bluuebunny/crossref_metadata_2025 huggingface dataset:
A Longitudinal Study to Determine the Effects of Mentoring on Middle School Youngsters by Nursing and Other College Students
Authors: Whiting Sylvia M. A. , Mallory James E.
Published: November 2007

PURPOSE:  This study aims to utilize nursing and other college students in conducting a mentoring project aimed at determining outcomes of behavior and attitude of high‐risk middle school students over a 5‐year period.

METHOD:  A quasi‐experimental study with a sample of fifth and sixth graders was conducted in which mentored subjects were tested using multiple instruments and school data to identify behavioral and attitudinal outcomes. Statistical analyses were conducted using chi‐square and one‐way analysis of variance.

FINDINGS:  Academically below‐average males in the treatment group were the only cohort demonstrating significant change across all measures. The magnitude of change in this cohort, however, did significantly affect treatment group outcomes overall. Females in both treatment and control groups reflected similar changes.

CONCLUSIONS:  Mentoring of schoolchildren is difficult to accomplish using college mentors because of time and schedule commitments. When college mentors are used, grade allocation seems to be a stronger incentive than when payment is the sole reward. Males whose grades are below average demonstrated positive outcomes from the mentoring experience.
Use of Psychiatric Nurse Practitioner Students to Provide Services in Rural School‐Based Health Clinics
Authors: Grossman Janet , Laken Marilyn , Stevens Janet , Hughes‐Joyner Frederica , Sholar Michael , Gormley Captain Kevin
Published: November 2007

Seventy to eighty percent of youth receiving mental health services receive these services in schools. Nurses have been identified as the second major provider of mental health services in the schools, yet little has been written about the role of psychiatric mental health nurses in rural school‐based clinics or how they were trained in this role. This paper describes an innovative clinical experience for graduate students to shape the role of advanced psychiatric mental health nurses in rural, minority schools using evidence‐based approaches. The authors describe the context, theoretical frameworks, role development, outcomes, and lessons learned.
Cost‐efficacy in measuring farmland biodiversity – lessons from the Farm Scale Evaluations of genetically modified herbicide‐tolerant crops
Authors: Qi A. , Perry J.N. , Pidgeon J.D. , Haylock L.A. , Brooks D.R.
Published: November 2007

Measuring farmland biodiversity is time‐consuming and costly. Operational data from the Farm Scale Evaluation of genetically modified crops project were collated to identify the financial and time costs of each of the 14 protocols used. A subset of 113 of the 266 experimental sites was used. The mean overall cost per site was £19 453 (£ of 2002). Laboratory time was almost 2.5 times that in the field. The most costly protocol was soil surface invertebrates because it required species level identification. The ‘bees and butterflies’ protocol at £418 per site was particularly cost‐effective. The six vegetation protocols accounted for 65% and the six arthropod protocols accounted for 29% of the total costs. The recommended reduction from 12 to 3 transects would have saved £1356 per site, 6% of total budget. A minimalist approach using the single‐season seedbank protocol would cost £3437 per site. The effect of geographical spread of sites on cost was small because of clustering of sites and the large number of protocols. Careful selection of ecological indicators can save considerable resources.
Research Article: The N‐Terminal Domain of 2′,3′‐Cyclic Nucleotide 3′‐Phosphodiesterase Harbors a GTP/ATP Binding Site
Authors: Stingo Stefania , Masullo Mariorosario , Polverini Eugenia , Laezza Chiara , Ruggiero Immacolata , Arcone Rosaria , Ruozi Enrica , Piaz Fabrizio Dal , Malfitano Anna Maria , D’Ursi Anna Maria , Bifulco Maurizio
Published: November 2007

The interaction between 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase and guanine/adenine nucleotides was investigated. The binding of purine nucleotides to 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase was revealed by both direct and indirect methods. In fact, surface plasmon resonance experiments, triphosphatase activity measurements, and fluorescence experiments revealed that 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase binds purine nucleotide triphosphates with an affinity higher than that displayed for diphosphates; on the contrary, the affinity for both purine monophosphates and pyrimidine nucleotides was negligible. An interpretation of biological experimental data was achieved by a building of 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase N‐terminal molecular model. The structural elements responsible for nucleotide binding were identified and potential complexes between the N‐terminal domain of CNP‐ase and nucleotide were analyzed by docking simulations. Therefore, our findings suggest new functional and structural property of the N‐terminal domain of CNPase.
Recent Research on Changes in Genomic Regulation and Protein Expression in Intracerebral Haemorrhage
Authors: Cannon Jason R. , Xi Guohua , Keep Richard F.
Published: November 2007

Intracerebral haemorrhage (ICH) is a devastating form of stroke that accounts for roughly 10% of all strokes and the effects on those that survive are often debilitating. To date, no suitable therapy exists. Recent work has examined alterations in gene and protein expression after ICH. The focus of this review is to outline the current knowledge of changes in genetic and protein expression after ICH and how those changes may affect the course of brain injury. Both animal and human data are reviewed.
Characterization of ouabain‐induced noradrenaline and acetylcholine release from in situ cardiac autonomic nerve endings
Authors: Yamazaki T. , Akiyama T. , Kitagawa H. , Komaki F. , Mori H. , Kawada T. , Sunagawa K. , Sugimachi M.
Published: November 2007

Aim:  Although ouabain modulates autonomic nerve ending function, it is uncertain whether ouabain‐induced releasing mechanism differs between in vivo sympathetic and parasympathetic nerve endings. Using cardiac dialysis, we examined how ouabain induces neurotransmitter release from autonomic nerve ending.

Methods:  Dialysis probe was implanted in left ventricle, and dialysate noradrenaline (NA) or acetylcholine (ACh) levels in the anaesthetized cats were measured as indices of neurotransmitter release from post‐ganglionic autonomic nerve endings.

Results:  Locally applied ouabain (100 μm) increased in dialysate NA or ACh levels. The ouabain‐induced increases in NA levels remained unaffected by cardiac sympathetic denervation and tetrodotoxin (Na+ channel blocker, TTX), but the ouabain‐induced increases in ACh levels were attenuated by TTX. The ouabain‐induced increases in NA levels were suppressed by pretreatment with desipramine (NA transport blocker) and augmented by reserpine (vesicle NA transport blocker). In contrast, the ouabain‐induced increases in ACh levels remained unaffected by pretreatment with hemicholinium‐3 (choline transport blocker) but suppressed by vesamicol (vesicle ACh transport blocker). The ouabain‐induced increases in NA levels were suppressed by pretreatment with ω‐conotoxin GVIA (N‐type Ca2+ channel blocker), verapamil (L‐type Ca2+ channel blocker) and TMB‐8 (intracellular Ca2+ antagonist). The ouabain‐induced increases in ACh levels were suppressed by pretreatment with ω‐conotoxin MVIIC (P/Q‐type Ca2+ channel blocker), and TMB‐8.

Conclusions:  Ouabain‐induced NA release is attributable to the mechanisms of regional exocytosis and/or carrier‐mediated outward transport of NA, from stored NA vesicle and/or axoplasma, respectively, while the ouabain‐induced ACh release is attributable to the mechanism of exocytosis, which is triggered by regional depolarization. At both sympathetic and parasympathetic nerve endings, the regional exocytosis is because of opening of calcium channels and intracellular calcium mobilization.
Photosensitizing and Radiosensitizing Effects of Hypericin on Human Renal Carcinoma Cells in Vitro
Authors: Wessels Johannes Theodor , Busse Ann‐Christin , Rave‐Fränk Margret , Zänker Stephan , Hermann Robert , Grabbe Eckhardt , Müller Gerhard‐Anton
Published: November 2007

The renal cell carcinoma (RCC) is extremely resistant to chemotherapy and radiotherapy. The prognosis of patients with metastatic RCC still remains poor, the median survival is less than 12 months. Therefore, new therapeutic options are desirable. The aim of this study was to investigate the photosensitizing and radiosensitizing effects of hypericin on human RCC cells in vitro. First the RCC‐derived cell lines A498 and ACHN were incubated with different concentrations of hypericin. In vitro uptake and intracellular distribution of hypericin were confirmed by fluorescence microscopy. Subsequently cells were illuminated and irradiated with a dose of 2–8 Gy, respectively. Finally, metabolic activity, apoptosis and clonogenic survival were investigated. Uptake of hypericin was observed for almost all cells. Hypericin treatment combined with illumination led to a 94–97% decrease in metabolic activity and caused apoptosis in nearly 100% of RCC cells. Hypericin enhanced the radiosensitivity of A498 cells in vitro. The clonogenic survival after irradiation was significantly reduced by hypericin treatment. Taken together, the photosensitizing and radiosensitizing effects of hypericin on human RCC cells we found in this investigation could be of clinical relevance, e.g. for radiotherapy and intraoperative photodynamic therapy, respectively.
Characteristics of Dentists Providing Dental Care to Publicly Insured Patients
Authors: Pourat Nadereh , Roby Dylan H. , Wyn Roberta , Marcus Marvin
Published: November 2007

Objective: This study aims to identify the practice and patient care characteristics of dentists who provide care to publicly insured patients, beyond currently available existing information, which is typically limited to demographics of such dentists.

Methods: A cross‐section of dentists in private practices in California was surveyed, with a 46 percent average adjusted response rate. The sample included 3,180 generalists or specialists who provided general care in private practice. Characteristics of dentists who provided care to publicly insured patients were examined in descriptive analyses. The independent association of dentist characteristics with the provision of any care and the provision of care to a significant number of publicly insured patients were examined in logistic regression analyses.

Results: Over 40 percent of dentists saw public patients. Regression analyses revealed that dentists who spent more time in periodontic and surgical care, saw more walk‐in patients, had multilingual capacity, accepted reduced fees, had more minority patients, had fewer hygienists, or had multiple practice locations were more likely than those without such characteristics to provide care to publicly insured patients.

Conclusions: Dentists who care for publicly insured patients appear to have practices that are different from those who do not, in terms of delivery of patient care and practice structure. Such differences have implications for the access to and quality of dental health care of publicly insured patients. The success of public programs and policies aimed at ensuring access to dental care depends on ability and willingness of dentists to accommodate public patients’ needs.
Household Expenditure in Dental Health Care: National Estimations in Mexico for 2000, 2002, and 2004
Authors: Pérez‐Núñez Ricardo , Vargas‐Palacios Armando , Ochoa‐Moreno Ivan , Medina‐Solis Carlo Eduardo
Published: November 2007

Objective: To estimate the expenditure on dental care of Mexican households, analyze their trends, and determine the factors associated with the decision to spend and the amount of money spent in 2000, 2002, and 2004.

Material and Methods: Using the National Survey of Household Income and Expenditure for 2000, 2002, and 2004, the national dental health care expenditure was calculated. To facilitate comparability across years, all expenditure was converted to pesos of 2004, using the National Consumer Price Index (11.201 pesos per USD). Proportion of households incurring catastrophic expenditures was also estimated. To evaluate the association between environmental, household, and individual characteristics with the amount of dental health care expenditure, the Heckman regression model was used to control for self‐selection bias.

Results: More than 6,467 million pesos (MP) were spent in 2000 (8.5 percent of all households had some expenditure), over 3,925 MP in 2002 (4 percent households), and above 5,136 MP in 2004 (5 percent households), with an average expenditure of $806, $1,000, and $987 pesos, respectively. Prevalence of catastrophic expenditure because of dental health care was 0.8 percent in 2000 compared to 0.01 and 1.8 percent in 2002 and 2004, respectively. The Heckman model showed that municipal development, stratum, and age of the head of household significantly influenced the amount spent on dental care in all 3 years. Household capacity to pay and wealth index had a positive and statistically significant association in the 3 years with the preceding decision to spend.

Conclusions: Variables associated with the amount of expenditure and the decision of spending support the existence of inequities in health care financing in the Mexican population.
Multidetector computed tomographic angiography of the cardiovascular system
Authors: Burrill Joshua , Dabbagh Zaid , Gollub Frank , Hamady Mohamed
Published: November 2007

The introduction of multidetector computed tomography MDCT is considered a dramatic development in CT imaging that has direct implication in the imaging of various systems, in particular the cardiovascular system. The advantages of MDCT are an enormous increase in imaging acquisition speed, more coverage of the patient, and high spatial resolution. This article reviews the recent developments in CT angiography and discusses the clinical application relevant to diagnosis and endovascular treatment of cardiovascular diseases.
ANALYTIC PATTERNS FOR CHAOTIC EQUATIONS
Authors: CONTE R.
Published: November 2007

Chaotic evolution equations sometimes display regular patterns (fronts, kinks, holes), which often correspond to closed form analytic solutions. In the dissipative-dispersive Kuramoto and Sivashinsky travelling wave reduction u(x − ct), νu‴ + bu″ + μu′ + u2/2 + A = 0, ν ≠ 0, with (ν,b,μ,A) constants, such analytic solutions are known for heteroclinic solutions, but one has also observed (Toh, 1987) homoclinic solutions without corresponding analytic solutions yet. We review the search for the most general analytic solution admissible by this chaotic differential equation. Several investigations, both analytic by the Painlevé test (Thual and Frisch, 1986) and numerical by Padé approximants (Yee, Conte, Musette, 2003) indicate its quite probable single valuedness for any (ν,b,μ,A). Moreover, Nevanlinna theory on the growth of solutions near infinity rules out (Eremenko, 2005) the possibility for the singularities of this unknown closed form single valued expression to be only poles.

We propose a qualitative closed form involving a deformed elliptic function.
q-BREATHERS IN FPU-LATTICES — SCALING AND PROPERTIES FOR LARGE SYSTEMS
Authors: FLACH SERGEJ , KANAKOV OLEG I. , MISHAGIN KONSTANTIN G. , IVANCHENKO MIKHAIL V.
Published: November 2007

Recently q-breathers - time-periodic solutions which localize in the space of normal modes and maximize the energy density for some mode vector q0 - were obtained for finite nonlinear lattices. We scale these solutions to arbitrarily large lattices in various lattice dimensions. We study the scaling consequence for previously obtained analytical estimates of the localization length of q-breathers for β-FPU and α-FPU lattices. The first finding is that the degree of localization depends only on intensive quantities and is size independent. Secondly, a critical wave vector km is identified, which depends on one effective nonlinearity parameter, q-breathers minimize the localization length at k0 = km and completely delocalize in the limit k0 → 0, π.
EXTREME FLUCTUATIONS OF FINITE-TIME LYAPUNOV EXPONENTS IN CHAOTIC SYSTEMS
Authors: LAI YING-CHENG
Published: November 2007

Finite-time Lyapunov exponents of a chaotic attractor typically exhibit fluctuations about their asymptotic values. In computations or in experiments large fluctuations of these exponents are of concern, as they can lead to incorrect estimates of the actual exponents. We find that in common situations where a chaotic attractor contains two distinct dynamically connected components, such as one after crisis or arising in random dynamical systems, the extreme fluctuations of the finite-time exponents follow a universal, exponential distribution. We develop a physical analysis based on the random-matrix theory and provide numerical evidence to substantiate the finding.
NOSÉ-HOOVER AND LANGEVIN THERMOSTATS DO NOT REPRODUCE THE NONEQUILIBRIUM BEHAVIOR OF LONG-RANGE HAMILTONIANS
Authors: BALDOVIN FULVIO , ORLANDINI ENZO
Published: November 2007

We compare simulations performed using the Nosé-Hoover and the Langevin thermostats with the Hamiltonian dynamics of a long-range interacting system in contact with a reservoir. We find that while the statistical mechanics equilibrium properties of the system are recovered by all the different methods, the Nosé-Hoover and the Langevin nonequilibrium results differ from the Hamiltonian ones.
TEMPERATURE FLUCTUATIONS FOR FINITE CLASSICAL SPIN-HALF PARTICLES
Authors: WANG X. , LIU Q. H.
Published: November 2007

For the classical spin 1/2 system, a canonical ensemble theory for finite number of particles is developed to show that when the temperature approaches to 0K and in thermodynamic limit, the temperature fluctuation [Formula: see text] itself does not diverge, but the product of the particle number N and [Formula: see text] as [Formula: see text] does.
EVOLUTIONARY DYNAMICS OF COMPETING BOOLEAN NETWORK AGENTS
Authors: WANG BING-HONG , YUAN BAOSHENG
Published: November 2007

We investigate the dynamics of network minority games on Kauffman's NK networks (Kauffman nets) and growing directed networks (GDNets). We show that the dynamics and the associated phase structure of the game depend crucially on the structure of the underlying network. The dynamics on GDNets is very stable for all values of the connection number K, in contrast to the dynamics on Kauffman's NK networks, which becomes chaotic when K > Kc= 2. For Kauffman nets with K > 3, the evolutionary scheme has no effect on the dynamics (it remains chaotic) and the performance of the MG resembles that of a random choice game (RCG).
GREEN'S FUNCTION AND SUPER-PARTICLE METHODS FOR KINETIC SIMULATION OF HETEROEPITAXY
Authors: LAM CHI-HANG , LUNG M. T.
Published: November 2007

Arrays of nanosized three dimensional islands are known to self-assemble spontaneously on strained heteroepitaxial thin films. We simulate the dynamics using kinetic Monte Carlo method based on a ball and spring lattice model. Green's function and super-particle methods which greatly enhance the computational efficiency are explained.
MEASURE ENTANGLEMENT OF BIPARTITE SYSTEM BY A NEW NONLOCAL EFFECT
Authors: MENG SHAO-YING , FU LI-BIN , LIU JIE
Published: November 2007

The state of a bipartite system may be changed by a cyclic operation applied on one of its subsystem. The change is a nonlocal effect, and can be detected only by measuring the two parts jointly. By employing the Hilbert-Schmidt metric, we can quantify such nonlocal effects via measuring the distance between initial and final state. By making use of the new nonlocal effect we can measure the entanglement of bipartite system. For qubit pair, we show that this measurement is equivalent to degree of entanglement and consists with the Bell inequality.
Our Work with Cyanogenic Plants
Authors: Conn Eric E.
Published: November 2007

The author identifies three individuals who played major roles in the development of his scientific career: his chemistry professor at the University of Colorado, Reuben Gustavson; his Ph.D. supervisor at the University of Chicago, Birgit Vennesland; and his friend and departmental colleague of 55 years at the University of California, Paul Stumpf. He also mentions students, postdoctoral scholars, and professional colleagues he encountered during his career of nearly 50 years as a plant biochemist. Finally, the article describes the author's research on cyanogenic plants. These plants contain hydrogen cyanide in a bound form that is usually released when the plant tissue is macerated. Cyanogenic plants contain cyanogenic glycosides in which the hydroxyl groups of cyanohydrins (α-hydroxynitriles) of aldehydes or ketones are covalently linked to a sugar, usually D-glucose. The biosynthesis, localization, and degradation, by hydrolysis, of these compounds have been examined, especially in sorghum and flax seedlings.
Regulation of Renal Function by the Gastrointestinal Tract: Potential Role of Gut-Derived Peptides and Hormones
Authors: Michell A.R. , Debnam E.S. , Unwin R.J.
Published: November 2007

The concept of a regulatory link between the gastrointestinal tract and kidneys is not new. The idea that dietary intake and composition can affect renal function is perhaps self-evident, but defining this relationship, especially in terms of sensors and effectors, is proving more difficult. That the gastrointestinal tract can exert some control over renal function was strengthened by the early observation that oral ingestion of a sodium chloride load has a greater natriuretic effect than when the same amount is given intravenously. This effect was subsequently shown to be independent of changes in aldosterone and atrial natriuretic peptide, although not necessarily angiotensin-II. However, the nature of any intestinal natriuretic peptide remains uncertain, despite suggestions that various gut-derived hormones, including guanylin and uroguanylin, may be involved. There is also an emerging concept of gastrointestinal taste and taste-like receptor mechanisms present throughout the gastrointestinal tract, which may govern the excretion of other key electrolytes, including potassium and phosphate. The evidence for gut sensors of nutrients such as proteins, amino acids, glucose, and acid is now becoming more established. Thus, we can anticipate the existence and eventual characterization of several gut ion sensors.
TNF-α inhibition reduces renal injury in DOCA-salt hypertensive rats
Authors: Elmarakby Ahmed A. , Quigley Jeffrey E. , Imig John D. , Pollock Jennifer S. , Pollock David M.
Published: November 2007

Studies suggest that the inflammatory cytokine TNF-α plays a role in the prognosis of end-stage renal diseases. We previously showed that TNF-α inhibition slowed the progression of hypertension and renal damage in angiotensin II salt-sensitive hypertension. Thus, we hypothesize that TNF-α contributes to renal inflammation in a model of mineralocorticoid-induced hypertension. Four groups of rats ( n = 5 or 6) were studied for 3 wk with the following treatments: 1) placebo, 2) placebo + TNF-α inhibitor etanercept (1.25 mg·kg−1·day−1 sc), 3) deoxycorticosterone acetate + 0.9% NaCl to drink (DOCA-salt), or 4) DOCA-salt + etanercept. Mean arterial blood pressure (MAP) measured by telemetry increased in DOCA-salt rats compared with baseline (177 ± 4 vs. 107 ± 3 mmHg; P < 0.05), and TNF-α inhibition had no effect in the elevation of MAP in these rats (177 ± 8 mmHg). Urinary protein excretion significantly increased in DOCA-salt rats compared with placebo (703 ± 76 vs. 198 ± 5 mg/day); etanercept lowered the proteinuria (514 ± 64 mg/day; P < 0.05 vs. DOCA-salt alone). Urinary albumin excretion followed a similar pattern in each group. Urinary monocyte chemoattractant protein (MCP)-1 and endothelin (ET)-1 excretion were also increased in DOCA-salt rats compared with placebo (MCP-1: 939 ± 104 vs. 43 ± 7 ng/day, ET-1: 3.30 ± 0.29 vs. 1.07 ± 0.03 fmol/day; both P < 0.05); TNF-α inhibition significantly decreased both MCP-1 and ET-1 excretion (409 ± 138 ng/day and 2.42 ± 0.22 fmol/day, respectively; both P < 0.05 vs. DOCA-salt alone). Renal cortical NF-κB activity also increased in DOCA-salt hypertensive rats, and etanercept treatment significantly reduced this effect. These data support the hypothesis that TNF-α contributes to the increase in renal inflammation in DOCA-salt rats.
Implications of a Neurosurgical Intervention in a Patient with a Surgically Repaired Hypoplastic Left Heart Syndrome
Authors: Cirak Bayram , Wang Paul , Avellino Anthony M.
Published: November 2007

Hypoplastic left heart syndrome (HLHS) accounts for 4–9% of congenital heart disease in children. The mortality rate among children with HLHS undergoing cardiac repair is well documented, but comparable data for noncardiac surgical procedures are not well known. Medically intractable epilepsy is one of those problems, which arises as a complication of cardiovascular surgery in HLHS and necessitates neurosurgical intervention. There is no published knowledge about neurosurgical procedures performed in children with HLHS in the English literature. Thus, we present a 10-year-old boy who developed medically intractable epilepsy after cardiac surgery for HLHS. The aim of this study is to outline the pre-, intra- and postoperative precautions needed for neurosurgical intervention in HLHS patients to decrease morbidity and mortality.
Effect of a New α2δ Ligand PD-217014 on Visceral Hypersensitivity Induced by 2,4,6-Trinitrobenzene Sulfonic Acid in Rats
Authors: Ohashi Katsuyo , Kawai Mitsuhisa , Ninomiya Noriko , Taylor Charles , Kurebayashi Yoichi
Published: November 2007

PD-217014, a new GABA analog (1α,3α,5α-3-aminomethyl-bicyclo[3.2.0]heptane-3-acetic acid), inhibited [3H]-gabapentin binding to α2δ subunit of voltage-gated calcium channels in a concentration-dependent manner (Ki = 18 nmol/l). Oral treatment with PD-217014 significantly inhibited the visceral hypersensitivity induced by an intra-colonic injection of trinitrobenzene sulfonic acid in rats. The anti-hyperalgesic effect of PD-217014 increased in a dose-dependent manner, and reached a plateau level at 60 mg/kg p.o. The visceral analgesia produced by PD-217014 at 30 and 60 mg/kg p.o. correlated with blood concentrations within 4 h after dosing, and maximal efficacy was obtained 2 h after dosing when the maximal blood concentration was achieved at either dose. These results indicate that PD-217014 is a potent α2δ ligand and possesses visceral analgesic activity.
Elevated Platelet β-Secretase Activity in Mild Cognitive Impairment
Authors: Liu W.W. , Todd S. , Craig D. , Passmore A.P. , Coulson D.T.R. , Murphy S. , Irvine G.B. , Johnston J.A.
Published: November 2007

Background/Aims: We have recently reported that platelet activity of the rate-limiting enzyme for β-amyloid peptide production is elevated in established Alzheimer’s disease. Laboratory investigation of the very early stages of dementia provides an opportunity to investigate pathological mechanisms before advanced disease hinders interpretation. Mild cognitive impairment (MCI) exists prior to obvious dementia, and is associated with increased risk of conversion to overt disease. Methods: We developed and used a fluorimetric assay to quantify platelet membrane β-secretase activity in 52 patients with MCI and 75 controls. Results: Platelet membrane β-secretase activity was 24% higher in individuals with MCI compared to controls (p = 0.001, unpaired t test with Welch correction). Conclusion: Elevated platelet β-secretase activity in subjects with MCI is an area for further study in relation to the etiology and diagnosis of MCI.
Effect of Bradykinin Receptor Antagonists on Vincristine- and Streptozotocin-Induced Hyperalgesia in a Rat Model of Chemotherapy-Induced and Diabetic Neuropathy
Authors: Bujalska Magdalena , Tatarkiewicz Jan , Gumułka Stanisław Witold
Published: November 2007

The role of bradykinin receptor blockade in the development of neuropathies caused by diabetes mellitus and vincristine was examined. The effects of a potent and selective B1 receptor antagonist (des-Arg10-HOE 140) as well as a specific antagonist of B2 receptors (HOE 140) were investigated. Both agents significantly decreased hyperalgesia caused otherwise by vincristine. In a diabetic neuropathy model, both agents almost completely suppressed hyperalgesia in the first 10 days of the study. However, from day 11 after administration of streptozotocin, the action of des-Arg10-HOE 140 was significantly weaker than that of HOE 140. The results of the study suggest involvement of both B1 and B2 receptors in transmission of nociceptive stimuli in the vincristine-induced as well as diabetic neuropathy model.
Home Ventilation for Children with Chronic Respiratory Failure in Istanbul
Authors: Oktem S. , Ersu R. , Uyan Z.S. , Cakir E. , Karakoc F. , Karadag B. , Kiyan G. , Dagli E.
Published: November 2007

Background: The number of children on home mechanical ventilation (HMV) has increased markedly in Europe and North America but little is known about the HMV use and outcomes in children in Turkey. Objective: To review clinical conditions and outcome of children who were discharged from the hospital on respiratory support. Methods: Thirty-four patients assessed at the Marmara University Hospital in Istanbul who had been receiving ventilatory support at home for more than 3 months were included in the study. Results: Thirty-four patients with a median age of 5.1 years were discharged home with ventilatory support. HMV was started in 2001 at our institution and the number of children treated has increased substantially since then (2001: n = 1, 2002: n = 3, 2003: n = 3, 2004: n = 2, 2005: n = 14, 2006: n = 11).Ventilatory support was started at a median age of 1.8 years and continued for 13 months. Eleven (32.4%) patients received invasive mechanical ventilation via tracheostomy and 23 (67.6%) patients received noninvasive mechanical ventilation. Sixteen children (47.1%) were on noninvasive mechanical ventilation via nasal mask while 7 (20.6%) used a face mask. Seven (20.6%) patients received ventilatory support for 24 h and 27 (79.4%) patients were supported only during sleep. Twenty-four (70.6%) children received supplemental oxygen in addition to ventilatory support. Three patients successfully came off ventilatory support; 11 patients died during follow-up. None of the patients had home nursing and there were no life-threatening complications. Conclusions: A rapidly rising trend of HMV use in chronic respiratory failure (CRF) has been observed in this study. HMV can be safely applied in selected children with CRF with close monitoring and proper follow-up in developing countries despite the lack of home nursing.
Neuropeptidergic Mediators of Spontaneous Physical Activity and Non-Exercise Activity Thermogenesis
Authors: Teske J.A. , Billington C.J. , Kotz C.M.
Published: November 2007

Lean individuals have high levels of spontaneous physical activity (SPA) and the energy expenditure derived from that activity, termed non-exercise activity thermogenesis or NEAT, appears to protect them from obesity. Conversely, obesity in different human populations is characterized by low levels of SPA and NEAT. Like in humans, elevated SPA in rats appears to protect against obesity: obesity-resistant rats have significantly greater SPA and NEAT than obesity-prone rats. We review the literature on brain mechanisms important in mediating SPA and NEAT. The focus is on neuropeptides, including cholecystokinin, corticotropin-releasing hormone (also known as corticotropin-releasing factor), neuromedin U, neuropeptide Y, leptin, agouti-related protein, orexin-A (also known as hypocretin-1), and ghrelin. We also review information regarding interactions between these neuropeptides and dopamine, a neurotransmitter important in mediating motor function. Finally, we present evidence that elevated signaling of pathways mediating SPA and NEAT may protect against weight gain and obesity.
Vildagliptin, a Novel Dipeptidyl Peptidase IV Inhibitor, Has No Pharmacokinetic Interactions With the Antihypertensive Agents Amlodipine, Valsartan, and Ramipril in Healthy Subjects
Authors: He Yan‐Ling , Ligueros‐Saylan Monica , Sunkara Gangadhar , Sabo Ron , Zhao Charlie , Wang Yibin , Campestrini Joelle , Pommier Françoise , Dole Kiran , Marion Alan , Dole Willia P. , Howard Dan
Published: November 2007

We conducted 3 open–label, multiple–dose, 3‐period, randomized, crossover studies in healthy subjects to assess the potential pharmacokinetic interaction between vildagliptin, a novel dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes, and representatives of 3 commonly prescribed antihypertensive drug classes: (1) the calcium channel blocker, amlodipine; (2) the angiotensin receptor blocker, valsartan; and (3) the angiotensin‐converting enzyme inhibitor, ramipril. Coadministration of vildagliptin 100 mg with amlodipine 5 mg, valsartan 320 mg, or ramipril 5 mg had no clinically significant effect on the pharmacokinetics of these drugs. The 90% confidence intervals of the geometric mean ratios for area under the plasma concentration–time curve from time zero to 24 hours (AUC0–24h) and maximum plasma concentration (Cmax) for vildagliptin, amlodipine, and ramipril (and its active metabolite, ramiprilat) were contained within the acceptance range for bioequivalence (0.80–1.25). Valsartan AUC0–24h and Cmax increased by 24% and 14%, respectively, following coadministration of vildagliptin, but this was not considered clinically significant. Vildagliptin was generally well tolerated when given alone or in combination with amlodipine, valsartan, or ramipril in healthy subjects at steady state. No adjustment in dosage based on pharmacokinetic considerations is required should vildagliptin be coadministered with amlodipine, valsartan, or ramipril in patients with type 2 diabetes and hypertension.
Comparative evaluation of gene-set analysis methods
Authors: Liu Qi , Dinu Irina , Adewale Adeniyi J , Potter John D , Yasui Yutaka
Published: November 2007

Background

Multiple data-analytic methods have been proposed for evaluating gene-expression levels in specific biological pathways, assessing differential expression associated with a binary phenotype. Following Goeman and Bühlmann's recent review, we compared statistical performance of three methods, namely Global Test, ANCOVA Global Test, and SAM-GS, that test "self-contained null hypotheses" Via. subject sampling. The three methods were compared based on a simulation experiment and analyses of three real-world microarray datasets.

Results

In the simulation experiment, we found that the use of the asymptotic distribution in the two Global Tests leads to a statistical test with an incorrect size. Specifically, p-values calculated by the scaled χ
2 distribution of Global Test and the asymptotic distribution of ANCOVA Global Test are too liberal, while the asymptotic distribution with a quadratic form of the Global Test results in p-values that are too conservative. The two Global Tests with permutation-based inference, however, gave a correct size. While the three methods showed similar power using permutation inference after a proper standardization of gene expression data, SAM-GS showed slightly higher power than the Global Tests. In the analysis of a real-world microarray dataset, the two Global Tests gave markedly different results, compared to SAM-GS, in identifying pathways whose gene expressions are associated with p53 mutation in cancer cell lines. A proper standardization of gene expression variances is necessary for the two Global Tests in order to produce biologically sensible results. After the standardization, the three methods gave very similar biologically-sensible results, with slightly higher statistical significance given by SAM-GS. The three methods gave similar patterns of results in the analysis of the other two microarray datasets.

Conclusion

An appropriate standardization makes the performance of all three methods similar, given the use of permutation-based inference. SAM-GS tends to have slightly higher power in the lower α-level region (i.e. gene sets that are of the greatest interest). Global Test and ANCOVA Global Test have the important advantage of being able to analyze continuous and survival phenotypes and to adjust for covariates. A free Microsoft Excel Add-In to perform SAM-GS is available from http://www.ualberta.ca/~yyasui/homepage.html.
Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets
Authors: Grayson T Hilton , Ohms Stephen J , Brackenbury Therese D , Meaney Kate R , Peng Kaiman , Pittelkow Yvonne E , Wilson Susan R , Sandow Shaun L , Hill Caryl E
Published: November 2007

Background

Hypertension is a complex disease with many contributory genetic and environmental factors. We aimed to identify common targets for therapy by gene expression profiling of a resistance artery taken from animals representing two different models of hypertension. We studied gene expression and morphology of a saphenous artery branch in normotensive WKY rats, spontaneously hypertensive rats (SHR) and adrenocorticotropic hormone (ACTH)-induced hypertensive rats.

Results

Differential remodeling of arteries occurred in SHR and ACTH-treated rats, involving changes in both smooth muscle and endothelium. Increased expression of smooth muscle cell growth promoters and decreased expression of growth suppressors confirmed smooth muscle cell proliferation in SHR but not in ACTH. Differential gene expression between arteries from the two hypertensive models extended to the renin-angiotensin system, MAP kinase pathways, mitochondrial activity, lipid metabolism, extracellular matrix and calcium handling. In contrast, arteries from both hypertensive models exhibited significant increases in caveolin-1 expression and decreases in the regulators of G-protein signalling, Rgs2 and Rgs5. Increased protein expression of caveolin-1 and increased incidence of caveolae was found in both smooth muscle and endothelial cells of arteries from both hypertensive models.

Conclusion

We conclude that the majority of differences in gene expression found in the saphenous artery taken from rats with two different forms of hypertension reflect distinctive morphological and physiological alterations. However, changes in common to caveolin-1 expression and G protein signalling, through attenuation of Rgs2 and Rgs5, may contribute to hypertension through augmentation of vasoconstrictor pathways and provide potential targets for common drug development.
Identification and regulation of expression of a gene encoding a filamentous hemagglutinin-related protein in Bordetella holmesii
Authors: Link Stefanie , Schmitt Karin , Beier Dagmar , Gross Roy
Published: November 2007

Background

Bordetella holmesii is a human pathogen closely related to B. pertussis, the etiological agent of whooping cough. It is able to cause disease in immunocompromised patients, but also whooping cough-like symptoms in otherwise healthy individuals. However, virtually nothing was known so far about the underlying virulence mechanisms and previous attempts to identify virulence factors related to those of B. pertussis were not successful.

Results

By use of a PCR approach we were able to identify a B. holmesii gene encoding a protein with significant sequence similarities to the filamentous hemagglutinin (FHA) of B. avium and to a lesser extent to the FHA proteins of B. pertussis, B. parapertussis, and B. bronchiseptica. For these human and animal pathogens FHA is a crucial virulence factor required for successful colonization of the host. Interestingly, the B. holmesii protein shows a relatively high overall sequence similarity with the B. avium protein, while sequence conservation with the FHA proteins of the human and mammalian pathogens is quite limited and is most prominent in signal sequences required for their export to the cell surface. In the other Bordetellae expression of the fhaB gene encoding FHA was shown to be regulated by the master regulator of virulence, the BvgAS two-component system. Recently, we identified orthologs of BvgAS in B. holmesii, and here we show that this system also contributes to regulation of fhaB expression in B. holmesii. Accordingly, the purified BvgA response regulator of B. holmesii was shown to bind specifically in the upstream region of the fhaB promoter in vitro in a manner similar to that previously described for the BvgA protein of B. pertussis. Moreover, by deletion analysis of the fhaB promoter region we show that the BvgA binding sites are relevant for in vivo transcription from this promoter in B. holmesii.

Conclusion

The data reported here show that B. holmesii is endowed with a factor highly related to filamentous hemagglutinin (FHA), a prominent virulence factor of the well characterized pathogenic Bordetellae. We show that like in the other Bordetellae the virulence regulatory BvgAS system is also involved in the regulation of fhaB expression in B. holmesii. Taken together these data indicate that in contrast to previous notions B. holmesii may in fact make use of virulence mechanisms related to those described for the other Bordetellae.
Tuberous sclerosis preclinical studies: timing of treatment, combination of a rapamycin analog (CCI-779) and interferon-gamma, and comparison of rapamycin to CCI-779
Authors: Messina Michael P , Rauktys Aubrey , Lee Laifong , Dabora Sandra L
Published: November 2007

Background

Tuberous Sclerosis Complex (TSC) is an autosomal dominant hamartoma disorder with variable expression for which treatment options are limited. TSC is caused by a mutation in either theTSC1orTSC2genes, whose products, hamartin and tuberin, function as negative regulators in the highly-conserved mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin (also known as sirolimus), an mTOR inhibitor, has been shown to reduce disease severity in rodent models of TSC and is currently being evaluated in clinical trials in human populations. The cytokine interferon-gamma (IFN-γ) is also a potential therapeutic agent for TSC. A high-expressing IFN-γ allele has been associated with reduced disease severity in human TSC patients and it has been shown in mouse models that treatment with exogenous IFN-γ reduces disease severity.

Results

Here, we examine the effects of treatingTsc2+/-mice at different time points with a rapamycin analog (CCI-779) as a single agent or with a combination of CCI-779 and IFN-γ. We observed that administering a short course of CCI-779 or CCI-779 plus IFN-γ reduced the severity of kidney lesions if administered after such lesions develop. As long as treatment is given after lesions arise, altering the time period during which treatment was given did not significantly impact the effect of the treatment on disease severity. We did not observe a significant benefit of combination therapy relative to treatment with a rapamycin analog alone inTsc2+/-mice. We also compared timing of treatment and two mTOR inhibitors (rapamycin and CCI-779) in nude mice bearingTsc2-/-tumors.

Conclusion

Preventing the genesis of TSC-related kidney lesions inTsc2+/-mice is not an effective treatment strategy; rather, the presence of growing tumors appears to be the most important factor when determining an appropriate treatment schedule. Treatment with rapamycin was more effective in reducing tumor growth and improving survival in nude mice bearingTsc2-/-tumors and also resulted in higher rapamycin levels in blood, brain, and kidney tissue than treatment with an equal milligram dose of CCI-779. We anticipate these results will influence future preclinical and clinical trials for TSC.
Psychiatric assessment of suicide attempters in Japan: a pilot study at a critical emergency unit in an urban area
Authors: Yamada Tomoki , Kawanishi Chiaki , Hasegawa Hana , Sato Ryoko , Konishi Akiko , Kato Daiji , Furuno Taku , Kishida Ikuko , Odawara Toshinari , Sugiyama Mitsugi , Hirayasu Yoshio
Published: November 2007

Background

The incidence of suicide has increased markedly in Japan since 1998. As psychological autopsy is not generally accepted in Japan, surveys of suicide attempts, an established risk factor of suicide, are highly regarded. We have carried out this study to gain insight into the psychiatric aspects of those attempting suicide in Japan.

Methods

Three hundred and twenty consecutive cases of attempted suicide who were admitted to an urban emergency department were interviewed, with the focus on psychosocial background and DSM-IV diagnosis. Moreover, they were divided into two groups according to the method of attempted suicide in terms of lethality, and the two groups were compared.

Results

Ninety-five percent of patients received a psychiatric diagnosis: 81% of subjects met the criteria for an axis I disorder. The most frequent diagnosis was mood disorder. The mean age was higher and living alone more common in the high-lethality group. Middle-aged men tended to have a higher prevalence of mood disorders.

Conclusion

This is the first large-scale study of cases of attempted suicide since the dramatic increase in suicides began in Japan. The identification and introduction of treatments for psychiatric disorders at emergency departments has been indicated to be important in suicide prevention.
Molecular dynamics simulation of human LOX-1 provides an explanation for the lack of OxLDL binding to the Trp150Ala mutant
Authors: Falconi Mattia , Biocca Silvia , Novelli Giuseppe , Desideri Alessandro
Published: November 2007

Background

Dimeric lectin-like oxidized low-density lipoprotein receptor-1 LOX-1 is the target receptor for oxidized low density lipoprotein in endothelial cells. In vivo assays revealed that in LOX-1 the basic spine arginine residues are important for binding, which is lost upon mutation of Trp150 with alanine. Molecular dynamics simulations of the wild-type LOX-1 and of the Trp150Ala mutant C-type lectin-like domains, have been carried out to gain insight into the severe inactivating effect.

Results

The mutation does not alter the dimer stability, but a different dynamical behaviour differentiates the two proteins. As described by the residues fluctuation, the dynamic cross correlation map and the principal component analysis in the wild-type the two monomers display a symmetrical motion that is not observed in the mutant.

Conclusion

The symmetrical motion of monomers is completely damped by the structural rearrangement caused by the Trp150Ala mutation. An improper dynamical coupling of the monomers and different fluctuations of the basic spine residues are observed, with a consequent altered binding affinity.