Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is an integral membrane protein of the smooth endoplasmic reticulum. However, we detected an HO-1 immunoreactive signal in the nucleus of cultured cells after exposure to hypoxia and heme or heme/hemopexin. Under these conditions, a faster migrating HO-1 immunoreactive band was enriched in nuclear extracts, suggesting that HO-1 was cleaved to allow nuclear entry. This was confirmed by the absence of immunoreactive signal with an antibody against the C terminus and the lack of a C-terminal sequence by gas chromatographymass spectrometry. Incubation with leptomycin B prior to hypoxia abolished nuclear HO-1 and the faster migrating band on Western analysis, suggesting that this process was facilitated by CRM1. Furthermore, preincubation with a cysteine protease inhibitor prevented nuclear entry of green fluorescent proteinlabeled HO-1, demonstrating that protease-mediated C-terminal cleavage was also necessary for nuclear transport of HO-1. Nuclear localization was also associated with reduction of HO activity. HO-1 protein, whether it was enzymatically active or not, mediated activation of oxidant-responsive transcription factors, including activator protein-1. Nevertheless, nuclear HO-1 protected cells against hydrogen peroxide-mediated injury equally as well as cytoplasmic HO-1. We speculate that nuclear localization of HO-1 protein may serve to up-regulate genes that promote cytoprotection against oxidative stress.Heme oxygenase (HO) 3 catalyzes the degradation of heme and the formation of biliverdin and carbon monoxide. It is highly inducible in response to various stimuli, including oxidative stress, heavy metals, UV radiation, and inflammation (1-4). Cytoprotective roles for HO have been demonstrated in many models; however, the mechanisms by which this occurs are still under intensive study. Many have speculated that either heme catabolites, such as biliverdin, or its derivative, bilirubin, and carbon monoxide or the degradation of the pro-oxidant heme results in cytoprotection against oxidative stress (5-7). Nevertheless, all of the by-products of the HO reaction, despite being potentially cytoprotective, are also cytotoxic. Bilirubin is a potent neurotoxin (8), as is carbon monoxide (9). Furthermore, the HO reaction releases iron, which could interact with cellular oxidants to generate the hydroxyl radical (10). Transfection with an inactive HO-1 mutant protein results in cytoprotection against chemically induced oxidative stress (11). Because this effect of the mutant HO-1 could not be attributable to changes in heme catabolites, it alludes to a role for the HO-1 protein itself. Furthermore, the inactive form of HO-1 increased catalase and glutathione content (11). This suggests that the HO-1 protein itself may play a role in cellular signaling. If this were true, HO-1 would need to migrate to the nucleus or produce nuclear changes that affect transcription. There are several examples of cytoplasmic enzymes serving in nuclear functi...

BackgroundImplementation of evidence-based practice (EBP) is regarded as core competence to improve healthcare quality. In the current study, we investigated the EBP of six groups of professionals: physicians, nurses, pharmacists, physical therapists, technicians, and other allied healthcare personnel.MethodsA structured questionnaire survey of regional hospitals throughout Taiwan was conducted by post in 2011. Questionnaires were mailed to all healthcare workers of 11 randomly selected hospitals. Linear and logistic regression models were used to examine predictors for implementing EBP.ResultsIn total, 6,160 returned questionnaires, including 645 from physicians, 4,206 from nurses, 430 from pharmacists, 179 from physical therapists, 537 from technicians, and 163 from other allied healthcare professionals, were valid for the analysis. Physicians and pharmacists were more aware of EBP than were the other professional groups (p < 0.001). Positive attitudes toward and beliefs in EBP were significantly lower among nurses than in the other groups (p < 0.001). Physicians had more sufficient knowledge and skills of EBP than did the other professionals (p < 0.001); in addition, they implemented EBP for clinical decision-making more often and perceived fewer personal barriers to EBP (p < 0.001). Multivariate logistic regression analyses showed that EBP implementation was associated with the following characteristics of participants: EBP training, having a faculty position, academic degree, one's profession, and perceptions (beliefs, attitudes, knowledge, skills and barriers).ConclusionsThis study depicts various levels of EBP implementation among medical, nursing, pharmacological, and allied healthcare personnel. There were significant differences in their implementation of EBP. We observed that certain factors were associated with EBP implementation, including personal backgrounds and perceptions toward EBP. The data suggest that strategies for enhancing EBP implementation should differ for various groups of professionals.

BackgroundAlthough a number of studies have investigated correlations of maternal age with birth outcomes, an extensive assessment using age as a continuous variable is lacking. In the current study, we estimated age-specific risks of adverse birth outcomes in childbearing women.MethodNational population-based data containing maternal and neonatal information were derived from the Health Promotion Administration, Taiwan. A composite adverse birth outcome was defined as at least anyone of stillbirth, preterm birth, low birth weight, macrosomia, neonatal death, congenital anomaly, and small for gestational age (SGA). Singletons were further analyzed for outcomes of live birth in relation to each year of maternal age. A log-binomial model was used to adjust for possible confounders of maternal and neonatal factors.ResultsIn total, 2,123,751 births between 2001 and 2010 were utilized in the analysis. The risk of a composite adverse birth outcome was significantly higher at extreme maternal ages. In specific, risks of stillbirth, neonatal death, preterm birth, congenital anomaly, and low birth weight were higher at the extremes of maternal age. Furthermore, risk of macrosomia rose proportionally with an increasing maternal age. In contrast, risk of SGA declined proportionally with an increasing maternal age. The log-binomial model showed greater risks at the maternal ages of <26 and > 30 years for a composite adverse birth outcome.ConclusionsInfants born to teenagers and women at advanced age possess greater risks for stillbirth, preterm birth, neonatal death, congenital anomaly, and low birth weight. Pregnancies at advanced age carry an additional risk for macrosomia, while teenage pregnancies carry an additional risk for SGA. The data suggest that the optimal maternal ages to minimize adverse birth outcomes are 26∼30 years.