Plos One
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Ataxia telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein activated in response to DNA damage. We recently reported that ATM plays a protective role in myocardial remodeling following β-adrenergic receptor stimulation. Here we investigated the role of ATM in cardiac remodeling using myocardial infarction (MI) as a model. ⋯ Left ventricular (LV) structure, function, apoptosis, fibrosis, and protein levels of apoptosis- and fibrosis-related proteins were examined in wild-type (WT) and ATM heterozygous knockout (hKO) mice 7 days post-MI. Infarct sizes were similar in both MI groups. However, infarct thickness was higher in hKO-MI group. Two dimensional M-mode echocardiography revealed decreased percent fractional shortening (%FS) and ejection fraction (EF) in both MI groups when compared to their respective sham groups. However, the decrease in %FS and EF was significantly greater in WT-MI vs hKO-MI. LV end systolic and diastolic diameters were greater in WT-MI vs hKO-MI. Fibrosis, apoptosis, and α-smooth muscle actin staining was significantly higher in hKO-MI vs WT-MI. MMP-2 protein levels and activity were increased to a similar extent in the infarct regions of both groups. MMP-9 protein levels were increased in the non-infarct region of WT-MI vs WT-sham. MMP-9 protein levels and activity were significantly lower in the infarct region of WT vs hKO. TIMP-2 protein levels similarly increased in both MI groups, whereas TIMP-4 protein levels were significantly lower in the infarct region of hKO group. Phosphorylation of p53 protein was higher, while protein levels of manganese superoxide dismutase were significantly lower in the infarct region of hKO vs WT. In vitro, inhibition of ATM using KU-55933 increased oxidative stress and apoptosis in cardiac myocytes.
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Acute kidney injury (AKI) and acute lung injury (ALI) are serious complications of sepsis. AKI is often viewed as a late complication of sepsis. Notably, the onset of AKI relative to ALI is unclear as routine measures of kidney function (BUN and creatinine) are insensitive and increase late. In this study, we hypothesized that AKI and ALI would occur simultaneously due to a shared pathophysiology (i.e., TNF-α mediated systemic inflammatory response syndrome [SIRS]), but that sensitive markers of kidney function would be required to identify AKI. ⋯ ALI and AKI occur together early in the course of sepsis and TNF-α plays a role in the early pathogenesis of both.
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Endocannabinoids (ECs) and related N-acyl-ethanolamides (NAEs) play important roles in stress response regulation, anxiety and traumatic memories. In view of the evidence that circulating EC levels are elevated under acute mild stressful conditions in humans, we hypothesized that individuals with traumatic stress exposure and post-traumatic stress disorder (PTSD), an anxiety disorder characterized by the inappropriate persistence and uncontrolled retrieval of traumatic memories, show measurable alterations in plasma EC and NAE concentrations. ⋯ PTSD appears to be associated with changes in plasma EC/NAE concentrations. This may have pathophysiological and diagnostic consequences but will need to be reproduced in larger cohorts.
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Postoperative respiratory complications are a major cause of mortality following liver transplantation (LT). Noninvasive ventilation (NIV) appears to be effective for respiratory complications in patients undergoing solid organ transplantation; however, mortality has been high in patients who experienced reintubation in spite of NIV therapy. The predictors of reintubation following NIV therapy after LT are not exactly known. ⋯ Because controlled preoperative infection, ABO-incompatibility or pneumonia prior to the start of NIV were independent risk factors for reintubation following NIV, caution should be used in applying NIV in patients with these conditions considering the high rate of mortality in patients requiring reintubation following NIV.
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Burn wounds are severely stressful events that can have a significant impact on the mental health of patients. However, the impact of burns on individuals with different personality traits can be different. The present study aimed to investigate the impact of dispositional optimism on the subjective well-being of burn patients, and mainly focused on the confirmation of the mediator role of psychological resilience. 410 burn patients from five general hospitals in Xi'an accomplished the revised Life Orientation Test, Connor-Davidson Resilience Scale, and Subjective Well-Being (SWB) scale. ⋯ Structural equation modelling indicated that psychological resilience partially mediated the relationship between dispositional optimism and SWB. The current findings extended prior reports and shed some light on how dispositional optimism influenced SWB. Limitations of the study were considered and suggestions for future studies were also discussed.