3,537 research outputs found

    Daniel Mowry Cemetery Condition Reports

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    This cemetery contains 85 burials. Transcriptions here include all of the markings on each stone located within the cemetery. Additionally, if stones were illegible a rubbing of the stone was completed. Both headstones and footstones are included in the transcription report

    Foundations as Network Strategists, Weavers, and Managers: Learning From One Foundation’s Journey and Results

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    This article shares insights from a five-year evaluation of the Oral Health 2020 network, an effort by the DentaQuest Foundation to align and strengthen efforts in service of a national movement to improve oral health. The evaluation helped to place the foundation’s journey in the context of a broader field seeking new approaches to achieve deep and sustainable social change. The foundation’s approach was informed by several ideas that have gained momentum in the social sector, including collective impact, networks, systems change, and equity – all of which challenged the foundation to take a nontraditional approach that combined the roles of network hub, weaver, and backbone organization. Six years in, the network has achieved notable successes, but along the way the foundation and its partners learned numerous lessons about what it takes to build and sustain a national network. This article shares those lessons, and also considers changes in federal policy and their implications

    IL-18-induced expression of high-affinity IL-2R on murine NK cells is essential for NK-cell IFN-Ξ³ production during murine Plasmodium yoelii infection.

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    Early production of pro-inflammatory cytokines, including IFN-Ξ³, is essential for control of blood-stage malaria infections. We have shown that IFN-Ξ³ production can be induced among human natural killer (NK) cells by coculture with Plasmodium falciparum infected erythrocytes, but the importance of this response is unclear. To further explore the role of NK cells during malaria infection, we have characterized the NK-cell response of C57BL/6 mice during lethal (PyYM) or nonlethal (Py17XNL) P. yoelii infection. Ex vivo flow cytometry revealed that NK cells are activated within 24 h of Py17XNL blood-stage infection, expressing CD25 and producing IFN-Ξ³; this response was blunted and delayed during PyYM infection. CD25 expression and IFN-Ξ³ production were highly correlated, suggesting a causal relationship between the two responses. Subsequent in vitro experiments revealed that IL-18 signaling is essential for induction of CD25 and synergizes with IL-12 to enhance CD25 expression on splenic NK cells. In accordance with this, Py17XNL-infected erythrocytes induced NK-cell CD25 expression and IFN-Ξ³ production in a manner that is completely IL-18- and partially IL-12-dependent, and IFN-Ξ³ production is enhanced by IL-2. These data suggest that IL-2 signaling via CD25 amplifies IL-18- and IL-12-mediated NK-cell activation during malaria infection

    Suppression of Plasmodium falciparum by serum collected from a case of Plasmodium vivax infection.

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    BACKGROUND: It has frequently been reported that Plasmodium vivax suppressed Plasmodium falciparum and ameliorated disease severity in patients infected with these two species simultaneously. The authors investigate the hypothesis that immunological responses stimulated by P. vivax may play a role in suppressing co-infecting P. falciparum. METHODS: Sera, taken sequentially from one of the authors (YN) during experimental infection with P. vivax, were added to in vitro cultures of P. falciparum. Cross-reactive antibodies against P. falciparum antigens, and cytokines were measured in the sera. RESULTS: Significant growth inhibitory effects upon P. falciparum cultures (maximally 68% inhibition as compared to pre-illness average) were observed in the sera collected during an acute episode. Such inhibitory effects showed a strong positive temporal correlation with cross-reactive antibodies, especially IgM against P. falciparum schizont extract and, to a lesser degree, IgM against Merozoite Surface Protein (MSP)-119. Interleukin (IL)-12 showed the highest temporal correlation with P. vivax parasitaemia and with body temperatures in the volunteer. CONCLUSION: These results suggest the involvement by cross-reactive antibodies, especially IgM, in the interplay between plasmodial species. IL-12 may be one of direct mediators of fever induction by rupturing P. vivax schizonts, at least in some subjects. Future studies, preferably of epidemiological design, to reveal the association between cross-reactive IgM and cross-plasmodial interaction, are warranted

    Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate.

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    BACKGROUND: Safe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. Oral activated charcoal (oAC) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. In preparation for possible efficacy trials in human malaria, we sought to determine whether oAC would i) reduce mortality due to experimental cerebral malaria (ECM) in mice, ii) modulate immune and inflammatory responses associated with ECM, and iii) affect the pharmacokinetics of parenteral artesunate in human volunteers. METHODS/PRINCIPAL FINDINGS: We found that oAC provided significant protection against P. berghei ANKA-induced ECM, increasing overall survival time compared to untreated mice (p<0.0001; hazard ratio 16.4; 95% CI 6.73 to 40.1). Protection from ECM by oAC was associated with reduced numbers of splenic TNF(+) CD4(+) T cells and multifunctional IFNgamma(+)TNF(+) CD4(+) and CD8(+) T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, we conducted a randomized controlled open label trial in 52 human volunteers (ISRCTN NR. 64793756), administering artesunate (AS) in the presence or absence of oAC. We demonstrated that co-administration of oAC was safe and well-tolerated. In the 26 subjects further analyzed, we found no interference with the pharmacokinetics of parenteral AS or its pharmacologically active metabolite dihydroartemisinin. CONCLUSIONS/SIGNIFICANCE: oAC protects against ECM in mice, and does not interfere with the pharmacokinetics of parenteral artesunate. If future studies succeed in establishing the efficacy of oAC in human malaria, then the characteristics of being inexpensive, well-tolerated at high doses and requiring no sophisticated storage would make oAC a relevant candidate for adjunct therapy to reduce mortality from severe malaria, or for immediate treatment of suspected severe malaria in a rural setting. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64793756

    IFN-Ξ³-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain.

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    It is well established that IFN-Ξ³ is required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the temporal and tissue-specific cellular sources of IFN-Ξ³ during P. berghei ANKA infection have not been investigated, and it is not known whether IFN-Ξ³ production by a single cell type in isolation can induce cerebral pathology. In this study, using IFN-Ξ³ reporter mice, we show that NK cells dominate the IFN-Ξ³ response during the early stages of infection in the brain, but not in the spleen, before being replaced by CD4(+) and CD8(+) T cells. Importantly, we demonstrate that IFN-Ξ³-producing CD4(+) T cells, but not innate or CD8(+) T cells, can promote the development of ECM in normally resistant IFN-Ξ³(-/-) mice infected with P. berghei ANKA. Adoptively transferred wild-type CD4(+) T cells accumulate within the spleen, lung, and brain of IFN-Ξ³(-/-) mice and induce ECM through active IFN-Ξ³ secretion, which increases the accumulation of endogenous IFN-Ξ³(-/-) CD8(+) T cells within the brain. Depletion of endogenous IFN-Ξ³(-/-) CD8(+) T cells abrogates the ability of wild-type CD4(+) T cells to promote ECM. Finally, we show that IFN-Ξ³ production, specifically by CD4(+) T cells, is sufficient to induce expression of CXCL9 and CXCL10 within the brain, providing a mechanistic basis for the enhanced CD8(+) T cell accumulation. To our knowledge, these observations demonstrate, for the first time, the importance of and pathways by which IFN-Ξ³-producing CD4(+) T cells promote the development of ECM during P. berghei ANKA infection

    Insulin glargine in a Brazilian State : an assessment of drug utilization, effectiveness and value to provide future direction

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    The cost and utilisation of the insulin analogue (Insulin glargine) has grown appreciably in the State of Minas Gerais in Brazil in recent years, with costs growing on average by 291% per year. This growth has been driven by an increasing number of successful law suits and a 536% price differential between insulin glargine and neutral protamine Hagedorn (NPH) insulin. One way forward to address concerns with its growing utilisation is to undertake a systematic review assessing the efficacy and safety of insulin glargine compared with NPH insulin in patients with Type I diabetes. As a result, provide published data to support future recommended activities by the State to limit its use
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