data ingest; calibration of models to data; model‐data benchmarking; and data assimilation and ecological forecasting. This community‐driven approach is key to meeting the pressing needs of science and society in the 21st century

Chronic in vivo depletion of CD4 T cells begun in utero inhibits gut B cell differentiation.

We studied the role of CD4 T cells on the ontogeny of mucosal IgA compartment. We treated C57 BL/6 mice, beginning in utero and for 4 weeks thereafter, with anti-CD4 monoclonal antibody. Mice were evaluated at 1, 3, and 5 weeks after stopping the treatment. At 1 week, anti-CD4-treated mice had no detectable CD4 T cells in spleen or Peyer\u27s patches. These CD4-depleted mice demonstrated a 40% reduction of surface Peyer\u27s patch IgA+ B cells and a marked decrease in jejunal IgA secretion. By 5 weeks, CD4 T cells were detectable in spleen and Peyer\u27s patch and the number of surface IgA+ B cells in Peyer\u27s patch was increased, but they remained less than the control levels. Jejunal IgA secretion recovered to the control level by 5 weeks. LPS induced normal levels of in vitro IgM secretion by Peyer\u27s patch B cells in anti-CD4-treated mice; thus, treatment with anti-CD4 does not nonspecifically inhibit the gut B cell compartment. This study demonstrates that CD4 T cell depletion begun in utero significantly inhibits the differentiation of mucosal B cells to IgA-secreting cells and partially inhibits switching to IgA+ B cells in Peyer\u27s patch

The effect of partial in vivo depletion of CD4 T cells by monoclonal antibody. Evidence that incomplete depletion increases IgG production and augments in vitro thymic-dependent antibody responses.

In vivo depletion or inactivation of CD4 T cells by monoclonal antibody inhibits of T-cell-dependent immune responses and, in some cases, ameliorates clinical autoimmune disease. Impairment of T cell function occurs in situations where mice are treated with relatively large doses of anti-CD4 antibody. When adult (C57BL/6xDBA/2)F1 mice were treated with a low dose of anti-CD4 antibody augmentation of certain thymic-dependent responses occurred. Twice-weekly injections of 50 micrograms of monoclonal antibody GK1.5 for a period of three weeks resulted in a 50% reduction of splenic CD4 T cells. Mice that were partially depleted of CD4 T cells exhibited a 55% increase in serum IgG levels with a 165% increase in serum IgG1. Simulation of spleen cells from these mice with LPS resulted in a significant increase in differentiation of IgG secretion. When spleen cells from partially CD4-depleted mice were challenged in vitro with SRBC, they mounted a direct PFC response that was more than four times the observed PFC response of mice that received either saline or rat IgG. These findings indicate that partial depletion/inactivation of CD4 T cells by in vivo administration of anti-CD4 monoclonal antibody results in a significant augmentation of certain T-cell-dependent humoral responses