bluuebunny/crossref_metadata_2025 huggingface dataset:
Unforeseen decreases in dissolved oxygen levels affect tube formation kinetics in collagen gels
Authors: Abaci Hasan Erbil , Truitt Rachel , Tan Scott , Gerecht Sharon
Published: May 2011

The availability of oxygen (O2) is a critical parameter affecting vascular tube formation. In this study, we hypothesize that dissolved oxygen (DO) levels in collagen gels change during the three-dimensional (3D) culture of human umbilical vein endothelial cells (HUVECs) in atmospheric conditions and that such changes affect the kinetics of tube formation through the production of reactive oxygen species (ROS). We demonstrate a decrease in O2 tension during 3D cultures of HUVECs. Noninvasive measurements of DO levels during culture under atmospheric conditions revealed a profound decrease that reached as low as 2% O2 at the end of 24 h. After media replacement, DO levels rose rapidly and equilibrated at ∼15% O2, creating a reoxygenated environment. To accurately estimate DO gradients in 3D collagen gels, we developed a 3D mathematical model and determined the Michaelis-Menten parameters, Vmax and Km, of HUVECs in collagen gels. We detected an increase in ROS levels throughout the culture period. Using diphenyliodonium to inhibit ROS production resulted in the complete inhibition of tube formation. Interference RNA studies further showed that hypoxia-inducible factors (HIFs)-1α and -2α are not involved in the formation of 3D tubes in collagen gels. We conclude that ROS affect the tubulogenesis process through HIFα-independent pathways, where the levels of ROS are influenced by the uncontrolled variations in DO levels. This study is the first demonstration of the critical and unexpected role of O2 during 3D in vitro culture models of tubulogenesis in atmospheric conditions.
Cholinergic and glutamatergic agonists induce gamma frequency activity in dorsal subcoeruleus nucleus neurons
Authors: Simon Christen , Kezunovic Nebojsa , Williams D. Keith , Urbano Francisco J. , Garcia-Rill E.
Published: May 2011

The dorsal subcoeruleus nucleus (SubCD) is involved in generating two signs of rapid eye movement (REM) sleep: muscle atonia and ponto-geniculo-occipital (PGO) waves. We tested the hypothesis that single cell and/or population responses of SubCD neurons are capable of generating gamma frequency activity in response to intracellular stimulation or receptor agonist activation. Whole cell patch clamp recordings (immersion chamber) and population responses (interface chamber) were conducted on 9- to 20-day-old rat brain stem slices. All SubCD neurons ( n = 103) fired at gamma frequency when subjected to depolarizing steps. Two statistically distinct populations of neurons were observed, which were distinguished by their high (>80 Hz, n = 24) versus low (35–80 Hz, n = 16) initial firing frequencies. Both cell types exhibited subthreshold oscillations in the gamma range ( n = 43), which may underlie the gamma band firing properties of these neurons. The subthreshold oscillations were blocked by the sodium channel blockers tetrodotoxin (TTX, n = 21) extracellularly and N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314) intracellularly ( n = 5), indicating they were sodium channel dependent. Gamma frequency subthreshold oscillations were observed in response to the nonspecific cholinergic receptor agonist carbachol (CAR, n = 11, d = 1.08) and the glutamate receptor agonists N-methyl-d-aspartic acid (NMDA, n = 12, d = 1.09) and kainic acid (KA, n = 13, d = 0.96), indicating that cholinergic and glutamatergic inputs may be involved in the activation of these subthreshold currents. Gamma band activity also was observed in population responses following application of CAR ( n = 4, P < 0.05), NMDA ( n = 4, P < 0.05) and KA ( n = 4, P < 0.05). Voltage-sensitive, sodium channel-dependent gamma band activity appears to be a part of the intrinsic membrane properties of SubCD neurons.
The therapeutic potential of hydrogen sulfide: separating hype from hope
Authors: Olson Kenneth R.
Published: May 2011

Hydrogen sulfide (H2S) has become the hot new signaling molecule that seemingly affects all organ systems and biological processes in which it has been investigated. It has also been shown to have both proinflammatory and anti-inflammatory actions and proapoptotic and anti-apoptotic effects and has even been reported to induce a hypometabolic state (suspended animation) in a few vertebrates. The exuberance over potential clinical applications of natural and synthetic H2S-“donating” compounds is understandable and a number of these function-targeted drugs have been developed and show clinical promise. However, the concentration of H2S in tissues and blood, as well as the intrinsic factors that affect these levels, has not been resolved, and it is imperative to address these points to distinguish between the physiological, pharmacological, and toxicological effects of this molecule. This review will provide an overview of H2S metabolism, a summary of many of its reported “physiological” actions, and it will discuss the recent development of a number of H2S-donating drugs that show clinical potential. It will also examine some of the misconceptions of H2S chemistry that have appeared in the literature and attempt to realign the definition of “physiological” H2S concentrations upon which much of this exuberance has been established.
Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle
Authors: Gurd Brendon J. , Yoshida Yuko , McFarlan Jay T. , Holloway Graham P. , Moyes Chris D. , Heigenhauser George J. F. , Spriet Lawrence , Bonen Arend
Published: May 2011

Silent mating type information regulator 2 homolog 1 (SIRT1)-mediated peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) deacetylation is potentially key for activating mitochondrial biogenesis. Yet, at the whole muscle level, SIRT1 is not associated with mitochondrial biogenesis (Gurd, BJ, Yoshida Y, Lally J, Holloway GP, Bonen A. J Physiol 587: 1817–1828, 2009). Therefore, we examined nuclear SIRT1 protein and activity in muscle with varied mitochondrial content and in response to acute exercise. We also measured these parameters after stimulating mitochondrial biogenesis with chronic muscle contraction and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) administration in rodents and exercise training in humans. In skeletal and heart muscles, nuclear SIRT1 protein was negatively correlated with indices of mitochondrial density (citrate synthase activity, CS; cytochrome oxidase IV, COX IV), but SIRT1 activity was positively correlated with these parameters ( r > 0.98). Acute exercise did not alter nuclear SIRT1 protein but did induce a time-dependent increase in nuclear SIRT1 activity. This increase in SIRT1 activity was temporally related to increases in mRNA expression of genes activated by PGC-1α. Both chronic muscle stimulation and AICAR increased mitochondrial biogenesis and muscle PGC-1α, but not nuclear PGC-1α. Concomitantly, muscle and nuclear SIRT1 protein contents were reduced, but nuclear SIRT1 activity was increased. In human muscle, training-induced mitochondrial biogenesis did not alter muscle or nuclear SIRT1 protein content, but it did increase muscle and nuclear PGC-1α and SIRT1 activity. Thus, nuclear SIRT1 activity, but not muscle or nuclear SIRT1 protein content, is associated with contraction-stimulated mitochondrial biogenesis in rat and human muscle, possibly via AMPK activation.
Environmental factors responsible for switching on the SO42−excretory system in the kidney of seawater eels
Authors: Watanabe Taro , Takei Yoshio
Published: May 2011

Eels are unique in that they maintain lower plasma SO42−concentration in SO42−-rich (∼30 mM) seawater (SW) than in SO42−-poor (<0.3 mM) freshwater (FW), showing drastic changes in SO42−regulation between FW and SW. We previously showed that the expression of renal SO42−transporter genes, FW-specific Slc13a1 and SW-specific Slc26a6a, changes profoundly after transfer of FW eels to SW, which results in the decrease in plasma SO42−concentration after 3 days in SW. In this study, we attempted to identify the environmental factor(s) that trigger the switching of SO42−regulation using changes in plasma and urine SO42−concentrations and expression of the transporter genes as markers. Transfer of FW eels to 30 mM SO42−or transfer of SW eels to SO42−-free SW did not change the SO42−regulation. Major divalent cations in SW, Mg2+(50 mM) and Ca2+(10 mM), were also ineffective, but 50 mM NaCl was effective for switching the SO42−regulation. Further analyses using choline-Cl and Na-gluconate showed that Cl−is a primary factor and Na+is permissive for the Cl−effect. Since plasma SO42−and Cl−concentrations were inversely correlated, we injected various solutions into the blood and found that Cl−alone triggered the switching from FW to SW-type regulation. Furthermore, the inhibitor of Na-Cl cotransporter (NCC) added to media significantly impaired the expression of SW-specific Slc26a6a in 150 mM NaCl. In summary, it appears that Cl−ions in SW are taken up into the circulation via the NCC together with Na+, and the resultant increase in plasma Cl−concentration enhances SO42−excretion by the kidney through downregulation of absorptive Slc13a1 and upregulation of excretory Slc26a6a, resulting in low plasma SO42−concentration in SW.
Fetal uninephrectomy in male sheep alters the systemic and renal responses to angiotensin II infusion and AT1R blockade
Authors: Singh Reetu R. , Moritz Karen M. , Wintour E. Marelyn , Jefferies Andrew J. , Iqbal Javed , Bertram John F. , Denton Kate M.
Published: May 2011

Fetal uninephrectomy (uni-x) at 100 days of gestation results in compensatory nephrogenesis in the remaining kidney, resulting in a 30% reduction in total nephron number in male sheep. Recently, we showed that uni-x males at 6 mo of age have elevated arterial pressure, reduced renal blood flow (RBF), glomerular filtration rate (GFR), and low plasma renin levels (Singh R, Denton K, Bertram J, Jefferies A, Head G, Lombardo P, Schneider-Kolsky M, Moritz K. J Hypertens 27: 386–396, 2009; Singh R, Denton K, Jefferies A, Bertram J, Moritz K. Clin Sci (Lond) 118: 669–680, 2010). We hypothesized this was due to upregulation of the intrarenal renin-angiotensin system (RAS). In this study, renal responses to ANG II infusion and ANG II type 1 receptor (AT1R) blockade were examined in the same 6-mo-old male sheep. Uni-x animals had reduced levels of renal tissue and plasma renin and ANG II. Renal gene expression of renin, and gene and protein levels of AT1R and AT2R, were significantly lower in uni-x animals. In response to graded ANG II infusion, sham animals had the expected decrease in conscious RBF and GFR. Interestingly, the response was biphasic in uni-x sheep, with GFR initially decreasing, but then increasing at higher ANG II doses (34 ± 7%; Pgroup × treatment< 0.001), due to a paradoxical decrease in renal vascular resistance ( Pgroup × treatment< 0.001). In response to AT1R blockade, while GFR and RBF responded similarly between groups, there was a marked increase in sodium excretion in uni-x compared with sham sheep (209 ± 35 vs. 25 ± 12%; P < 0.001). In conclusion, in 6-mo-old male sheep born with a single kidney, these studies demonstrate that this is a low-renin form of hypertension, in which responses to ANG II are perturbed and the intrarenal RAS is downregulated.
Effects of 8 wk of voluntary unloaded wheel running on K+ tolerance and excitability of soleus muscles in rat
Authors: Broch-Lips Martin , de Paoli Frank , Pedersen Thomas Holm , Overgaard Kristian , Nielsen Ole Bækgaard
Published: May 2011

During intense exercise, efflux of K+ from working muscles increases extracellular K+ ([K+]o) to levels that can compromise muscle excitability and hence cause fatigue. In this context, the reduction in the exercise-induced elevation of [K+]o observed after training in humans is suggested to contribute to the increased performance after training. Although a similar effect could be obtained by an increase in the tolerance of muscle to elevated [K+]o, this possibility has not been investigated. To examine this, isolated soleus muscles from sedentary (sedentary) rats and from rats that had voluntarily covered 13.1 ± 0.7 km/day in an unloaded running wheel for 8 wk (active) were compared. In muscles from active rats, the loss of force induced by exposure to an elevated [K+]o of 9 mM was 42% lower than in muscles from sedentary rats ( P < 0.001). This apparent increase in K+ tolerance in active rats was associated with an increased excitability as evident from a 33% reduction in the electrical current needed to excite individual muscle fibers ( P < 0.0009). Moreover, muscles from active rats had lower Cl− conductance, higher maximal rate of rise of single-fiber action potentials (AP), and higher Na+/K+ pump content. When stimulated intermittently at 6.5 mM K+, muscles from active rats displayed better endurance than muscles from sedentary rats, whereas no difference was found when the muscles were stimulated continuously at 30 or 120 Hz. We conclude that voluntary running increases muscle excitability, leading to improved tolerance to elevated [K+]o.
Stability in a frontal plane model of balance requires coupled changes to postural configuration and neural feedback control
Authors: Bingham Jeffrey T. , Choi Julia T. , Ting Lena H.
Published: May 2011

Postural stability depends on interactions between the musculoskeletal system and neural control mechanisms. We present a frontal plane model stabilized by delayed feedback to analyze the effects of altered stance width on postural responses to perturbations. We hypothesized that changing stance width alters the mechanical dynamics of the body and limits the range of delayed feedback gains that produce stable postural behaviors. Surprisingly, mechanical stability was found to decrease as stance width increased due to decreased effective inertia. Furthermore, due to sensorimotor delays and increased leverage of hip joint torque on center-of-mass motion, the magnitudes of the stabilizing delayed feedback gains decreased as stance width increased. Moreover, the ranges of the stable feedback gains were nonoverlapping across different stance widths such that using a single neural feedback control strategy at both narrow and wide stances could lead to instability. The set of stable feedback gains was further reduced by constraints on foot lift-off and perturbation magnitude. Simulations were fit to experimentally measured kinematics, and the identified feedback gains corroborated model predictions. In addition, analytical gain margin of the linearized system was found to predict step transitions without the need for simulation. In conclusion, this model offers a method to dissociate the complex interactions between postural configuration, delayed sensorimotor feedback, and nonlinear foot lift-off constraints. The model demonstrates that stability at wide stances can only be achieved if delayed neural feedback gains decrease. This model may be useful in explaining both expected and paradoxical changes in stance width in healthy and neurologically impaired individuals.
Resequencing DCDC5 in the Flanking Region of an LD‐SNP Derived from a Kidney‐Yang Deficiency Syndrome Family
Authors: Zhou Li Ping , Liu Wei Wei , Zhang Tian E. , Li Wei Hong , Tan Ling Ling , Li Wan Zhen , Qin Yu Hua , Yang Hong Ya , Duan Azure , Wang Mi Qu , Ding Wei Jun
Published: May 2011

Objective. To explore the genetic traits of Kidney‐yang deficiency syndrome (KDS). Design. Twelve KDS subjects and three spouses from a typical KDS family were recruited. Their genomic DNA samples were genotyped by Affymetrix 100K single‐nucleotide polymorphism (SNP) arrays. The linkage disequilibrium (LD) SNPs were generated using GeneChip DNA analysis software (GDAS, Affymetrix). Genes located within 100 bp of the flanks of LD SNPs were mined via GeneView. 29 exons of the doublecortin domain containing 5 (DCDC5), a representative gene within the flank of an LD SNP, were resequenced. Results. Five LD SNPs display midrange linkage with KDS. Two genes with established functions, DCDC5 and Leucyl‐tRNA synthetase, were mined in the flanks of LD SNPs. Resequencing of DCDC5 revealed a nonsynonymous variation, in which 3764T/A was replaced by C/G. Accordingly, the Ser1172 was substituted by Pro1172. The S1172P substitution effect was evaluated as “possibly damaging” by PolyPhen. Conclusion. We have identified a genomic variation of DCDC5 based on the LD SNPs derived from a KDS family. DCDC5 and other genes surrounding these SNPs display some relationships with key symptoms of KDS.
Unusual Noncommunicating Isolated Enteric Duplication Cyst in Adults
Authors: Gümüş Metehan , Kapan Murat , Gümüş Hatice , Önder Akin , Girgin Sadullah
Published: May 2011

Duplication cysts are rare gastrointestinal congenital abnormalities and can occur anywhere within the gastrointestinal tract. Duplication cysts are firmly attached to or share the wall of the alimentary tract and have a common blood supply with the adjacent segment of the bowel. Completely isolated duplication cysts are an extremely rare variety of gastrointestinal duplications with their own exclusive blood supply, and they do not communicate with the intestine. These cysts are usually diagnosed during early childhood, and very rarely detected in adults, mostly incidentally, due to a lack of symptoms. A 28-year-old male was admitted to our hospital with a chief complaint of lower abdominal pain and distention and a palpable mass for 1 month. Based upon computed tomography and sonographic findings, a small bowel duplication cyst was tentatively diagnosed. The cyst had no connection to the gastrointestinal tract. Herein we report the case of a noncommunicating isolated ileal duplication cyst in an adult. Resection of the cyst was performed safely without requiring bowel resection.
Improving the Management of Late-Life Depression in Primary Care: Barriers and Facilitators
Authors: Sussman Tamara , Yaffe Mark , McCusker Jane , Parry David , Sewitch Maida , Van Bussel Lisa , Ferrer Ilyan
Published: May 2011

The objectives of this study were to elicit Canadian health professionals' views on the barriers to identifying and treating late-life depression in primary care settings and on the solutions felt to be most important and feasible to implement. A consensus development process was used to generate, rank, and discuss solutions. Twenty-three health professionals participated in the consensus process. Results were analysed using quantitative and qualitative methods. Participants generated 12 solutions. One solution, developing mechanisms to increase family physicians' awareness of resources, was highly ranked for importance and feasibility by most participants. Another solution, providing family physicians with direct mental health support, was highly ranked as important but not as feasible by most participants. Deliberations emphasized the importance of case specific, as needed support based on the principles of shared care. The results suggest that practitioners highly value collaborative care but question the feasibility of implementing these principles in current Canadian primary care contexts.
Prevalence, Spinal Alignment, and Mobility of Lumbar Spinal Stenosis with or without Chronic Low Back Pain: A Community-Dwelling Study
Authors: Miyakoshi Naohisa , Hongo Michio , Kasukawa Yuji , Ishikawa Yoshinori , Shimada Yoichi
Published: May 2011

Although lumbar spinal stenosis (LSS) occurs almost universally with aging, little is known regarding its actual prevalence and relationships to chronic low back pain (CLBP) in the general population. The presence of CLBP in subjects with LSS may have negative impacts on spinal alignment and mobility. This study evaluated the prevalence of LSS using a self-administered, self-reported history questionnaire in 630 community-dwelling individuals ≥50 years old. Subjects with LSS were further divided into LSS+CLBP and LSS alone groups, and spinal alignment and mobility were compared using a computer-assisted device. Prevalence of LSS was 10.8% in this cohort. Subjects in the LSS+CLBP group () showed a significantly more kyphotic lumbar spinal alignment with limited lumbar extension (), resulting in a stooped trunk compared to subjects in the LSS alone group (). However, no significant difference in spinal mobility was seen between groups.
Generating Solar Sail Trajectories in the Earth-Moon System Using Augmented Finite-Difference Methods
Authors: Wawrzyniak Geoffrey G. , Howell Kathleen C.
Published: May 2011

Using a solar sail, a spacecraft orbit can be offset from a central body such that the orbital plane is displaced from the gravitational center. Such a trajectory might be desirable for a single-spacecraft relay to support communications with an outpost at the lunar south pole. Although trajectory design within the context of the Earth-Moon restricted problem is advantageous for this problem, it is difficult to envision the design space for offset orbits. Numerical techniques to solve boundary value problems can be employed to understand this challenging dynamical regime. Numerical finite-difference schemes are simple to understand and implement. Two augmented finite-difference methods (FDMs) are developed and compared to a Hermite-Simpson collocation scheme. With 101 evenly spaced nodes, solutions from the FDM are locally accurate to within 1740 km. Other methods, such as collocation, offer more accurate solutions, but these gains are mitigated when solutions resulting from simple models are migrated to higher-fidelity models. The primary purpose of using a simple, lower-fidelity, augmented finite-difference method is to quickly and easily generate accurate trajectories.
Characterization of the Evolution of Nonlinear Uniform Cellular Automata in the Light of Deviant States
Authors: Pal Choudhury Pabitra , Sahoo Sudhakar , Chakraborty Mithun
Published: May 2011

Dynamics of a nonlinear cellular automaton (CA) is, in general asymmetric, irregular, and unpredictable as opposed to that of a linear CA, which is highly systematic and tractable, primarily due to the presence of a matrix handle. In this paper, we present a novel technique of studying the properties of the State Transition Diagram of a nonlinear uniform one‐dimensional cellular automaton in terms of its deviation from a suggested linear model. We have considered mainly elementary cellular automata with neighborhood of size three, and, in order to facilitate our analysis, we have classified the Boolean functions of three variables on the basis of number and position(s) of bit mismatch with linear rules. The concept of deviant and nondeviant states is introduced, and hence an algorithm is proposed for deducing the State Transition Diagram of a nonlinear CA rule from that of its nearest linear rule. A parameter called the proportion of deviant states is introduced, and its dependence on the length of the CA is studied for a particular class of nonlinear rules.
Glycemic Index and Glycemic Load and Their Association with C-Reactive Protein and Incident Type 2 Diabetes
Authors: van Woudenbergh Geertruida J. , Kuijsten Anneleen , Sijbrands Eric J. G. , Hofman Albert , Witteman Jacqueline C. M. , Feskens Edith J. M.
Published: May 2011

Objective. To investigate whether the Glycemic Index (GI) or Glycemic Load (GL) of a diet is associated with C-reactive Protein (CRP) and risk of type 2 diabetes in a prospective study.Materials and Methods. Our analysis included 4,366 participants who did not have diabetes at baseline. During follow-up 456 diabetes cases were confirmed. Dietary GI and GL were derived from a food-frequency questionnaire and its association with CRP was examined cross-sectionally using linear regression models. The association of GI and GL with diabetes incidence was examined using Cox proportional hazard models.Results. GL, but not GI, was associated with lnCRP at baseline (bGL=0.11per 50 units;P=.01). When comparing the highest to the lowest tertile of GI with respect to diabetes incidence, a Relative Risk (RR) of 0.95 [95%CI 0.75, 1.21] was found after adjustment for lifestyle and nutritional factors. For GL the RR for diabetes incidence was 1.00 [95%CI 0.74, 1.36]. Additional adjustment for CRP did not change RRs.Conclusion. Since GI was not associated with CRP and risk of type 2 diabetes, it is unlikely that a high GI diet induces the previously shown positive association between CRP and risk of type 2 diabetes by increasing CRP concentrations.
Lafutidine 10 mg versus Rabeprazole 20 mg in the Treatment of Patients with Heartburn-Dominant Uninvestigated Dyspepsia: A Randomized, Multicentric Trial
Authors: Dewan Bhupesh , Philipose Nisha
Published: May 2011

Background. Empirical therapy with antisecretory agents like PPIs and H2RAs has long been the traditional approach in the initial management of uninvestigated dyspepsia.Aim. The objective of the study was to examine relief of dyspepsia with lafutidine, a second-generationH2-RA, and rabeprazole and to compare their efficacy.Methods. This was a randomized, open, comparative trial in adult uninvestigated dyspeptic patients, who had at least moderate severity of symptoms, defined as a score of≥4 on a 7-point global overall symptom (GOS) scale, and were randomized to receive once daily either lafutidine 10 mg or rabeprazole 20 mg for 4 weeks.Results. A total of 236 patients were enrolled, out of which 194 patients were included in the analysis. At the end of week 4, a significant difference was observed for symptom relief (lafutidine 89.90% versus rabeprazole 65.26%,P<.01) and symptom resolution (lafutidine 70.71% versus rabeprazole 25.26%,P<.01). Both the drugs were well tolerated.Conclusion. Both lafutidine and rabeprazole provide symptom relief in patients with heartburn-dominant uninvestigated dyspepsia. The present study confirms the appropriateness of lafutidine as an empiric treatment and superior efficacy for primary care practice patients with dyspepsia.
Hopf Bifurcation for a Model of HIV Infection of CD4+ T Cells with Virus Released Delay
Authors: Yang Jun-Yuan , Wang Xiao-Yan , Li Xue-Zhi
Published: May 2011

A viral model of HIV infection of CD4+ T‐cells with virus
released period is formulated, and the effect of this released period on the stability of the equilibria is investigated. It is shown that the introduction of the viral released period can destabilize the system, and the period solution may arise. The direction and stability of the Hopf bifurcation are also discussed. Numerical simulations are presented to illustrate the results.
The Effect of Ionic Liquids on the Corrosion Inhibition of Copper in Acidic Chloride Solutions
Authors: Scendo M. , Uznanska J.
Published: May 2011

The influence of the concentration of the 1-Butyl-3-methylimidazolium chloride (BMIMCl) and 1-Butyl-3-methylimidazolium bromide (BMIMBr) as ionic liquids (ILs) on the corrosion inhibition of copper in 1.0 M Cl−solutions of pH 1.0 was studied. The investigation involved electrochemical polarization methods as well as electrochemical quartz crystal microbalance (EQCM) technique and scanning electron microscopy (SEM). The inhibition efficiency increases with an increase in the concentration of BMIMCl and BMIMBr. Adherent layers of inhibitors were postulated to account for the protective effect. Both of the compounds act as a mixed-type inhibitor. The values of standard free energy of adsorption suggest the chemical adsorption BMIMCl and BMIMBr on the copper surface.
Popliteal Cysts in Paediatric Patients: Clinical Characteristics and Imaging Features on Ultrasound and MRI
Authors: Neubauer Henning , Morbach Henner , Schwarz Tobias , Wirth Clemens , Girschick Hermann , Beer Meinrad
Published: May 2011

Popliteal cysts, or Baker cysts, are considered rare in children and may exhibit particular features, as compared with adults. We studied data from 80 paediatric patients with 55 Baker cysts, examined over a period of 7 years, and correlated clinical presentation with findings on ultrasonography and MRI. Prevalence of popliteal cysts was 57% in arthritic knees, 58% with hypermobility syndrome, and 28% without risk factors. Only one patient had a trauma history and showed an ipsilateral cyst. Mean cyst volume was 3.4 mL; cysts were larger in boys. Patients with arthritis had echogenic cysts in 53%. Cyst communication with the joint space was seen in 64% on ultrasonography and 86% on MRI. In conclusion, Baker cysts are a common finding in a clinically preselected paediatric population. Children with Baker cysts should be assessed for underlying arthritis and inherited joint hypermobility, while sporadic Baker cysts appear to be common, as well.
Rectal Atresia—Operative Management with Endoscopy and Transanal Approach: A Case Report
Authors: Stenström Pernilla , Clementson Kockum Christina , Arnbjörnsson Einar
Published: May 2011

The aim of this study is to present the technique and outcome of the management of a newborn child with rectal atresia. A girl born with rectal atresia was diagnosed during physical examination and confirmed with X-ray. The anatomic appearance of the external anus, and lower pelvis was normal. The rectal ending was located 2 cm cranial from the anus and the distance between the rectal endings was 2 cm. A colostomy was established. At the age of five months the child was operated on with a rectal anastomosis using the endoscopic and transanal approach. Closure of the colostomy was performed at the age of ten months. The rectal anastomosis was treated with rectal dilatation weekly in order to avoid stricture. The patient was faecally continent at followup one and three months postoperatively. In conclusion, the endoscopic and transanal approach is an alternative to other surgical techniques in the management of rectal atresia.
Can Thrifty Gene(s) or Predictive Fetal Programming for Thriftiness Lead to Obesity?
Authors: Baig Ulfat , Belsare Prajakta , Watve Milind , Jog Maithili
Published: May 2011

Obesity and related disorders are thought to have their roots in metabolic “thriftiness” that evolved to combat periodic starvation. The association of low birth weight with obesity in later life caused a shift in the concept from thrifty gene to thrifty phenotype or anticipatory fetal programming. The assumption of thriftiness is implicit in obesity research. We examine here, with the help of a mathematical model, the conditions for evolution of thrifty genes or fetal programming for thriftiness. The model suggests that a thrifty gene cannot exist in a stable polymorphic state in a population. The conditions for evolution of thrifty fetal programming are restricted if the correlation between intrauterine and lifetime conditions is poor. Such a correlation is not observed in natural courses of famine. If there is fetal programming for thriftiness, it could have evolved in anticipation of social factors affecting nutrition that can result in a positive correlation.
Real‐Time Vehicle Routing for Repairing Damaged Infrastructures Due to Natural Disasters
Authors: Chen Huey-Kuo , Chou Huey-Wen , Ho Ping-Shan , Wang Hsuan
Published: May 2011

We address the task of repairing damaged infrastructures as a series of multidepot vehicle‐routing problems with time windows in a time‐rolling frame. The network size of the tackled problems changes from time to time, as new disaster nodes will be added to and serviced disaster nodes will be deleted from the current network. In addition, an inaccessible disaster node would become accessible when one of its adjacent disaster nodes has been repaired. By the “take‐and‐conquer” strategy, the repair sequence of the disaster nodes in the affected area can be suitably scheduled. Thirteen instances were tested with our proposed heuristic, that is, Chen et al.′s approach. For comparison, Hsueh et al.′s approach (2008) with necessary modification was also tested. The results show that Chen et al.′s approach performs slightly better for larger size networks in terms of objective value.
A Multivariable Adaptive Control Approach for Stabilization of a Cart‐Type Double Inverted Pendulum
Authors: Hassanzadeh I. , Nejadfard A. , Zadi M.
Published: May 2011

This paper considers the design and practical implementation of linear‐based controllers for a cart‐type double inverted pendulum (DIPC). A constitution of two linked pendulums placed on a sliding cart, presenting a three Degrees of Freedom and single controlling input structure. The controller objective is to keep both pendulums in an up‐up unstable equilibrium point. Modeling is based on the Euler‐Lagrange equations, and the resulted nonlinear model is linearized around up‐up position. First, the LQR method is used to stabilize DIPC by a feedback gain matrix in order to minimize a quadratic cost function. Without using an observer to estimate the unmeasured states, in the next step we make use of LQG controller which combines the Kalman‐Bucy filter estimation and LQR feedback control to obtain a better steady‐state performance, but poor robustness. Eventually, to overcome the unknown nonlinear model parameters, an adaptive controller is designed. This controller is based on Model Reference Adaptive System (MRAS) method, which uses the Lyapunov function to eliminate the defined state error. This controller improves both the steady‐state and disturbance responses.
Racial and Ethnic Disparities in Colorectal Cancer Screening Persisted Despite Expansion of Medicare's Screening Reimbursement
Authors: White Arica , Vernon Sally W. , Franzini Luisa , Du Xianglin L.
Published: May 2011

Objective: We examined the effect of Medicare's expansion of colorectal cancer (CRC) screening test reimbursement on racial/ethnic disparities in CRC screening.

Methods: CRC screening was ascertained for Medicare beneficiaries (n = 30,893), aged 70 to 89, who had no history of any tumor and resided in 16 Surveillance, Epidemiology and End Results regions of the United States from 1996 to 2005. CRC screening tests were identified in the 5% sample of Medicare claims. Age–gender-adjusted percentages and -adjusted odds of receiving any guideline-specific CRC screening [i.e., annual fecal occult blood test (FOBT), sigmoidoscopy every 5 years or colonoscopy every 10 years] by race/ethnicity and Medicare coverage expansion period (i.e., prior to FOBT coverage, FOBT coverage only, and post–colonoscopy coverage) were reported.

Results: CRC screening increased as Medicare coverage expanded for white and black Medicare beneficiaries. However, blacks were less likely than whites to receive screening prior to FOBT coverage (OR = 0.74, 95% CI: 0.61–0.90), during FOBT coverage only (OR = 0.66, 95% CI: 0.52–0.83) and after colonoscopy coverage (OR = 0.80, 95% CI: 0.68–0.95). Hispanics were less likely to receive screening after colonoscopy coverage (OR = 0.73, 95% CI: 0.54–0.99).

Conclusions: Despite the expansion of Medicare coverage for CRC screening tests, racial/ethnic differences in CRC screening persisted over time in this universally insured population, especially for blacks and Hispanics. Future studies should explore other factors beyond health insurance that may contribute to screening disparities in this and younger populations.

Impact: Although CRC screening rates increased over time, they were still low according to recommendations. More effort is needed to increase CRC screening among all Medicare beneficiaries. Cancer Epidemiol Biomarkers Prev; 20(5); 811–7. ©2011 AACR.
Prediagnostic Circulating Parathyroid Hormone Concentration and Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort
Authors: Fedirko Veronika , Riboli Elio , Bueno-de-Mesquita H. Bas , Rinaldi Sabina , Pischon Tobias , Norat Teresa , Jansen Eugène H. J. M. , van Duijnhoven Fränzel J. B. , Tjønneland Anne , Olsen Anja , Overvad Kim , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Engel Pierre , Kaaks Rudolf , Teucher Birgit , Boeing Heiner , Buijsse Brian , Trichopoulou Antonia , Trichopoulos Dimitrios , Lagiou Pagona , Sieri Sabina , Vineis Paolo , Panico Salvatore , Palli Domenico , Tumino Rosario , van Gils Carla H. , Peeters Petra H. M. , Chirlaque Maria-Dolores , Gurrea Aurelio Barricarte , Rodríguez Laudina , Molina-Montes Esther , Dorronsoro Miren , Bonet Catalina , Palmqvist Richard , Hallmans Göran , Key Timothy J. , Tsilidis Konstantinos K , Khaw Kay-Tee , Romieu Isabelle , Straif Kurt , Wark Petra A. , Romaguera Dora , Jenab Mazda
Published: May 2011

Background: Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC).

Methods: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating prediagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95% CI) for the association between circulating PTH and CRC risk.

Results: In multivariate analyses [including adjustment for 25(OH)D concentration] with a priori defined cutoff points, high levels of serum PTH (≥65 ng/L) compared with medium PTH levels of 30–65 ng/L were associated with increased CRC risk (RR = 1.41, 95% CI: 1.03–1.93). In analyses by sex, the CRC risk was 1.77 (95% CI: 1.14–2.75) and 1.15 (95% CI: 0.73–1.84) in men and women, respectively (Pheterogeneity = 0.01). In subgroup analyses by anatomical subsite, the risk for colon cancer was RR = 1.56, 95% CI: 1.03–2.34, and for rectal cancer RR = 1.20, 95% CI: 0.72–2.01 (Pheterogeneity = 0.21). Effect modification by various risk factors was examined.

Conclusions: The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men.

Impact: To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated. Cancer Epidemiol Biomarkers Prev; 20(5); 767–78. ©2011 AACR.
Reversals of Association for Pap, Colorectal, and Prostate Cancer Testing among Hispanic and Non-Hispanic Black Women and Men
Authors: Rakowski William , Clark Melissa A. , Rogers Michelle L. , Weitzen Sherry H.
Published: May 2011

Background: Several studies have found that Hispanics and non-Hispanic blacks have statistically significantly higher adjusted OR for cancer screening tests compared to non-Hispanic whites, even though their crude percentages were lower than, or about equal to, those for the non-Hispanic whites. Most documentation is for mammography. This article investigates the prevalence of such unadjusted-to-adjusted “reversed associations” (RA) for Pap, colorectal, and prostate testing. We also investigate large percent changes (LPC) to the unadjusted ORs.

Methods: Data were from the 2004/2006/2008 Behavioral Risk Factor Surveillance System (BRFSS) and the 2000/2003/2005/2008 National Health Interview Survey (NHIS). Analyses used a consistent set of covariates.

Results: RAs were more common for non-Hispanic blacks than Hispanics, but Hispanics had a greater number of LPCs. RAs and LPCs occurred more often for Pap testing than colorectal and prostate testing. However, results from the BRFSS and NHIS were often not consistent.

Conclusions: Attention should be given to the National Breast and Cervical Cancer Early Detection Program, as well as public programs addressing other cancers, as possible contributors to RAs and LPCs. Hispanics may show more RAs in analyses of future data. Discrepancies between the BRFSS and the NHIS also must be recognized and explained.

Impact: This research highlights the need for vigilance regarding the results of analyses to identify race/ethnicity as a correlate of cancer screening. Results also direct attention to aspects of the results of multivariable analysis other than ORs and confidence intervals. Cancer Epidemiol Biomarkers Prev; 20(5); 876–89. ©2011 AACR.
Smoking, Secondhand Smoke, and Cotinine Levels in a Subset of EPIC Cohort
Authors: Baltar Valéria Troncoso , Xun Wei W. , Chuang Shu-Chun , Relton Caroline , Ueland Per Magne , Vollset Stein Emil , Midttun Øivind , Johansson Mattias , Slimani Nadia , Jenab Mazda , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Fagherazzi Guy , Kaaks Rudolf , Rohrmann Sabine , Boeing Heiner , Weikert Cornelia , Bueno-de-Mesquita H. Bas , Boshuizen Hendriek C , van Gils Carla H. , Peeters Petra H.M. , Agudo Antonio , Barricarte Aurelio , Navarro Carmen , Rodríguez Laudina , Castaño José Maria Huerta , Larrañaga Nerea , Pérez Maria José Sánchez , Khaw Kay-Tee , Wareham Nick , Allen Naomi E. , Crowe Francesca , Gallo Valentina , Norat Teresa , Tagliabue Giovanna , Masala Giovanna , Panico Salvatore , Sacerdote Carlota , Tumino Rosario , Trichopoulou Antonia , Lagiou Pagona , Bamia Christina , Rasmuson Torgny , Hallmans Göran , Roswall Nina , Tjønneland Anne , Riboli Elio , Brennan Paul , Vineis Paolo
Published: May 2011

Background: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index.

Results: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001).

Conclusions: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels.

Impact: This study strengthens the evidence for the benefits of a smoking ban in public places. Cancer Epidemiol Biomarkers Prev; 20(5); 869–75. ©2011 AACR.
Reproductive and Hormonal Factors and Lung Cancer Risk in the NIH-AARP Diet and Health Study Cohort
Authors: Brinton Louise A. , Gierach Gretchen L. , Andaya Abegail , Park Yikyung , Schatzkin Arthur , Hollenbeck Albert R. , Spitz Margaret R.
Published: May 2011

Background: Lung cancer exhibits unique patterns among women including high adenocarcinoma rates among nonsmokers. Inconsistent findings about hormonal factors on risk may reflect incomplete control for confounding, misclassification of exposures, or insufficient attention to variation by histology.

Methods: Among 185,017 women, ages 50 to 71 years, recruited during 1995 and 1996 for the NIH-AARP (American Association of Retired Persons) Diet and Health Study, we identified 3,512 incident lung cancers (including 276 in never smokers) in follow-up through December 2006. Multivariable Cox proportional hazards models estimated relative risks (RR) and 95% CIs for self-reported hormonally related risk factors.

Results: After adjustment for smoking and other confounders, subjects with late menarche were at reduced risk, with the association specific for adenocarcinomas (RR = 0.72 for menarche 15+ vs. <11, Ptrend < 0.01). Subjects with early ages at ovarian cessation (either from natural menopause or bilateral oophorectomy) were at an increased risk for adenocarcinomas and squamous cell tumors, but the associations were strongest for smokers, suggesting either residual confounding or an enhanced effect of menopausally related factors among subjects with decreased endogenous estrogens. In contrast, we saw no relationships of risk with either parity, age at first birth, or exogenous hormone use.

Conclusions: Elevated levels of hormones may adversely affect lung function early in life while assisting with cellular and immunologic responses later in life. Additional attention toward the role of hormonal factors may further our understanding of lung carcinogenesis.

Impact: Our findings provide some support for a role of hormonal factors in the etiology of lung cancer, although the mechanisms appear complicated. Cancer Epidemiol Biomarkers Prev; 20(5); 900–11. ©2011 AACR.
No Association of Risk Variants for Diabetes and Obesity with Breast Cancer: The Multiethnic Cohort and PAGE Studies
Authors: Chen Fang , Wilkens Lynne R. , Monroe Kristine R. , Stram Daniel O. , Kolonel Laurence N. , Henderson Brian E. , Marchand Loïc Le , Haiman Christopher A.
Published: May 2011

Background: Body mass index is an established risk factor for postmenopausal breast cancer. Epidemiologic studies have also reported a positive association between type 2 diabetes (T2D) and breast cancer risk.

Methods: To investigate a genetic basis linking these common phenotypes with breast cancer, we tested 31 common variants for T2D and obesity in a case–control study of 1,915 breast cancer cases and 2,884 controls nested within the Multiethnic Cohort (MEC) study.

Results: Following adjustment for multiple tests, we found no significant association between any variant and breast cancer risk. Summary scores comprising the numbers of risk alleles for T2D and/or obesity were also not found to be significantly associated with breast cancer risk.

Conclusions: Our findings provide no evidence for association between established T2D and/or obesity risk variants and breast cancer risk among women of various ethnicities.

Impact: These results suggest that the potential for a shared biology between T2D/obesity and breast cancer is not due to pleiotropic effects of these risk variants. Cancer Epidemiol Biomarkers Prev; 20(5); 1039–42. ©2011 AACR.
Metformin Amplifies Chemotherapy-Induced AMPK Activation and Antitumoral Growth
Authors: Rocha Guilherme Z. , Dias Marília M. , Ropelle Eduardo R. , Osório-Costa Felipe , Rossato Franco A. , Vercesi Anibal E. , Saad Mario J.A. , Carvalheira José B.C.
Published: May 2011

Purpose: Metformin is a widely used antidiabetic drug whose anticancer effects, mediated by the activation of AMP-activated protein kinase (AMPK) and reduction of mTOR signaling, have become noteworthy. Chemotherapy produces genotoxic stress and induces p53 activity, which can cross-talk with AMPK/mTOR pathway. Herein, we investigate whether the combination of metformin and paclitaxel has an effect in cancer cell lines.

Experimental Design: Human tumors were xenografted into severe combined immunodeficient (SCID) mice and the cancer cell lines were treated with only paclitaxel or only metformin, or a combination of both drugs. Western blotting, flow cytometry, and immunohistochemistry were then used to characterize the effects of the different treatments.

Results: The results presented herein show that the addition of metformin to paclitaxel leads to quantitative potentialization of molecular signaling through AMPK and a subsequent potent inhibition of the mTOR signaling pathway. Treatment with metformin and paclitaxel resulted in an increase in the number of cells arrested in the G2–M phase of the cell cycle, and decreased the tumor growth and increased apoptosis in tumor-bearing mice, when compared with individual drug treatments.

Conclusion: We have provided evidence for a convergence of metformin and paclitaxel induced signaling at the level of AMPK. This mechanism shows how different drugs may cooperate to augment antigrowth signals, and suggests that target activation of AMPK by metformin may be a compelling ally in cancer treatment. Clin Cancer Res; 17(12); 3993–4005. ©2011 AACR.