R-Process Nucleosynthesis in MHD Jet Explosions of Core-Collapse Supernovae

We investigate $r$-process nucleosynthesis during the magnetohydrodynamical (MHD) explosion of supernova in a massive star of 13 $M_{\odot}$. Contrary to the case of the spherical explosion, jet-like explosion due to the combined effects of the rotation and magnetic field lowers the electron fraction significantly inside the layers above the iron core. We find that the ejected material of low electron fraction responsible for the $r$-process comes out from the silicon rich layer of the presupernova model. This leads to the production up to the third peak in the solar $r$-process elements. We examine whether the fission affects the $r$-process paths by using the full nuclear reaction network with both the spontaneous and $\beta$-delayed fission included. Moreover, we pay particular attention how the mass formula affects the $r$-process peaks with use of two mass formulae. It is found that both formulae can reproduce the global abundance pattern up to the third peak though detailed distributions are rather different. We point out that there are variations in the $r$-process nucleosynthesis if the MHD effects play an important role in the supernova explosion.Comment: 19 pages with 7 figures, submitted to Ap

Numerical simulation of river channel processes with bank erosion in steep curved channel

River morphodynamics and sediment transportRiver morphology and morphodynamic

Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex

Peer reviewedPublisher PD

CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma.

BackgroundCytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC.MethodsExpression of CYP1B1 was determined in RCC cell lines, and tissue microarrays of 96 RCC and 25 normal tissues. To determine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses.ResultsFirst, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines compared to normal kidney tissue. This trend was also observed in RCC samples (p < 0.01). Interestingly, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, migration and invasion of RCC cells. In addition, reduction of CYP1B1 induced cellular apoptosis in Caki-1. We also found that these anti-tumor effects on RCC cells caused by CYP1B1 depletion may be due to alteration of CDC20 and DAPK1 expression based on gene microarray and confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expression in clinical samples.ConclusionsCYP1B1 may promote RCC development by inducing CDC20 expression and inhibiting apoptosis through the down-regulation of DAPK1. Our results demonstrate that CYP1B1 can be a potential tumor biomarker and a target for anticancer therapy in RCC

Functional role and tobacco smoking effects on methylation of CYP1A1 gene in prostate cancer.

Cytochrome P450 (CYP) 1A1 is a phase I enzyme that can activate various compounds into reactive forms and thus, may contribute to carcinogenesis. In this study, we investigated the expression, methylation status, and functional role of CYP1A1 on prostate cancer cells. Increased expression of CYP1A1 was observed in all cancer lines (PC-3, LNCaP, and DU145) compared to BPH-1 (P < 0.05); and was enhanced further by 5-aza-2'-deoxycytidine treatment (P < 0.01). Methylation-specific PCR (MSP) and sequencing of bisulfite-modified DNA of the xenobiotic response element (XRE) enhancer site XRE-1383 indicated promoter methylation as a regulator of CYP1A1 expression. In tissue, microarrays showed higher immunostaining of CYP1A1 in prostate cancer than normal and benign prostatic hyperplasia (BPH; P < 0.001), and methylation analyses in clinical specimens revealed significantly lower methylation levels in cancer compared to BPH at all enhancer sites analyzed (XRE-1383, XRE-983, XRE-895; P < 0.01). Interestingly, smoking affected the XRE-1383 site where the methylation level was much lower in cancer tissues from smokers than non-smokers (P < 0.05). CYP1A1 levels are thus increased in prostate cancer and to determine the functional effect of CYP1A1 on cells, we depleted the gene in LNCaP and DU145 by siRNA. We observe that CYP1A1 knockdown decreased cell proliferation (P < 0.05) and increased apoptosis (P < 0.01) in both cell lines. We analyzed genes affected by CYP1A1 silencing and found that apoptosis-related BCL2 was significantly down-regulated. This study supports an oncogenic role for CYP1A1 in prostate cancer via promoter hypomethylation that is influenced by tobacco smoking, indicating CYP1A1 to be a promising target for prostate cancer treatment

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb

Assessment of smoking care by stroke specialists in patients with recent TIA and minor stroke: an international prospective registry-based cohort study

Objectives: The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA). Design and setting: The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study. Participants: From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort). Outcomes: Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model. Results: Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080). Conclusion: In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE

Epidemiology and Outcomes of Critically Ill Children at Risk for Pediatric Acute Respiratory Distress Syndrome:A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study

OBJECTIVES: Interventional trials aimed at pediatric acute respiratory distress syndrome prevention require accurate identification of high-risk patients. In this study, we aimed to characterize the frequency and outcomes of children meeting "at risk for pediatric acute respiratory distress syndrome" criteria as defined by the Pediatric Acute Lung Injury Consensus Conference. DESIGN: Planned substudy of the prospective multicenter, international Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study conducted during 10 nonconsecutive weeks (May 2016-June 2017). SETTING: Thirty-seven international PICUs. PATIENTS: Three-hundred ten critically ill children meeting Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the frequency of children at risk for pediatric acute respiratory distress syndrome and rate of subsequent pediatric acute respiratory distress syndrome diagnosis and used multivariable logistic regression to identify factors associated with subsequent pediatric acute respiratory distress syndrome. Frequency of at risk for pediatric acute respiratory distress syndrome was 3.8% (95% CI, 3.4-5.2%) among the 8,122 critically ill children who were screened and 5.8% (95% CI, 5.2-6.4%) among the 5,334 screened children on positive pressure ventilation or high-flow oxygen. Among the 310 at-risk children, median age was 2.1 years (interquartile range, 0.5-7.3 yr). Sixty-six children (21.3%) were subsequently diagnosed with pediatric acute respiratory distress syndrome, a median of 22.6 hours (interquartile range, 9.8-41.0 hr) later. Subsequent pediatric acute respiratory distress syndrome was associated with increased mortality (21.2% vs 3.3%; p < 0.001) and longer durations of invasive ventilation and PICU care. Subsequent pediatric acute respiratory distress syndrome rate did not differ by respiratory support modality at the time of meeting at risk criteria but was independently associated with lower initial saturation:FIO2 ratio, progressive tachycardia, and early diuretic administration. CONCLUSIONS: The Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria identify critically ill children at high risk of pediatric acute respiratory distress syndrome and poor outcomes. Interventional trials aimed at pediatric acute respiratory distress syndrome prevention should target patients early in their illness course and include patients on high-flow oxygen and positive pressure ventilation

Rationale and design of a multicenter randomized study for evaluating vascular function under uric acid control using the xanthine oxidase inhibitor, febuxostat : the PRIZE study

Background: Xanthine oxidase inhibitors are anti-hyperuricemic drugs that decrease serum uric acid levels by inhibiting its synthesis. Xanthine oxidase is also recognized as a pivotal enzyme in the production of oxidative stress. Excess oxidative stress induces endothelial dysfunction and inflammatory reactions in vascular systems, leading to atherosclerosis. Many experimental studies have suggested that xanthine oxidase inhibitors have anti-atherosclerotic effects by decreasing in vitro and in vivo oxidative stress. However, there is only limited evidence on the clinical implications of xanthine oxidase inhibitors on atherosclerotic cardiovascular disease in patients with hyperuricemia. We designed the PRIZE study to evaluate the effects of febuxostat on a surrogate marker of cardiovascular disease risk, ultrasonography-based intima-media thickness of the carotid artery in patients with hyperuricemia. Methods: The study is a multicenter, prospective, randomized, open-label and blinded-endpoint evaluation (PROBE) design. A total of 500 patients with asymptomatic hyperuricemia (uric acid >7.0 mg/dL) and carotid intima-media thickness ≥1.1 mm will be randomized centrally to receive either febuxostat (10–60 mg/day) or non-pharmacological treatment. Randomization is carried out using the dynamic allocation method stratified according to age (<65, ≥65 year), gender, presence or absence of diabetes mellitus, serum uric acid (<8.0, ≥8.0 mg/dL), and carotid intima-media thickness (<1.3, ≥1.3 mm). In addition to administering the study drug, we will also direct lifestyle modification in all participants, including advice on control of body weight, sleep, exercise and healthy diet. Carotid intima-media thickness will be evaluated using ultrasonography performed by skilled technicians at a central laboratory. Follow-up will be continued for 24 months. The primary endpoint is percentage change in mean intima-media thickness of the common carotid artery 24 months after baseline, measured by carotid ultrasound imaging. Conclusions: PRIZE will be the first study to provide important data on the effects of febuxostat on atherosclerosis in patients with asymptomatic hyperuricemia

Efficacy of a hybrid assistive limb in post-stroke hemiplegic patients: a preliminary report

<p>Abstract</p> <p>Background</p> <p>Robotic devices are expected to be widely used in various applications including support for the independent mobility of the elderly with muscle weakness and people with impaired motor function as well as support for nursing care that involves heavy laborious work. We evaluated the effects of a hybrid assistive limb robot suit on the gait of stroke patients undergoing rehabilitation.</p> <p>Methods</p> <p>The study group comprised 16 stroke patients with severe hemiplegia. All patients underwent gait training. Four patients required assistance, and 12 needed supervision while walking. The stride length, walking speed and physiological cost index on wearing the hybrid assistive limb suit and a knee-ankle-foot orthosis were compared.</p> <p>Results</p> <p>The hybrid assistive limb suit increased the stride length and walking speed in 4 of 16 patients. The patients whose walking speed decreased on wearing the hybrid assistive limb suit either had not received sufficient gait training or had an established gait pattern with a knee-ankle-foot orthosis using a quad cane. The physiological cost index increased after wearing the hybrid assistive limb suit in 12 patients, but removal of the suit led to a decrease in the physiological cost index values to equivalent levels prior to the use of the suit.</p> <p>Conclusions</p> <p>Although the hybrid assistive limb suit is not useful for all hemiplegic patients, it may increase the walking speed and affect the walking ability. Further investigation would clarify its indication for the possibility of gait training.</p