Plos One
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Clinical Trial
Histones-mediated lymphocyte apoptosis during sepsis is dependent on p38 phosphorylation and mitochondrial permeability transition.
Lymphocyte apoptosis is one reason for immunoparalysis seen in sepsis, although the triggers are unknown. We hypothesized that molecules in plasma, which are up-regulated during sepsis, may be responsible for this. In this study, peripheral lymphocyte apoptosis caused by extracellular histones was confirmed both in mouse and human primary lymphocytes, in which histones induced lymphocyte apoptosis dose-dependently and time-dependently. ⋯ The results showed that H4 neutralization antibody dose-dependently blocked lymphocyte apoptosis caused by septic plasma in vitro. These data demonstrate for the first time that extracellular histones, especially H4, play a vital role in lymphocyte apoptosis during sepsis which is dependent on p38 phosphorylation and mitochondrial permeability transition. Neutralizing H4 can inhibit lymphocyte apoptosis, indicating that it could be a potential target in clinical interventions for sepsis associated immunoparalysis.
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Observational Study
Temperature variability during delirium in ICU patients: an observational study.
Delirium is an acute disturbance of consciousness and cognition. It is a common disorder in the intensive care unit (ICU) and associated with impaired long-term outcome. Despite its frequency and impact, delirium is poorly recognized by ICU-physicians and -nurses using delirium screening tools. A completely new approach to detect delirium is to use monitoring of physiological alterations. Temperature variability, a measure for temperature regulation, could be an interesting component to monitor delirium, but whether temperature regulation is different during ICU delirium has not yet been investigated. The aim of this study was to investigate whether ICU delirium is related to temperature variability. Furthermore, we investigated whether ICU delirium is related to absolute body temperature. ⋯ Our study suggests that temperature variability is increased during ICU delirium.
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In Peru, a country with constrained health resources, breast cancer control is characterized by late stage treatment and poor survival. To support breast cancer control in Peru, this study aims to determine the cost-effectiveness of different breast cancer control interventions relevant for the Peruvian context. ⋯ Our analysis suggests that breast cancer control in Peru should be oriented towards early detection through combining fixed and mobile mammography screening (age 45-69) triennially. However, a phased introduction of triennial CBE screening (age 40-69) with upfront FNA in non-urban settings, and both CBE (age 40-49) and fixed mammography screening (age 50-69) in urban settings, seems a more feasible option and is also cost-effective. The implementation of this intervention is only meaningful if awareness raising, diagnostic, referral, treatment and basic palliative services are simultaneously improved, and if financial and organizational barriers to these services are reduced.
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Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. ⋯ Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer.
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Historical Article
Unequal trends in coronary heart disease mortality by socioeconomic circumstances, England 1982-2006: an analytical study.
Coronary heart disease (CHD) remains a major public health burden, causing 80,000 deaths annually in England and Wales, with major inequalities. However, there are no recent analyses of age-specific socioeconomic trends in mortality. We analysed annual trends in inequalities in age-specific CHD mortality rates in small areas in England, grouped into deprivation quintiles. ⋯ Age-standardised CHD mortality rates have declined substantially in England, with the steepest falls in the most affluent quintiles. However, this concealed contrasting patterns in underlying age-specific rates. From 2000, mortality rates levelled off in the youngest groups but accelerated in middle aged and older groups. Mortality analyses by small areas could provide potentially valuable insights into possible drivers of inequalities, and thus inform future strategies to reduce CHD mortality across all social groups.