69 research outputs found

    Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

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    Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al

    A prospective study of changes in anxiety, depression, and problems in living during chemotherapy treatments: effects of age and gender

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    PurposeMonitoring distress assessment in cancer patients during the treatment phase is a component of good quality care practice. Yet, there is a dearth of prospective studies examining distress. In an attempt to begin filling this gap and inform clinical practice, we conducted a prospective, longitudinal study examining changes in distress (anxiety, depression, and problems in living) by age and gender and the roles of age and gender in predicting distress.MethodsNewly diagnosed Brazilian cancer patients (N = 548) were assessed at three time points during chemotherapy. Age and gender were identified on the first day of chemotherapy (T1); anxiety, depression, and problems in living were self-reported at T1, the planned midway point (T2), and the last day of chemotherapy (T3).ResultsAt T1, 37 and 17% of patients reported clinically significant levels of anxiety and depression, respectively. At T3, the prevalence was reduced to 4.6% for anxiety and 5.1% for depression (p < .001). Patients 40-55 years, across all time points, reported greater anxiety and practical problems than patients >70 years (p < .03). Female patients reported greater emotional, physical, and family problems than their male counterparts (p < .04).ConclusionsFor most patients, elevated levels of distress noted in the beginning of treatment subsided by the time of treatment completion. However, middle-aged and female patients continued to report heightened distress. Evidence-based psychosocial intervention offered to at risk patients during early phases of the treatment may provide distress relief and improve outcomes over the illness trajectory while preventing psychosocial and physical morbidity due to untreated chronic distress

    Stable transmission of reversible modifications: maintenance of epigenetic information through the cell cycle

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    Even though every cell in a multicellular organism contains the same genes, the differing spatiotemporal expression of these genes determines the eventual phenotype of a cell. This means that each cell type contains a specific epigenetic program that needs to be replicated through cell divisions, along with the genome, in order to maintain cell identity. The stable inheritance of these programs throughout the cell cycle relies on several epigenetic mechanisms. In this review, DNA methylation and histone methylation by specific histone lysine methyltransferases (KMT) and the Polycomb/Trithorax proteins are considered as the primary mediators of epigenetic inheritance. In addition, non-coding RNAs and nuclear organization are implicated in the stable transfer of epigenetic information. Although most epigenetic modifications are reversible in nature, they can be stably maintained by self-recruitment of modifying protein complexes or maintenance of these complexes or structures through the cell cycle

    Deagrarianisation and forest revegetation in a biodiversity hotspot on the Wild Coast, South Africa

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    Deagraianisation is a worldwide phenomenon with widespread social, ecological and economic effects yet with little consensus on the local or higher level causes. There have been contested views on the causes and consequences of deagrarianisation on South Africa’s Wild Coast, which is an international biodiversity hotspot. Using GIS, household interviews and ecological sampling, we compared the perspectives of current and former cultivators as to why some have abandoned farming, whilst also tracking the uses and woody plant cover and composition of fields abandoned at different periods. The GIS analysis showed that field abandonment had been ongoing over several decades, with a decline from 12.5 % field cover in 1961 to 2.7 % in 2009. The area of forests and woodlands almost doubled in the corresponding period. There was a distinct peak in field abandonment during the time of political transition at the national level in the early 1990s. This political change led to a decrease in government support for livestock farming, which in turn resulted in reduced animal draught power at the household and community level, and hence reduced cropping. The study showed it is largely the wealthier households that have remained in arable agriculture and that the poorer households have abandoned farming. The abandoned fields show a distinct trend of increasing woody biomass and species richness with length of time since abandonment, with approximately three woody plant species added per decade. Most local respondents dislike the increases in forest and woodland extent and density because of anxiety about wild animals causing harm to crops and even humans, and the loss of an agricultural identity to livelihoods and the landscape

    A GP caregiver needs toolkit versus usual care in the management of the needs of caregivers of patients with advanced cancer: a randomized controlled trial

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    Background: Caring for a person with progressive cancer creates challenges for caregivers. However the needs of caregivers are often not assessed or recognised by health care providers. Research is also lacking in this area, with little knowledge relating to effective strategies to address the specific needs of caregivers. This paper outlines a study protocol aimed at developing and evaluating the effectiveness of a general practice-based intervention to better meet the needs of caregivers of patients with advanced cancer. Methods/Design: Two hundred and sixty caregivers will be randomised into each of two arms of the intervention (520 participants in total) through patients with advanced cancer attending medical and radiation oncology outpatient clinics at two tertiary hospital sites. Consenting caregivers will be followed up for six months, and telephone surveyed at baseline, 1, 3 and 6 months following their entry into the study or until the patient’s death, whichever occurs first. Assessment and management of the unmet needs of caregivers in the intervention arm will be facilitated through a specifically developed general practice-based strategy; caregivers in the control group will receive usual care. Qualitative interviews will be conducted with a sample of up to 20 caregivers and 10 GPs at the conclusion of their participation, to explore their views regarding the usefulness of the intervention. Discussion: This study will determine whether systematic assessment of caregiver needs supported by caregiver-specific information for General Practitioners is effective in alleviating the unmet needs experienced by caregivers caring for patients with advanced cancer. Trial registration number: ISRCTN: ISRCTN43614355

    Application of the effective formula of growth functional to quantitative description of growth of plant cells

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    An effective formula describing expansive plant growth is derived from the modified Lockhart/Ortega-type equation. Its applicability is demonstrated on selected experimental data extracted from available literature. Quantitative information about the “diffusion rate” (k 2) of the growth factors is obtained for two different model species in plant science: Arabidopsis thaliana L. belongs to the dicots and Zea mays L. belongs to the monocots. It is shown that the value of the diffusion rate may be useful in comparing different datasets and serve as a measure of reproducibility of standard measurements. Analysis of the formula and fits allows to identify and suggest a set of criteria for reporting future experiments, which would improve comparability and reproducibility of the results
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