bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurobiology Confirms Psychopathology
Authors: Zink Mathias , Englisch Susanne , Dressing Harald
Published: July 2008

Background: Psychopathological concepts of the 19th and early 20th century postulated an antagonism between psychotic and obsessive-compulsive disorders, assuming obsessions and compulsions to have protective effects on psychotic disintegration. Although both disorders have been subject to intense multimodal research, their pathogeneses are yet to be fully understood. Methods: Here, we discuss recent neurobiological findings pointing towards opposite directions which are strongly reminiscent of the historical psychopathological antagonism. Results: Obsessive-compulsive syndromes (OCS) are efficiently treated with serotonergic substances, while on the other hand modern antipsychotic drugs exert antiserotonergic effects. Especially these atypical antipsychotic substances, however, were found to involve the risk of inducing second-onset OCS. Dopamine antagonists are potent antipsychotic substances, whereas the partial dopamine agonist aripiprazole has been associated with an antiobsessive potency. Within the glutamatergic system, reduced NMDA-dependent glutamatergic neurotransmission is discussed to be one major pathomechanism of psychotic disorders, whilst NMDA antagonists have proven to be effective in improving treatment-resistant OCS. While neurogenetic findings seem to separate the populations in heterogeneous samples, detailed neuroimaging studies suggest that both disorders affect similar neurocircuits in different manners. Conclusions: With regard to these findings, future research on schizo-obsessive syndromes will have to be multimodal, integrating psychopathology, neuropsychology, functional imaging, neurogenetics and psychopharmacology. Prospective trials involving these methods might be able to elucidate the dysbalances of neurotransmission and to locate the neuroanatomical and neuropsychological correlates. In particular, this might contribute to defining schizophrenic patients at risk for developing second-onset OCS and to evaluating new treatment strategies in patients suffering from both psychosis and OCS.
Flexibility and Variability in Lexicon Usage among Yoruba-Speaking Nigerian Outpatients with Schizophrenia
Authors: Adewuya Abiola O. , Adewuya Abiodun O.
Published: July 2008

Background: The studies on language dysfunction in schizophrenia are few, inconclusive and have all been done in the western culture. There may be cross-cultural and cross-lingual differences in problems with speeches of patients with schizophrenia. This study aims to examine the flexibility or variability in the use of words among a group of Nigerian patients with schizophrenia compared with healthy controls. Sampling and Methods: The spoken samples of 48 outpatients with schizophrenia and 48 matched controls were assessed using the mean segmental type-token ratio (MSTTR). The sociodemographic and clinical variables of the patients with schizophrenia were also compared with their MSTTR scores. Results: The MSTTR score for the patients with schizophrenia was significantly lower compared with that of healthy controls (p < 0.001). The factors independently associated with a lower MSTTR in patients with schizophrenia include younger age at onset of illness, presence of negative formal thought disorder and simple or hebephrenic subtype of schizophrenia. Conclusions: The problem with flexibility and variability in lexicon usage among patients with schizophrenia is a cross-cultural phenomenon. The MSTTR may have value in predicting clinical judgements of thought disorder or in identifying deviant language. These may have broad potentials for application in longitudinal and pathogenetic studies of schizophrenia.
Adiponectin Is Related to Carotid Artery Plaque and a Predictor of Cardiovascular Outcome in a Cohort of Non-Diabetic Peritoneal Dialysis Patients
Authors: Yu Zan-zhe , Ni Zhao-hui , Gu Le-yi , Lin Ai-wu , Fang Wei , Yao Qiang , Lindholm Bengt , Qian Jia-qi
Published: July 2008

Aims: Adiponectin is an adipocytokine with antiatherogenic and anti-inflammatory properties. We investigated associations between circulating adiponectin, inflammation and cardiovascular disease in peritoneal dialysis patients. Methods: A prospective study was performed in 59 non-diabetic patients. The concentrations of serum adiponectin, biochemical data and ultrasound of carotid artery were measured at enrollment. The patients were followed up to 39 months mainly for cardiovascular events. Results: The serum adiponectin concentration was elevated and inversely related to C-reactive protein and interleukin-6 in the patients. The adiponectin level of patients with carotid plaques was significantly lower than in those without plaques (p < 0.01). Kaplan-Meier analysis showed that the cumulative survival without new cardiovascular events was better in patients with higher adiponectin levels than in those with lower adiponectin levels. Conclusion: Serum adiponectin levels are inversely related with markers of systemic inflammation and signs of atherosclerosis which may explain why hyperadiponectinemia in this study was associated with better cardiovascular outcome.
Simvastatin-Induced Rhabdomyolysis and Acute Renal Injury
Authors: Waness Abdelkarim , Bahlas Sami , Al Shohaib Saad
Published: July 2008

Simvastatin is one of the most commonly prescribed CoA reductase inhibitors. The safety profile of this drug has been widely discussed in the medical and consumer advocacy communities. Like other statins, simvastatin can cause a serious and potentially life-threatening complication: rhabdomyolysis. We describe a case of simvastatin-induced rhabdomyolysis complicated by acute renal failure requiring urgent hemodialysis. The relative safety of simvastatin compared to other HMG-CoA reductase inhibitors and the conditions that can potentiate its toxicity are discussed. The clinical features of rhabdomyolysis, and subsequent acute renal failure, and their treatment modalities are presented.
Volume Overload in Patients Treated with Continuous Ambulatory Peritoneal Dialysis Associated with Reduced Circadian Blood Pressure Variation
Authors: Yang Ji-Hong , Cheng Li-Tao , Gu Yue , Tang Li-Jun , Wang Tao , Lindholm M. Bengt , Axelsson Jonas
Published: July 2008

Background: While a high blood pressure (BP) in patients receiving maintenance ambulatory peritoneal dialysis (CAPD) is associated with congestive heart failure and an increased mortality, the relevance of diurnal variations in BP is unknown. Methods:In a prospective study, we enrolled 76 prevalent patients receiving stable CAPD (age 60.4 ± 13.8 years; 37 males). BP was measured over 24 h using an automated device. We also performed routine clinical and biochemical measurements, as well as the Karnofsky index to evaluate physical activity. Volume status was assessed using bioimpedance analysis. Results: 69 patients (with an average time on dialysis of 24.4 ± 22.5 months) completed the study. Of these, 16 patients experienced a drop in BP >10% at night (dippers), while 53 patients did not (non-dippers). Comparing these two groups, dippers had significantly lower extracellular water (ECW) (13.8 ± 2.1 vs. 15.9 ± 3.3 l; p < 0.05), normalized extracellular water (nECW) (0.22 ± 0.05 vs. 0.26 ± 0.04 l/m; p < 0.05), and serum albumin (38.2 ± 2.9 vs. 35.9 ± 3.7 g/l; p < 0.05). Age, Karnofsky index, vintage, residual renal Kt/V and peritoneal Kt/V, total Kt/V, dose of antihypertensive drugs, mean systolic and diastolic BP did not significantly differ between these groups. Correlation analysis showed the coefficient of variation (CV) of BP positively correlated with E/T (r2 = 0.292; p < 0.05), diabetic (r2 = 0.267; p < 0.05), male (r2 = 0.257; p < 0.05), nECW (r2 = 0.278; p < 0.05) and ECW (r2 = 0.249; p < 0.05) negatively correlated with albumin (r2 = –0.280; p < 0.05). Furthermore, in a multivariate linear regression model, E/T, albumin and sex were independently associated with CV for BP. Conclusions: We show that reduced BP variation is common in CAPD patients and associated with volume overload and hypoalbuminemia. Furthermore, the relationship between nutritional, inflammatory status and dipping needs further studies.
Eczematous Dermatosis and Thrombocytosis Induced by Efalizumab: Two New Side Effects
Authors: Firmin D. , Roguedas A.M. , Lemasson G. , Abgrall J.F. , Misery L.
Published: July 2008

Efalizumab was authorized to be put on the market in France starting July 21, 2005. Its efficacy and tolerance profile in plaque psoriasis at a dose of 1 mg·kg–1 weekly in a subcutaneous injection have been studied in phase III trials. At the current moment, more than 3,500 patients have been included in clinical trials. Flu-like symptoms (fever, chills, headaches, nausea, vomiting, myalgia) are the most frequent adverse events. On the skin, a localized papular rash or the aggravation of the psoriasis in an edematous or even pustular form are the two most regularly observed complications. At the biological level, hyperlymphocytosis and a temporary increase in alkaline phosphatases without clinical consequences are the most frequent anomalies. We report 2 adverse events under efalizumab that to our knowledge have never been described: a case of an eczematous rash and a case of thrombocytosis.
Immunocytochemical Detection of Occult Tumor Cells in the Bone Marrow: Prognostic Impact on Early Stages of Lung Cancer
Authors: Nosotti M. , Tosi D. , Palleschi A. , Rosso L. , Mendogni P. , Santambrogio L.
Published: July 2008

Objectives: This study was designed to verify the prognostic impact of occult tumor cells in the bone marrow of stage I and II non-small-cell lung cancer patients using cytokeratin as a micrometastatic marker. Methods: One hundred and fifty-two patients with stage I and II non-small-cell lung cancer, who underwent radical surgery by pulmonary lobectomy, were entered into the study. Bone marrow from fragments of resected ribs, and primary tumors were stained by anti-cytokeratin 18 antibody. Fourteen bone marrow specimens from patients without malignancy were used as a control group. Cancer recurrence was the study end point. Results: All the primary tumors were positive for cytokeratin; occult tumor cells were detected in 38 bone marrow specimens (25%). The prevalence of the occult tumor cells was not related to age, gender, tumor stage, histological differentiation or grade. The mean follow-up time was 35.3 months; 68 patients developed recurrence; the mean time for recurrence was 21.2 months. The general disease-free interval was not related to the presence of occult tumor cells in the bone marrow. This result did not change when grouping the patients by tumor stage. The stage was the best predictor of cancer recurrence (Cox proportional hazards model ratio: 2.09; p = 0.0026). Conclusions: This study confirms that immunocytochemical analysis detects occult tumor cells in the bone marrow of at least 25% of patients surgically treated for stage I and II non-small-cell lung cancer. These occult tumor cells do not have any impact on the disease-free interval.
Molecular Characterization of Human Impacted Third Molars: Diversification of Compartments
Authors: Schoenebeck B. , Hartschen H.J. , Schindel M. , Degistirici O. , Siemonsmeier J. , Goetz W. , Thie M.
Published: July 2008

To gain more insight into the development of human teeth, we characterized different compartments of impacted third molars at two developmental stages by assessing expression levels of a set of genes. We considered genes known to be essential for the development of teeth and ectomesenchyme as well as genes covering characteristic features of stemness. Molars were divided into the operculum, periodontal ligament, developing pulp and, using a new approach, the pad-like tissue beneath the developing pulp. Markers for ectomesenchyme and tooth development known from rodents were assayed by semiquantitative PCR and every compartment was assigned its own signature of gene expression. The expression of markers characteristic of stem cells pointed to multipotent features. The expression patterns found shift in the course of development underscoring the relevance of these genes involved in human tooth development. The results suggest an inherent asymmetry between the developing pulp and pad-like tissue established early in tooth development. A microarray analysis of cells derived from pad-like tissue and pulp proper was performed to obtain cues regarding the consequences of tissue diversification. Both sets of data support the validity of our new approach to the subdivision of the developing tooth, by indicating a compartment-dependent commitment of isolated cells probably due to the postulated asymmetry within the developing tooth germ.
Modes of Action of the New Arylguanidine Abafungin beyond Interference with Ergosterol Biosynthesis and in vitro Activity against Medically Important Fungi
Authors: Borelli C. , Schaller M. , Niewerth M. , Nocker K. , Baasner B. , Berg D. , Tiemann R. , Tietjen K. , Fugmann B. , Lang-Fugmann S. , Korting H.C.
Published: July 2008

Background:In contrast to the increasing numbers of agents for the treatment of invasive fungal infections, discoveries of new antifungal agents with therapeutic value in dermatomycoses are reported only rarely. Methods: Abafungin (chemical abstracts service registry No. 129639-79/8) is the first member of a novel class of synthetic antifungal compounds, the arylguanidines. It was first synthesized at Bayer AG, Leverkusen, Germany, and its antifungal action was discovered during the screening of H2-receptor antagonists based on the structure of famotidine. To obtain insight into its mode of action and antifungal activity, various tests were carried out with different fungal pathogensin vitro. Results: Abafungin was found to have potent antifungal activity. Furthermore, mode-of-action studies suggested that abafungin exerts its antifungal activity regardless of whether the pathogens are growing or in a resting state. One target of abafungin was found to be the inhibition of transmethylation at the C-24 position of the sterol side chain, catalyzed by the enzyme sterol-C-24-methyltransferase. A second action of abafungin seems to be a direct effect on the fungal cell membrane.Conclusion: The observed characteristics of abafungin indicate that abafungin might be a promising antifungal agent defining a new class of antimycotics.
Direction-Induced Effects of Visually Guided Weight-Shifting Training on Standing Balance in the Elderly
Authors: Hatzitaki Vassilia , Amiridis Ioannis G. , Nikodelis Thomas , Spiliopoulou Styliani
Published: July 2008

Background: Controversial findings exist in the literature with respect to the efficacy of visually guided weight-shifting (WS) training as a means of improving balance in healthy older adults. Objective: The purpose of this study was to investigate the impact of two direction-specific, visually guided WS training protocols on standing balance of healthy elderly women. Methods: Forty-eight community-dwelling elderly women, all free of any neurological or musculoskeletal impairment, were randomly assigned into: a group that practiced WS in the anterior/posterior direction (A/P group, n = 19), a group that practiced WS in the medio/lateral direction (M/L group, n = 15) and a control group (n = 14). Participants performed 12 training sessions of visually guided WS (3 sessions a week for 25 minutes per session). Static balance was measured before and after training in normal (bipedal) quiet stance (NQS) and sharpened-Romberg stance (SRS) by recording center of pressure (CoP) variations and angular segment kinematics. Results: In NQS, neither of the two training protocols had a significant impact on postural sway measures, although a significant decrease in interlimb asymmetry of CoP displacement was noted for the A/P group. In SRS, A/P training induced a significant reduction of CoP displacement, lower limb pitch and upper trunk roll rotation. Conclusion: The results of the study stress the importance of using direction-specific WS tasks in balance training, particularly in the A/P direction, in order to improve control of static balance in elderly women.
Transcription of Genes Coding for Metabolic Key Functions in Nitrosomonas europaea during Aerobic and Anaerobic Growth
Authors: Beyer Sonja , Gilch Stefan , Meyer Ortwin , Schmidt Ingo
Published: July 2008

Nitrosomonas europaea can grow under conditions of chemolithoautotrophic aerobic (oxygen as oxidant) as well as anaerobic [nitrogen dioxide (NO2) as oxidant] nitrification or chemoorganotrophic anaerobic pyruvate-dependent denitrification. In this study, the adaptation of the transcription (mRNA synthesis/concentration) of N. europaea to aerobic and anaerobic growth conditions was evaluated and the transcription of genes coding for metabolic key functions was analyzed: nitrogen and energy metabolism (amoA, hao, rh1, nirK, norB, nsc, aceE, ldhA, ppc, gltA, odhA, coxA), carbon dioxide fixation (cbbL), gluconeogenesis (ppsA), cell growth (ftsZ), and oxidative stress (sodB). During aerobic ammonia oxidation the specific activities of ammonia oxidation, nitrite reduction, and the growth rates correlated with the transcription level of the corresponding genes amoA/hao, nirK/norB/nsc, and cbbL/ftsZ. In anaerobically ammonia-oxidizing cells of N. europaea, the cellular mRNA concentrations of amoA, hao, rh1,coxA, cbbL, ftsZ, and sodB were reduced compared with aerobically nitrifying cells, but the mRNA levels of nirK, norB, and nsc were significantly increased. During anaerobic pyruvate-dependent denitrification, the mRNA abundance of nirK, norB, nsc, aceE, gltA, and odhA was increased, while the concentrations of amoA,hao, rh1, coxAcbbL, ftsZ, and sodB were significantly reduced. Temperature, pH value, and NH4+, O2, NO, and NO2 concentrations had comparatively small effects on the transcription of the studied genes.
Low HDL Cholesterol Is a Risk Factor for Deficit and Decline in Memory in Midlife
Authors: Singh-Manoux Archana , Gimeno David , Kivimaki Mika , Brunner Eric , Marmot Michael G.
Published: July 2008

Objective—

The purpose of this study was to examine the relationship between fasting serum lipids and short-term verbal memory in middle-aged adults.

Methods and Results—

Total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and memory were measured twice, at mean ages 55 and 61, in 3673 male and female participants of the Whitehall II study. Short-term verbal memory was assessed using a 20-word list. Logistic regression was used to model associations between ATP-III categories of lipids and memory deficit (recall of ≤4 words) and decline (decrease of ≥2 words). Analyses were adjusted for education, occupational position, coronary heart disease, stroke, hypertension, use of medication, diabetes, smoking, and alcohol consumption. Compared to high HDL-C (≥60 mg/dL), low HDL-C (<40 mg/dL) was associated with greater odds of memory deficit at the first (OR=1.27; 95% confidence interval [CI]=0.91 to 1.77) and second wave of this study (OR=1.53; 95% CI=1.04 to 2.25) in fully adjusted analysis. Decrease in HDL-C over the 5-year follow-up period was associated with decline in memory in the adjusted analysis (OR=1.61; 95% CI=1.19 to 2.16); no interaction with APOE e4 status was present.

Conclusions—

HDL-C levels are potentially modifiable, and our results suggest that low HDL-C is associated with poor memory and decline in memory in middle-aged adults.
Outcome of Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy
Authors: Sorajja Paul , Valeti Uma , Nishimura Rick A. , Ommen Steve R. , Rihal Charanjit S. , Gersh Bernard J. , Hodge David O. , Schaff Hartzell V. , Holmes David R.
Published: July 2008

Background—

The clinical efficacy of alcohol septal ablation for drug-refractory hypertrophic cardiomyopathy remains unclear. This study examines the outcome of alcohol septal ablation performed at a tertiary hypertrophic cardiomyopathy referral center.

Methods and Results—

Among 601 patients with severely symptomatic obstructive hypertrophic cardiomyopathy referred for alcohol septal ablation or myectomy from 1998 to 2006, 138 patients (median age, 64 years; 39% men) chose to undergo ablation. Procedural complications included death in 1.4%, sustained ventricular arrhythmias in 3%, tamponade in 3%, and pacemaker implantation in 20%. This rate was higher than a combined complication rate of 5% in age- and gender-matched patients who had undergone septal myectomy at Mayo Clinic (
P
<0.0001). Four-year survival free of all mortality was 88.0% (95% confidence interval, 79.4 to 97.5%), which was similar to that of the age- and gender-matched patients who had undergone myectomy (
P
=0.18). Six patients had documented ventricular arrhythmias after ablation, 4 of whom had successful intervention. Four-year survival free of death and severe New York Heart Association class III/IV symptoms after septal ablation was 76.4%, and 71 patients (51%) became asymptomatic. Myectomy patients ≤65 years of age had significantly better survival free of death and severe symptoms (
P
=0.01).

Conclusions—

Alcohol septal ablation is an efficacious procedure if performed in an experienced institution and may resolve symptoms in a subset of patients with obstructive hypertrophic cardiomyopathy. However, the procedural complication rate exceeds that of myectomy. Patients ≤65 years of age have better symptom resolution with myectomy. No impairment in short-term survival was noted in this nonrandomized study, but the long-term outcome remains unknown.
Longitudinal Tracking of Recipient Macrophages in a Rat Chronic Cardiac Allograft Rejection Model With Noninvasive Magnetic Resonance Imaging Using Micrometer-Sized Paramagnetic Iron Oxide Particles
Authors: Ye Qing , Wu Yijen L. , Foley Lesley M. , Hitchens T. Kevin , Eytan Danielle F. , Shirwan Haval , Ho Chien
Published: July 2008

Background—

Long-term survival of heart transplants is hampered by chronic rejection (CR). Studies indicate the involvement of host macrophages in the development of CR; however, the precise role of these cells in CR is unclear. Thus, it is important to develop noninvasive techniques to serially monitor the movement and distribution of recipient macrophages in chronic cardiac allograft rejection in vivo.

Methods and Results—

We have employed a rat heterotopic working-heart CR model for a magnetic resonance imaging experiment. Twenty-one allograft (PVG.1U→PVG.R8) and 9 isograft (PVG.R8→PVG.R8) transplantations were performed. Recipient macrophages are labeled via intravenous injection of micron-sized paramagnetic iron oxide particles (0.9 μm in diameter) at a dose of 4.5 mg Fe per rat 1 day before transplantation. Serial in vivo magnetic resonance images were acquired for up to 16 weeks. The migration of labeled recipient cells in our CR model, in which cardiac CR is evident at 3 weeks and most extensive by 16 weeks after transplantation, can be assessed with the use of in vivo magnetic resonance imaging for >100 days after a single micron-sized paramagnetic iron oxide injection. The location and distribution of labeled recipient cells were confirmed with magnetic resonance microscopy and histology.

Conclusions—

This approach may improve our understanding of the immune cells involved in CR and the management of heart transplantation. Moreover, this study demonstrates the feasibility of noninvasively observing individual targeted cells over long time periods by serial in vivo magnetic resonance imaging.
Specific Jagged-1 Signal From Bone Marrow Microenvironment Is Required for Endothelial Progenitor Cell Development for Neovascularization
Authors: Kwon Sang-Mo , Eguchi Masamichi , Wada Mika , Iwami Yo , Hozumi Katsuhito , Iwaguro Hideki , Masuda Haruchika , Kawamoto Atsuhiko , Asahara Takayuki
Published: July 2008

Background—

Despite accumulating evidence that proves the pivotal role of endothelial progenitor cells (EPCs) in ischemic neovascularization, the key signaling cascade that regulates functional EPC kinetics remains unclear.

Methods and Results—

In this report, we show that inactivation of specific Jagged-1 (Jag-1)–mediated Notch signals leads to inhibition of postnatal vasculogenesis in hindlimb ischemia via impairment of proliferation, survival, differentiation, and mobilization of bone marrow–derived EPCs. Bone marrow–derived EPCs obtained from
Jag-1
−/−
mice, but not Delta-like (
Dll)-1
−/−
mice, demonstrated less therapeutic potential for ischemic neovascularization than EPCs from the wild type. In contrast, a gain-of-function study using 3T3 stromal cells overexpressing Notch ligand revealed that Jag-1–mediated Notch signals promoted EPC commitment, which resulted in enhanced neovascularization. The impaired neovascularization in
Jag-1
−/−
mice was profoundly rescued by transplantation of Jag-1–stimulated EPCs.

Conclusions—

These data indicate that specific Jag-1–derived Notch signals from the bone marrow microenvironment are critical for EPC–mediated vasculogenesis, thus providing an important clue for modulation of strategies for therapeutic neovascularization.
Population-Based Prevention of Obesity
Authors: Kumanyika Shiriki K. , Obarzanek Eva , Stettler Nicolas , Bell Ronny , Field Alison E. , Fortmann Stephen P. , Franklin Barry A. , Gillman Matthew W. , Lewis Cora E. , Poston Walker Carlos , Stevens June , Hong Yuling
Published: July 2008

Obesity is a major influence on the development and course of cardiovascular diseases and affects physical and social functioning and quality of life. The importance of effective interventions to reduce obesity and related health risks has increased in recent decades because the number of adults and children who are obese has reached epidemic proportions. To prevent the development of overweight and obesity throughout the life course, population-based strategies that improve social and physical environmental contexts for healthful eating and physical activity are essential. Population-based approaches to obesity prevention are complementary to clinical preventive strategies and also to treatment programs for those who are already obese. This American Heart Association scientific statement aims: 1) to raise awareness of the importance of undertaking population-based initiatives specifically geared to the prevention of excess weight gain in adults and children; 2) to describe considerations for undertaking obesity prevention overall and in key risk subgroups; 3) to differentiate environmental and policy approaches to obesity prevention from those used in clinical prevention and obesity treatment; 4) to identify potential targets of environmental and policy change using an ecological model that includes multiple layers of influences on eating and physical activity across multiple societal sectors; and 5) to highlight the spectrum of potentially relevant interventions and the nature of evidence needed to inform population-based approaches. The evidence-based experience for population-wide approaches to obesity prevention is highlighted.
Prediction of First Events of Coronary Heart Disease and Stroke With Consideration of Adiposity
Authors: Wilson Peter W.F. , Bozeman Samuel R. , Burton Tanya M. , Hoaglin David C. , Ben-Joseph Rami , Pashos Chris L.
Published: July 2008

Background—

Prediction of coronary heart disease (CHD) and cerebrovascular disease (CeVD) can aid healthcare providers and prevention programs. Previous reports have focused on traditional cardiovascular risk factors; less information has been available on the role of overweight and obesity.

Methods and Results—

Baseline data from 4780 Framingham Offspring Study adults with up to 24 years of follow-up were used to assess risk for a first CHD event (angina pectoris, myocardial infarction, or cardiac death) alone, first CeVD event (acute brain infarction, transient ischemic attack, and stroke-related death) alone, and CHD and CeVD events combined. Accelerated failure time models were developed for the time of first event to age, sex, cholesterol, high-density lipoprotein cholesterol, diabetes mellitus (DM), systolic blood pressure, smoking status, and body mass index (BMI). Likelihood-ratio tests of statistical significance were used to identify the best-fitting predictive functions. Age, sex, smoking status, systolic blood pressure, ratio of cholesterol to high-density lipoprotein cholesterol, and presence of DM were highly related (
P
<0.01 for all) to the development of first CHD events, and all of the above except sex and DM were highly related to the first CeVD event. BMI also significantly predicted the occurrence of CHD (
P
=0.05) and CeVD (
P
=0.03) in multivariable models adjusting for traditional risk factors. The magnitude of the BMI effect was reduced but remained statistically significant when traditional variables were included in the prediction models.

Conclusions—

Greater BMI, higher systolic blood pressure, higher ratio of cholesterol to high-density lipoprotein cholesterol, and presence of DM were all predictive of first CHD events, and all but the presence of DM were predictive of first CeVD events. These results suggest that common pathophysiological mechanisms underlie the roles of BMI, DM, and systolic blood pressure as predictors for first CHD and CeVD events.
Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats
Authors: Michea Luis , Villagrán Andrea , Urzúa Alvaro , Kuntsmann Sonia , Venegas Patricio , Carrasco Loreto , Gonzalez Magdalena , Marusic Elisa T.
Published: July 2008

Chronic renal failure causes left ventricular hypertrophy, but the molecular mechanisms involved remain unknown. We, therefore, investigated whether the mineralocorticoid receptor is implicated in the cardiac hypertrophy observed in uremic rats and whether mineralocorticoid receptor blockade could be protective in chronic renal failure. Experimental groups were: control rats, uremic rats (NPX) with 5/6 nephrectomy (5 weeks), and NPX rats fed with spironolactone for 5 weeks. Systolic blood pressure was increased in both NPX rats and NPX rats fed with spironolactone for 5 weeks. Echocardiography revealed concentric left ventricular hypertrophy in uremia, which was attenuated by spironolactone. Enlarged cardiomyocyte size was observed in both left and right ventricles of NPX rats, an effect that was prevented by spironolactone. Mineralocorticoid receptor antagonism attenuated the increase of ventricular brain natriuretic peptide mRNA levels induced by nephrectomy. Left ventricular gene expressions of aldosterone synthase, mineralocorticoid receptor, and hydroxysteroid dehydrogenase type 2 were the same in the 3 groups, whereas gene expression of the glucocorticoid receptor was significantly diminished in chronic renal failure rats. No significant differences in cardiac aldosterone were observed between control rats and NPX rats, although NPX rats fed with spironolactone for 5 weeks showed increased plasma aldosterone levels. However, a significant increase in serum and glucocorticoid-inducible kinase-1 mRNA expression and protein was present in the NPX group; spironolactone treatment significantly reduced serum and glucocorticoid-inducible kinase-1 mRNA and protein in the left ventricle. Uremic rats exhibited a significant increase of superoxide production and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits expression (NOX-2, NOX-4, and p47
phox
) in the left ventricle, which was prevented by the mineralocorticoid receptor antagonist. Our findings provide evidence of the beneficial effects of spironolactone in cardiac hypertrophy and cardiac oxidative stress in chronic renal failure.
Efficacy and Safety of the Angiotensin Receptor Blocker Valsartan in Children With Hypertension Aged 1 to 5 Years
Authors: Flynn Joseph T. , Meyers Kevin E.C. , Neto Jose Pacheco , de Paula Meneses Rejane , Zurowska Aleksandra , Bagga Arvind , Mattheyse Lionel , Shi Victor , Gupte Jitendra , Solar-Yohay Susan , Han Guangyang
Published: July 2008

The efficacy and safety of valsartan were studied in 90 children (mean age: 3.2 years; 60% male; 30% black) with systolic blood pressure (SBP) ≥95th percentile. Nineteen percent received valsartan in addition to previous antihypertensive therapy. Subjects were randomly assigned to low-, medium-, or high-dose valsartan for 2 weeks (phase 1) and then reassigned randomly to placebo or to remain on the same valsartan dose for 2 additional weeks (phase 2). After this, subjects were enrolled into a 52-week, open-label phase during which valsartan was dosed to achieve SBP <95th percentile. Statistically significant reductions in SBP and diastolic blood pressure of ≈8.5 mm Hg and 5.7 mm Hg, respectively, were observed at the end of phase 1 in all of the valsartan dose groups. SBP and diastolic blood pressure were also significantly lower during phase 2 in valsartan recipients compared with placebo recipients. SBP <95th percentile was achieved in 77.3% of subjects during the open-label phase. Adverse events were minor and occurred at similar frequencies in each of the 3 dose groups in phase 1 and at equal frequencies in the valsartan and placebo arms in phase 2. Serious adverse events and drug-related adverse events occurred infrequently during both the double-blind (2.2% and 5.6%, respectively) and open-label (14.8% and 6.8%, respectively) portions of the study. Valsartan treatment had no demonstrable negative effects on growth and development. In this study, the first trial of an antihypertensive agent conducted in children <6 years of age, valsartan effectively lowered SBP and diastolic blood pressure compared with placebo.
Physiological Interaction Between α-Adducin and
WNK1-NEDD4L
Pathways on Sodium-Related Blood Pressure Regulation
Authors: Manunta Paolo , Lavery Gail , Lanzani Chiara , Braund Peter S. , Simonini Marco , Bodycote Claire , Zagato Laura , Delli Carpini Simona , Tantardini Cristina , Brioni Elena , Bianchi Giuseppe , Samani Nilesh J.
Published: July 2008

The kidney plays an important role in salt and blood pressure (BP) homeostasis. In previous studies, variants in the genes for α-adducin (ADD1), WNK1, and NEDD4L, which all regulate renal sodium absorption, have been associated with increased BP. However, findings have been inconsistent. We tested whether this is because of physiological interactions between the effects of variants in these genes. We assessed the single and combined effects of the ADD1 (Gly460Trp), WNK1 (rs880054 A/G), and NEDD4L (rs4149601 G/A) polymorphisms on renal and BP response to an acute Na load (n=344 subjects), BP decrease after 1 month of treatment with 12.5 mg of hydrochlorothiazide (n=193), and ambulatory 24-hour BP (n=690). Individually, the variants showed modest effects on some of the studied phenotypes. We found the ADD1 Trp allele to be permissive for the effects of variants of the other genes. In combination, the same variants (ADD1 Trp/WNK1 GG/Nedd4L GA+AA) showed a consistent effect on renal Na handling (
P
=0.009) and acute BP response to a saline infusion (
P
=0.021), BP lowering after thiazide treatment (
P
=0.008), and nocturnal systolic BP (
P
=0.044). Physiological interaction between the ADD1 and WNK1-NEDD4L pathways influences the effects of variants in these genes on sodium-related BP regulation. Relatively common alleles in the ADD1, WNK1, and NEDD4L genes when present in combination may have significant effects on renal sodium handling, BP, and antihypertensive response to thiazides.
Motor-induced Suppression of the Auditory Cortex
Authors: Aliu Sheye O. , Houde John F. , Nagarajan Srikantan S.
Published: July 2008

Sensory responses to stimuli that are triggered by a self-initiated motor act are suppressed when compared with the response to the same stimuli triggered externally, a phenomenon referred to as motor-induced suppression (MIS) of sensory cortical feedback. Studies in the somatosensory system suggest that such suppression might be sensitive to delays between the motor act and the stimulus onset, and a recent study in the auditory system suggests that such MIS develops rapidly. In three MEG experiments, we characterize the properties of MIS by examining the M100 response from the auditory cortex to a simple tone triggered by a button press. In Experiment 1, we found that MIS develops for zero delays but does not generalize to nonzero delays. In Experiment 2, we found that MIS developed for 100-msec delays within 300 trials and occurs in excess of auditory habituation. In Experiment 3, we found that unlike MIS for zero delays, MIS for nonzero delays does not exhibit sensitivity to sensory, delay, or motor-command changes. These results are discussed in relation to suppression to self-produced speech and a general model of sensory motor processing and control.
The Long Road to Automation: Neurocognitive Development of Letter–Speech Sound Processing
Authors: Froyen Dries J. W. , Bonte Milene L. , van Atteveldt Nienke , Blomert Leo
Published: July 2008

In transparent alphabetic languages, the expected standard for complete acquisition of letter–speech sound associations is within one year of reading instruction. The neural mechanisms underlying the acquisition of letter–speech sound associations have, however, hardly been investigated. The present article describes an ERP study with beginner and advanced readers in which the influence of letters on speech sound processing is investigated by comparing the MMN to speech sounds presented in isolation with the MMN to speech sounds accompanied by letters. Furthermore, SOA between letter and speech sound presentation was manipulated in order to investigate the development of the temporal window of integration for letter–speech sound processing. Beginner readers, despite one year of reading instruction, showed no early letter–speech sound integration, that is, no influence of the letter on the evocation of the MMN to the speech sound. Only later in the difference wave, at 650 msec, was an influence of the letter on speech sound processing revealed. Advanced readers, with 4 years of reading instruction, showed early and automatic letter–speech sound processing as revealed by an enhancement of the MMN amplitude, however, at a different temporal window of integration in comparison with experienced adult readers. The present results indicate a transition from mere association in beginner readers to more automatic, but still not “adult-like,” integration in advanced readers. In contrast to general assumptions, the present study provides evidence for an extended development of letter–speech sound integration.
Parameterization of Eddy Fluxes near Oceanic Boundaries
Authors: Ferrari Raffaele , McWilliams James C. , Canuto Vittorio M. , Dubovikov Mikhail
Published: July 2008

In the stably stratified interior of the ocean, mesoscale eddies transport materials by quasi-adiabatic isopycnal stirring. Resolving or parameterizing these effects is important for modeling the oceanic general circulation and climate. Near the bottom and near the surface, however, microscale boundary layer turbulence overcomes the adiabatic, isopycnal constraints for the mesoscale transport. In this paper a formalism is presented for representing this transition from adiabatic, isopycnally oriented mesoscale fluxes in the interior to the diabatic, along-boundary mesoscale fluxes near the boundaries. A simple parameterization form is proposed that illustrates its consequences in an idealized flow. The transition is not confined to the turbulent boundary layers, but extends into the partially diabatic transition layers on their interiorward edge. A transition layer occurs because of the mesoscale variability in the boundary layer and the associated mesoscale–microscale dynamical coupling.
Response of the Antarctic Circumpolar Current to Atmospheric Variability
Authors: Sallée J. B. , Speer K. , Morrow R.
Published: July 2008

Historical hydrographic profiles, combined with recent Argo profiles, are used to obtain an estimate of the mean geostrophic circulation in the Southern Ocean. Thirteen years of altimetric sea level anomaly data are then added to reconstruct the time variable sea level, and this new dataset is analyzed to identify and monitor the position of the two main fronts of the Antarctic Circumpolar Current (ACC) during the period 1993–2005. The authors relate their movements to the two main atmospheric climate modes of the Southern Hemisphere: the Southern Annular Mode (SAM) and the El Niño–Southern Oscillation (ENSO). The study finds that although the fronts are steered by the bathymetry, which sets their mean pathway on first order, in flat-bottom areas the fronts are subject to large meandering because of mesoscale activity and atmospheric forcing. While the dominant mode of atmospheric variability in the Southern Hemisphere, SAM, is relatively symmetric, the oceanic response of the fronts is not, showing substantial regional differences. Around the circumpolar belt the fronts vary in latitude, exposing them to different Ekman transport anomalies induced by the SAM. Three typical scenarios occur in response to atmospheric forcing: poleward movement of the frontal structure in the Indian Basin during positive SAM events, an equatorward movement in the central Pacific, and an intensification without substantial meridional movement in the Indo-Pacific basin. The study also shows the geographical regions that are dominated by a SAM or ENSO response at low and high frequencies.
A Coupled Air–Sea Response Mechanism to Solar Forcing in the Pacific Region
Authors: Meehl Gerald A. , Arblaster Julie M. , Branstator Grant , van Loon Harry
Published: July 2008

The 11-yr solar cycle [decadal solar oscillation (DSO)] at its peaks strengthens the climatological precipitation maxima in the tropical Pacific during northern winter. Results from two global coupled climate model ensemble simulations of twentieth-century climate that include anthropogenic (greenhouse gases, ozone, and sulfate aerosols, as well as black carbon aerosols in one of the models) and natural (volcano and solar) forcings agree with observations in the Pacific region, though the amplitude of the response in the models is about half the magnitude of the observations. These models have poorly resolved stratospheres and no 11-yr ozone variations, so the mechanism depends almost entirely on the increased solar forcing at peaks in the DSO acting on the ocean surface in clear sky areas of the equatorial and subtropical Pacific. Mainly due to geometrical considerations and cloud feedbacks, this solar forcing can be nearly an order of magnitude greater in those regions than the globally averaged solar forcing. The mechanism involves the increased solar forcing at the surface being manifested by increased latent heat flux and evaporation. The resulting moisture is carried to the convergence zones by the trade winds, thereby strengthening the intertropical convergence zone (ITCZ) and the South Pacific convergence zone (SPCZ). Once these precipitation regimes begin to intensify, an amplifying set of coupled feedbacks similar to that in cold events (or La Niña events) occurs. There is a strengthening of the trades and greater upwelling of colder water that extends the equatorial cold tongue farther west and reduces precipitation across the equatorial Pacific, while increasing precipitation even more in the ITCZ and SPCZ. Experiments with the atmosphere component from one of the coupled models are performed in which heating anomalies similar to those observed during DSO peaks are specified in the tropical Pacific. The result is an anomalous Rossby wave response in the atmosphere and consequent positive sea level pressure (SLP) anomalies in the North Pacific extending to western North America. These patterns match features that occur during DSO peak years in observations and the coupled models.
Effects of Black Carbon Aerosols on the Indian Monsoon
Authors: Meehl Gerald A. , Arblaster Julie M. , Collins William D.
Published: July 2008

A six-member ensemble of twentieth-century simulations with changes to only time-evolving global distributions of black carbon aerosols in a global coupled climate model is analyzed to study the effects of black carbon (BC) aerosols on the Indian monsoon. The BC aerosols act to increase lower-tropospheric heating over South Asia and reduce the amount of solar radiation reaching the surface during the dry season, as noted in previous studies. The increased meridional tropospheric temperature gradient in the premonsoon months of March–April–May (MAM), particularly between the elevated heat source of the Tibetan Plateau and areas to the south, contributes to enhanced precipitation over India in those months. With the onset of the monsoon, the reduced surface temperatures in the Bay of Bengal, Arabian Sea, and over India that extend to the Himalayas act to reduce monsoon rainfall over India itself, with some small increases over the Tibetan Plateau. Precipitation over China generally decreases due to the BC aerosol effects. There is a weakened latitudinal SST gradient resulting from BC aerosols in the model simulations as seen in the observations, and this is present in the multiple-forcings experiments with the Community Climate System Model, version 3 (CCSM3), which includes natural and anthropogenic forcings (including BC aerosols). The BC aerosols and consequent weakened latitudinal SST gradient in those experiments are associated with increased precipitation during MAM in northern India and over the Tibetan Plateau, with some decreased precipitation over southwest India, the Bay of Bengal, Burma, Thailand, and Malaysia, as seen in observations. During the summer monsoon season, the model experiments show that BC aerosols have likely contributed to observed decreasing precipitation trends over parts of India, Bangladesh, Burma, and Thailand. Analysis of single ensemble members from the multiple-forcings experiment suggests that the observed increasing precipitation trends over southern China appear to be associated with natural variability connected to surface temperature changes in the northwest Pacific.
Intraseasonal Variability in Diurnal Rainfall over New Guinea and the Surrounding Oceans during Austral Summer
Authors: Ichikawa Hiroki , Yasunari Tetsuzo
Published: July 2008

High-resolution Tropical Rainfall Measuring Mission (TRMM) rainfall data for six wet seasons (December–March) were used to investigate the time and space structure of the diurnal cycle of rainfall over and around New Guinea, a major island of the Maritime Continent. The diurnal cycle shows a systematic modulation associated with intraseasonal variability in the large-scale circulation pattern, with regimes associated with low-level easterlies or westerlies over the island. Lower-tropospheric easterly (westerly) wind components correspond to periods of inactive (active) convection over the islands that are associated with the passage of intraseasonal atmospheric disturbances such as the Madden–Julian oscillation (MJO). A striking feature is the diurnal rainfall that develops over the central mountain ranges in the evening and propagates toward the southwest (northeast) of the island with an inferred phase speed of about 2–3 m s−1 under low-level easterly (westerly) flow. In the case of the easterly regime, diurnal rainfall is strongly concentrated over the southwestern part of the island, inhibited from spreading offshore southwest of New Guinea. Under the westerly regime, in contrast, the rainfall area spread far and wide along the low-level westerlies from the island toward the Pacific Ocean. Significant offshore rainfall propagation extending from the island appears during the night over the north-northeastern coast and moves with a phase speed of about 7–8 m s−1, reaching the open ocean the following day. Possible processes for controlling the variability in diurnal rainfall through the interaction between large-scale circulation and previously denoted complex local circulation over the island are discussed.