Plos One
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Circulating cell-free DNA (cfDNA) released from cancerous tissues has been found to harbor tumor-associated alterations and to represent the molecular composition of the tumor. Recent advances in technologies, especially in next-generation sequencing, enable the analysis of low amounts of cfDNA from body fluids. We analyzed the exomes of tumor tissue and matched serum samples to investigate the molecular representation of the tumor exome in cfDNA. ⋯ Although not all tissue variants could be confirmed in the matched serum, up to 57% of the tumor variants were reflected in matched cfDNA with mutations in PIK3CA, ALK, and PTEN as well as variants at COSMIC annotated sites in all six patients analyzed. Moreover, cfDNA revealed a mutation in MTOR, which was not detected in the matched tissue, potentially from an untested region of the heterogeneous primary tumor or from a distant metastatic clone. WES of cfDNA may provide additional complementary molecular information about clinically relevant mutations and the clonal heterogeneity of the tumors.
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The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. ⋯ Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.
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Post-traumatic stress disorder (PTSD) stands out as a major mental illness; however, little is known about effective policies for mitigating the problem. The importance and complexity of PTSD raise critical questions: What are the trends in the population of PTSD patients among military personnel and veterans in the postwar era? What policies can help mitigate PTSD? To address these questions, we developed a system dynamics simulation model of the population of military personnel and veterans affected by PTSD. The model includes both military personnel and veterans in a "system of systems." This is a novel aspect of our model, since many policies implemented at the military level will potentially influence (and may have side effects on) veterans and the Department of Veterans Affairs. ⋯ In a postwar period, current health policy interventions (e.g., screening and treatment) have marginal effects on mitigating the problem of PTSD, that is, the current screening and treatment policies must be revolutionized to have any noticeable effect. Furthermore, the simulation results show that it takes a long time, on the order of 40 years, to mitigate the psychiatric consequences of a war. Policy and financial implications of the findings are discussed.
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Observational Study
Family Caregivers Who Would Be Unwilling to Provide Care at the End of Life Again: Findings from the Health Survey for England Population Survey.
Family caregivers provide significant care at the end of life. We aimed to describe caregiver characteristics, and of those unwilling to repeat this role under the same circumstances. ⋯ A significant group of caregivers would be unwilling to provide care again. Older people and those who had not used palliative care services were more likely to be unwilling to care again. Barriers preventing access for disadvantaged groups need to be overcome.
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Prior studies have suggested intraaortic balloon pump (IABP) have a neutral effect on acute myocardial infarction (AMI) patients with cardiogenic shock (CS). However, the effects of IABP on patients with severe CS remain unclear. We therefore investigated the benefits of IABP in AMI patients with severe CS undergoing coronary revascularization. ⋯ The use of IABP in patients with myocardial infarction and severe cardiogenic shock undergoing coronary revascularization did not improve the outcomes of recurrent myocardial infarction and cardiovascular death. However, it did reduce the incidence of dialysis, stroke, pneumonia and sepsis during hospitalization.