bluuebunny/crossref_metadata_2025 huggingface dataset:
The Probability of Restenosis, Contralateral Disease Progression, and Late Neurologic Events following Carotid Endarterectomy: A Long-Term Follow-Up Study
Authors: Fluri F. , Engelter S.T. , Wasner M. , Stierli P. , Merlo A. , Lyrer P.A.
Published: November 2008

Background: Most studies that have reported on the progression of ipsilateral and/or contralateral internal carotid artery (ICA) stenosis are restricted to a few years. Methods: Based on a single-center carotid endarterectomy (CEA) registry, we sought all patients with CEA for symptomatic high-grade ICA stenosis between 1970 and 2002. 361 CEA patients (mean age 66 years, 73% male) with annual carotid ultrasound and clinical follow-up were identified. Kaplan-Meier analysis was used to estimate the occurrence of (i) progressive ICA stenosis or restenosis of either the operated or contralateral side, and (ii) cerebrovascular events over time of either the operated or contralateral side. Results: Progressive ICA disease was more likely on the contralateral than on the ipsilateral ICA (hazard ratio 2.71; CI 1.8–4.1, p < 0.001). After 5 years, the probability for progressive ICA disease was 5.2% for the ipsilateral versus 15.8% for the contralateral ICA. After 15 years, the likelihood was 37% for both sides. In the presence of progressive restenosis of the ipsilateral ICA, the 20-year probability of further ischemic cerebrovascular events was 50% compared to 18% in patients without ICA disease progression. For the contralateral ICA, the probability of further ischemic events was 24.5% in patients with ICA disease progression compared to 9.6% without ICA disease progression (15 years). Conclusion: 15 years after CEA, one third of the patients can be expected to develop progressive ICA disease. While ICA disease progression seems to be more prominent on the contralateral ICA within the first years, this difference fades out after 15 years. One out of 2 patients with ipsilateral ICA disease progression can be expected to have a recurrent cerebral ischemic event within 15 years. It remains to be determined whether consequent application of high-dose statins, optimal blood pressure management and antithrombotic therapy can reduce this rate.
Levels of Catecholamines, Arginine Vasopressin and Atrial Natriuretic Peptide in Hypotensive Extremely Low Birth Weight Infants in the First 24 Hours after Birth
Authors: Ezaki Shoichi , Suzuki Keiji , Kurishima Clara , Miura Masumi , Moriwaki Koichi , Arakawa Hiroshi , Kunikata Tetsuya , Sobajima Hisanori , Tamura Masanori
Published: November 2008

Background: Extremely low birth weight infants (ELBWI) often suffer from severe hypotension in the early neonatal period. However, few previous studies have ever revealed plasma levels of vasoactive substances which regulate the cardiovascular system in ELBWI. Objective: To study plasma levels of vasoactive substances in ELBWI with hypotension during the first 24 h of life. Methods: 22 ELBWI with hypotension (gestational age 26.4 ± 1.9 weeks; birth weight 751 ± 135 g) were involved in the study. After initial volume therapy, the infants were arbitrarily divided into two groups depending on requirement of dopamine dosage: severe hypotension group (SH; dopamine >10 μg/kg/min, n = 9) and mild hypotension group (MH; dopamine ≤10 μg/kg/min, n = 13). Plasma levels of dopamine, norepinephrine, epinephrine, arginine vasopressin, and atrial natriuretic peptide were measured at admission and at 24 h after birth. Results: Infants in the SH group had higher plasma dopamine than infants in the MH group both at admission (median; range: 14,410; 224–46,770 vs. 7,900; 32–21,220 pg/ml, p < 0.05) and at 24 h (80,920; 494–146,100 vs. 25,680; 10,130–63,180 pg/ml; p < 0.05). The norepinephrine/dopamine ratio (median; range) was lower in the SH group than in the MH group at admission (0.3; 0.0–1.0 vs. 1.1; 0.1–25.1; p < 0.01). Plasma levels of atrial natriuretic peptide or arginine vasopressin were not different between the two groups. Conclusions: ELBWI with SH may have decreased conversion of dopamine to norepinephrine. We speculate that this mechanism may contribute to development of SH in ELBWI.
Investigation of Antimicrobial Activities of Indole-3-Aldehyde Hydrazide/Hydrazone Derivatives
Authors: Gurkok Gokce , Altanlar Nurten , Suzen Sibel
Published: November 2008

Background: Indoles and hydrazone-type compounds constitute an important class of compounds for new drug development in order to discover an effective compound against multi-drug-resistant microbial infections. Methods: A series of indole-3-aldehyde and 5-bromoindole-3-aldehyde hydrazide and hydrazones was evaluated for their in vitro antimicrobial activities using the 2-fold serial dilution technique against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, Bacillus subtilis and Candida albicans. The minimum inhibitory concentration (MIC) was determined for test compounds and for the reference standards sultamicillin, ampicillin, fluconazole and ciprofloxacin. Results: Compounds possessed a broad spectrum of activity having MIC values of 6.25–100 mg/ml against the tested microorganisms. Compounds 1a–1j, in particular, displayed better activity against MSRA and significant activity against S. aureus relative to ampicillin. Unexpectedly, indole nicotinic acid hydrazides showed no significant activity while indole anisic acid hydrazides displayed better activity. Conclusion: The results may be instructive to researchers attempting to gain more understanding of the antimicrobial activity of indole hydrazide/hydrazone-type compounds.
Vitamin K2 Inhibits the Growth of Hepatocellular Carcinoma via Decrease of Des-Gamma-Carboxy Prothrombin
Authors: Ma Meng , Qu Xian-Jun , Mu Guo-Ying , Chen Ming-Hui , Cheng Yan-Na , Kokudo Norihiro , Tang Wei , Cui Shu-Xiang
Published: November 2008

Background: Des-γ-carboxy prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells in the absence of vitamin K. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. Hence, we aimed to examine the efficacy of vitamin K2 on the production of DCP as well as tumor cell growth and invasion. Methods: Cell growth and viability were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The in vivo efficacy of vitamin K2 was examined in nude mice bearing HCC cells. A 24-well transwell chamber was used to evaluate the motility and invasive ability of HCC cells. Levels of DCP in supernatant of cultures and in serum of mice were measured using an electrochemiluminescence immunoassay method. Western blot and immunohistochemical analysis were employed to evaluate the expression of DCP in HCC. Results: Vitamin K2 (2–40 μM) significantly decreased the levels of DCP production in supernatant of PLC/PRF/5 and HepG2 cells and in serum of nude mice bearing HCC xenografts. The inhibition of DCP was also observed using the assays of Western blot analysis in HCC cultures and immunohistochemical analysis in HCC xenografts in mice. As a result of administration of vitamin K2, the capacity of HCC growth was inhibited and the invasion and migration of tumor cells were decreased. Furthermore, the inhibitory effects of HCC growth were also observed in vivo and the sensitivitywas well correlated with the decrease of DCP in the serum of mice. Conclusion: Vitamin K2 might suppress the growth and invasion of HCC cells via decrease of DCP.
The Effects of Chiral Isolates of Methadone on the Cardiac Potassium Channel IKr
Authors: Lin Congrong , Somberg Trudie , Molnar Janos , Somberg John
Published: November 2008

Objectives: Methadone is a synthetic opioid, an analgesic and an antiaddictive. QT prolongation as well as torsade de pointes ventricular tachycardia and death have been reported with methadone. Methadone’s proarrhythmic toxicity is related to the inhibition of cardiac IKr channel and prolongation of the action potential. We hypothesized that the 2 isomers of methadone may have different effects on the IKr channel. Methods: The effects of the isomers on IKr were evaluated by using an oocytes system with heterogeneously expressed human ether-a-go-go-related gene (HERG) using the 2 electrode voltage clamp technique. r- and s-methadone were obtained by employing chiral high-performance liquid chromatography, separating methadone into 2 isolates, with optical rotations of –141 and +143 degrees. Results: At concentrations of 0.01, 0.03, 0.1, 1 and 3 mM, r/s-methadone produced a dose-dependent inhibition of HERG by 17 ± 5, 23 ± 4, 40 ± 4, 57 ± 3, 69 ± 3 and 80 ± 1%, respectively. The IC50 of r/s-methadone was 0.21 ± 0.02 mM. At 0.1, 0.3 and 1 mM, s-methadone reduced HERG current by 50 ± 4, 76 ± 5 and 87 ± 5%, respectively, while r-methadone reduced HERG current by 26 ± 4, 53 ± 3 and 77 ± 3%, respectively. Conclusions: There was a significant difference (p < 0.01) in the percentage of current inhibition between r- and s-methadone, at 0.1 and 0.3 mM (52% reduction). Thus, r-methadone may be a safer agent due to less QT effect.
Chronic Administration of SMP-534 Ameliorates Renal Dysfunction in 5/6 Nephrectomized Rats
Authors: Tsujimura Tsuyoshi , Nagamine Jun , Sugaru Eiji , Nakagawa Tsutomu , Ono-Kishino Michiko , Tokunaga Teruhisa , Kitoh Makoto , Nagata Ryu , Taiji Mutsuo
Published: November 2008

Background/Aims: Chronic kidney disease (CKD) is the common cause of end-stage renal disease. Antihypertensive agents are clinically used to inhibit the progression of CKD. However, these agents cannot completely prevent progression to renal failure. We have previously reported that 5-chloro-2-{(1E)-3-[2-(4-methoxybenzoyl)-4-methyl-1H- pyrrol-1-yl]prop-1en-1-yl}-N-(methylsulfonyl)benzamide (SMP-534) improves renal disease and prevents the production of extracellular matrix in vitro. Additionally, SMP-534 inhibits glomerular fibrosis and provides renoprotection in vivo. In the present study, we investigated the effect of SMP-534 on renal dysfunction in a 5/6 nephrectomized (5/6Nx) rat model. Method: Five groups of rats were studied: sham operated, 5/6Nx + vehicle, 5/6Nx + SMP-534 30 mg/kg, 5/6Nx + SMP-534 60 mg/kg and 5/6Nx + SMP-534 90 mg/kg. Treatment with SMP-534 began 13 weeks after surgery, when hypertension and renal insufficiency had developed. Serum creatinine, blood urea nitrogen levels, creatinine clearance and urinary albumin were measured at specific time points. Results: Serum creatinine and blood urea nitrogen levels were significantly reduced in SMP-534-treated groups. In addition, SMP-534 dose-dependently suppressed the increase in urinary albumin excretion observed in 5/6Nx rats. Moreover, survival rates were improved in SMP-534-treated groups. Conclusion: We have shown in this study that chronic oral administration of SMP-534 improves renal dysfunction in 5/6Nx rats. These findings indicate that SMP-534 may be a new therapeutic agent for the treatment of CKD.
How to Best Define Patients with Moderate Chronic Kidney Disease
Authors: Emara Mahmoud , Zahran Ahmed , Abd El Hady Hassan , Shoker Ahmed
Published: November 2008

Background: The objective of this study was to identify which formula may best identify moderate chronic kidney disease (CKD) (glomerular filtration rate (GFR) cut-off of 60 ml/min/1.73 m2). Methods: We compared the performances of 14 serum creatinine (Scr) and 11 cystatin C (Cys C) estimated GFR equations using inulin clearance (Clin) as the reference test in a stable CKD population of 101 patients. Scatter, coefficient of variation, bias, precision, accuracy within 30% ranges from the reference method, agreements and receiving operating characteristics (ROC) of each test were compared. Results: ROC analysis identified Davis, Salzar, Virga and Cockcroft-Gault as the most sensitive (≥85%) and the isotope dilution mass spectrometry (IDMS), Edwards, MacIsaac as the most specific (95%) to define the GFR cut-off level of 60 ml/min/1.73 m2. Area under the ROC curve (AUC) was generally >0.8 (p ≤ 0.0001). 2 × 2 contingency tables to define CKD demonstrated sensitivity of 90% for Davis, while the IDMS was the most specific (95%). Among the Cys-C-based equations, Filler was the most sensitive (83%) and MacIsaac was the most specific (95%). Conclusion: The current equations lack consistent good performance to define CKD. The MDRD-IDMS equation missed 30% but demonstrated a high specificity to confirm those with moderate CKD. A combination of two equations, one sensitive and another specific, may be required for epidemiological studies.
Screening for Proteinuria and Chronic Kidney Disease Risk Factors in Kinshasa: A World Kidney Day 2007 Study
Authors: Sumaili Ernest K. , Nseka Nazaire M. , Lepira François B. , Krzesinski Jean Marie , Makulo Jean Robert R. , Bukabau Justine B. , Nkoy Josée B. , Mokoli Vieux M. , Longokolo Murielle M. , Owandjalola Julie A. , Kayembe Patrick K.
Published: November 2008

Background: Although screening programs for chronic kidney disease (CKD) may be of great value, these programs are not yet implemented in the Democratic Republic of Congo. This study focused on proteinuria and examined its prevalence in terms of the number needed to screen for the different risk factors of CKD. Such knowledge would guide the utility of population screening to prevent end-stage renal disease. Methods: A cross-sectional survey was conducted in Kinshasa on the Second World Kidney Day. A sample of 3,018 subjects was interviewed and the following measurements were performed: blood pressure, body mass index, glycemia and urine protein. Logistic regression analysis was used to identify determinants of proteinuria. Results: The prevalence of proteinuria was 17.1% (95% CI 15.8–18.6). Other CKD risk factors identified were: hypertension, diabetes mellitus, obesity and metabolic syndrome. To identify 1 case of proteinuria, one would need to screen 4 persons with diabetes, 5 persons with hypertension, 4 subjects having metabolic syndrome, 5 persons aged ≥72 years and 9 persons without any of the conditions mentioned above. Age, overweight and diabetes were the strongest factors associated with proteinuria. Conclusions: This study indicates that proteinuria and traditional risk factors for CKD are very prevalent in Kinshasa. Realistic policies to stem these conditions should be a public health priority.
Endothelial Activation Markers in Anemic Non-Dialysis Chronic Kidney Disease Patients
Authors: Patel Tejas V. , Mittal Bharati V. , Keithi-Reddy Sai Ram , Duffield Jeremy S. , Singh Ajay K.
Published: November 2008

Background/Aims: Anemia in chronic kidney disease is an independent predictor of cardiovascular disease (CVD). We explored the relationship between anemia and markers of inflammation and endothelial activation in non-dialysis chronic kidney disease (ND-CKD) patients to understand this mechanism. Methods: Cross-sectional analysis was performed on 30 adult ND-CKD patients for markers of inflammation and endothelial activation using a multiplexed immunoassay. Data were analyzed according to the anemic status defined by the modified World Health Organization criteria. Results: Seventeen patients were classified as anemic. Baseline characteristics by anemic status were similar except that anemic patients were older (p = 0.006), had lower estimated glomerular filtration rate (eGFR; p = 0.01) and higher prevalence of CVD (p = 0.02). Compared to non-anemic patients, log-transformed values of fibrinogen (p = 0.012); von Willebrand factor (vWF, p = 0.008), vascular cell adhesion molecule-1 (VCAM-1, p = 0.025) and C-reactive protein (p = 0.043) were elevated in anemic patients. Serum ferritin (p = 0.93) and serum albumin (p = 0.06) were not different. Age and eGFR-adjusted logistic regression analysis showed that anemic patients had increased odds for a composite of higher median values of fibrinogen, vWF and VCAM-1 (p = 0.01, odds ratio 8.1, 95% CI 1.08–111.0). Conclusion: We report the association of anemia with elevated markers of endothelial activation in ND-CKD patients. Longitudinal studies are needed to confirm our findings.
An Assessment of Symptomatic Relief after Carpal Tunnel Release in Patients on Haemodialysis
Authors: Khan Umar Daraz
Published: November 2008

Patients receiving haemodialysis for chronic kidney disease are at risk of developing β2-microglobulin-related carpal tunnel syndrome (CTS). There is a lack of evidence regarding outcome of this complication following surgical treatment. The current study specifically addressed the relief of symptoms after carpal tunnel release in this particular group of patients. Materials and Method: 26 carpal tunnel release operations were performed in 19 patients (12 males, 7 females) between 1992 and 1996. The mean age of the patients was 59 years (range 41–78) with a mean duration of haemodialysis of 12.6 years. Patients were dialysed the day before surgery with low-dose heparin. All procedures were performed using 1% Xylocaine with adrenaline 1:200,000 without tourniquet as day cases. Relief of weakness of the hand, tingling, pain at rest, pain on use, nocturnal paraesthesiae and scar pain were assessed. Results: All outcome measures showed marked improvement and 84% (16/19) of patients were satisfied with the outcome. One patient showed worsening of pain at rest and pain on use of hand. Conclusion: Release of carpal tunnel in patients on haemodialysis helps alleviation of symptoms due to median nerve compression and improves the function of hand and quality of life in the majority of patients. There can still be a small minority of patients who may not show any improvement and a few may rarely get worse.
Atorvastatin Increases Erythropoietin-Stimulating Agent Hyporesponsiveness in Maintenance Hemodialysis Patients: Role of Anti-Inflammation Effects
Authors: Chiang Chih-Kang , Yang Shao-Yu , Peng Yu-Sen , Hsu Shih-Ping , Pai Mei-Fen , Huang Jen-Wen , Hung Kuan-Yu , Wu Kuan-Dun
Published: November 2008

Erythropoietin-stimulating agent (ESA) hyporesponsiveness is aggravated by chronic inflammation in maintenance hemodialysis (MHD) patients. Dyslipidemia is prevalent in MHD patients. Statin therapy has been demonstrated to not only be effective in lowering lipid levels, but also numerous pleiotropic effects including anti-inflammatory, anti-fibrotic and endothelial function improvement. Recently, a retrospective study has shown that statin therapy decreases ESA requirements in MHD patients. We conducted a prospective study to analyze the effect of statin therapy on ESA hyporesponsiveness, and especially emphasized its anti-inflammatory benefits in MHD patients. This prospective study enrolled 30 patients with baseline cholesterol >220 mg/dl. Low-dose atorvastatin (10 mg/day) was prescribed for 12 weeks. We prospectively recorded patients’ biochemistry and hematological profiles, ESA prescription and some inflammatory markers at baseline, 4 weeks and 12 weeks. Statistically significant changes were noted after 4 and 12 weeks of statin therapy for cholesterol (272.5 ± 41.1 to 184.4 ± 37.6 and 196.4 ± 40.2 mg/dl, p < 0.05) and ESA hyporesponsiveness, which demonstrated as erythropoietin to hematocrit ratio (EHR) (129.3 ± 58.2 to 122.3 ± 53.5 and 121.0 ± 53.3 EPO U/Hct/week, p < 0.05). Mean values for proinflammatory cytokines included interleukin-6 and tumor necrotic factor-α levels decreased by 30.8 and 10.6%, respectively. Thus, these data suggest that statin therapy may improve ESA hyporesponsiveness in dialysis patients. This improvement in ESA hyporesponsiveness is associated with the effects of statins on inflammation.
Bromocriptine Administration Reduces Hyperphagia and Adiposity and Differentially Affects Dopamine D2 Receptor and Transporter Binding in Leptin-Receptor-Deficient Zucker Rats and Rats with Diet-Induced Obesity
Authors: Davis Lisa M. , Michaelides Michael , Cheskin Lawrence J. , Moran Timothy H. , Aja Susan , Watkins Paul A. , Pei Zhengtong , Contoreggi Carlo , McCullough Karen , Hope Bruce , Wang Gene Jack , Volkow Nora D. , Thanos Panayotis K.
Published: November 2008

Background: The dopamine (DA) D2 receptor (D2R) agonist bromocriptine (BC) decreases body fat in animal and human models and increases lean muscle mass, improves glucose intolerance and insulin resistance, and reduces triglycerides and free fatty acids. We have previously shown a negative correlation between D2R and body weight in obese individuals and in rodents, and that chronic food restriction increases D2R binding in genetically obese rats. The purpose of this study was to assess whether the antiobesity and metabolic effects of BC are related to changes in midbrain DA and D2R activity by measuring D2R and DA transporter (DAT) binding in a genetic (leptin-receptor-deficient) and environmental (diet-induced) rodent obesity model. Methods: Obese (fa/fa) (leptin-receptor-deficient), lean (FA/FA) Zucker rats and rats with diet-induced obesity (DIO) were treated with 10 mg/kg BC for 4 weeks. Body weight, food intake, locomotor activity and blood glucose levels were measured along with D2R- and DAT-binding levels using in vitro receptor autoradiography. Results: BC decreased food intake and body fat and increased locomotor activity in both the (fa/fa) and DIO rats. Furthermore, BC increased D2R binding in (fa/fa) but not in DIO rats. Finally, BC increased DAT binding in DIO rats but not in the (fa/fa) rats. Conclusion: These observations are all consistent with the existence of unique leptin-DA interactions and the hypothesis that there is hyposensitivity of the DA system in obesity.
Alveolar Macrophage from Cigarette Smoke-Exposed Mice Inhibits B Lymphocyte Proliferation Stimulated with LPS
Authors: Ishida T. , Pinkerton K.E. , Takeuchi M.
Published: November 2008

Background: Smokers have higher incidences of pulmonary diseases. This increased susceptibility may result from cigarette smoke (CS)-induced impairment of the pulmonary immune system. However, the mechanism(s) is not fully understood. Objective: The aim of this study was to investigate the mechanism of the effect of alveolar macrophages (AM) from CS-exposed mice on B lymphocyte proliferation stimulated with bacterial lipopolysaccharide (LPS). Methods: Mice were exposed to CS using a Hamburg smoking machine, and AM were obtained by bronchoalveolar lavage. Lymphocytes were harvested from spleen in normal mice. AM-mediated B lymphocyte proliferation stimulated with LPS was assessed by the 3H-thymidine method, using lymphocytes as responding cells and AM from CS-exposed or non-CS-exposed mice. Generations of superoxide and hydrogen peroxide were analyzed by flow cytometory, using hydroethidine and dichlorofluorescein diacetate. Results: AM from CS-exposed mice significantly inhibited B lymphocyte proliferation stimulated with LPS compared with AM from non-CS-exposed mice. Generations of superoxide and hydrogen peroxide were significantly increased in CS-exposed AM compared with non-CS-exposed AM. Inhibition of B lymphocyte proliferation stimulated with LPS by AM from CS-exposed mice was clearly recovered by superoxide dismutase and catalase. Conclusions: These results suggest that the inhibition by CS-exposed AM of LPS-induced B lymphocyte proliferation may be caused by the increased superoxide and hydrogen peroxide generation of CS. Therefore, these immunological inhibitions by CS could be associated with increased risk of pulmonary diseases.
Downloadable Algorithm to Reduce Inappropriate Shocks Caused by Fractures of Implantable Cardioverter-Defibrillator Leads
Authors: Swerdlow Charles D. , Gunderson Bruce D. , Ousdigian Kevin T. , Abeyratne Athula , Stadler Robert W. , Gillberg Jeffrey M. , Patel Amisha S. , Ellenbogen Kenneth A.
Published: November 2008

Background—

The primary method for monitoring implantable cardioverter-defibrillator lead integrity is periodic measurement of impedance. Sprint Fidelis leads are prone to pace-sense lead fractures, which commonly present as inappropriate shocks caused by oversensing.

Methods and Results—

We developed and tested an algorithm to enhance early identification of lead fractures and to reduce inappropriate shocks. This lead-integrity algorithm, which can be downloaded into presently implanted implantable cardioverter-defibrillators, alerts the patient and/or physician when triggered by either oversensing or excessive increases in impedance. To reduce inappropriate shocks, the lead-integrity algorithm increases the number of intervals to detect (NID) ventricular fibrillation when triggered. The lead-integrity algorithm was tested on data from 15 970 patients with Fidelis leads (including 121 with clinically diagnosed fractures) and 95 other fractured leads confirmed by analysis of returned product. The effect of the NID on inappropriate shocks was tested in 92 patients with 927 shocks caused by lead fracture. Increasing the NID reduced inappropriate shocks (
P
<0.0001). The lead-integrity algorithm provided at least a 3-day warning of inappropriate shocks in 76% (95% CI, 66 to 84) of patients versus 55% (95% CI, 43 to 64) for optimal impedance monitoring (
P
=0.007). Its positive predictive value was 72% for lead fractures and 81% for lead fractures or header-connector problems requiring surgical intervention. The false-positive rate was 1 per 372 patient-years of monitoring.

Conclusions—

A lead-integrity algorithm developed for download into existing implantable cardioverter-defibrillators increases short-term warning of inappropriate shocks in patients with lead fractures and reduces the likelihood of inappropriate shocks. It is the first downloadable RAMware to enhance the performance of nominally functioning implantable cardioverter-defibrillators and the first implantable cardioverter-defibrillator monitoring feature that triggers real-time changes in ventricular fibrillation detection parameters to reduce inappropriate shocks.
Cross-Talk Between Mineralocorticoid and Angiotensin II Signaling for Cardiac Remodeling
Authors: Di Zhang An , Cat Aurelie Nguyen Dinh , Soukaseum Christelle , Escoubet Brigitte , Cherfa Aïcha , Messaoudi Smail , Delcayre Claude , Samuel Jane-Lise , Jaisser Frederic
Published: November 2008

Experimental and clinical studies show that aldosterone/mineralocorticoid receptor (MR) activation has deleterious effects in the cardiovascular system that may cross-talk with those of angiotensin II (Ang II). This study, using a transgenic mouse model with conditional and cardiomyocyte-restricted overexpression of the human MR, was designed to assess the cardiac consequences of Ang II treatment and cardiomyocyte MR activation. Two-month-old MHCtTA/tetO-hMR double transgenic males (DTg) with conditional, cardiomyocyte-specific human MR expression, and their control littermates were infused with Ang II (200 ng/kg per minute) or vehicle via osmotic minipump. Ang II induced similar increases in systolic blood pressure in control and DTg mice but a greater increase in left ventricle mass/body weight in DTg than in control mice. In DTg mice, Ang II–induced left ventricle hypertrophy and diastolic dysfunction without affecting systolic function, as assessed by echography. These effects were associated with an increase in the expression of collagens and fibronectin, matrix metalloproteinase 2 and matrix metalloproteinase 9 activities, and histological fibrosis. Ang II treatment of DTg mice did not affect inflammation markers, but oxidative stress was substantially increased, as indicated by gp91 expression, apocynin-inhibitable NADPH oxidase activity, and protein carbonylation. These molecular and functional alterations were prevented by pharmacological MR antagonism. Our findings indicate that the effects of Ang II and MR activation in the heart are additive. This observation may be relevant to the clinical use of MR or of combined Ang II type 1 receptor-MR antagonists for hypertrophic cardiomyopathies or for heart failure, particularly when diastolic dysfunction is associated with preserved systolic function.
Changes in Serum Potassium Mediate Thiazide-Induced Diabetes
Authors: Shafi Tariq , Appel Lawrence J. , Miller Edgar R. , Klag Michael J. , Parekh Rulan S.
Published: November 2008

Thiazides, recommended as first-line antihypertensive therapy, are associated with an increased risk of diabetes. Thiazides also lower serum potassium. To determine whether thiazide-induced diabetes is mediated by changes in potassium, we analyzed data from 3790 nondiabetic participants in the Systolic Hypertension in Elderly Program, a randomized clinical trial of isolated systolic hypertension in individuals aged ≥60 years treated with chlorthalidone or placebo. Incident diabetes was defined by self-report, antidiabetic medication use, fasting glucose ≥126 mg/dL, or random glucose ≥200 mg/dL. The mediating variable was change in serum potassium during year 1. Of the 459 incident cases of diabetes during follow-up, 42% occurred during year 1. In year 1, the unadjusted incidence rates of diabetes per 100 person-years were 6.1 and 3.0 in the chlorthalidone and placebo groups, respectively. In year 1, the adjusted diabetes risk (hazard ratio) with chlorthalidone was 2.07 (95% CI: 1.51 to 2.83;
P
<0.001). After adjustment for change in serum potassium, the risk was significantly reduced (hazard ratio: 1.54; 95% CI: 1.09 to 2.17;
P
=0.01); the extent of risk attenuation (41%; 95% CI: 34% to 49%) was consistent with a mediating effect. Each 0.5-mEq/L decrease in serum potassium was independently associated with a 45% higher adjusted diabetes risk (95% CI: 24% to 70%;
P
<0.001). After year 1, chlorthalidone use was not associated with increased diabetes risk. In conclusion, thiazide-induced diabetes occurs early after initiating treatment and appears to be mediated by changes in serum potassium. Potassium supplementation might prevent thiazide-induced diabetes. This hypothesis can and should be tested in a randomized trial.
Dietary Salt Activates an Endothelial Proline-Rich Tyrosine Kinase 2/c-Src/Phosphatidylinositol 3-Kinase Complex to Promote Endothelial Nitric Oxide Synthase Phosphorylation
Authors: Ying Wei-Zhong , Aaron Kristal , Sanders Paul W.
Published: November 2008

Although many laboratories have shown that dietary NaCl (salt) intake increases NO production in rodents and humans, the mechanism has not been uncovered. In the present study, pharmacological and dominant-negative strategies were used to show that feeding a formulated diet containing increased amounts of salt to young male Sprague-Dawley rats induced the formation of an endothelial cell-signaling complex that contained proline-rich tyrosine kinase 2, c-Src (also known as pp60c-src), and phosphatidylinositol 3-kinase. In the setting of a high-salt diet, proline-rich tyrosine kinase 2 served as the scaffold for c-Src–mediated phosphatidylinositol 3-kinase activation. Phosphatidylinositol 3-kinase was the upstream activator of protein kinase B (Akt), which was responsible for phosphorylation of the rat endothelial isoform of NO synthase at S1176 and thereby promoted the increase in NO production. The combined findings illustrated the crucial role for a proline-rich tyrosine kinase 2–signaling complex in the endothelial response to salt intake.
Pre-negotiation and its Limits in Ethno-National Conflicts: A Systematic Analysis of Process and Outcomes in the Cyprus Negotiations
Authors: Schiff Amira
Published: November 2008

The repeated failures of negotiation in ethno-national conflicts highlight the importance of studying the relationship between the pre-negotiation process and the results of the subsequent formal negotiations. This study examines various factors that contributed to a decision by adversaries to initiate official negotiations, and how these factors affected the prospects for a negotiated agreement. Furthermore, it suggests that certain elements in the pre-negotiation process portend the nature of the changes in the parties' political positions (tactical or strategic) and the parties' readiness to reach an agreement. An exploration is presented using a case study of the negotiations over the Cyprus conflict in 2004 which resulted in the ultimate rejection by the negotiating parties of the Annan Plan in late March of 2004. We examine the connection between the pre-negotiation process, from the end of 2003 until February 13, 2004, and the failure of the formal negotiations in March 2004. The analysis indicates that the deficient method and process of the pre-negotiations that took place regarding the Cyprus conflict determined the subsequent failure of the negotiations. The early detection of such factors in other negotiations over ethno-national conflicts may mitigate the causes that lead to failure, or perhaps assist in managing the process differently, so as to facilitate a more positive outcome.
The Universal and the Particular Christian Unity in a Post-Modern World
Authors: Gros Jeffrey
Published: November 2008

The Netherlands' Catholic Reformed text on the Church, local and universal, is an important contribution to international ecumenical discussions, informed by the particular context of the history of these churches in the low countries. This essay focuses on the importance of the theme and the method of this dialogue, and its contribution to understanding how the ecumenical movement is contextualized and communicated through the educational priorities of the churches. The essay relates this text, from a particular national dialogue, to the international Reformed Catholic dialogue and to issues of the wider ecumenical movement.
A Reformed Response to Local and Universal Dimensions of the Church
Authors: Janssen Allan
Published: November 2008

This article begins by reviewing ways in which Reformed churches have given expression to the universal dimension of the church within its preference for the church's local expression. The marks of the church, the confession of the church, its church order and its understanding of office all give expression to the universal dimension of the church. The proposal that the universal dimension be more strongly emphasized at the 'intermediate level' will be received gladly by Reformed churches but it also challenges Reformed churches to consider the personal dimension of universality as well as to re-emphasize the universal dimension both in congregational life and at a supra-national level.
The Church as Sacrament of the Kingdom: A Reformed Commentary
Authors: Brinkman Martien
Published: November 2008

One of the most promising aspects of the text of the third phase of the International Roman-Catholic-Reformed Dialogue might be the suggestion to reflect upon the idea of the church as 'sacrament of the kingdom' (no.231). In this contribution, I shall take up that suggestion and develop a fourfold approach of the sacraments in which the interconnectedness of church and kingdom plays a crucial role. I shall deal with the soteriological, the ecclesiological, the eschatological and the symbolic aspect respectively. Deliberately, I begin with the soteriological aspect because the first and main thing sacraments do is to point to our salvation. Salvation implies, however, a mediation of salvation and hence the ecclesiological aspect follows the soteriological aspect. The mediation of the church always points beyond itself to the kingdom of God. That is the eschatological aspect. And every reference to the eschaton always has the form of the symbol as the focal point of the 'already' and 'not yet' character of the kingdom of God. We label that as the symbolic aspect. My conclusion will be that the fruitfulness of the suggestion to speak about the church as 'sacrament of the kingdom' depends on the preparedness to reap the results of the ecumenical discussions since Vatican II.
Religious Rights for Minorities in a Policy of Recognition
Authors: van der Ven Johannes
Published: November 2008

Religion plays an important role in today's multicultural society, especially when it comes to religious rights for minorities. Granting these rights stems from an endeavour to transcend a politics of tolerance, even a politics of respect, and to treat them in terms of a politics of recognition. Assigning these rights implies that some principles need to be critically reflected upon: the individualistic interpretation of minority rights, the separationist interpretation of the separation between church and state, the secularist interpretation of religious freedom, and the uniformistic interpretation of the state's legal unity. In granting minorities religious rights, one comes across the importance of their personal law, including marriage law and family law. To incorporate such personal law into the legal systems of Western society, one could apply the distinction between the domains of status demarcation, that refers to entering and belonging to a community, and property distribution, that relates to the rights and duties implicit in these social bonds. The former may be provided for by religious law, the later, by secular law. However, the question is whether marriage under religious law, and rights and duties under secular law can solve the problems women suffer from, especially in the case of polygyny.
Revisiting the “Simple View of Reading” in a Group of Children With Poor Reading Comprehension
Authors: Georgiou George K. , Das J.P. , Hayward Denyse
Published: November 2008

According to Gough and Tunmer's Simple View of Reading, Reading Comprehension = Decoding (D) × Listening Comprehension (C). The purpose of this study was to evaluate the model with a sample of First Nations children, known to have average decoding and listening comprehension but poor reading comprehension. In addition, the authors examined the contribution of naming speed and phonological awareness to reading comprehension beyond the effects of D and C. Consistent with the findings of previous studies, the children exhibited poor reading comprehension despite average performance in decoding and listening comprehension, a finding that challenges the simple view of reading. The results also revealed that an additive model (D + C) fitted the data equally well as a product model (D × C). Neither naming speed nor phonological awareness accounted for unique variance.
Real Time Software-in-the-Loop Simulation for Control Performance Validation
Authors: Xiang Chen  , Salem Meranda , Das Tuhin , Xiaoqun Chen
Published: November 2008

This paper illustrates an effective real-time software-in-the-loop (SIL) simulation technique for control design performance validation through two case studies in automotive systems: electric power steering (EPS) control and drive control for a switch reluctance motor (SRM) powered by a fuel cell. This technique, if implemented appropriately, will be able to shorten the prototyping time for control system research and development in both academic and industrial areas. The two cases presented involve complicated dynamics: road/tire steering dynamics and chemical/electrical dynamics in a fuel cell, for which software packages are available to simulate. Therefore, for the purpose of steering and SRM drive control performance validation, successful real-time simulation is desired through interfacing with these software, i.e. making software package in the loop. The case studies presented in this paper demonstrate the effectiveness of this concept. The presented real-time SIL simulation is conducted on a two-node computer platform engineered by RT-Lab, operating in fixed-step real time. Comparison between real-time and off-line simulation is also presented.
Modeling and Simulation of the Thermal and Psychrometric Transient Response of All-Electric Ships, Internal Compartments and Cabinets
Authors: Ordonez J.C. , Vargas J.V.C. , Hovsapian R.
Published: November 2008

We introduce a general computational model for all-electric ships and internal compartments (open and closed domains) that contain heat sources and sinks. A simplified physical model, which combines principles of classical thermodynamics and heat transfer, is developed and the resulting three-dimensional (3D) differential equations are discretized in space using a 3D cell-centered volume element scheme. The combination of the proposed simplified physical model with the adopted finite volume scheme for the numerical discretization of the differential equations is therefore called a volume element model (VEM). Two case studies are presented: a simulation of a whole ship at sea, and one of the ship's internal compartments (or cabinet). The proposed model was utilized to simulate numerically the steady-state responses of the systems in both cases. Of particular interest in the first case is the possibility of predicting the ship's thermal signature at sea. Mesh refinements were conducted to ensure the convergence of the numerical results. The converged mesh in both cases was relatively coarse (175 and 320 cells) and therefore the solutions were obtained with low computational time. Since accuracy and low computational time are combined, the model is shown to be efficient and could be used as a tool for simulation, design and optimization of thermal management of all-electric ships, internal compartments and cabinets. Finally, experiments are conducted in a test-bed facility to demonstrate, from simulated sea conditions, how to quantify the electric motors transient heat rejection to cooling water and the environment in a notional all-electric ship, with the objective of serving as known heat generation inputs to the mathematical model to simulate the transient thermal response of the entire ship and its compartments.
A Multidiscipline and Multi-rate Modeling Framework for Planar Solid-oxide-fuel-cell based Power-Conditioning System for Vehicular APU
Authors: Mazumder Sudip K. , Pradhan Sanjaya K. , Hartvigsen Joseph , Rancruel Diego , von Spakovsky Michael R. , Khaleel Moe
Published: November 2008

A numerical modeling framework for planar solid-oxide fuel cell (PSOFC) based vehicular auxiliary power unit (APU) is developed. The power-conditioning system (PCS) model comprises the comprehensive transient models of PSOFC, balance-of-plant and power-electronics subsystems (BOPS and PES, respectively) and application load (AL). It can be used for resolving the interactions among PSOFC, BOPS, PES and AL, control design and system optimization and studying fuel-cell durability. The PCS model has several key properties including: (i) it can simultaneously predict spatial as well as temporal dynamics; (ii) it has two levels of abstraction: comprehensive (for detailed dynamics) and reduced-order (for fast simulation); and (iii) the fast-simulation model can be implemented completely in Simulink/Matlab environment, thereby significantly reducing the cost as well as time and provides the avenue for real-time simulation and integration with vehicular power-train models employing the widely used ADVISOR. The computational overhead and accuracy of the fast-simulation and comprehensive models are compared. Significant savings in time compared to using the former were obtained, without compromising accuracy.
High-Speed Real-Time Simulation for Power Electronic Systems
Authors: Word Dale , Bednar Richard , Zenor John J. , Hingorani Nari G.
Published: November 2008

Real-time simulators have been used as an aid to power system design for many years. Over time, scaled-down physical models and analog computer-based simulators have given way to real-time simulators based on digital technology. Another trend has been the need for shorter and shorter frame times for these digital real-time simulators. Modern power electronic systems use highfrequency Pulse-Width Modulated (PWM) controllers. Indications are that frame times of 2 μS are needed for PWM switching frequencies of 10 KHz. As frequencies increase further it is possible that frame times of less than 1 μS may be required.

In order to achieve these very short frame times, the implementation of this type of simulator requires careful selection of the methods and technologies used. The first involves thorough analysis of the integration method chosen, to ensure that it provides the performance, stability and accuracy required. Additionally, the choice of computing platform is crucial to provide the computational support to meet these very aggressive timing requirements.
Bullying and Stress in Early Adolescence
Authors: Konishi Chiaki , Hymel Shelley
Published: November 2008

Prior research from Norway and Japan has demonstrated positive relationships between stress and bullying—The more stress students experience, the more they engage in bullying. The modest correlations, however, suggest that other variables may moderate the stress-bullying link, serving as protective factors that make such negative responses to stress less likely for some individuals. This study examined the stress-buffering roles of coping and social support in reducing the likelihood of bullying in response to stress. Students in Grades 5-7 ( N = 312) completed questionnaires assessing stress levels (daily hassles, stressful events), coping strategies (active, avoidance, distraction, support seeking), social support (from peers, family, teachers), and bullying. Consistent with previous research, correlational analyses indicated that stress is significantly related to self-reported bullying but not to peer-assessed bullying. Regression analyses revealed that family support moderated and distraction coping amplified the stress-bullying relationship.
Math Achievement in Early Adolescence
Authors: Puklek Levpušček Melita , Zupančič Maja
Published: November 2008

Contributions of parental involvement in educational pursuits as well as math teachers' classroom behavior to students' motivation and performance in math were investigated. By the end of the first school term, 365 Slovene eighth graders reported on their parents' academic involvement (pressure, support, and help) and their math teachers' behavior in the classroom (support, academic press, and mastery goal). During the second term, the students filled-in the questionnaires on their motivational beliefs about math, and at the end of the school year, their final math grade was obtained from school records. Both of the social contexts significantly predicted students' outcomes. Students' perceptions of math teachers' behavior were predictive of both motivational beliefs and achievement in math, over and above the acount of students' evaluations of their parents' involvement. Furthermore, parental academic pressure and support were directly (negatively) related to students' math grades. The contributions of parental pressure, math teachers' academic press, and teachers' mastery goal on math achievement were mediated through the students' self-efficacy in this school course.
Early Predictors of Adolescent Depression
Authors: Mazza James J. , Abbott Robert D. , Fleming Charles B. , Harachi Tracy W. , Cortes Rebecca C. , Park Jisuk , Haggerty Kevin P. , Catalano Richard F.
Published: November 2008

This study examined the longitudinal relationship of early elementary predictors to adolescent depression 7 years later. The sample consisted of 938 students who have been part of a larger longitudinal study that started in 1993. Data collected from parents, teachers, and youth self-reports on early risk factors when students were in 1st and 2nd grade were compared to adolescent self-reported depression 7 years later. Regression analyses were conducted with each risk factor separately and combined, while also examining gender and the gender × risk factor interaction. Results showed that the risk factors predominately in the individual characteristic group (depression, anxiety, and antisocial behavior) were predictive of depression 7 years later. Gender differences among the longitudinal risk factors were also found in relation to adolescent depression. Discussion of the results focuses on the practice of children’s mental health assessment and implications for the development of prevention and intervention programs for depression.