bluuebunny/crossref_metadata_2025 huggingface dataset:
The Potential Role of mTOR Inhibitors in Non-Small Cell Lung Cancer
Authors: Gridelli Cesare , Maione Paolo , Rossi Antonio
Published: February 2008

Learning Objectives

After completing the course, the reader will be able to: Describe the PI3K growth pathway.Describe the molecular mechanism of action of mTOR inhibitors.Describe the preliminary clinical results of mTOR inhibitors in NSCLC.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com

The mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, which plays a critical role in regulating basic cellular functions including cellular growth and proliferation. Currently, the mTOR inhibitor rapamycin and its analogues (CCI-779, RAD001, AP23573), which induce cell-cycle arrest in the G1 phase, are being evaluated in cancer clinical trials. The mTOR inhibitors appear to be well tolerated, with skin reactions, stomatitis, myelosuppression, and metabolic abnormalities the most common toxicities seen. These adverse events are transient and reversible with interruption of dosing. Several pieces of evidence suggest a certain antitumor activity, including tumor regressions and prolonged stable disease, which has been reported among patients with a variety of malignancies, including non-small cell lung cancer (NSCLC). These promising preliminary clinical data have stimulated further research in this setting. Here, we review the basic structure of the pathway together with current results and future developments of mTOR inhibitors in the treatment of NSCLC patients.
The Ethical Justification for Minor Sibling Bone Marrow Donation: A Case Study
Authors: Pentz Rebecca D. , Haight Ann E. , Noll Robert B. , Barfield Raymond , Pelletier Wendy , Davies Stella , Alderfer Melissa A. , Hinds Pamela S.
Published: February 2008

Using a case study of a mentally delayed minor sibling donating bone marrow for his older sister, we discuss an alternative ethical justification for minor donation. The accepted justification for permitting minor siblings to donate bone marrow or peripheral blood stem cells is that the donor will benefit because of the greater likelihood of survival and less suffering of the sibling. Based on the limited data from four small retrospective studies of the risks and benefits for minor donors, we argue that there is a possibility, illustrated by this case, that the donor may not benefit, particularly if the transplant is unsuccessful. We, therefore, encourage the oncology community to increase support for minor donors, particularly mentally delayed ones. We also argue that the donation can be ethically justified based on the donor's familial duty to his sister. The basis of familial duties is complex, including such factors as the nature, intimacy, and history of the relationship and the specific risks and benefits to all involved. We examine each of these factors for our case study.
Bone morphogenetic protein-4 interacts with activin and GnRH to modulate gonadotrophin secretion in LβT2 gonadotrophs
Authors: Nicol L , Faure M-O , McNeilly J R , Fontaine J , Taragnat C , McNeilly A S
Published: February 2008

We have shown previously that, in sheep primary pituitary cells, bone morphogenetic proteins (BMP)-4 inhibits FSHβ mRNA expression and FSH release. In contrast, in mouse LβT2 gonadotrophs, others have shown a stimulatory effect of BMPs on basal or activin-stimulated FSHβ promoter-driven transcription. As a species comparison with our previous results, we used LβT2 cells to investigate the effects of BMP-4 on gonadotrophin mRNA and secretion modulated by activin and GnRH. BMP-4 alone had no effect on FSH production, but enhanced the activin+GnRH-induced stimulation of FSHβ mRNA and FSH secretion, without any effect on follistatin mRNA. BMP-4 reduced LHβ mRNA up-regulation in response to GnRH (±activin) and decreased GnRH receptor expression, which would favour FSH, rather than LH, synthesis and secretion. In contrast to sheep pituitary gonadotrophs, which express only BMP receptor types IA (BMPRIA) and II (BMPRII), LβT2 cells also express BMPRIB. Smad1/5 phosphorylation induced by BMP-4, indicating activation of BMP signalling, was the same whether BMP-4 was used alone or combined with activin±GnRH. We hypothesized that activin and/or GnRH pathways may be modulated by BMP-4, but neither the activin-stimulated phosphorylation of Smad2/3 nor the GnRH-induced ERK1/2 or cAMP response element-binding phosphorylation were modified. However, the GnRH-induced activation of p38 MAPK was decreased by BMP-4. This was associated with increased FSHβ mRNA levels and FSH secretion, but decreased LHβ mRNA levels. These results confirm 1. BMPs as important modulators of activin and/or GnRH-stimulated gonadotrophin synthesis and release and 2. important species differences in these effects, which could relate to differences in BMP receptor expression in gonadotrophs.
Opposite sexual dimorphism of 3,4-dihydroxyphenylalanine decarboxylase in the kidney and small intestine of mice
Authors: López-Contreras Andrés J , Galindo Jesús D , López-García Carlos , Castells Maria T , Cremades Asunción , Peñafiel Rafael
Published: February 2008

3,4-Dihydroxyphenylalanine decarboxylase (DDC; also known as l-amino acid decarboxylase) is involved in the synthesis of dopamine, norepinephrine, and serotonin, and also acts as an androgen receptor co-regulator protein. In contrast to other amino acid decarboxylases that are modulated by sex hormones, little is known about the influence of these hormones on DDC regulation. In the present work, we studied the influence of gender in the expression of DDC in different mouse tissues. Among the different organs studied, including brain, liver, kidney, intestine, heart, adrenal gland, and skeletal muscle, only kidney and small intestine showed a sex-dependent dimorphism in DDC expression. In the kidney, levels of DDC activity, DDC mRNA, and protein were remarkably higher in females than in males. On the contrary, in the small intestine, male mice displayed higher levels of DDC activity than females but they did not correlate precisely with mRNA levels. This dimorphism was dependent on androgens, since male castration and treatment of female mice with testosterone propionate, oppositely affected DDC levels in kidney and small intestine. However, estrogen ablation or treatment with estradiol did not significantly affect DDC activity in these tissues. Immunocytochemical analysis revealed that DDC was mainly located in the proximal straight tubular cells of the kidney and in the cytoplasm of enterocytes. These data and the fact that renal DDC inversely correlated with renal sodium reabsorption suggest that renal and intestinal gender dimorphism in DDC could be related to sex-related differences in sodium balance observed between males and females.
Heads or tails? Stressor-specific expression of corticotropin-releasing factor and urotensin I in the preoptic area and caudal neurosecretory system of rainbow trout
Authors: Bernier Nicholas J , Alderman Sarah L , Bristow Erin N
Published: February 2008

Corticotropin-releasing factor (CRF)- and urotensin I (UI)-expressing cells of the preoptic area (POA) and caudal neurosecretory system (CNSS) are considered key contributors to the regulation of the stress response in fish; however, the expression pattern of these neurons to environmental and social challenges have not been compared in a single study. Therefore, we characterized in rainbow trout (Oncorhynchus mykiss) the central distribution of CRF and UI expression and quantified the POA and CNSS mRNA levels of both transcripts in response to hyperammonemia, hypoxia, isolation, or subordination. The tissue distribution demonstrated that the POA and the CNSS are dominant sites of CRF and UI expression. Comparison of the plasma cortisol levels in response to the diverse treatments showed that subordination was the most severe stressor followed by hyperammonemia, isolation, and hypoxia. In the POA, with the exception of subordination that had no effect on UI expression, all stressors resulted in increase in CRF and UI mRNA levels. In the CNSS, while hyperammonemia was associated with increase in CRF and UI mRNA levels, and hypoxia induced an increase in CRF expression, isolation caused a decrease in the expression of both transcripts, and subordination had no effect. Independent of the stressor, we found strong positive correlations between CRF and UI expression in the POA and the CNSS, and no correlation in the expression of either gene between regions. Overall, the results demonstrate that the contribution of POA and CNSS CRF and UI neurons to the stress response in rainbow trout is stressor-, time-, and region-specific.
Dimerization and oligomerization of G-protein-coupled receptors: debated structures with established and emerging functions
Authors: Szidonya László , Cserző Miklós , Hunyady László
Published: February 2008

Dimerization or oligomerization of G-protein-coupled receptors (GPCRs) is a novel concept, which may lead to the reevaluation of the actions of pharmacological ligands, hormones, neurotransmitters, and other mediators acting on GPCRs. Although a large number of data obtained using different biophysical, biochemical and structural methods, and functional approaches argue for dimerization or oligomerization of these receptors, several publications criticized the applied methods and challenged the concept. The aim of this paper is to review the data that support the concept of receptor oligomerization, and the most important arguments against it. We conclude that it will require major methodical improvements to obtain decisive proof, whether GPCRs exist in their native membrane environments as homo- or heterodimeric or oligomeric complexes, in which receptor monomers have stable direct interactions. However, overwhelming amounts of data suggest that many GPCRs exhibit functional properties that require direct or indirect interactions between clustered receptors. Although it is difficult to conclude, about the exact nature of these interactions, dimerization or oligomerization of GPCRs is a useful paradigm for pharmacologists to study properties of receptors, which require functionally important clustering of receptors, such as trafficking of newly synthesized receptors to the cell surface, allosteric modulation of ligand binding, signaling specificity, co-internalization, or cross-inhibition of GPCRs.
Thermally adaptive response‐time compensation for LCDs
Authors: Lee Ki‐Chan , Moon Seung‐Hwan , Kim Nam‐Deog , Berkeley Brian H. , Kim Sang Soo
Published: February 2008

Abstract— This paper presents thermally adaptive driving (TAD) technology for response‐time compensation (RTC) of an LCD with an integrated sensor. The TAD system is comprised of an analog sensor, an analog sensor signal conditioning, and a digital feedback algorithm. The integrated thermal sensor provides accurate temperature measurement of the liquid‐crystal layer. The TAD controller has an eight‐step look‐up‐table (LUT) and compensates response time based on the panel temperature. The TAD system reduces response time by nearly 34% over the temperature range 0–60°C. This paper also presents a thermal sensor which has been integrated onto an LCD. The sensor uses metal (Mo/Al) film as a temperature detection layer, and its fabrication requires no manufacturing process changes. The sensor shows very good linearity, sensitivity, and reliability.
Electrical simulations of doped multilayer organic light‐emitting diodes (OLEDs) under temperature stress for high current densities
Authors: Pinot Christophe , Cloarec Héle`ne , Doyeux Henri , Haas Gunther , Maindron Tony , Prat Christophe , Vaufrey David , Bonnassieux Yvan
Published: February 2008

Abstract— This work aims at explaining and predicting the influence of the thickness of organic materials, dye doping, and space‐charge effects on charge‐carrier transport at different operating temperatures for high current densities (50 ≤ J ≤ 7000 mA/cm2). For the purpose of determining these influences, current‐voltage characteristics for typical electrically doped multilayer organic light‐emitting diodes (OLEDs) have been simulated. The results of the simulations concur with experimental data.
Advances towards high‐resolution pack‐and‐go displays: A survey
Authors: Majumder Aditi , Bhasker Ezekiel S. , Juang Ray
Published: February 2008

Abstract—Tiled displays provide high resolution and large scale simultaneously. Projectors can project on any available surface. Thus, it is possible to create a large high‐resolution display by simply tiling multiple projectors on any available regular surface. The tremendous advancement in projection technology has made projectors portable and affordable. One can envision displays made of multiple such projectors that can be packed in one's car trunk, carried from one location to another, deployed at each location easily to create a seamless high‐resolution display, and, finally, dismantled in minutes to be taken to the next location — essentially a pack‐and‐go display. Several challenges must be overcome in order to realize such pack‐and‐go displays. These include allowing for imperfect uncalibrated devices, uneven non‐diffused display surfaces, and a layman userviacomplete automation in deployment that requires no user invention. We described the advances we have made in addressing these challenges for the most common case of planar display surfaces. First, we present a technique to allow imperfect projectors. Next, we present a technique to allow a photometrically uncalibrated camera. Finally, we present a novel distributed architecture that renders critical display capabilities such as self‐calibration, scalability, and reconfigurability without any user intervention. These advances are important milestones towards the development of easy‐to‐use multi‐projector displays that can be deployed anywhere and by anyone.
Digital enhancement of television signals for people with visual impairments: Evaluation of a consumer product
Authors: Fullerton Matthew , Peli Eli
Published: February 2008

Abstract— Technology to improve the clarity of video for home‐theater viewers is available utilizing a low‐cost enhancement chip (DigiVision DV1000). The impact of such a device on the preference for enhanced video was tested for people with impaired vision and normally sighted viewers. Viewers with impaired vision preferred the enhancement effects more than normally sighted viewers. Preference for enhancement was correlated with loss in contrast sensitivity and visual acuity. Preference increased with increased enhancement settings (designed for those with normal vision) in the group with vision impairments. This suggests that higher enhancement levels may be of even greater benefit, and a similar product could be designed to meet the needs of the large, growing population of elderly television viewers with impaired vision.
“Rice Is Essential but Tiresome; You Should Get Some Noodles”: Doi Moi and the Political Economy of Men’s Extramarital Sexual Relations and Marital HIV Risk in Hanoi, Vietnam
Authors: Phinney Harriet M.
Published: February 2008

Research from around the world has suggested that married women’s greatest risk for contracting HIV is from having sexual intercourse with their husbands. On the basis of 6 months of ethnographic research in Hanoi, Vietnam, I argue that the contemporary nature of the HIV epidemic in Hanoi is shaped by 3 interrelated policies implemented in 1986 as part of the government’s new economic policy, Doi Moi (Renovation). Together, these policies structure men’s opportunities for extramarital sexual relations and encourage wives to acquiesce to their husbands’ sexual infidelity, putting both at risk of HIV. I propose 4 structural intervention strategies that address the policies that contribute to men’s opportunities for extramarital liaisons and to marital HIV risk.
Returning to the “Homeland”: Work-Related Ethnic Discrimination and the Health of Japanese Brazilians In Japan
Authors: Asakura Takashi , Gee Gilbert C. , Nakayama Kazuhiro , Niwa Sayuri
Published: February 2008

Objectives. We investigated whether self-reported ethnic discrimination in the workplace was associated with well-being among Japanese Brazilians who had returned to Japan. Further, we examined interactions between discrimination and education on well-being.

Methods. We obtained data from a cross-sectional survey of Japanese Brazilian workers (n = 313) conducted in 2000 and 2001. Outcomes were self-rated health, psychological symptoms as measured by the 12-item General Health Questionnaire (GHQ-12) score, and a checklist of somatic symptoms.

Results. Reports of ethnic discrimination were associated with increased risk of poor self-rated health and psychological symptoms (GHQ-12 score), after we controlled for self-assessed workload, supportive relations at work, physically dangerous working conditions, workplace environmental hazards, shift work, number of working hours, age, gender, marital status, income, education, Japanese lineage, length of residence, and Japanese language proficiency. Further, the relationship between discrimination and self-rated health and somatic symptoms was most robust for those with the least education.

Conclusions. Ethnic discrimination appears to be a correlate of morbidity among Japanese Brazilian migrants. Future research should investigate how educational and workplace interventions may reduce discrimination and possibly improve health.
Paternal Smoking and Increased Risk of Infant and Under-5 Child Mortality in Indonesia
Authors: Semba Richard D. , de Pee Saskia , Sun Kai , Best Cora M. , Sari Mayang , Bloem Martin W.
Published: February 2008

We examined the relationship between paternal smoking and child mortality. Among 361 021 rural and urban families in Indonesia, paternal smoking was associated with increased infant mortality (rural, odds ratio [OR] = 1.30; 95% confidence interval [CI] = 1.24, 1.35; urban, OR = 1.10; 95% CI = 1.01, 1.20), and under-5 child mortality (rural, OR = 1.32; 95% CI = 1.26, 1.37; urban, OR = 1.14; 95% CI = 1.05, 1.23). Paternal smoking diverts money from basic necessities to cigarettes and adversely affects child health; tobacco control should therefore be considered among strategies to improve child survival.
Combining Continuous Fluid Typing, Wireline Formation Testers, and Geochemical Measurements for an Improved Understanding of Reservoir Architecture
Authors: Elshahawi Hani , Venkataramanan Lalitha , McKinney Daniel , Flannery Matthew , Mullins Oliver C. , Hashem Mohamed
Published: February 2008

Identifying compartmentalization and understanding reservoir structure are of critical importance to reservoir development. Traditional methods of identifying reservoir compartmentalization, such as drillstem tests and extended well tests, often become impractical in deepwater settings, with costs approaching the costs of new wells and emissions becoming increasingly undesirable. Thus, compartments often have to be identified by some other means.

Individual formation-pressure measurements, downhole fluid analysis (DFA), and geochemistry are known to provide important information about reservoir architecture. When these powerful methods are combined systematically and applied to data sets, the resulting synergy delivers a much more accurate and robust picture of the reservoir. In this paper, we review a number of case studies in which we have successfully combined continuous fluid/facies mapping, pressure-gradient measurements, DFA, and geochemistry for a reservoir-continuity assessment in a diverse range of geological settings, including a wide range of field sizes, structural environments, reservoir lithologies, and oil types. Particular emphasis is placed on comparing the strengths and limitations of the different techniques in revealing reservoir architecture, especially vertical-permeability barriers. We present a number of unambiguous cases, for which multiple data streams might be viewed as being somewhat redundant. More-ambiguous cases, in which the multiple data streams are required to make a robust assessment of key reservoir properties, are also presented.
A Semianalytical Method To Predict Well Deliverability in Gas-Condensate Reservoirs
Authors: Chowdhury Nitin , Sharma Ravi , Pope Gary A. , Sepehrnoori Kamy
Published: February 2008

A fine-grid simulation is needed to capture the buildup of a condensate bank near wells operating below the dewpoint pressure. However, full-field simulations with a sufficiently fine grid will often not be feasible or will require very long computational times. A semianalytical method has been developed that can be used to predict the gas- and condensate-production rates from such wells accurately and that has some advantages over the pseudopressure approach. The semianalytical method includes the effects of capillary number (high velocity) and non-Darcy flow. The new method has been implemented in a compositional-reservoir simulator and verified with fine-grid compositional simulation results for both lean and rich gas-condensate fluids. Pressures, saturations, relative permeabilities, viscosities, and densities calculated with the semianalytical method are in excellent agreement with the results of fine-grid compositional simulations. Coarse-grid simulations with gridblock sizes on the order of 200 ft, coupled with the semianalytical method in gridblocks with wells, yielded production rates as accurate as fine-grid simulations with gridblock sizes on the order of 2 ft. The method was tested for single-layer, multilayer, and multiwell gas-condensate reservoirs and was found to give accurate results.
Modeling of Geomechanics in Naturally Fractured Reservoirs
Authors: Bagheri M. , Settari A.
Published: February 2008

Conventional modeling of fractured reservoirs treats fracture-system permeability and porosity as static (or pressure-dependent) data. Recent attempts at coupling geomechanics focused on the permeability but used crude empirical relations and treated the fluid flow as single porosity. This study takes advantage of the joint-mechanics theory to develop general, rigorous coupling between the fluid-flow equation and deformation of fractured media. Both porosity and permeability coupling are considered.

The geomechanical part uses the equivalent-continuum approach, considering both rock- and fracture-deformation properties. Multiple sets of fractures with any dip and strike angle can be defined. The stiffness of fractures varies with the effective stress according to a law typical for joints.

The main novelty of this work is that the geomechanics solution is decomposed into matrix and fracture parts and used to compute their dynamic porosity and permeability separately. This approach rigorously captures the effect of fractured-media deformation on the dual-porosity-flow part of the coupled system and allows the permeability and porosity variations to be based on measurable joint properties. Generally, fracture deformations produce changes of the permeability tensor in both magnitude and orientation, which in turn influences reservoir flow and compaction behavior.

The main issue studied was the variation in the permeability of the fracture system. The examples show that fracture deformation has a significant effect on productivity or injectivity and that anisotropy of the permeability tensor develops from deformation. The results provide an initiative for implementing the case of full-tensor permeability.
Sweep-Improvement Options for the Daqing Oil Field
Authors: Wang Dongmei , Han Peihui , Shao Zhenbo , Hou Weihong , Seright R. S.
Published: February 2008

This paper investigates the potential of various approaches for improving sweep in parts of the Daqing oil field that have been enhanced-oil-recovery (EOR) targets. Our studies indicated that the polymer flood should have provided excellent sweep throughout the vast majority of the patterns under consideration. However, because alkaline/surfactant/polymer (ASP) flooding is being considered to increase recovery efficiency from the Daqing oil field, mobility control and sweep improvement will be especially important and challenging during implementation of any future ASP process.

Fractures were present in a number of Daqing wells (both injectors and producers). Because the fractures were narrow and far from the wellbore, severe channeling did not occur. On the contrary, fractures near the wellbore aided reservoir sweep. Nearwellbore fractures increased the injectivity index substantially during the injection of polymer solutions and increased oil-productivity index in the production wells. These observations may be valuable during implementation of future floods where very-low-mobility chemical (i.e., ASP) banks must be injected to maintain mobility control.

Several modes of polymer degradation were considered, with mechanical (shear) degradation being of greatest concern. Appropriate use of near-wellbore fractures may mitigate mechanical degradation effectively, as well as improving injectivity.

Several new polymers show potential for cost-effective improvements at Daqing. Increased polymer concentration was also considered. A number of other approaches are (or have been) under investigation, including colloidal dispersion gels, foams, ASP foams, steam, microbes, and polymer solutions prepared with reduced salinity.
Development and optimisation of VFA driven DEAMOX process for treatment of strong nitrogenous anaerobic effluents
Authors: Kalyuzhnyi S. V. , Gladchenko M. A. , Kang Ho , Mulder A. , Versprille A.
Published: February 2008

The recently proposed DEAMOX (DEnitrifying AMmonium OXidation) process combines the anammox reaction with autotrophic denitrifying conditions using sulphide as an electron donor for the production of nitrite from nitrate within an anaerobic biofilm. This paper firstly presents a feasibility study of the DEAMOX process using synthetic (ammonia + nitrate) wastewater where sulphide is replaced by volatile fatty acids (VFA) as a more widespread electron donor for partial denitrification. Under the influent N-NH4+/N-NO3− and COD/N-NO3− ratios of 1 and 2.3, respectively, the typical efficiencies of ammonia removal were around 40% (no matter whether a VFA mixture or only acetate were used) for nitrogen loading rates (NLR) up to 1236 mg N/l/d. This parameter increased to 80% by increasing the influent COD/N-NO3− ratio to 3.48 and decreasing the influent N-NH4+/N-NO3− ratio to 0.29. As a result, the total nitrogen removal increased to 95%. The proposed process was further tested with typical strong nitrogenous effluent such as reject water (total N, 530–566 mg N/l; total COD, 1530–1780 mg/l) after thermophilic sludge anaerobic digestion. For this, the raw wastewater was split and partially (∼50%) fed to a nitrifying reactor (to generate nitrate) and the remaining part (∼50%) was directed to the DEAMOX reactor where this stream was mixed with the nitrified effluent. Stable process performance up to NLR of 1,243 mg N/l/d in the DEAMOX reactor was achieved resulting in 40, 100, and 66% removal of ammonia, NOx−, and total nitrogen, respectively.
FACTORS AFFECTING HOPELESSNESS LEVELS OF TURKISH PRETEENAGERS ATTENDING PRIMARY SCHOOL: A STRUCTURAL EQUATION MODEL
Authors: Yilmaz Veysel , Turkum Ayşe Sibel
Published: February 2008

This study was designed to determine the factors affecting hopelessness about the future of 10–12-year-old Turkish primary school students. Firstly, descriptive factor analysis was applied in order to determine the factors affecting hopelessness levels, then a structural equation
model (SEM) was utilized to describe the relationship between the specified factors and hopelessness; these relationships were tested by LISREL 8.54. The results indicated that the preteenagers' level of hopelessness was adversely affected by support received from parents and friends.
The hopelessness level was also significantly affected by the preteenagers' positive self-definition and parents' educational level.
PREJUDICES AGAINST, AND SOCIAL RESPONSIBILITIES TOWARDS, THE DISABLED
Authors: Tufan Ismail
Published: February 2008

Common prejudices disguised in various forms against the disabled are discussed in this paper. Specifically, it was investigated whether socially responsible behaviors can be stimulated by providing information about the life conditions of the disabled. Two hypotheses were proposed
and tested. Alterations in the nondisabled participants' perception of the disabled were evaluated through analysis of the results with regard to age, level of education, and income. Furthermore, relations between the independent variables and the tendency to participate in social activities
which can be regarded as socially responsible behaviors were investigated. Results show that Turkish society could pay more attention to the questions of how life conditions of the disabled can be improved and how they can be enabled to participate more in social life. In particular, members
of society should revise aspects of their perception of the disabled that are incorrect or ill informed.
Malonyl CoenzymeA Decarboxylase Regulates Lipid and Glucose Metabolism in Human Skeletal Muscle
Authors: Bouzakri Karim , Austin Reginald , Rune Anna , Lassman Michael E. , Garcia-Roves Pablo M. , Berger Joel P. , Krook Anna , Chibalin Alexander V. , Zhang Bei B. , Zierath Juleen R.
Published: February 2008

OBJECTIVE—Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary human skeletal muscle.

RESEARCH DESIGN AND METHODS—We used siRNA to silence MCD gene expression in cultured human myotubes from healthy volunteers (seven male and seven female) with no known metabolic disorders. Thereafter, we determined lipid and glucose metabolism and signal transduction under basal and insulin-stimulated conditions.

RESULTS—RNA interference–based silencing of MCD expression (75% reduction) increased malonyl-CoA levels twofold and shifted substrate utilization from lipid to glucose oxidation. RNA interference–based depletion of MCD reduced basal palmitate oxidation. In parallel with this reduction, palmitate uptake was decreased under basal (40%) and insulin-stimulated (49%) conditions compared with myotubes transfected with a scrambled sequence. MCD silencing increased basal and insulin-mediated glucose oxidation 1.4- and 2.6-fold, respectively, compared with myotubes transfected with a scrambled sequence. In addition, glucose transport and cell-surface GLUT4 content was increased. In contrast, insulin action on IRS-1 tyrosine phosphorylation, tyrosine-associated phosphatidylinositol (PI) 3-kinase activity, Akt, and glycogen synthase kinase (GSK) phosphorylation was unaltered between myotubes transfected with siRNA against MCD versus a scrambled sequence.

CONCLUSIONS—These results provide evidence that MCD silencing suppresses lipid uptake and enhances glucose uptake in primary human myotubes. In conclusion, MCD expression plays a key reciprocal role in the balance between lipid and glucose metabolism.
Interaction of Oral Antidiabetic Drugs With Hepatic Uptake Transporters
Authors: Bachmakov Iouri , Glaeser Hartmut , Fromm Martin F. , König Jörg
Published: February 2008

OBJECTIVE—The uptake of drugs into hepatocytes is a key determinant for hepatic metabolism, intrahepatic action, their subsequent systemic plasma concentrations, and extrahepatic actions. In vitro and in vivo studies indicate that many drugs used for treatment of cardiovascular diseases (e.g., oral antidiabetic drugs, statins) are taken up into hepatocytes by distinct organic anion transporters (organic anion transporting polypeptides [OATPs]; gene symbol SLCO/SLC21) or organic cation transporters (OCTs; gene symbol SLC22). Because most patients with type 2 diabetes receive more than one drug and inhibition of drug transporters has been recognized as a new mechanism underlying drug-drug interactions, we tested the hypothesis of whether oral antidiabetic drugs can inhibit the transport mediated by hepatic uptake transporters.

RESEARCH DESIGN AND METHODS—Using stably transfected cell systems recombinantly expressing the uptake transporters OATP1B1, OATP1B3, OATP2B1, or OCT1, we analyzed whether the antidiabetic drugs repaglinide, rosiglitazone, or metformin influence the transport of substrates and drugs (for OATPs, sulfobromophthalein [BSP] and pravastatin; for OCT1, 1-methyl-4-phenylpyridinium [MPP+] and metformin).

RESULTS—Metformin did not inhibit the uptake of OATP and OCT1 substrates. However, OATP-mediated BSP and pravastatin uptake and OCT1-mediated MPP+ and metformin uptake were significantly inhibited by repaglinide (half-maximal inhibitory concentration [IC50] 1.6–5.6 μmol/l) and rosiglitazone (IC50 5.2–30.4 μmol/l).

CONCLUSIONS—These in vitro results demonstrate that alterations of uptake transporter function by oral antidiabetic drugs have to be considered as potential mechanisms underlying drug-drug interactions.
Wear Simulation of Resin Composites and the Relationship to Clinical Wear
Authors: Barkmeier W. W. , Latta M. A. , Erickson R. L. , Wilwerding T. M.
Published: February 2008

Clinical Relevance

Laboratory wear simulation may be useful for estimating the relative clinical wear rates of new resin composite materials.
Validation and Reliability of Visual Assessment with a Shade Guide for Tooth-Color Classification
Authors: Meireles S. S. , Demarco F. F. , Santos I. S. , Dumith S. C. , Bona A. Della
Published: February 2008

Clinical Relevance

The results of this study showed that the visual assessment of tooth color using the Vitapan Classical shade guide is a valid method for distinguishing between light and dark tooth colors.
Effect of Two In-office Whitening Agents on the Enamel Surface In Vivo: A Morphological and Non-contact Profilometric Study
Authors: Cadenaro M. , Breschi L. , Nucci C. , Antoniolli F. , Visintini E. , Prati C. , Matis B. A. , Di Lenarda R.
Published: February 2008

Clinical Relevance

This in vivo study supports the hypothesis that the use of in-office bleaching agents is a safe and reliable procedure, inducing no structural damage to the enamel surface, even after prolonged and repeated applications.
Are low‐productive plant communities responsive to nutrient addition? Evidence from sand pioneer grassland
Authors: Storm Christian , Suss Karin
Published: February 2008

Question:

What is the effect of nutrient addition on primary production, phytodiversity and succession of a very unproductive plant community (ca. 100 g.m‐2.a‐1)?

Location:

A nutrient‐poor, calcareous inland sand ecosystem in the northern upper Rhine valley, Germany.

Methods:

Within a five‐fold replicated randomized block design, 10‐m2plots were given six single or combined applications of nitrogen, phosphorus, potassium and other essential nutrients for four years. An organic carbon treatment was included as a measure to immobilize soil nitrogen. Data were analysed by mixed linear models.

Results:

Productivity of above‐ground vascular plant species doubled after nitrogen addition. Additional nutrient elements did not increase productivity further. The cover of ten species and the height of 15 (out of 19 examined) species were significantly enhanced by nutrient addition.Centaurea stoebeis nitrogen‐limited and exhibits a decisive impact on total above‐ground vascular species productivity. Nutrients did not affect phytodiversity. Low‐dosage nitrogen addition (25 kg .ha‐1a‐1) and organic carbon treatment had no significant impact. However, long‐term effects cannot be excluded.

Conclusions:

The productivity of the examined plant community is responsive to nutrient addition. Although the response is actually more pronounced than in plant communities with higher initial productivity, productivity remained at a low level. Nutrient limitation (mostly phosphorus + nitrogen co‐limitation) of many individual species across all life forms is shown. Total above‐ground vascular plant productivity is nitrogen‐limited. No species were suppressed completely, nor has there yet been an encroachment of new species. However, high‐dosage nitrogen addition resulted in accelerated succession.
Long-term outcome following radical temporal bone resection for lateral skull base malignancies: a neurosurgical perspective
Authors: Kawahara Nobutaka , Sasaki Tomio , Asakage Takahiro , Nakao Kazunari , Sugasawa Masashi , Asato Hirotaka , Koshima Isao , Saito Nobuhito
Published: February 2008

Object

Primary temporal bone malignancy is a rare form of tumor for which the therapeutic strategy remains controversial. In this study, the authors reviewed their experience with radical temporal bone resection (TBR) of such lesions and analyzed the long-term results to provide treatment recommendations.

Methods

Between 1994 and 2006, 17 patients (10 men and 7 women) underwent total or subtotal TBR for primary temporal bone malignancies. Tumors were graded according to the University of Pittsburgh system. The effects of surgical margins and tumor extensions on patient survival were analyzed using the Kaplan–Meier method.

Results

All tumors, except 1, were graded T4 (most advanced). Subtotal TBR was performed in 14 patients, and total TBR was performed in 3. The surgical margin was tumor negative in 10 patients and tumor positive in 7. For large tumors extending into the infratemporal fossa or encroaching on the jugular foramen, orbitozygomatic (3 patients) and posterior transjugular (4 patients) approaches were combined with the standard approach, and en bloc resection with a negative margin was achieved in all cases but 1. The follow-up time ranged from 0.3–11.6 years (mean 3.3 years). The 5-year recurrence-free and disease-specific survival rates were 67.5 and 60.1%, respectively. When a negative surgical margin was achieved, the survival rates improved to 100 and 89%, respectively.

Conclusions

The neurosurgical skull base technique could improve the probability of en bloc resection with a tumor-free margin for extensive temporal bone malignancies, which would cure a subset of patients. The active participation of neurosurgeons would improve patient care in this field.
Fulminant Guillain–Barré syndrome after closed head injury: a potentially reversible cause of an ominous examination
Authors: Rivas Sharon , Douds G. Logan , Ostdahl Roger H. , Harbaugh Kimberly S.
Published: February 2008

✓ Fulminant Guillain–Barré syndrome (GBS) is a rapidly progressive form of polyneuropathy in which patients demonstrate eventual flaccid quadriplegia and an absence of brainstem function. Most patients present after a mild upper respiratory or gastrointestinal illness and have nondiagnostic cerebral imaging studies. The authors present a case of fulminant GBS that developed in a 55-year-old alcoholic man 1 week after admission for a closed head injury. The details of this case and a discussion of GBS will be presented. This case provides evidence for combined central and peripheral nervous system involvement in severe cases of GBS. Recognition of fulminant GBS is important to prevent inappropriate declaration of brain death or withdrawal of support in the face of a potentially reversible process.
Prediction of prognosis in children with medulloblastoma by using immunohistochemical analysis and tissue microarray
Authors: Shim Kyu-Won , Joo Sun-Young , Kim Se-Hoon , Choi Joong-Uhn , Kim Dong-Seok
Published: February 2008

Object

Medulloblastoma is the most common malignant neuroepithelial tumor found in children. Several reports have described efforts to identify the prognostic significance of various patterns of pathological and immunohistochemical features in medulloblastoma, but the published data appear to be controversial. The authors therefore attempted to demonstrate these prognostic factors convincingly in a retrospective study performed in patients with medulloblastoma.

Methods

The data used were obtained in 58 patients with medulloblastoma who were > 3 years of age and in whom > 1 year of follow-up was available after the maximal resection, craniospinal irradiation, and chemotherapy treatments. These assessments were performed to compare the immunohistochemical features to cellular differentiation, the proliferation index (PI), the apoptotic index (AI), and oncogenesis revealed by TrkC and c-erbB-3. In addition, the authors tried to determine the prognostic utility of these results in this tumor category.

Results

There was no statistically significant correlation between the prognosis and the degree of cell differentiation, but a positive correlation was noted between the PI and the AI in a tumor mass. The number of cases with a PI > 10% was significantly greater in the group of tumors in patients with recurrent medulloblastoma. A close association between the PI as a continuous variable and the progression-free and overall survival was also found. Most importantly, the PI is the only significant prognostic factor for the overall survival of patients with medulloblastoma.

Conclusions

Therefore, the authors suggest that the PI is directly linked to the prognostic factor for medulloblastoma and that immunohistochemical staining is a potentially powerful tool for predicting the prognosis of patients with medulloblastoma.
Surgical strategies and seizure control in pediatric patients with dysembryoplastic neuroepithelial tumors: a single-institution experience
Authors: Minkin Krasimir , Klein Olivier , Mancini Josette , Lena Gabriel
Published: February 2008

Object

Dysembryoplastic neuroepithelial tumors (DNTs) are commonly associated with medically resistant epilepsy that usually starts in childhood. Presurgical workup and surgical strategies remain controversial. The authors present a study of long-term seizure outcome after noninvasive presurgical investigations and different surgical strategies were used in a series of pediatric patients.

Methods

Twenty-four children who underwent operations at a single center between 1986 and 2006 were eligible for this retrospective study. The authors reviewed medical records including sex, age at seizure onset, age at surgery, seizure type and pharmacoresistance, lesion location, extent and complications of resection, histopathological findings, prescription of seizure and antiepileptic drugs, outcome, and tumor recurrence.

Results

At the last follow-up examination (range 1–16 years after initial treatment, mean 6.7 years) 20 children (83.3%) were seizure free. The authors did not find the rundown phenomenon in any of the patients. Complete antiepileptic drug withdrawal was achieved in 12 children (50%). In 4 of 15 children with temporal DNTs, the lesionectomy alone failed to control seizures. These results could be explained by the wider epileptogenic zone. The only significant predictor for favorable seizure outcome was an absence of preoperative generalized seizures.

Conclusions

In children with extratemporal DNTs the results suggest that complete lesionectomy alone without invasive presurgical investigations are effective for long-term seizure control. For children with temporal DNTs not invading the amygdalohippocampal complex, extensive presurgical evaluations seem indicated. The absence of preoperative generalized seizures was associated with a better seizure outcome.
Management of complicated shunt infections: a clinical report
Authors: James Hector E. , Bradley John S.
Published: February 2008

Object

The authors present their experience with a protocol for the treatment of patients with complicated shunt infections.

Methods

Complicated shunt infections are defined for the purpose of this protocol as multiple compartment hydrocephalus, multiple organism shunt infection, severe peritonitis, or infections in other sites of the body. The initial treatment protocol for these patients was 3 weeks of intravenous antibiotic therapy and 2 weeks of twice daily intraventricular/intrashunt antibiotic therapy. Cerebrospinal fluid (CSF) cultures were monitored during therapy and obtained again 48 hours after completion. The shunt was completely replaced. Additionally, follow-up cultures were obtained in all patients 3–6 months after therapy was completed.

Results

A cure of the infection was achieved in all patients as defined by negative cultures obtained at completion of antibiotic therapy and in follow-up studies. The follow-up period was 2–11 years (mean 4.4 ± 2.5 years). The treatment protocol was modified in the patients treated after 1991, and 18 patients were treated with this modified treatment regime. In these patients, intraventricular antibiotics were administered only once daily for 14 days, and the CSF was cultured 24 hours after antibiotic therapy had been stopped instead of after 48 hours. The results were similar to those obtained with the initial protocol.

Conclusions

Based on their prospective nonrandomized series, the authors believe that patients with complicated shunt infections can be successfully treated with 2 weeks of intraventricular antibiotic therapy administered once daily, concurrent with 3 weeks of intravenous antibiotic therapy. This protocol reduces length of treatment and hospital stay, and avoids recurrence of infection.
Adverse facial edema associated with off-label use of recombinant human bone morphogenetic protein–2 in cranial reconstruction for craniosynostosis
Authors: Shah M. Mohsin , Smyth Matthew D. , Woo Albert S.
Published: February 2008

✓The authors present a case of scalp and facial edema following craniofacial reconstruction for metopic craniosynostosis in which recombinant human bone morphogenetic protein–2 (rhBMP-2) was used to treat cranial defects related to the frontoorbital reconstruction. The extent of swelling, the onset, and duration were unusual for such cases and suggested a possible role of rhBMP-2 in inducing a local inflammatory response. The edema rapidly resolved after the patient underwent surgery to remove the rhBMP-2 implants.
Accuracy of pedicle screw insertion in the cervical spine for internal fixation using frameless stereotactic guidance
Authors: Rath Stefan A. , Moszko Slawomir , Schäffner Petra M. , Cantone Giuseppe , Braun Veit , Richter Hans-Peter , Antoniadis Gregor
Published: February 2008

Object

Although transpedicular fixation is a biomechanically superior technique, it is not routinely used in the cervical spine. The risk of neurovascular injury in this region is considered high because the diameter of cervical pedicles is very small and their angle of insertion into the vertebral body varies. This study was conducted to analyze the clinical accuracy of stereotactically guided transpedicular screw insertion into the cervical spine.

Methods

Twenty-seven patients underwent posterior stabilization of the cervical spine for degenerative instability resulting from myelopathy, fracture/dislocation, tumor, rheumatoid arthritis, and pyogenic spondylitis. Fixation included 1–6 motion segments (mean 2.2 segments). Transpedicular screws (3.5-mm diameter) were placed using 1 of 2 computer-assisted guidance systems and lateral fluoroscopic control. The intraoperative mean deviation of frameless stereotaxy was < 1.9 mm for all procedures.

Results

No neurovascular complications resulted from screw insertion. Postoperative computed tomography (CT) scans revealed satisfactory positioning in 104 (90%) of 116 cervical pedicles and in all 12 thoracic pedicles. A noncritical lateral or inferior cortical breach was seen with 7 screws (6%). Critical malplacement (4%) was always lateral: 5 screws encroached into the vertebral artery foramen by 40–60% of its diameter; Doppler sonographic controls revealed no vascular compromise. Screw malplacement was mostly due to a small pedicle diameter that required a steep trajectory angle, which could not be achieved because of anatomical limitation in the exposure of the surgical field.

Conclusions

Despite the use of frameless stereotaxy, there remains some risk of critical transpedicular screw malpositioning in the subaxial cervical spine. Results may be improved by the use of intraoperative CT scanning and navigated percutaneous screw insertion, which allow optimization of the transpedicular trajectory.