Plos One
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To determine the incidence and effect on mortality of early acute kidney injury in severely injured trauma patients using the Acute Kidney Injury Network creatinine criteria. ⋯ Applying the Acute Kidney Injury Network creatinine criteria in severely injured trauma patients, the incidence of early acute kidney injury was 6%. After correction for injury severity, development of early acute kidney injury was independently associated with significantly higher 30-day mortality.
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The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. ⋯ In this postoperative setting, the number of functionally active CYP2D6 alleles had an impact on oxycodone metabolism. The genotype also impacted analgesic consumption, thereby causing variation of equianalgesic doses piritramide : oxycodone. Different analgesic needs by genotypes were met by PCA technology in this postoperative cohort.
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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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Functional decline after hospitalization is a common adverse outcome in elderly. An easy to use, reproducible and accurate tool to identify those at risk would aid focusing interventions in those at higher risk. Handgrip strength has been shown to predict adverse outcomes in other settings. ⋯ Multivariate analysis showed that only males with low handgrip strength had an increased risk of functional decline at discharge (OR 0.88, 95% CI 0.79-0.98, p = 0.01), with a specificity of 91.3% and a cutoff point of 20.65 kg for handgrip strength. Females had not a significant association between handgrip strength and functional decline. Measurement of handgrip strength on admission to acute care facilities may identify male elderly patients at risk of having functional decline, and intervene consequently.
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Genetic interactions between Brn3 transcription factors in retinal ganglion cell type specification.
Visual information is conveyed from the retina to the brain via 15-20 Retinal Ganglion Cell (RGC) types. The developmental mechanisms by which RGC types acquire their distinct molecular, morphological, physiological and circuit properties are essentially unknown, but may involve combinatorial transcriptional regulation. Brn3 transcription factors are expressed in RGCs from early developmental stages, and are restricted in adults to distinct, partially overlapping populations of RGC types. Previously, we described cell autonomous effects of Brn3b (Pou4f2) and Brn3a (Pou4f1) on RGC axon and dendrites development. ⋯ Taken together these results complete our knowledge on the mechanisms of transcriptional control of RGC type specification. They demonstrate that Brn3b is required for the correct development of more RGC cell types than suggested by its expression pattern in the adult, but that several cell types, including some Brn3a, Brn3c or Melanopsin positive RGCs are Brn3b independent.