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Recent studies show that prostate cancer cells are able to survive in a hypoxic tumor environment, and the extent of tumor hypoxia correlates with poor clinical outcome. Androgen deprivation, the most common form of prostate cancer therapy, was itself shown to induce a state of transient hypoxia at the microenvironmental level. Because androgen receptor (AR) signaling plays a critical role in prostate cancer, we investigated the effect of hypoxia in regulating AR function. We found that in LNCaP prostate cancer cells, AR binding to the androgen-responsive element (ARE), prostate-specific antigen accumulation, and ARE-reporter gene activity were increased after hypoxia treatment. Hypoxia-enhanced AR function was also observed when AR was exogenously introduced into AR-null DU145 cells. Confocal microscopy and chromatin immunoprecipitation assays showed that AR translocation to the nucleus and AR recruitment to the prostate-specific antigen promoter were facilitated after hypoxia treatment. The AR stimulatory effect seemed to be ligand-dependent because it was abrogated when cells were cultured in an androgen-depleted medium, but was restored with the addition of R1881, a synthetic androgen. The sensitivity of AR activation to R1881 was also increased after hypoxia treatment. Although concentrations of <1 nmol/L R1881 did not induce ARE reporter activity under normoxic conditions, exposure to hypoxia greatly potentiated the AR response to low levels of R1881. Collectively, our results provide compelling evidence that changes in hypoxia/reoxygenation stimulate AR trans-activation and sensitization. The AR-stimulatory effect of an unstable tissue oxygenation milieu of a tumor is likely to contribute to treatment resistance and the emergence of recurrent prostate cancer.

Background-Analyzing the determinants of systolic anterior motion of the mitral valve and consequent left ventricular outflow tract (LVOT) obstruction in patients with asymmetrical septal hypertrophy requires a comprehensive 3-dimensional analysis of mitral leaflet (ML) area, papillary muscle (PM) geometry, and the distribution of left ventricular hypertrophy. Methods and Results-Real-time 3-dimensional echocardiography was performed in 47 patients with asymmetrical septal hypertrophy and 32 normal controls. Patients included 20 with resting LVOT obstruction (group I) and 27 without (group II). Customized software (Omni 4D) provided a validated measure of ML surface area, LVOT area, mitral annular area and nonplanarity, LVOT hypertrophy index by topography (percent area with wall thickness Ͼ16 mm), and 3-dimensional PM positions relative to annulus. ML area was more than twice as large in group I than normal and 1.4 times normal in group II (PϽ0.001). Group I patients were also characterized by higher LVOT hypertrophy index and medial and anterior displacements of both PMs, resulting in a shorter inter-PM distance. Independent determinants of LVOT obstruction were indexed total ML area (adjusted odds ratio, 5.651; 95% confidence interval, 1.573 to 20.304; Pϭ0.008) and inter-PM distance (adjusted odds ratio, 0.416; 95% confidence interval, 0.203 to 0.854; Pϭ0.0169). Minimal LVOT area during systole correlated well with peak LVOT pressure gradient (R 2 ϭ0.83, PϽ0.001); its independent determinants were left ventricular end-systolic volume (Pϭ0.0183), indexed total ML area (Pϭ0.0108), inter-PM distance (Pϭ0.0378), annular height (Pϭ0.0047), and LVOT hypertrophy index (Pϭ0.0098). Conclusions-Myocardium is not the only tissue affected in patients with asymmetrical septal hypertrophy, and primary changes of the mitral apparatus, including ML area increase and PM displacement, are independent determinants of LVOT obstruction and provide a comprehensive mechanism that determines leaflet slack and anteriorly directed motion. Abnormal PM-mitral valve geometry assessed by real-time 3-dimensional echocardiography can provide reasonable new targets for individualized intervention. (Circulation. 2010;122:1298-1307.)

We extracted the interlayer resistance between two layers in multilayer molybdenum disulfide (MoS2) field-effect transistors by confirming that contact resistances (Rcontact) measured using the four-probe measurements were similar, within ∼30%, to source/drain series resistances (Rsd) measured using the two-probe measurements. Rcontact values obtained from gated four-probe measurements exhibited gate voltage dependency. In the two-probe measurements, the Y-function method was applied to obtain the Rsd values. By comparing those two Rcontact (∼9.5 kΩ) and Rsd (∼12.3 kΩ) values in strong accumulation regime, we found the rationality that those two values had nearly the same properties, i.e., the Schottky barrier resistances and interlayer resistances. The Rsd values of devices with two-probe source/drain electrodes exhibited thickness dependency due to interlayer resistance changes. The interlayer resistance between two layers was also obtained as ∼2.0 Ω mm.

ObjectiveBystander cardiopulmonary resuscitation (CPR) is an important factor associated with improved survival rates and neurologic prognoses in cases of out-of-hospital cardiac arrest. We assessed how factors related to CPR education including timing of education, period from the most recent education session, and content, affected CPR willingness.MethodsIn February 2012, trained interviewers conducted an interview survey of 1,000 Daegu citizens through an organized questionnaire. The subjects were aged ≥19 years and were selected by quota sampling. Their social and demographic characteristics, as well as CPR and factors related to CPR education, were investigated. Chi-square tests and multivariate logistic regression analyses were used to evaluate how education-related factors affected the willingness to perform CPR.ResultsOf total 1,000 cases, 48.0% were male. The multivariate analyses revealed several factors significantly associated with CPR willingness: didactic plus practice group (adjusted odds ratio [AOR], 3.38; 95% confidence interval [CI], 2.3 to 5.0), group with more than four CPR education session (AOR, 7.68; 95% CI, 3.21 to 18.35), interval of less than 6 months from the last CPR education (AOR, 4.47; 95% CI 1.29 to 15.52), and education with automated external defibrillator (AOR, 5.98; 95% CI 2.30 to 15.53).ConclusionThe following were associated with increased willingness to perform CPR: practice sessions and automated electrical defibrillator training in public CPR education, more frequent CPR training, and shorter time period from the most recent CPR education sessions.

Background-Left ventricular (LV) apical rotation and twist can be estimated noninvasively by speckle-tracking echocardiography (STE). In this study, we tested whether apical rotation is an accurate index of LV contractility. Methods and Results-We measured LV basal and apical rotation by STE in 11 open-chest anesthetized mongrel dogs under 8 different inotropic stages before and after ligation of either left anterior descending (nϭ6) or circumflex coronary artery (nϭ5). We measured LV pressure simultaneously with a high-fidelity pressure catheter and calculated LV ejection fraction (EF) with the biplane Simpson method and 2D echocardiography. Maximal positive dP/dt (dP/dt max ) was used as the gold standard measurement of LV contractility. We compared LV twist and apical rotation and EF against dP/dt max by linear mixed model. LV apical rotation and twist showed dose-dependent increases and decreases after dobutamine and esmolol infusion, respectively. However, basal rotation did not change significantly during different inotropic conditions. There was a stronger association between dP/dt max and LV twist (R 2 ϭ0.747, PϽ0.001) and apical rotation (R

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The apoptotic effect of fluoxetine (FLX), an antidepressant, against human epithelial ovarian cancer cell lines OVCAR-3 and SK-OV-3 was investigated in relation to the mitochondria-mediated cell death process and nuclear factor (NF)-jB activation. FLX-induced mitochondrial membrane permeability change and formation of reactive oxygen species, leading to cell death. FLX-induced increase in mitochondrial Bax levels, decrease in cytosolic Bid and Bcl-2 levels, loss of the mitochondrial transmembrane potential, cytochrome c release, caspase-3 activation and up-regulation of p53. Oxidant scavengers and Bay 11-7085 [an inhibitor of nuclear factor kappaB (NF-jB) activation] prevented the FLX-induced cell death, increase in phosphorylated inhibitory jB-a and NF-jB p65 levels, and binding of NF-jB p65 to DNA. Results from this study suggest that FLX may exhibit apoptotic effect against ovarian cancer cell lines by inducing the mitochondrial membrane permeability change, which leads to cytochrome c release and subsequent caspase-3 activation, through reactive oxygen species-dependent activation of NF-jB.