177 research outputs found

    Preliminary study: Treatment with intramuscular interferon beta-1a results in increased levels of IL-12Rβ2+ and decreased levels of IL23R+ CD4+ T - Lymphocytes in multiple sclerosis

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    <p>Abstract</p> <p>Background</p> <p>There are a lack of biomarkers which can be used to predict clinical outcomes for multiple sclerosis (MS) patients receiving interferon beta (IFN-β). Thus the objective of this study was to characterize changes in CD4+ T-lymphocyte expression in an unbiased manner following initiation of intramuscular (IM) IFN-β-1a treatment, and then to verify those findings using marker-specific assays.</p> <p>Methods</p> <p>Peripheral blood specimens were collected from twenty MS patients before and after treatment with intramuscular (IM) IFN-β-1a and were used for isolation of mononuclear cells (PBMCs). mRNA expression patterns of negatively-selected CD4+ T-cells from the PBMCs were analyzed using microarray gene expression technology. IL-12 and IL-23 receptor levels on PBMC-derived CD4+ T-cells were analyzed by flow cytometry. The phosphorylation status of Stat4 was measured by performing densitometry on western blots.</p> <p>Results</p> <p>Microarray analyses demonstrated that mRNA expression of the IL-12Rβ2 gene was uniformly up-regulated in response to IFN-β-1a treatment and was associated with an increased number of IL-12Rβ2<sup>+ </sup>CD4<sup>+ </sup>T-cells by flow cytometry in 4 of 6 patients. This finding was substantiated by demonstrating that Stat4 phosphorylation, a transcription factor for IL-12, was increased after treatment. Conversely, the number of IL-23R<sup>+ </sup>CD4<sup>+ </sup>T-cells was decreased following treatment.</p> <p>Conclusions</p> <p>The IL-12 receptor shares a common subunit, the IL-12Rβ2, with the IL-23 receptor. Both of these receptors have a probable role in regulating IL-17 and TH-17 cells, important mediators of inflammation in multiple sclerosis (MS). Thus, the changes in the numbers of CD4<sup>+ </sup>T-cells expressing these receptors in response to IFN-β-1a treatment may point to an important mechanism of action for this drug, but further large scale studies are needed to confirm these preliminary observations.</p

    Psychological determinants of whole-body endurance performance

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    Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research. Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research. Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants. Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance. Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described

    An electronic application for rapidly calculating Charlson comorbidity score

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    BACKGROUND: Uncertainty regarding comorbid illness, and ability to tolerate aggressive therapy has led to minimal enrollment of elderly cancer patients into clinical trials and often substandard treatment. Increasingly, comorbid illness scales have proven useful in identifying subgroups of elderly patients who are more likely to tolerate and benefit from aggressive therapy. Unfortunately, the use of such scales has yet to be widely integrated into either clinical practice or clinical trials research. METHODS: This article reviews evidence for the validity of the Charlson Comorbidity Index (CCI) in oncology and provides a Microsoft Excel (MS Excel) Macro for the rapid and accurate calculation of CCI score. The interaction of comorbidity and malignant disease and the validation of the Charlson Index in oncology are discussed. RESULTS: The CCI score is based on one year mortality data from internal medicine patients admitted to an inpatient setting and is the most widely used comorbidity index in oncology. An MS Excel Macro file was constructed for calculating the CCI score using Microsoft Visual Basic. The Macro is provided for download and dissemination. The CCI has been widely used and validated throughout the oncology literature and has demonstrated utility for most major cancers. The MS Excel CCI Macro provides a rapid method for calculating CCI score with or without age adjustments. The calculator removes difficulty in score calculation as a limitation for integration of the CCI into clinical research. The simple nature of the MS Excel CCI Macro and the CCI itself makes it ideal for integration into emerging electronic medical records systems. CONCLUSIONS: The increasing elderly population and concurrent increase in oncologic disease has made understanding the interaction between age and comorbid illness on life expectancy increasingly important. The MS Excel CCI Macro provides a means of increasing the use of the CCI scale in clinical research with the ultimate goal of improving determination of optimal treatments for elderly cancer patients

    Perspectives on advance directives in Japanese society: A population-based questionnaire survey

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    BACKGROUND: In Japan, discussion concerning advance directives (ADs) has been on the rise during the past decade. ADs are one method proposed to facilitate the process of communication among patients, families and health care providers regarding the plan of care of a patient who is no longer capable of communicating. In this paper, we report the results of the first in-depth survey on the general population concerning the preferences and use of ADs in Japan. METHOD: A self-administered questionnaire was sent via mail to a stratified random sampling of 560 residents listed in the residential registry of one district of Tokyo, Japan (n = 165,567). Association between correlating factors and specific preferences toward ADs was assessed using contingency table bivariate analysis and multivariate regression model to estimate independent contribution. RESULTS: Of the 560 questionnaires sent out, a total of 425 participants took part in the survey yielding a response rate of 75.9 %. The results of the present study indicate that: 1) the most important components to be addressed are the specifics of medical treatment at the end of life stage and disclosure of diagnosis and prognosis; 2) the majority of participants found it suitable to express their directives by word to family and/or physician and not by written documentation; 3) there is no strong need for legal measures in setting up an AD; 4) it is permissible for family and physician to loosely interpret one's directives; 5) the most suitable proxy is considered to be a family member, relative, or spouse. Multivariate analysis found the following five factors as significantly associated with preferences: 1) awareness regarding living wills, 2) experience with the use of ADs, 3) preferences for end-of-life treatment, 4) preferences for information disclosure, and 5) intentions of creating a will. CONCLUSIONS: Written ADs might be useful in the Japanese setting when the individual either wishes: 1) to not provide a lot of leeway to surrogates and/or caregivers, and/or 2) to ensure his or her directives in the cases of terminal illness, brain death, and pain treatment, as well as regarding information disclosure

    A 50% higher prevalence of life-shortening chronic conditions among cancer patients with low socioeconomic status

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    Background: Comorbidity and socioeconomic status (SES) may be related among cancer patients. Method : Population-based cancer registry study among 72 153 patients diagnosed during 1997-2006. Results : Low SES patients had 50% higher risk of serious comorbidity than those with high SES. Prevalence was increased for each cancer site. Low SES cancer patients had significantly higher risk of also having cardiovascular disease, chronic obstructive pulmonary diseases, diabetes mellitus, cerebrovascular disease, tuberculosis, dementia, and gastrointestinal disease. One-year survival was significantly worse in lowest vs highest SES, partly explained by comorbidity. Conclusion : This illustrates the enormous heterogeneity of cancer patients and stresses the need for optimal treatment of cancer patients with a variety of concomitant chronic conditions

    The Effect of Diet Quality and Wing Morph on Male and Female Reproductive Investment in a Nuptial Feeding Ground Cricket

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    A common approach in the study of life-history trade-off evolution is to manipulate the nutrient content of diets during the life of an individual in order observe how the acquisition of resources influences the relationship between reproduction, lifespan and other life-history parameters such as dispersal. Here, we manipulate the quality of diet that replicate laboratory populations received as a thorough test of how diet quality influences the life-history trade-offs associated with reproductive investment in a nuptial feeding Australian ground cricket (Pteronemobius sp.). In this species, both males and females make significant contributions to the production of offspring, as males provide a nuptial gift by allowing females to chew on a modified tibial spur during copulation and feed directing on their haemolymph. Individuals also have two distinct wing morphs, a short-winged flightless morph and a long-winged morph that has the ability to disperse. By manipulating the quality of diet over seven generations, we found that the reproductive investment of males and females were affected differently by the diet quality treatment and wing morph of the individual. We discuss the broader implications of these findings including the differences in how males and females balance current and future reproductive effort in nuptial feeding insects, the changing nature of sexual selection when diets vary, and how the life-history trade-offs associated with the ability to disperse are expected to differ among populations
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