PLoS medicine
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Dysfunction of the immune system has been documented in many types of cancers. The precise nature and molecular basis of immune dysfunction in the cancer state are not well defined. ⋯ Defects in interferon signaling represent novel, dominant mechanisms of immune dysfunction in cancer. These findings may be used to design therapies to counteract immune dysfunction in melanoma and to improve cancer immunotherapy.
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Epidemic influenza causes serious mortality and morbidity in temperate countries each winter. Research suggests that schoolchildren are critical in the spread of influenza virus, while the elderly and the very young are most vulnerable to the disease. Under these conditions, it is unclear how best to focus prevention efforts in order to protect the population. Here we investigate the question of how to protect a population against a disease when one group is particularly effective at spreading disease and another group is more vulnerable to the effects of the disease. ⋯ Given the limited amount of information about relevant parameters, we suggest that changes in vaccination strategy, while potentially promising, should be approached with caution. In particular, we find that, while switching vaccine to more active groups may protect vulnerable groups in many cases, switching too much vaccine, or switching vaccine under slightly different conditions, may lead to large increases in disease in the vulnerable group. This outcome is more likely when vaccine limitation is stringent, when mixing is highly structured, or when transmission levels are high.
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Hyperoxic ventilation (>21% O2) is widely used in medical practice for resuscitation, stroke intervention, and chronic supplementation. However, despite the objective of improving tissue oxygen delivery, hyperoxic ventilation can accentuate ischemia and impair that outcome. Hyperoxia results in, paradoxically, increased ventilation, which leads to hypocapnia, diminishing cerebral blood flow and hindering oxygen delivery. Hyperoxic delivery induces other systemic changes, including increased plasma insulin and glucagon levels and reduced myocardial contractility and relaxation, which may derive partially from neurally mediated hormonal and sympathetic outflow. Several cortical, limbic, and cerebellar brain areas regulate these autonomic processes. The aim of this study was to assess recruitment of these regions in response to hyperoxia and to determine whether any response would be countered by addition of CO2 to the hyperoxic gas mixture. ⋯ In this group of children, hyperoxic ventilation led to responses in brain areas that modify hypothalamus-mediated sympathetic and hormonal outflow; these responses were diminished by addition of CO2 to the gas mixture. This study in healthy children suggests that supplementing hyperoxic administration with CO2 may mitigate central and peripheral consequences of hyperoxia.