120 research outputs found

    Analysis of Gait Parameters and Knee Angles in Ultimate Frisbee Players: Implications for Balance and Injury

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    Biomechanics research investigating gait and balance of ultimate frisbee players is an unexplored topic. Ultimate requires a wide range of motions that could improve balance and is also a sport prone to frequent injury. This study explores the impact of playing ultimate on gait parameters associated with balance and knee angles associated with joint injury. Gait trials were conducted on 8 ultimate players and 8 control participants between the ages of 18 and 23 to obtain total double support time, stance phase time, single support time, load response time, abduction-adduction (AA) angles, internal-external (IE) rotation angles, and flexion angles of the dominant leg’s knee. Knee angles were obtained through the application of a Triangular Cosserat Point Element (TCPE) analysis for Soft-Tissue Artifact (STA) correction of knee kinematics. The gait parameters and knee angles were compared between ultimate players and control group participants using two-sample t tests. The results indicated that (1) playing ultimate may be used to improve balance, and (2) playing ultimate may reduce the range of IE rotation angles

    Differential selectivity of CIITA promoter activation by IFN-γ and IRF- 1 in astrocytes and macrophages: CIITA promoter activation is not affected by TNF-α

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    During demyelinating disease of the central nervous system (CNS), locally elevated cytokine levels may induce upregulation of MHC class II molecules on otherwise low expressing or negative cell types such as microglia and astrocytes, since IFN-γ has been shown to induce MHC class II expression on these cell types in vitro. While many transcription factors are involved with MHC class II expression, only the class II transactivator (CIITA) is tightly coordinated with IFN-γ-inducibility. Control of CIITA gene expression is complex, involving four distinct promoters, two of which (promoters III and IV) are IFN-γ-inducible in certain cell types. Here we demonstrate that IFN-γ treatment of rat astrocytes induces only CIITA promoter IV activity in contrast to the murine macrophage cell line RAW 264.7 that uses both IFN-γ-inducible promoters. In contrast to previously published reports, promoter IV activation is completely dependent upon an intact interferon regulatory factor-1 (IRF-1) but not STAT1 binding site using promoter constructs specifically mutated at these positions. Importantly, while TNF-α is able to synergize with IFN-γ to increase astrocyte MHC class II expression in vitro, we show that treatment of rat astrocytes with TNF-α has no effect on CIITA promoter activity. These data demonstrate that TNF-α augments MHC class II expression through a mechanism downstream or independent of CIITA induction

    Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson’s disease

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    Funded by The Parkinson's Disease Foundation The Wellcome Trust (WT080782MF) Biotechnology and Biological Sciences Research Council and the Royal Society Acknowledgment The authors are grateful to the staff of the Medical Research Facility for their help with the animal care. The authors have no conflicts of interest to declare.Peer reviewedPublisher PD

    Long-Term Survivors of Metastatic Colorectal Cancer Treated with Systemic Chemotherapy Alone: A North Central Cancer Treatment Group Review of 3811 Patients, N0144

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    Although systemic chemotherapy in patients with unresectable metastatic colorectal cancer (mCRC) is palliative in nature, some patients experience long-term remission beyond 5 years consequent to treatment with chemotherapy alone

    Selective Abrogation of Major Histocompatibility Complex Class II Expression on Extrahematopoietic Cells in Mice Lacking Promoter IV of the Class II Transactivator Gene

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    MHC class II (MHCII) molecules play a pivotal role in the induction and regulation of immune responses. The transcriptional coactivator class II transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice. These mice exhibit selective abrogation of interferon (IFN)-γ–induced MHCII expression on a wide variety of non-bone marrow–derived cells, including endothelia, epithelia, astrocytes, and fibroblasts. Constitutive MHCII expression on cortical thymic epithelial cells, and thus positive selection of CD4+ T cells, is also abolished. In contrast, constitutive and inducible MHCII expression is unaffected on professional antigen-presenting cells, including B cells, dendritic cells, and IFN-γ–activated cells of the macrophage lineage. pIV−/− mice have thus allowed precise definition of CIITA pIV usage in vivo. Moreover, they represent a unique animal model for studying the significance and contribution of MHCII-mediated antigen presentation by nonprofessional antigen-presenting cells in health and disease

    Maturation of Dendritic Cells Is Accompanied by Rapid Transcriptional Silencing of Class II Transactivator (Ciita) Expression

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    Cell surface expression of major histocompatibility complex class II (MHCII) molecules is increased during the maturation of dendritic cells (DCs). This enhances their ability to present antigen and activate naive CD4+ T cells. In contrast to increased cell surface MHCII expression, de novo biosynthesis of MHCII mRNA is turned off during DC maturation. We show here that this is due to a remarkably rapid reduction in the synthesis of class II transactivator (CIITA) mRNA and protein. This reduction in CIITA expression occurs in human monocyte-derived DCs and mouse bone marrow–derived DCs, and is triggered by a variety of different maturation stimuli, including lipopolysaccharide, tumor necrosis factor α, CD40 ligand, interferon α, and infection with Salmonella typhimurium or Sendai virus. It is also observed in vivo in splenic DCs in acute myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalitis. The arrest in CIITA expression is the result of a transcriptional inactivation of the MHC2TA gene. This is mediated by a global repression mechanism implicating histone deacetylation over a large domain spanning the entire MHC2TA regulatory region

    Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation

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    This study was supported by the British Heart Foundation (PG 09/002/ 2642). AJR is funded by King’s College London British Heart Foundation Centre of Excellence and EI was supported by the Department of Health via National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St Tomas’ NHF Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. BG was supported by a British Heart Foundation studentship (FS/10/009/28166) and DC by an Arthritis Research UK Fellowship (18103)

    Updates in Gastrointestinal Oncology – insights from the 2008 44th annual meeting of the American Society of Clinical Oncology

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    We have reviewed the pivotal presentations rcelated to colorectal cancer (CRC) and other gastrointestinal malignancies from 2008 annual meeting of the American Society of Clinical Oncology (ASCO). We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. The report on KRAS status in patients with metastatic CRC receiving epidermal growth factor receptor (EGFR) targeted antibody treatment has led to a change in National Comprehensive Cancer Network guideline that recommends only patients with wild-type KRAS tumor should receive this treatment. The results of double biologics (bevacizumab and anti-EGFR antibody) plus chemotherapy as first-line treatment in patients with metastatic CRC has shown a worse outcome than bevacizumab-based regimen. Microsatellite Instability has again been confirmed to be an important predictor in patients with stage II colon cancer receiving adjuvant treatment

    Spiritual Well-Being and Self-Esteem in the Homeless

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    There is a paucity of research published regarding the human condition of homelessness. Based on the premise that spiritual well-being and self-esteem enhance quality of life and coping, this study sought to describe the spiritual well-being and self-esteem, as well as investigate the relationship between these variables, in a homeless population. The investigator tested three hypotheses: 1) there is a positive relationship between spiritual well-being and self-esteem in a homeless population; 2) there is a positive relationship between religious well-being and self-esteem in a homeless population ; and 3) there is a positive relationship between existential well-being and self-esteem in a homeless population. One hundred and one subjects were obtained via a convenience and systematic selective sampling technique from one Midwest metropolitan meal site and one Midwest metropolitan shelter site. A quantitative (descriptive correlational) as well as qualitative (grounded theory) approach was utilized. Ellison and Palputzian\u27s (1979) Spiritual Well-Being Scale and Rosenberg\u27s (1965) Self-Esteem Scale were administered to by each of the 101 subjects. In addition, a representative sample of 20 subjects responded to an open-ended interview process which was constructed by the investigator. The quantitative data was analyzed using the Pearson\u27s product moment correlation coefficient with a 0.05 level of significance. Constant comparative analysis of the qualitative data produced nine categories/recurrent themes describing the phenomena of interest and relationships between them. The three research hypotheses were accepted as predicted. There was a positive correlation between spiritual well-being and self-esteem (r=.5713), religious well-being and self-esteem (r=.4555), and existential well-being and self-esteem (r=.6068). A surprising finding was the very high level of spiritual well-being and self-esteem present in the population. The data in the qualitative analysis was strongly supportive of that found in the quantitative analysis. The data results demonstrate that there is a linking, overlap, or integration of the components of spiritual well-being and self-esteem. The nature of this relationship is an area for future research. Spiritual well-being and self-esteem may be valuable to the homeless in dealing with the complexities of everyday living by bringing a sense of peace, joy, and security. By facilitating growth and development of these dimensions, perhaps Nursing can assist the homeless cope with suffering and survival, and uplift the quality of their existence
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