bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy
Authors: Van Vliet Erwin A. , Aronica Eleonora , Redeker Sandra , Boer Karin , Gorter Jan A.
Published: August 2008

Purpose:  We previously showed that gene expression of synaptic vesicle protein 2A (SV2A), the binding site for the antiepileptic drug levetiracetam, is reduced during epileptogenesis in the rat. Since absence of SV2A has been associated with increased epileptogenicity, changes in expression of SV2A could have consequences for the progression of epilepsy. Therefore we investigated hippocampal SV2A protein expression of temporal lobe epilepsy (TLE) patients and in rats during epileptogenesis and in the chronic epileptic phase.

Methods:  SV2A immunocytochemistry and Western blot analysis were performed on the hippocampus of autopsy controls, patients that died from status epilepticus (SE), and pharmacoresistant TLE patients. In addition, in epileptic rats, SV2A expression was determined after SE during the acute, latent, and chronic epileptic phase.

Results:  In control tissue, presynaptic SV2A was expressed in all hippocampal subfields, with strongest expression in mossy fiber terminals. SV2A positive puncta were distributed in a patchy pattern over the somata and dendrites of neurons. SV2A decreased throughout the hippocampus of TLE patients with hippocampal sclerosis (HS), compared to autopsy control, SE, and non‐HS tissue. In most rats, SV2A was already decreased in the latent period especially in the inner molecular layer and stratum lucidum. Similarly as in humans, SV2A was also decreased throughout the hippocampus of chronic epileptic rats, specifically in rats with a progressive form of epilepsy.

Discussion:  These data support previous findings that reduced expression of SV2A could contribute to the increased epileptogenicity. Whether this affects the effectiveness of levetiracetam needs to be further investigated.
Imaging seizure activity: A combined EEG/EMG‐fMRI study in reading epilepsy
Authors: Salek‐Haddadi Afraim , Mayer Thomas , Hamandi Khalid , Symms Mark , Josephs Oliver , Fluegel Dominique , Woermann Friedrich , Richardson Mark P. , Noppeney Uta , Wolf Peter , Koepp Matthias J.
Published: August 2008

Purpose:  To characterize the spatial relationship between activations related to language‐induced seizure activity, language processing, and motor control in patients with reading epilepsy.

Methods:  We recorded and simultaneously monitored several physiological parameters [voice‐recording, electromyography (EMG), electrocardiography (ECG), electroencephalography (EEG)] during blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) in nine patients with reading epilepsy. Individually tailored language paradigms were used to induce and record habitual seizures inside the MRI scanner. Voxel‐based morphometry (VBM) was used for structural brain analysis. Reading‐induced seizures occurred in six out of nine patients.

Results:  One patient experienced abundant orofacial reflex myocloni during silent reading in association with bilateral frontal or generalized epileptiform discharges. In a further five patients, symptoms were only elicited while reading aloud with self‐indicated events. Consistent activation patterns in response to reading‐induced myoclonic seizures were observed within left motor and premotor areas in five of these six patients, in the left striatum (n = 4), in mesiotemporal/limbic areas (n = 4), in Brodmann area 47 (n = 3), and thalamus (n = 2). These BOLD activations were overlapping or adjacent to areas physiologically activated during language and facial motor tasks. No subtle structural abnormalities common to all patients were identified using VBM, but one patient had a left temporal ischemic lesion.

Discussion:  Based on the findings, we hypothesize that reflex seizures occur in reading epilepsy when a critical mass of neurons are activated through a provoking stimulus within corticoreticular and corticocortical circuitry subserving normal functions.
Preoperative amygdala fMRI in temporal lobe epilepsy
Authors: Bonelli Silvia B. , Powell Robert , Yogarajah Mahinda , Thompson Pamela J. , Symms Mark R. , Koepp Matthias J. , Duncan John S.
Published: August 2008

Purpose:  Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.

Methods:  We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty‐one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.

Results:  On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.

Discussion:  The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.
A blinded, crossover study of the efficacy of the ketogenic diet
Authors: Freeman John M. , Vining Eileen P.G. , Kossoff Eric H. , Pyzik Paula L. , Ye Xiaobu , Goodman Steven N.
Published: August 2008

Despite over 80 years of use, the ketogenic diet (KD) has never been tested in a blinded manner. Twenty children with intractable Lennox‐Gastaut syndrome (LGS) were fasted 36  h and then randomized to receive the classic KD in conjunction with a solution containing either 60 g/day of glucose or saccharin. Parents and physicians were blinded to both the solution composition and level of ketosis. A crossover to the KD with the alternate solution occurred following the sixth day and a repeat fast. A 24‐h electroencephalography (EEG) was obtained at baseline and after each arm. After administration of the solution, there was moderate evidence of a reduction in parent‐reported seizures between the glucose and saccharin arms, with a median difference of 1.5 seizures per day (p = 0.07). There was no reduction in the number of EEG‐identified events, with a median reduction of 7 events per day (p = 0.33). Ketosis was not completely eliminated in the glucose‐added arm.
Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine‐dependent seizures
Authors: Striano Pasquale , Battaglia Silvia , Giordano Lucio , Capovilla Giuseppe , Beccaria Francesca , Struys Eduard A. , Salomons Gajja S. , Jakobs Cornelis
Published: August 2008

Pyridoxine‐dependent seizures (PDS) is a rare autosomal recessive disorder causing intractable seizures in neonates and infants. Patients are typically resistant to conventional anticonvulsants but respond well to the administration of pyridoxine. We report two unrelated patients affected with PDS as a result of α‐aminoadipic semialdehyde (α‐AASA) dehydrogenase deficiency caused by pathogenic ALDH7A1/antiquitin mutations. Two of the three reported mutations are novel and result in erroneous splicing, as showed by messenger RNA (mRNA) studies.

So far, the vast majority of the patients clinically diagnosed as PDS show α‐AASA dehydrogenase deficiency, caused by mutations in the ALDH7A1 gene. However, despite the availability of reliable biomarkers, early consideration of a pyridoxine trial is still the most important issue in a child with therapy‐resistant seizures.
Source localization of scalp‐EEG interictal spikes in posterior cortex epilepsies investigated by HR‐EEG and SEEG
Authors: Gavaret Martine , Trébuchon Agnès , Bartolomei Fabrice , Marquis Patrick , McGonigal Aileen , Wendling Fabrice , Regis Jean , Badier Jean‐Michel , Chauvel Patrick
Published: August 2008

Purpose:  To determine the validity of scalp‐electroencephalography (EEG)‐interictal spike (IIS) source localization in posterior cortex epilepsies (PCE).

Methods:  Eleven patients with drug‐resistant PCE were studied with high‐resolution EEG (HR‐EEG) and stereoelectroencephalography (SEEG). Sixty‐four scalp channels, a realistic head model, and different algorithms [multiple signal classification (MUSIC) and equivalent current dipoles] were used. Results were compared to intracerebral SEEG recordings. For SEEG, a semiautomatic detection of intracerebral IIS was used, allowing a classification of intracerebral IIS into one of three groups: Medial, lateral, and mediolateral.

Results:  In the medial group (two patients), scalp‐EEG IIS were usually absent for one patient whereas for the other, scalp‐EEG was misleading. Indeed, scalp‐EEG IIS had a posterior projection, predominantly contralateral to the source. In the lateral group (two patients), scalp‐EEG IIS were subcontinuous and accurately localized. In the mediolateral group (seven patients), intracerebral interictal distribution was complex and bilateral for four of seven patients. Source localizations were able to determine only a part, whether lateral or medial, of the intracerebral interictal distribution.

Discussion:  The accuracy of scalp‐EEG IIS source localization is dependant on the type of intracerebral interictal distribution. In the most frequent type of PCE, patients proved to have a complex interictal distribution between both medial and lateral cortices, and source localizations always  underestimated intracerebral IIS. In cases where intracranial sources were quite focal, surface EEG sources were localized with accuracy, even in medial occipital lobe structures.
Oxcarbazepine, not its active metabolite, potentiates GABAA activation and aggravates absence seizures
Authors: Zheng Thomas , Clarke Alison L. , Morris Margaret J. , Reid Christopher A. , Petrou Steven , O'Brien Terence J.
Published: August 2008

Purpose:  Studies in genetic absence epileptic rats from Strasbourg (GAERS) indicate that enhancement of γ aminobutyric acid (GABAA) receptor activity is a critical mechanism in the aggravation of seizures by carbamazepine (CBZ). We examined whether structural analogs of CBZ, oxcarbazepine (OXC), and its active metabolite, monohydroxy derivative (MHD), also potentiate GABAA receptor current and aggravate seizures.

Methods:  In vitro studies in Xenopus oocytes compared the three drugs' effect on GABAA receptor currents. In vivo studies compared seizure activity in GAERS after intraperitoneal drug administration.

Results:  OXC potentiated GABAA receptor current and aggravated seizures in GAERS, similarly to the effect of CBZ. Conversely, MHD showed only a minor potentiation of GABAA receptor current and did not aggravate seizures.

Discussion:  A hydroxyl group at the C‐10 position on the CBZ tricyclic structure in MHD reduces GABAA receptor potentiation and seizure aggravation. Reports of the aggravation of absence seizures in patients taking OXC may result from circulating unmetabolized OXC rather than MHD.
The Confusion Assessment Method—A Tool for Delirium Detection by the Acute Pain Service
Authors: Friedman Zeev , Qin Jing , Berkenstadt Haim , Katznelson Rita
Published: August 2008

Introduction:  Delirium is an acute fluctuating disturbance in cognitive status, linked to increased morbidity and mortality. The purpose of this pilot study was to assess the feasibility in terms of required time and yield of delirium monitoring by the Acute Pain Service (APS) using the Confusion Assessment Method for Intensive Care Unit instrument.

Methods:  Patients undergoing surgery requiring more than 2 days of hospital stay were recruited. Each patient was assessed daily for 2 days after surgery using the Confusion Assessment Method for Intensive Care Unit. Patients were also assessed for orientation to person, place, and time. Any notes of confusion or delirium made by physicians or nursing staff were gathered.

Results:  145 patients were recruited. Each patient encounter required an average 2.3 ± 0.3 minutes for the assessment (95% CI). The incidence of delirium within 2 days after surgery was 7.6%. Only 18% of the patients diagnosed with delirium by the APS were noted as being confused by the medical or nursing staff.

Conclusions:  The use of this tool required little training, and only 2 minutes per patient. It detected more patients with delirium than did the standard nursing assessments or other patient‐clinician interactions. The use of this instrument by the pain service was feasible in terms of time consumption and most likely would be valuable in its yield. Early detection may help in initiating prompt treatment, eliminating known risk factors and thus reducing morbidity.
Electrodeposition of Fluorine‐Doped Calcium Phosphate Coatings onto Ti6Al4V Alloy—Chemical and Structural Characterization
Authors: Balamurugan A. , Benhayoune H. , Dumelie N. , Laquerriere P. , Ferreira J. M. F.
Published: August 2008

The present study reports on the development of fluorapatite (FAP) coatings on Ti6Al4V substrate through an electrodeposition (ED) technique. Sodium fluoride (NaF) has been used as source for fluorine incorporation in the apatite structure. The surface morphology and chemical composition of the obtained coatings were characterized by scanning electron microscopy associated with X‐ray microanalysis (SEM‐EDXS). The phase composition of the coatings was determined through X‐ray diffraction and Raman micro‐spectroscopic techniques. The quantitative X‐ray microanalysis confirmed fluorine incorporation into the apatite structure during ED process on Ti6Al4V alloy. The results from the present investigation revealed that the quality of the FAP coating solely depends on the amount of fluorine precursor used during ED process.
Bubble‐Free Aqueous Electrophoretic Deposition (EPD) by Pulse‐Potential Application
Authors: Besra Laxmidhar , Uchikoshi Tetsuo , Suzuki Tohru S. , Sakka Yoshio
Published: August 2008

A novel method based on the application of a square‐wave pulse potential of 50% duty cycle has been demonstrated to obtain dense bubble‐free deposits of alumina by constant voltage electrophoretic deposition (EPD) from an aqueous suspension. Application of continuous dc voltage invariably resulted in the incorporation of bubbles in the deposits. Bubbles in the deposit decreased progressively with decrease in the size of pulse width during the pulse potential EPD. A unique and narrow band of pulse width exists for each voltage within which a bubble‐free deposit is obtained. The band is wider at low applied voltages than at higher voltages. Such bands of pulse width were found to be independent of substrate material and occurred at the same range for stainless steel and nickel substrates, suggesting that the process may be generic and applicable to any conductive substrate. The green density of deposits obtained by pulse EPD has been found to be the same as those obtained by continuous dc voltage EPD. The cathodic pulse EPD produced uniform and homogeneous deposits and was more convenient and amenable to better control than anodic pulse EPD.
Ferroelectric Domain Morphology Evolution and Octahedral Tilting in Lead‐Free (Bi1/2Na1/2)TiO3–(Bi1/2K1/2)TiO3–(Bi1/2Li1/2)TiO3–BaTiO3 Ceramics at Different Temperatures
Authors: Tai Cheuk Wai , Choy Siu Hong , Chan Helen L. W.
Published: August 2008

Observations by in situ transmission electron microscopy (TEM) reveal the changes in domains morphology in 0.885(Bi1/2Na1/2)TiO3–0.05(Bi1/2K1/2)TiO3–0.015(Bi1/2Li1/2)TiO3–0.05BaTiO3 ceramics. Evolution of the macroscopic ferroelectric domains has been observed at 25°–180°C. The ferroelectric domains and their walls reduce progressively with increasing temperature. In the selected‐area electron diffraction patterns, the crystallographic evidence of antiferroelectric domain is not found over the temperature range, which provides the evidence that the ferroelectric–antiferroelectric transition does not occur in the ceramic. The temperature‐dependent forbidden 3/2 1/2 0 and superstructure 3/2 1/2 1/2 reflections indicate the presence of an in‐phase and anti‐phase octahedral tilting in the ceramic, respectively. Dark‐field TEM images show that the size of the octahedral tilted domains is smaller than 30 nm across and that these domains are uniformly distributed in the grains. The influence of the localized octahedral titling on the stability of ferroelectric domains and the temperature‐dependent properties is discussed in this paper.
Heavily Nitrogen‐Doped Dual‐Phase Titanium Oxide Thin Films by Reactive Sputtering and Rapid Thermal Annealing
Authors: Li Qi , Shang Jian Ku
Published: August 2008

A novel nonequilibrium approach combining low‐temperature reactive sputtering and rapid thermal annealing was developed to resolve the opposing requirements on crystallization and high dopant concentration for creating nitrogen‐doped TiO2(TiON) thin film with a mixture of anatase and rutile phases. The dual‐phase TiON has a higher visible‐light absorption and a smaller band gap than pure anatase TiON. Its superior photocatalytic performance was demonstrated by the highly hydrophilic conversion and faster photodegradation of organic pollutants under visible‐light illumination. Our work demonstrates that the crystal structure is a major factor in determining the visible‐light photocatalytic activity of TiON.
Pressureless Rapid Sintering of UO2 Assisted by High‐frequency Induction Heating Process
Authors: Yang Jae Ho , Kim Yong‐Woon , Kim Jong Hun , Kim Dong‐Joo , Kang Ki Won , Rhee Young Woo , Kim Keon Sik , Song Kun Woo
Published: August 2008

Heat generation of uranium dioxide (UO2) powder and its pressureless rapid sintering behaviors have been studied using a high‐frequency induction heating apparatus. The porous graphite housing has been used to prevent heat loss and to preheat the uranium oxides, simultaneously. At an elevated temperature, UO2 powder generated extra heat by itself. The synergism of individual heat generation between the graphite and UO2 powder could effectively heat the UO2 to the sintering temperature of 1700°C. Using this process, densification behavior of cylindrical and disk‐type UO2 green pellets according to the heating rate and grain structure of sintered UO2 pellets were investigated. Rapid sintering caused a large crack around the circumference of the sintered pellet. The formation of cracks could be avoided when the heating rate or sample dimension are properly reduced. A dense and crack‐free UO2 pellet with a relative density of up to 96% was produced within 5 min of the process time. The induction heat sintering process can be a potential candidate for the rapid fabrication of ceramics and composites.
Effect of Polyethylene Glycol on the Microstructure of Freeze‐Cast Alumina
Authors: Pekor Christopher M. , Kisa Predrag , Nettleship Ian
Published: August 2008

Freeze casting has been used to process a range of ceramics with oriented pore structures, and soluble polymers are often used to improve the strength of the material before sintering. This study examined the effect of polyethylene glycol (PEG) on the three distinct microstructural scales, which include the colony size, the pore size, and the secondary dendrite spacing. The results showed that the trends in pore size and secondary dendrite spacing were consistent with the effect of constitutional supercooling on the growth of ice crystals. In contrast, the effect of PEG on colony size appeared to be more pronounced and may reflect preferential adsorption on the prism faces of the growing ice crystals. For both alumina and PEG content, the observed effects were very much dependent on the temperature of the chill surface used in casting.
First‐Principles Calculations and Thermodynamic Modeling of the Al2O3–Nd2O3 System
Authors: Saal James E. , Shin Dongwon , Stevenson Adam J. , Messing Gary L. , Liu Zi‐Kui
Published: August 2008

Using first‐principles calculations, the enthalpies of formation of NdAlO3 and Nd4Al2O9 from neodymia and alumina are predicted to be −41.1 and −104.5 kJ/mol‐form, respectively, and Nd4Al2O9 is predicted to be a stable compound at all temperatures up to its peritectic decomposition temperature. In the case of NdAlO3, where reported experimental enthalpies of formation differ, our predicted value is used to determine which experimental value is more accurate. The enthalpies of formation calculated by the first‐principles method are combined with experimental phase equilibria to evaluate the Gibbs energies of phases in the Al2O3–Nd2O3 system. The resulting Gibbs energy functions are compared with previous modelings of the system and are shown to be an improvement as more thermochemical data have been included. The combined first‐principles/thermodynamic modeling approach employed in the current work shows promise in enabling the evaluation of important ceramic systems in which experimental thermochemical data are scarce.
Eight Hours of Hypotensive versus Normotensive Resuscitation in a Porcine Model of Controlled Hemorrhagic Shock
Authors: Skarda David E. , Mulier Kristine E. , George Mark E. , Beilman Greg J.
Published: August 2008

Objectives:  The aim of this study was to compare hypotensive and normotensive resuscitation in a porcine model of hemorrhagic shock.

Methods:  This was a prospective, comparative, randomized survival study of controlled hemorrhagic shock using 28 male Yorkshire‐Landrace pigs (15 to 25 kg). In 24 splenectomized pigs, the authors induced hemorrhagic shock to a systolic blood pressure (sBP) of 48 to 58 mm Hg (∼35% bleed). Pigs were randomized to undergo normotensive resuscitation (sBP of 90 mm Hg, n = 7), mild hypotensive resuscitation (sBP of 80 mm Hg, n = 7), severe hypotensive resuscitation (sBP of 65 mm Hg, n = 6), or no resuscitation (n = 4). The authors also included a sham group of animals that were instrumented and splenectomized, but that did not undergo hemorrhagic shock (n = 4). After the initial 8 hours of randomized pressure‐targeted resuscitation, all animals were resuscitated to a sBP of 90 mm Hg for 16 hours.

Results:  Animals that underwent severe hypotensive resuscitation were less likely to survive, compared with animals that underwent normotensive resuscitation. Mean arterial pressure (MAP) decreased with hemorrhage and increased appropriately with pressure‐targeted resuscitation. Base excess (BE) and tissue oxygen saturation (StO2) decreased in all animals that underwent hemorrhagic shock. This decrease persisted only in animals that were pressure target resuscitated to a sBP of 65 mm Hg.

Conclusions:  In this model of controlled hemorrhagic shock, initial severe hypotensive pressure‐targeted resuscitation for 8 hours was associated with an increased mortality rate and led to a persistent base deficit (BD) and to decreased StO2, suggesting persistent metabolic stress and tissue hypoxia. However, mild hypotensive resuscitation did not lead to a persistent BD or to decreased StO2, suggesting less metabolic stress and less tissue hypoxia.
Age‐Related Factors in the Relationship Between Foot Measurements and Living Stature and Body Weight
Authors: Atamturk Derya , Duyar Izzet
Published: August 2008

Abstract:  The measurements of feet and footprints are especially important in forensic identification, as they have been used to predict the body height and weight of victims or suspects. It can be observed that the subjects of forensic‐oriented studies are generally young adults. That is to say, researchers rarely take into consideration the body’s proportional changes with age. Hence, the aim of this study is to generate equations which take age and sex into consideration, when stature and body weight are estimated from foot and footprints dimensions. With this aim in mind, we measured the stature, body weight, foot length and breadth, heel breadth, footprint length and breadth, and footprint heel breadth of 516 volunteers (253 males and 263 females) aged between 17.6 and 82.9 years using standard measurement techniques. The sample population was divided randomly into two groups. Group 1, the study group, consisted of 80% of the sample (n = 406); the remaining 20% were assigned to the cross‐validation group or Group 2 (n = 110). In the first stage of the study, we produced equations for estimating stature and weight using a stepwise regression technique. Then, their reliability was tested on Group 2 members. Statistical analyses showed that the ratios of foot dimensions to stature and body weight change considerably with age and sex. Consequently, the regression equations which include these variables yielded more reliable results. Our results indicated that age and sex should be taken into consideration when predicting human body height and weight for forensic purposes.
Effects of cytomegalovirus infection on the mRNA expression of collagens and matrix metalloproteinases in gingival fibroblasts
Authors: Botero J. E. , Contreras A. , Parra B.
Published: August 2008

Background and Objective:  The purpose of this in vitro investigation was to study the effects of human cytomegalovirus infection on the mRNA expression for collagens I and III and for matrix metalloproteinases 1 and 2 in gingival fibroblasts.

Material and Methods:  Gingival fibroblasts were experimentally infected with the Towne strain of human cytomegalovirus and the kinetics of expression of mRNA for collagens I and III and for matrix metalloproteinases 1 and 2 was studied at different time‐points. Total RNA was isolated at the indicated time, and the reverse transcription–polymerase chain reaction was used to analyze the level of mRNA expression. In addition, gingival specimens were obtained from 14 periodontitis and from three non‐periodontitis subjects and mRNA analysis for collagens and metalloproteinases was carried out. Nested polymerase chain reaction was used to determine the presence or absence of human cytomegalovirus in subgingival samples from each subject.

Results:  The infection of gingival fibroblasts with human cytomegalovirus during a 0–72‐h period resulted in progressive reduction in the expression of mRNA for collagens I and III (p < 0.05). A higher concentration of human cytomegalovirus resulted in varying degrees of mRNA reduction, suggesting a virally mediated effect. Biopsies from human cytomegalovirus‐positive individuals with periodontitis had a higher expression of mRNA for collagens I and III than biopsies from human cytomegalovirus‐negative individuals. An up‐regulation in the mRNA expression of matrix metalloproteinases 1 and 2 over time was observed (p < 0.05). Analysis of mRNA expression in gingival biopsies demonstrated higher expression of matrix metalloproteinase‐1 in human cytomegalovirus‐positive periodontitis specimens compared with human cytomegalovirus‐negative periodontitis specimens.

Conclusion:  Altered expression of mRNA for collagens and metalloproteinases in human cytomegalovirus‐infected gingival fibroblasts should be considered as possible modifying mechanisms in periodontitis‐infected sites.
The gingipains from Porphyromonas gingivalis do not directly induce osteoclast differentiation in primary mouse bone marrow cultures
Authors: Fitzpatrick R. E. , Campbell P. D. , Sivagurunathan S. , Pagel C. N. , Potempa J. , Mackie E. J. , Pike R. N.
Published: August 2008

Background and Objective:  Porphyromonas gingivalis is a major aetiological agent in the development of periodontitis, the major clinical hallmark of which is bone resorption. The cysteine proteases (gingipains) produced by P. gingivalis have a critical role in the pathogenesis of the disease, and previous studies on whole bacteria have implicated these enzymes in osteoclastogenesis, a process which serves to upregulate bone resorption. The effects of the gingipains from P. gingivalis on osteoclast differentiation were investigated here to determine whether the enzymes directly contribute to osteoclastogenesis and thus to bone resorption.

Material and Methods:  The effects of the gingipains on osteoclast differentiation were investigated in primary mouse bone marrow cultures. The cultures harvested from C57BL6/J mice were incubated in the presence of parathyroid hormone, a known osteoclastogenic factor, or active/inactivated forms of three gingipains. Osteoclast differentiation was quantified by counting the number of multinucleated cells positive for tartrate‐resistant acid phosphatase, an enzyme marker for these cells.

Results:  After 10 days of culture, the gingipains, either active or inactive, failed to stimulate osteoclast differentiation in comparison to the parathyroid hormone.

Conclusion:  The data presented here demonstrate that the gingipains do not induce osteoclast differentiation in this system, indicating that the bacterium uses other mechanisms to induce bone loss.
Metabolism of melatonin by cytochrome P450s in rat liver mitochondria and microsomes
Authors: Semak Igor , Korik Elena , Antonova Maria , Wortsman Jacobo , Slominski Andrzej
Published: August 2008

Abstract:  In the present study we provide direct evidence for the involvement of rat microsomal cytochrome P450s in melatonin O‐demethylation and hydroxylation at two different positions: 2 and 6, as well as generation of N1‐acetyl‐N2‐formyl‐5‐methoxy‐kynuramine (AFMK) and two unknown products. Moreover, we found that mitochondrial cytochrome P450s also converts melatonin into AFMK, N‐acetylserotonin, 2‐hydroxymelatonin, 6‐hydroxymelatonin and the same two unknown products. Eadie–Hofstee plots for 6‐hydroxylation and O‐demethylation reactions were curvilinear for all tested fractions, suggestive of involvement of at least two components, one with a high affinity and low capacity, and another with a low affinity and high capacity. Mitochondrial cytochrome P450s exhibited higher affinity (suggesting lower Km value) and higher Vmax for melatonin 6‐hydroxylation and O‐demethylation for both high‐affinity and low‐affinity components as compared with microsomal enzymes. The intrinsic clearance for melatonin hydroxylation by high‐ and low‐affinity components displayed the highest values in all tested fractions, indicating that both mitochondrial and microsomal cytochrome P450s metabolize melatonin principally by 6‐hydroxylation, with O‐demethylation representing a minor metabolic pathway.
WRITING THE SELF: ETHICAL SELF‐FORMATION AND THE UNDEFINED WORK Of FREEDOM
Authors: Ambrosio John
Published: August 2008

Abstract In this essay, John Ambrosio examines the role of ascetic writing practices in Michel Foucault’s conception of ethical self‐formation. Ambrosio argues for an interpretation of Foucault’s later writings as representative of both an extension, and a dramatic break, from his previous writings — from demolishing the subject to embracing the notion of an autonomous and reflexive subject. Ambrosio further contends that Foucault’s notion of ethical self‐formation cannot be divorced from his genealogical method, and that his primary preoccupation near the end of his life was to counterbalance his strong notion of a disciplinary society with the recognition of a subject able to make ethical choices and thus to transform itself. Finally, Ambrosio examines the implications of this for educators and argues that Foucault’s conception of ethical self‐formation through ascetic writing practices provides a powerful tool for teachers who seek to improve and transform their pedagogy.
THE COURSE OF “CULTURE” IN MULTICULTURALISM
Authors: McDonough Tim
Published: August 2008

Abstract In this essay Tim McDonough analyzes a number of different positions within the ongoing discussion on multicultural education in order to provide a conceptual map of the development of the term “culture.” His examination of the discourse begins with liberal multiculturalism; moves through the stages of difference, critical, and poststructural multiculturalism; and ends with what he terms “transfigurative multiculturalism.” McDonough describes how a conception of culture as a field of collective symbolic work has been arrived at through a dialectical movement of the concept across these different phases of multicultural discourse. This review does not attempt to provide a comprehensive account of the complex discourse of multiculturalism. Rather, McDonough charts a course representative of the field for the purpose of enhancing the readers’ understanding of “transfigurative” multiculturalism, which represents a fresh approach in the continuing inquiry into democratic multicultural education in an increasingly global society.
ON THE PUBLIC AND CIVIC PURPOSES OF EDUCATION
Authors: Abowitz Kathleen Knight
Published: August 2008

Abstract In this review essay, Kathleen Knight Abowitz discusses three recent books related to democratic public life and schooling: Susan H. Fuhrman and Marvin Lazerson’s The Public Schools, Walter C. Parker’s Teaching Democracy: Unity and Diversity in Public Life, and Kevin McDonough and Walter Feinberg’s Education and Citizenship in Liberal‐Democratic Societies. Abowitz details how each text is inspired by meanings of liberal democracy that evolved during the Enlightenment era, in which individual rights were constitutionally coded and equality came to be a powerful social and educational ideal, and how each book also takes up different sorts of Enlightenment traditions of public life and education, attempting to revitalize their meanings for public education today. Yet while these books are inspiring and instructive in numerous ways, they are also notable for the issues they fail to take into theoretical account, particularly the colonization of public spheres by the private and market‐based spheres of commerce, and the ways in which increasing ecological crisis calls for new ways of conceiving our political and educational frameworks.
DYNAMIC OUTPUT RESPONSE REVISITED: THE INDIAN CASH CROPS
Authors: KANWAR Sunil , SADOULET Elisabeth
Published: August 2008

Diverse instruments have been used to encourage developing agriculture. In the process, billions of dollars have been spent on providing incentives to peasants. Given scarce resources, an important concern has been the issue of what policy instruments to emphasize. In this regard, useful policy information can be gleaned from the role of expected profits (revenue and input prices), assets (irrigation and infrastructure), and relevant risks, in evoking peasant response. Using panel data for the period 1967/1968 to 1999/2000 pertaining to seven major Indian cash crops cultivated across 14 major states, we find strong evidence of a differential producer response in the post‐liberalization phase, although the important variables per se are much the same. Our results suggest that the preferred policy ought to emphasize availability of irrigation, affordable fertilizer, and rural infrastructure, rather than incessant increases in output prices.
Natural Honey Modulates Physiological Glycemic Response Compared to Simulated Honey and D‐Glucose
Authors: Ahmad A. , Azim M.K. , Mesaik M.A. , Nazimuddin  , Khan R.A.
Published: August 2008

ABSTRACT:  The present study is undertaken to find out the relative glycemic tolerance of natural honey compared with simulated honey and D‐glucose using oral glucose tolerance tested up to 180 min. Twenty‐six healthy human subjects with mean age of 28.6 ± 9.3 y were randomly divided into 3 groups, that is, natural honey consumers (NHC; n= 13), simulated honey consumers (AHC; n= 6), and D‐glucose consumers (DGC; n= 7). After recording fasting blood glucose, the participants consumed either natural honey or simulated honey or D‐glucose (1g/kg body weight). Subsequently, additional plasma glucose levels (PGLs) were recorded at 60, 120, and 180 min. At 60 min, DGC and AHC group members exhibited similar PGL elevation (that is, 52% and 47%, respectively) compared to NHC group with only 20% increment. On the other hand, after 180 min, 20% decrease in PGL was observed in the DGC group compared to 9.75% reduction in the NHC group. These observations are primarily in line with earlier studies. Results analyzed by one‐way analysis of variance (ANOVA) showed significant differences between all 3 tested groups with F‐statistic (19.96) and P value (< 0.005). Coefficient of variation of the NHC, AHC, and DGC groups were 14.8%, 20.2%, and 27.5%, respectively. Posthoc tests showed that glucose response was significantly lower in the NHC group at all time points (P < 0.005) compared to the AHC and DGC groups. In conclusion, natural honey stabilizes physiological glycemic response with rebound recovery of PGL.
A Comparison of the Blood Pressure Changes of Lumiracoxib With Those of Ibuprofen and Naproxen
Authors: Farkouh Michael E. , Verheugt Freek W. A. , Ruland Sean , Kirshner Howard , Jeger Raban , Gitton Xavier , Krammer Gerhard , Stricker Kirstin , Sallstig Peter , Mellein Bernhard , Matchaba Patrice , Chesebro James H.
Published: August 2008

The 52‐week Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) investigated the gastrointestinal and cardiovascular safety profile of lumiracoxib 400 mg once daily compared with 2 traditional nonsteroidal anti‐inflammatory drugs (NSAIDs): ibuprofen 800 mg 3 times daily and naproxen 500 mg twice daily. Data from TARGET were analyzed to examine the effect of lumiracoxib compared with ibuprofen and naproxen on blood pressure (BP), incidence of de novo and aggravated hypertension, prespecified edema events, and congestive heart failure. Lumiracoxib resulted in smaller changes in BP as early as week 4. Least‐squares mean change from baseline at week 4 for systolic BP was +0.57 mm Hg with lumiracoxib compared with +3.14 mm Hg with ibuprofen (P<.0001) and +0.43 with lumiracoxib compared with +1.80 mm Hg with naproxen (P<.0001). In conclusion, the use of lumiracoxib and traditional NSAIDs results in differing BP changes; these might be of clinical relevance.
Blood Pressure Control in Patients With Comorbidities
Authors: Schmieder Roland E. , Ruilope Luis M.
Published: August 2008

Hypertension frequently coexists with obesity, diabetes, hyperlipidemia, or the metabolic syndrome; their association with cardiovascular disease is well established. The identification and management of these risk factors is an important part of the overall management of hypertensive patients. Because patients in these special populations are more predisposed to target organ damage (TOD), stringent targets for blood pressure (BP) control have been set in clinical guidelines. However, clinical trial and real‐life evidence suggest that these targets are difficult to achieve. Patients with these comorbidities are more likely to require combination therapy, yet physicians are often reluctant to adjust the number and doses of medications to achieve target BP. There is a particular need for effective 24‐hour BP control in these patients, due to the increased likelihood of nondipping status, which is a risk factor for TOD and mortality. Not all available antihypertensives are equally effective in controlling BP over 24 hours, and some may exacerbate underlying metabolic abnormalities.
Effect of Socioeconomic Status on Food Availability and Cost of the Dietary Approaches to Stop Hypertension (DASH) Dietary Pattern
Authors: Young Christopher M. , Batch Bryan C. , Svetkey Laura P.
Published: August 2008

The authors assessed food availability and cost of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and patients' opinion concerning diet and blood pressure by surveying grocery stores and clinic patients in low‐ and high‐socioeconomic status (SES) areas of Boston, Massachusetts. The proportion of DASH items found in stores in low‐ and high‐SES communities was not significantly different (46.5% compared with 75%; P=.2896). The cost of eating a DASH meal plan was significantly more expensive in high‐SES communities ($40.20 compared with $30.73 per week; P=.0413). The authors' results suggest that DASH diet foods are available in low‐ and high‐SES communities, but there is a strong trend toward less food availability in low‐SES communities. Eating the DASH diet, however, is more expensive in high‐SES communities. Increased information, food availability, and affordability are likely to lead to more widespread adoption of the DASH diet.
Barriers to Optimal Hypertension Control
Authors: Ogedegbe Gbenga
Published: August 2008

There is an obvious gap in the translation of clinical trial evidence into practice with regards to optimal hypertension control. The three major categories of barriers to BP control are patient‐related, physician‐related, and medical environment/health care system factors. Patient‐related barriers include poor medication adherence, beliefs about hypertension and its treatment, depression, health literacy, comorbidity, and patient motivation. The most pertinent is medication adherence, given its centrality to the other factors. The most salient physician‐related barrier is clinical inertia—defined, as the failure of health care providers to initiate or intensify drug therapy in a patient with uncontrolled BP. The major reasons for clinical inertia are: 1) overestimation of the amount of care that physicians provide; 2) lack of training on how to attain target BP levels; and 3) clinicians' use of soft reasons to avoid treatment intensification by adopting a “wait until next visit” approach in response to patients' excuses.
Cultural Organizations and the State: Art and State Support in Contemporary Britain
Authors: Alexander Victoria D.
Published: August 2008

Only a small proportion of research in the sociological field of arts and culture is on the state and its effects. Literature which touches on this topic often comes from the policy arena and the wide variety of disciplines interested in public policy. Research tends to focus on two key themes: funding and censorship. But the effects of state actions are much broader. Moreover, state support is often set in opposition to the market, but markets and state systems usually exist together. It is ironic that the effects of the state on cultural organizations are increasingly studied at just this point in time, when states are scaling back their involvement and privatization is coming to the fore. Focusing on cultural organizations usually associated with the fine arts (museums and performing arts organizations), I illustrate some of these themes with a discussion of recent events in the UK.
From C. P. Ellis to School Integration: The Social Psychology of Conflict Reduction
Authors: Kelly Sean , Collett Jessica L.
Published: August 2008

In this article, the authors review social psychological theories of intergroup conflict reduction. Emphasis is placed on three interrelated social conditions which facilitate conflict reduction: intergroup contact, superordinate goals, and shared identities. Bridging experimental research with real‐world studies of schooling, these concepts are applied to understanding the process of school integration. Social contexts which present conflicting parties with a new shared goal and identity, as well as opportunities to become familiar with others beyond stereotypes and anxious reactions, dramatically increase the likelihood of diffusing conflict.
Multiple effects of bevacizumab in angiogenesis: implications for its use in age‐related macular degeneration
Authors: Carneiro Angela , Falcão Manuel , Azevedo Isabel , Falcão Reis Fernando , Soares Raquel
Published: August 2008

Purpose:  This study aimed to elucidate the precise effects of bevacizumab in all steps in the neovascularization process in endothelial cells.

Methods:  Human umbilical vein endothelial cells (HUVECs) were incubated with bevacizumab at concentrations within the clinically established range or with identical amounts of excipient. Cell cytotoxicity (evaluated by MTT assay), proliferation (by BrdU incorporation assay), apoptosis (by TUNEL assay), migration (by double‐chamber assay) and vessel assembly in matrigel‐coated plates were assessed in vitro. Mouse plug matrigel assays were performed to confirm in vitro results.

Results:  Incubation of HUVECs with bevacizumab did not present cytotoxicity. Concentrations comparable with those after intravitreal doses of bevacizumab significantly reduced proliferation and migration capacity, and increased apoptotic rates in these cells. In addition, bevacizumab led to a significant decrease in the assembly of capillary‐like structures on matrigel assay in comparison with excipient‐treated cells. Further substantiating these in vitro findings, bevacizumab also inhibited angiogenesis in a mouse plug matrigel assay, as evaluated by haemoglobin content levels.

Conclusions:  These results demonstrate that clinical doses of bevacizumab are able to prevent several steps of the angiogenic process. Bevacizumab is thus currently recommended for treating disorders that present augmented angiogenesis.
An objective model for slow orientation kinetics in concentrated fiber suspensions: Theory and rheological evidence
Authors: Wang Jin , O’Gara John F. , Tucker Charles L.
Published: August 2008

Recent experiments suggest that short fibers in concentrated suspensions align more slowly as a function of strain than models based on Jeffery’s equation predict. We develop an objective model that captures the slow orientation kinetics exhibited by short-fiber suspensions. The standard moment-tensor equation of fiber orientation is used to find equations for the change rates of the eigenvalues and eigenvectors of the orientation tensor. As a phenomenological assumption, the growth rates of the eigenvalues are reduced by a constant scalar factor, while the rotation rate expressions for the eigenvectors are unchanged. The eigenvalue/eigenvector equations are then reassembled as a tensor equation. An equivalent kinetic theory is also developed. The new model is tested in a variety of flows, and found to exhibit slower kinetics than the standard model but similar steady-state orientations. The model provides an excellent fit to the shear stress transient in a shear reversal experiment with a 30% glass fiber filled polybutylene terephthalate resin melt, and we show how this experiment can be used to determine the parameters of the model.
Coarse-grained modeling of macromolecular solutions using a configuration-based approach
Authors: Venkataramani V. , Sureshkumar R. , Khomami B.
Published: August 2008

An accurate, configuration-based, coarse-grained model for dilute macromolecular solutions is presented. The basic approach relies on exploring the macromolecular configurational diversity present in the flow of dilute polymeric solutions and identifying and partitioning the most frequently observed configurations, e.g., folds, half dumbbells, kinks, dumbbells, coils, and stretched states. The probability of finding any one of these configurations is calculated using a master configuration map that dictates the conditional probability of finding a configuration with a given chain extension. Each configuration class is modeled using a dumbbell description with a suitably modified drag coefficient. The configuration-based model is implemented using a Brownian dynamics simulation and the predictions are compared with the corresponding bead-spring model and finitely extensible nonlinear elastic dumbbell in homogeneous steady shear and uniaxial extension. Finally, prospects for model improvement are discussed.