bluuebunny/crossref_metadata_2025 huggingface dataset:
Genes encoding critical transcriptional activators for murine neural tube development and human spina bifida: a case-control study
Authors: Lu Wei , Guzman Adrian R , Yang Wei , Chapa Claudia J , Shaw Gary M , Greene Robert M , Pisano M Michele , Lammer Edward J , Finnell Richard H , Zhu Huiping
Published: October 2010

Background

Spina bifida is a malformation of the neural tube and is the most common of neural tube defects (NTDs). The etiology of spina bifida is largely unknown, although it is thought to be multi-factorial, involving multiple interacting genes and environmental factors. Mutations in transcriptional co-activator genes-Cited2,p300,Cbp,Tfap2α,Carm1andCart1result in NTDs in murine models, thus prompt us to investigate whether homologues of these genes are associated with NTDs in humans.

Methods

Data and biological samples from 297 spina bifida cases and 300 controls were derived from a population-based case-control study conducted in California. 37 SNPs withinCITED2,EP300,CREBBP,TFAP2A,CARM1andALX1were genotyped using an ABI SNPlex assay. Odds ratios and 95% confidence intervals were calculated for alleles, genotypes and haplotypes to evaluate the risk for spina bifida.

Results

Several SNPs showed increased or decreased risk, includingCITED2rs1131431 (OR = 5.32, 1.04~27.30),EP300rs4820428 (OR = 1.30, 1.01~1.67),EP300rs4820429 (OR = 0.50, 0.26~0.50, in whites, OR = 0.7, 0.49~0.99 in all subjects),EP300rs17002284 (OR = 0.43, 0.22~0.84),TFAP2Ars3798691 (OR = 1.78, 1.13~2.87 in Hispanics),CREBBPrs129986 (OR = 0.27, 0.11~0.69),CARM1rs17616105 (OR = 0.41, 0.22~0.72 in whites). In addition, one haplotype block inEP300and one inTFAP2Aappeared to be associated with increased risk.

Conclusions

Modest associations were observed inCITED2,EP300,CREBBP,TFAP2AandCARM1but notALX1. However, these modest associations were not statistically significant after correction for multiple comparisons. Searching for potential functional variants and rare causal mutations is warranted in these genes.
Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene
Authors: Becks Lisa , Prince Misty , Burson Hannah , Christophe Christopher , Broadway Mason , Itoh Ken , Yamamoto Masayuki , Mathis Michael , Orchard Elysse , Shi Runhua , McLarty Jerry , Pruitt Kevin , Zhang Songlin , Kleiner-Hancock Heather E
Published: October 2010

Background

Activation of nuclear factor erythroid 2-related factor (Nrf2), which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE). We hypothesized that (1) the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2) that Nrf2 knockout (KO) mice would be more susceptible to mammary carcinogenesis.

Methods

Premalignant lesions and mammary carcinomas were induced by medroxyprogesterone acetate and 7,12-dimethylbenz[a]anthracene treatment. The 10-week pre-malignant study was performed in which 8 groups of 10 each female wild-type (WT) and KO mice were fed either control diet or diets containing auraptene (500 ppm). A carcinogenesis study was also conducted in KO vs. WT mice (n = 30-34). Comparisons between groups were evaluated using ANOVA and Kaplan-Meier Survival statistics, and the Mann-Whitney U-test.

Results

All mice treated with carcinogen exhibited premalignant lesions but there were no differences by genotype or diet. In the KO mice, there was a dramatic increase in mammary carcinoma growth rate, size, and weight. Although there was no difference in overall survival, the KO mice had significantly lower mammary tumor-free survival. Also, in the KO mammary carcinomas, the active forms of NF-κB and β-catenin were increased ~2-fold whereas no differences in oxidized proteins were observed. Many other tumors were observed, including lymphomas. Interestingly, the incidences of lung adenomas in the KO mice were significantly higher than in the WT mice.

Conclusions

We report, for the first time, that there was no apparent difference in the formation of premalignant lesions, but rather, the KO mice exhibited rapid, aggressive mammary carcinoma progression.
Association between actual weight status, perceived weight and depressive, anxious symptoms in Chinese adolescents: a cross-sectional study
Authors: Tang Jie , Yu Yizhen , Du Yukai , Ma Ying , Zhu Huiping , Liu Zhuoya
Published: October 2010

Backgroud

The purpose of this study was to describe actual measured weight and perceived weight and to explore associations with depressive, anxiety symptoms in school adolescents in China.

Methods

A sample of 1144 Chinese adolescents was randomly selected from four schools in Wuhan, China, including 665 boys and 479 girls with ages ranging between 10 and 17 years. Actual measured weight and height and perceived weight status were compared to anxiety and depressive symptoms measured using the revised Self-Rating Anxiety Scale and Children's Depression Inventory. A general linear model was used to compare differences in psychological symptoms among the teenagers with different measured and perceived weights.

Results

When compared with standardized weight tables (WHO age- and gender-specific body mass index (BMI) cutoffs (2007 reference)), girls were more likely to misperceive themselves as overweight, whereas more boys misclassified their weight status as underweight. The adolescents who perceived themselves as overweight were more likely to experience depressive and anxiety symptoms (except girls) than those who perceived themselves as normal and/or underweight. However, no significant association was found between depressive and anxiety symptoms actual measured weight status.

Conclusions

Perceived weight status, but not the actual weight status, was associated with psychological symptoms.
Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial
Authors: Schofer Markus D , Block Jon E , Aigner Julia , Schmelz Andreas
Published: October 2010

Background

We compared the healing response of tibial delayed unions between subjects treated with low-intensity pulsed ultrasound (LIPUS) (n = 51) and subjects treated with a sham device (n = 50). Fracture age was ≥ 4 months in all cases. Study personnel and participants were blinded to random treatment assignment throughout the study.

Methods

This multi-center randomized sham-controlled trial was undertaken at six hospitals in Germany. Adult patients who had sustained a tibial shaft fracture that subsequently showed inadequate progress toward healing (i.e., delayed union) were enrolled and randomized to receive either LIPUS (Exogen 2000/2000+, Smith & Nephew GmbH, Schenefeld, Germany) or an identical nonoperative sham device. The daily treatment duration was 20 minutes, for a period of 16 weeks. Subjects randomly assigned to active treatment had the ultrasound pressure wave signal set at the following parameters: 1.5 MHz frequency, 1 kHz repetition rate, 200 μs pulse duration, 30 mW/cm2 spatial intensity. Progress toward healing was estimated from changes in bone mineral density (BMD) and gap area as determined from computed tomography scans. Intention-to-treat analysis was conducted using a multiple imputation methodology.

Results

Based on log-transformed data, mean improvement in BMD was 1.34 (90% confidence interval (CI) 1.14 to 1.57) times greater for LIPUS-treated subjects compared to sham (p = 0.002). A mean reduction in bone gap area also favored LIPUS treatment (p = 0.014).

Conclusions

These findings demonstrate significantly greater progress toward bone healing after LIPUS treatment compared to no LIPUS treatment in subjects with established delayed unions of the tibia.
Dietary fatty acid composition alters 11β-hydroxysteroid dehydrogenase type 1 gene expression in rat retroperitoneal white adipose tissue
Authors: Vara Prasad Sakamuri SS , Jeya Kumar Shanmugam S , Kumar Putcha Uday , Qadri Syed SYH , Vajreswari Ayyalasomayajula
Published: October 2010

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active formsin vivo. Adipose-specific overexpression of 11β-HSD1 induces metabolic syndrome in mice, whereas 11β-HSD1 null mice are resistant to it. Dietary trans and saturated fatty acids (TFAs and SFAs) are involved in the development of metabolic syndrome, whereas polyunsaturated fatty acids (PUFA) offer protection against this. Here, we report the effects of chronic feeding of different diets containing vanaspati (TFA rich), palm oil (SFA rich) and sunflower oil (PUFA rich) at 10%level on 11β-HSD1 gene expression in rat retroperitoneal adipose tissue. 11β-HSD1 gene expression was significantly higher in TFA rich diet-fed rats compared to SFA rich diet-fed rats, which in turn was significantly higher than PUFA rich diet-fed rats. Similar trend was observed in the expression of CCAAT-enhancer binding protein-α (C/EBP-α), the main transcription factor required for the expression of 11β-HSD1. We propose that TFAs and SFAs increase local amplification of glucocorticoid action in adipose tissue by upregulating 11β-HSD1 by altering C/EBP-α-gene expression. The increased levels of glucocorticoids in adipose tissue may lead to development of obesity and insulin resistance, thereby increasing the risk of developing metabolic syndrome.
Mechanics of head fold formation: investigating tissue-level forces during early development
Authors: Varner Victor D. , Voronov Dmitry A. , Taber Larry A.
Published: October 2010

During its earliest stages, the avian embryo is approximately planar. Through a complex series of folds, this flat geometry is transformed into the intricate three-dimensional structure of the developing organism. Formation of the head fold (HF) is the first step in this cascading sequence of out-of-plane tissue folds. The HF establishes the anterior extent of the embryo and initiates heart, foregut and brain development. Here, we use a combination of computational modeling and experiments to determine the physical forces that drive HF formation. Using chick embryos cultured ex ovo, we measured: (1) changes in tissue morphology in living embryos using optical coherence tomography (OCT); (2) morphogenetic strains (deformations) through the tracking of tissue labels; and (3) regional tissue stresses using changes in the geometry of circular wounds punched through the blastoderm. To determine the physical mechanisms that generate the HF, we created a three-dimensional computational model of the early embryo, consisting of pseudoelastic plates representing the blastoderm and vitelline membrane. Based on previous experimental findings, we simulated the following morphogenetic mechanisms: (1) convergent extension in the neural plate (NP); (2) cell wedging along the anterior NP border; and (3) autonomous in-plane deformations outside the NP. Our numerical predictions agree relatively well with the observed morphology, as well as with our measured stress and strain distributions. The model also predicts the abnormal tissue geometries produced when development is mechanically perturbed. Taken together, the results suggest that the proposed morphogenetic mechanisms provide the main tissue-level forces that drive HF formation.
Monoclonal free light chains can be found in heavy chain diseases
Authors: López-Anglada L , Puig N , Díez-Campelo M , Alonso-Ralero L , Barrena S , Aparicio M A , Gutiérrez N C , García-Sanz R
Published: October 2010

Heavy chain diseases (HCDs) are rare B-cell lymphoproliferative neoplasias characterized by the production of a monoclonal component consisting of a truncated monoclonal Ig heavy chain without the associated light chain. Among them, patients with gamma-HCD are so rare that no more than 150 cases can be found in the literature. In this paper, we report one additional case: an 83-year-old man with a gamma-HCD, in whom a kappa light chain component was detected in the serum by using the serum free light-chain assessment and in addition monoclonal kappa cytoplasmic expression was detected in bone marrow plasma cells by flow cytometric analysis. In the work-up of the patient, the underlying anatomopathological lymphoproliferative disease corresponded to a lymphoplasmacytic lymphoma, as it is stated in the current World Health Organization classification (2008), with both lymphadenopathic and bone marrow infiltration. As in other cases, several autoimmune manifestations (antiphospholipidic syndrome and immune thrombocytopenia) were present during the course of the disease in this patient. This case report illustrates a new case of gamma-HCD, in which serum free light-chain analysis and flow cytometry represented a valuable tool for diagnosis, a finding that could be very important for the future management of these patients.
Effect of recipient-derived cells on the progression of familial amyloidotic polyneuropathy after liver transplantation: a retrospective study
Authors: Ohya Yuki , Jono Hirofumi , Nakamura Masaaki , Hayashida Shintaro , Ueda Mitsuharu , Obayashi Konen , Misumi Shogo , Asonuma Katsuhiro , Ando Yukio , Inomata Yukihiro
Published: October 2010

Background

Some familial amyloidotic polyneuropathy (FAP) patients show the post-transplant progression of the clinical symptoms. Although the presence of recipient-derived cells in transplanted livers has been reported, no studies investigating the functional significance of this post-transplant chimerism in transplanted FAP patients were performed. The aims of this study were to evaluate amyloidogenic transthyretin (ATTR) production of recipient-derived cells and the relationship between the protein from recipient-derived cells and the progression of FAP symptoms after liver transplantation (LT).

Methods

Seven FAP ATTR Val30Met patients who underwent LT were included in this study. In one male patient with sex-mismatched donor, fluorescence in situ hybridization (FISH) method was performed on a liver biopsy sample using DNA probes for visualizing X and Y chromosomes to detect the recipient-derived cells. In three patients including the FISH-analysed patient, ATTR mRNA expression in transplanted livers was evaluated by the polymerase chain reaction (PCR)–restriction fragment length polymorphism method and realtime quantitative reverse transcription–PCR. In five of the seven patients, ATTR in serum protein expression was measured by mass spectrometry.

Results

One FAP patient has 3.1% recipient-derived cells in the transplanted liver. The ATTR mRNA was not expressed in any of the three transplanted livers. The ATTR was not detected in any sera of the sampled patients.

Conclusion

Although the FAP patient had recipient-derived cells in the transplanted liver, the recipient-derived cells did not contribute to the production of ATTR in our specific case. The effect of recipient-derived cells on the post-transplant progression of FAP symptoms may be negligible.
The measurement, definition, aetiology and clinical consequences of neonatal transient hypothyroxinaemia
Authors: Williams Fiona , Hume Robert
Published: October 2010

This review focuses on neonatal transient hypothyroxinaemia, a condition characterized by temporary postnatal reductions in concentrations of Total T4 or Free T4, with normal or low concentrations of thyroid stimulating hormone (TSH). There is neither an agreed quantitative definition, nor an agreed mode of measurement for the condition. Transient hypothyroxinaemia is not routinely monitored yet it is thought to affect about 50% of preterm infants; it was thought to be without long-term sequelae but observational studies indicate that neurodevelopment may be compromised. The aetiology of transient hypothyroxinaemia is complex. There are significant contributions from the withdrawal of maternal–placental thyroxine transfer, hypothalamic–pituitary–thyroid immaturity, developmental constraints on the synthesis and peripheral metabolism of iodothyronines and iodine deficiency. It is not possible to distinguish clinically, or from laboratory measurements, whether transient hypothyroxinaemia is an independent condition or simply a consequence of non-thyroidal illness and/or drug usage. An answer to this question is important because studies of thyroid hormone replacement have been instigated, with mixed results. Until the aetiology of transient hypothyroxinaemia is better understood it would seem prudent not to routinely supplement preterm infants with thyroid hormones. Iodine deficiency, non-thyroidal illness and drug usage are the most modifiable risk factors for transient hypothyroxinaemia and are the clear choices for attempts at reducing its incidence. We suggest that transient hypothyroxinaemia in preterm infants is defined as a normal or low TSH concentration in conjunction with a concentration of Total T4, that is ≤10th percentile of cord Total T4 of the equivalent gestational age had the infant remained in utero.
The effect of GH replacement therapy on different fat compartments: a whole-body magnetic resonance imaging study
Authors: Egger A , Buehler T , Boesch C , Diem P , Stettler C , Christ E R
Published: October 2010

Objective

Patients with GH deficiency (GHD) are insulin resistant with an increase in visceral fat mass (FM). Whether this holds true when sedentary control subjects (CS) are matched for waist has not been documented.

GH replacement therapy (GHRT) results in a decrease in FM. Whether the decrease in FM is mainly related to a reduction in visceral FM remains to be proven. The aim was to separately assess visceral and subcutaneous FM in relation to insulin resistance (IR) in GHD patients before and after GHRT and in sedentary CS.

Methods

Ten patients with GHD were investigated before and 6 months after GHRT. Sedentary CS matched for age, gender, body mass index, and waist were assessed. Exercise capacity was measured as VO2maxusing an incremental work load on a treadmill. Visceral and subcutaneous FM were measured using whole-body magnetic resonance imaging and IR by the homeostasis model assessment of IR (HOMA-IR) index.

Results

GHD patients had a non-significantly lower VO2maxbut did not have increased subcutaneous and visceral FM compared with CS. GHRT resulted in a similar relative decrease in subcutaneous and visceral FM. Compared with CS, GHD patients showed a lower HOMA-IR. GHRT tended to increase HOMA-IR.

Conclusion

Matching for waist and separate assessment of visceral and subcutaneous FM may be critical in the evaluation of body composition and IR in GHD patients before and after GHRT.
Impairment of insulin receptor signal transduction in placentas of intra-uterine growth-restricted newborns and its relationship with fetal growth
Authors: Street M E , Viani I , Ziveri M A , Volta C , Smerieri A , Bernasconi S
Published: October 2010

Objective

Intra-uterine growth restriction (IUGR) is related to a higher incidence of type 2 diabetes mellitus. We previously reported reduced adiponectin and increased interleukin 6 (IL6) concentrations in IUGR placentas, which are features of insulin resistance. We aimed to investigate placental insulin receptor (IR) function and activation in human placenta and subsequently the relationships of insulin signalling peptides with placental protein content in IL6, insulin, resistin and adiponectin, and with parameters of fetal growth.

Design and methods

Whole villous tissue was collected from 18 IUGR and 24 appropriate for gestational age (AGA) placentas of comparable gestational age. Insulin signalling peptides, suppressors of cytokine signalling-2 (SOCS2), insulin, adiponectin, resistin, and IL6 concentrations were determined by using western immunoblotting or specific research kits.

Results

The amount of total IR was similar in both groups but activated IR significantly higher in IUGR. Total IR substrate-1 (IRS1) was increased in IUGR, whereas total IRS2 and activated IRS1 were similar. AKT content was reduced and activated AKT was undetectable in IUGR placentas. c-Jun N-terminal kinase content was reduced in IUGR. Total and activated ERK1/2 was similar in IUGR and AGA groups, and total SOCS2 was increased in IUGR. IL6 lysate concentrations correlated with AKT content and activated IR. Correlations were found also with adiponectin and resistin. SOCS2 correlated negatively with all growth parameters at birth.

Conclusions

IR was more activated in placentas of IUGR compared with AGA; however, signal transduction downstream of the receptor was impaired. The increase in activated IR could be in favour of a compensatory mechanism to increase insulin sensitivity. Close relationships of insulin action in placenta with fetal growth were shown.
Bioethanol Production from Rice Straw in the MAFF Research Project, Japan
Authors: Tokuyasu Ken
Published: October 2010

Rice straw is among the most abundant herbaceous biomass, and regarded as the central feedstock for bioethanol production in Japan. We found that significant amounts of soft carbohydrates (SCs), defined as carbohydrates readily recoverable by mere extraction from the biomass or brief enzymatic saccharification, exist in rice straw in the form of free glucose, free fructose, sucrose, starch, and β-1,3-1,4-glucan. Based on the finding, we proposed a simple method for bioethanol production from rice straw samples with SCs, by a heat treatment for sterilization and starch gelatinization, followed by simultaneous saccharification/fermentation with Saccharomyces cerevisiae. This method would offer an efficient process for bioethanol production without the aid of harsh thermo/chemical pretreatment step.
X-ray Tomographic Characterization of Natural Polymer Composites and Correlation of Bulk Mechanical Properties
Authors: Pakzad Anahita , Mainwaring Paul , Heiden Patricia A. , Shahbazian Yassar Reza
Published: October 2010

In this research, cellulose micro-crystals (CMC) were used to reinforce a bio-polymer, polycaprolactone (PCL). Mechanical properties were tested using nanoindentation. Electron microscopy imaging and a new technique called x-ray ultra microscopy and microtomography (XuM) were used to investigate the distribution of the filler in the matrix. We could demonstrate a clear correlation between the spatial distribution of CMC-PCL composites and their nanomechanical properties.
Quantitative Mechanical Mapping of Biomolecules in Fluid
Authors: Su Chanmin , Hu Shuiqing , Hu Yan , Erina Natalia , Slade Andrea
Published: October 2010

Though atomic force microscopy (AFM) interrogates biological materials through mechanical interactions, achieving quantitative mechanical information such as modulus and adhesion at high resolution has been a challenging task. A technology for nanometer scale mechanical property mapping, peak force tapping (PFT), was developed to achieve high resolution imaging and quantitative mechanical measurements simultaneously. PFT controls instantaneous interaction force and record force spectroscopy at each pixel to calculate mechanical properties. A feedback loop maintains a constant peak force, a local maximum point in the force spectroscopy, at the level of Pico Newtons throughout the imaging process. Such high precision force controls enable application of ultra-sharp probe to image biological samples in vitro and achieve molecular resolution in protein membranes. More importantly a full suite of mechanical properties, modulus, adhesion, energy dissipation and deformation are mapped concurrent with topographic imaging. To calculate nanomechanical properties reliably cantilever spring constant and tip shape were calibrated systematically. A method to accurately determine cantilever spring constant, capable of wafer scale cantilever calibration, was developed and tested against traceable force methods. With the knowledge of tip shape, derived from morphological dilation method using a reference sample, mechanical properties measured at the nanometer scale was compared with bench mark materials ranging from 0.7 MPa to 70 GPa. The same method was also applied to OmpG membranes, Lambda DNA strings, as well as live cells. The limitation of the measurement accuracy in biology samples will be discussed.
Statistics of Single Cell Mechanics Investigated by Atomic Force Microscopy
Authors: Hiratsuka Shinichiro , Mizutani Yusuke , Cai PingGen , Tsuchiya Masahiko , Tokumoto Hiroshi , Kawahara Koichi , Okajima Takaharu
Published: October 2010

We have developed the atomic force microsocpy (AFM) to measure the complex shear modulus, G*, of a large number of cells. In the AFM technique, live cells were arranged in a micro-fabricated glass substrate under the physiological conditions, and the AFM force measurement was examined in many different cells automatically. The results shown in the previous studies revealed that the frequency-dependent G* was well fitted to the so-called structural damping model, which consists of a single power-law function with a Newtonian viscous effect. However, the detail relationship has not been understood. The aim of this study was to verify the relationship between the storage and loss moduli. As results, we found that the relation between the hysteresivity (the ratio of the storage and loss moduli) and the power-law exponent was in good agreement with the structural damping model, and the result was the same as that observed in magnetic twisting cytometry (MTC), in which cells were cultured on flat substrates. This result indicated that the AFM technique presented here becomes a useful technique for precisely measuring the statistical behavior of single cell rheology.
A Novel AFM-MEA Platform for Studying the Real Time Mechano-Electrical Behavior of Cardiac Myocytes
Authors: Saenz Cogollo Jose Francisco , Tedesco Mariateresa , Martinoia Sergio , Raiteri Roberto
Published: October 2010

We present a novel experimental platform based on a combined Atomic Force Microscopy (AFM) and Micro-Electrode Array (MEA) set-up. We have used it to measure minimal changes in the morphological/mechanical properties of electrically active cell cultures as well as to measure the changes in the extracellular electrical activity when a single cell is stimulated by means of the AFM tip. In particular, we studied the dynamical changes in cell elasticity of embryonic rat cardiac myocytes along the contraction-relaxation cycle. Applying high load indentations, we also recorded the effects of mechanical stimulations on the cell electrophysiology. The dynamic elastic modulus of the cell related to the contraction-relaxation cycle reveals a temporal behavior that closely follows the changes in cell height. Observed values of dynamic elastic modulus at a maximum indentation depth of 1500nm varied between 8.93 ± 0.78 kPa during systolic (contraction) phase and 4.26 ± 0.47 kPa during diastolic (relaxation) phase. Induced electrophysiological responses were observed when applying loads in the range 40-150 nN. The probability P of recording an induced electrical response (P = 0.16 for a maximum load of 100nN) increased with the maximum applied load. Pulling-like stimulations due to the tip-cell adhesion could also evocate electrical responses.
Long-lifetime All-polymer Artificial Muscle Transducers
Authors: Kornbluh Roy , Wong-Foy Annjoe , Pelrine Ron , Prahlad Harsha , McCoy Brian
Published: October 2010

The dielectric elastomer, a particularly attractive type of electroactive polymer, uses commercial polymers such as acrylic and silicone elastomers. The technology has been limited in application by perceived lifetime issues. By addressing several lifetime issues, lifetimes of more than one million cycles, and in some cases beyond ten million cycles, were achieved with a variety of transducer configurations (including operation in generator mode) under a variety of operating conditions (including high humidity). Dielectric elastomers can produce maximum actuation strains of more than 100% and specific energy density exceeding that of known electric-field induced technology. Performance testing for dielectric elastomer actuators has typically been for peak-performance or “over-driven” conditions with short operational lifetimes (typically 100s or 1000s of cycles), particularly under conditions such as high humidity. By minimizing electric field and mechanical strain concentration factors, long lifetimes (>1 million cycles) with acrylic transducers were achieved with actuation strains as great as 40% areal strain (and up to 100% areal strain in generator mode). Actuators in a dry environment had an almost 20x increase in lifetime over actuators at ambient humidity (about 50% RH) at the same driving field conditions. Long actuation lifetimes were also achieved in a 100% RH environment and when fully submerged in salt water at reduced operating strain and field. In 100% RH, lifetimes of several million cycles were achieved at 4% strain. In underwater operation, 6 out of 11 actuators survived for >10 million cycles with an electric field limited to 32 MV/m and approximately 2% strain. The demonstrated lifecycle improvements are applicable to a variety of uses of dielectric elastomers, including haptic interface devices, pumps (implantable and external), optical positioners, and “artificial muscles” to replace small damaged muscles. Continued improvements in materials, actuator design, and packaging, combined with management of operational conditions as described here, should support new practical application of this promising technology.
An Evaluation of Biocompatibility of Indigenously Produced Pure Titanium: An Experimental Study in Rabbits
Authors: Chittaranjan Bhogisetty , Murthy Late Bhamidipati Sreerama , Ravindranath Turaga
Published: October 2010

The indigenously produced pure titanium dental implants are economical and useful for common human use in India. The aim of this study is to test the biocompatibility of the indigenously produced pure titanium dental implant material obtained from the Defense Metallurgical Research Laboratory, Hyderabad, India, and the Institute of Nuclear Medicine and Allied Science, Delhi, India. An experimental study in rabbits was done to study the amount of ordered bone formation around the screw and cylinder type of indigenously produced pure titanium metal implant specimens. The experimental animals were killed at 4, 6, 8, 12, and 16 weeks from the date of implantation. The histopathological examination of the animals killed at 16 weeks demonstrates the presence of osteoblastic cell proliferation and early ordered bone formation toward the implant site, indicating signs of osseointegration of both screw- and cylinder-type indigenously produced pure titanium specimens.
Maintenance Requirements Associated With Mandibular Implant Overdentures: Clinical Results After First Year of Service
Authors: Bilhan Hakan , Geckili Onur , Mumcu Emre , Bilmenoglu Caglar
Published: October 2010

The aim of this clinical study was to evaluate the prosthodontic maintenance requirements during the first year of service of mandibular overdentures supported by interforaminal implants and to assess the influence of attachment type, implant number, and bite force on these requirements. Fifty-nine patients treated with mandibular implant overdentures between the years 2004 and 2009 and appearing in the 12th-month recall were included in this study. The overdentures constituted 4 groups: 2 single interforaminal implants (1 group with locator and 1 group with ball attachments), 3 single interforaminal implants, 3 splinted interforaminal implants (bar), and 4 splinted interforaminal implants (bar). During the examination, prosthetic parameters such as occlusion, tissue adaptation, condition of the retentive mechanism (matrice and patrice), and the condition of the denture-bearing tissues were evaluated and recorded. No statistically significant relation was found between attachment type, bite force values, implant number, and the occurring complications except the need for relining, which was found significantly more in the ball attachments than in other attachment groups (P  =  .03). After 12 months following the overdenture insertion, there seems to be no relation between occurring complications and patient-related factors, such as maximum bite force, age, and gender, as well as factors related to the overdentures such as number and type of attachments.
Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan-Induced Febrile Neutropenia
Authors: Bol Jessica M. , Jong Floris A. , Schaik Ron H. , Sparreboom Alex , Fessem Marianne A. , Geijn Fleur E. , Daele Paul L. , Verweij Jaap , Sleijfer Stefan , Mathijssen Ron H.
Published: October 2010

Objective.

Mannose-binding lectin (MBL) is important in the innate immune response. MBL2 gene polymorphisms affect MBL expression, and genotypes yielding low MBL levels have been associated with an elevated risk for infections in hematological cancer patients undergoing chemotherapy. However, these reported associations are inconsistent, and data on patients with solid tumors are lacking. Here, we investigated the effects of MBL2 genotypes on irinotecan-induced febrile neutropenia in patients with solid tumors.

Patients and Methods.

Irinotecan-treated patients were genotyped for the MBL2 gene. Two promoter (−550 H/L and −221 X/Y) and three exon polymorphisms (52 A/D, 54 A/B, and 57 A/C) were determined, together with known risk factors for irinotecan-induced toxicity. Neutropenia and febrile neutropenia were recorded during the first course.

Results.

Of the 133 patients, 28% experienced severe neutropenia and 10% experienced febrile neutropenia. No associations were found between exon polymorphisms and febrile neutropenia. However, patients with the H/H promoter genotype, associated with high MBL levels, experienced significantly more febrile neutropenia than patients with the H/L and L/L genotypes (20% versus 13% versus 5%). Moreover, patients with the HYA haplotype encountered significantly more febrile neutropenia than patients without this high MBL-producing haplotype (16% versus 4%). In the subgroup with wild-type exon polymorphisms (A/A), patients with the high MBL promoter phenotype had the highest incidence of febrile neutropenia, regardless of known risk factors.

Conclusion.

Patients with high MBL2 promoter genotypes and haplotypes seem more at risk for developing febrile neutropenia. If confirmed, these preliminary findings may contribute to more individualized approaches of irinotecan treatment.
Hepatitis B Reactivation and Rituximab in the Oncology Practice
Authors: Villadolid Jeryl , LaPlant Kourtney D. , Markham Merry Jennifer , Nelson David R. , George Thomas J.
Published: October 2010

Learning Objectives

After completing this course, the reader will be able to: Perform screening for prior hepatitis B viral exposure in all patients with hematologic malignancies who will receive rituximab as part of their therapy.Implement prophylactic antiviral therapy in patients who are positive for hepatitis B and who are being treated with rituximab.Monitor serum viral load and clinical signs of hepatic injury for at least six months following the completion of rituximab treatment in patients who are hepatitis B-sAg positive.

This article is available for continuing medical education credit at CME.TheOncologist.com

Rituximab use in hematology and oncology practice has significantly and positively improved the clinical outcomes in patients with a wide variety of B-cell lymphoproliferative disorders. However, emerging data reveal that there is a risk of viral hepatitis B reactivation in some patients treated with rituximab. Many of these cases result in treatment delays, inferior oncologic outcomes, increased morbidity, and more rarely fulminant hepatic decompensation and death. Indeed, the rituximab package insert and many clinical practice guidelines have been modified to reflect these concerns. The true incidence and mechanism of reactivation are still being elucidated. This article focuses on the current evidence that supports these recently revised clinical recommendations along with a review of the risk factors for reactivation, suggested monitoring, and preventative interventions.
New Results Will Change the Paradigm for Phase I Trials and Drug Approval
Authors: Chabner Bruce A.
Published: October 2010

The evidence that, when patients are appropriately selected, convincing benefit can be realized in the earliest of trials, setting the stage for rapid drug approval, is examined.
Tailoring Cognitive-Behavioral Therapy to Treat Anxiety Comorbid With Advanced Cancer
Authors: Greer Joseph A. , Park Elyse R. , Prigerson Holly G. , Safren Steven A.
Published: October 2010

Patients with advanced cancer often experience debilitating anxiety symptoms that interfere with quality of life and relate to worse medical outcomes. Although cognitive-behavioral therapy (CBT) is an empirically validated, first-line treatment for anxiety disorders, clinical trials of CBT for anxiety typically exclude patients with medical comorbidities in general, and those with terminal illnesses, such as advanced cancer, in particular. Moreover, CBT has generally targeted unrealistic fears and worries in otherwise healthy individuals with clinically significant anxiety symptoms. Consequently, traditional CBT does not sufficiently address the cognitive components of anxiety in patients with cancer, especially negative thought patterns that are rational but nonetheless intrusive and distressing, such as concerns about pain, disability, and death, as well as management of multiple stressors, changes in functional status, and burdensome medical treatments. In this article, we describe a treatment approach for tailoring CBT to the needs of this population. Three case examples of patients diagnosed with terminal lung cancer are presented to demonstrate the treatment methods along with outcome measures for anxiety and quality of life.
Subantimicrobial‐Dose Doxycycline and Cytokine‐Chemokine Levels in Gingival Crevicular Fluid
Authors: Emingil Gülnur , Gürkan Ali , Atilla Gül , Kantarci Alpdoğan
Published: October 2010

Background: The present randomized, double‐masked, placebo‐controlled, parallel‐arm study examines the impact of adjunctive subantimicrobial‐dose doxycycline (SDD) on the local inflammatory response through cytokine and chemokine levels in gingival crevicular fluid (GCF) samples from patients with chronic periodontitis.

Methods: Forty‐six patients with chronic periodontitis received scaling and root planing with or without adjunctive SDD. GCF samples were collected and clinical parameters including probing depth, clinical attachment level, gingival index, and plaque index were recorded every 3 months for 12 months. GCF tumor necrosis factor‐α, interleukin (IL)‐6, IL‐4, IL‐10, IL‐13, IL‐17, macrophage inhibitory protein 1α, macrophage inhibitory protein 1β, monocyte chemoattractant protein 1, and regulated on activated normal T‐cell expressed and secreted protein levels were determined by xMAP multiplex immunoassay.

Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (P <0.0125), whereas the SDD group showed significantly better reduction in gingival index, probing depth, and gain in clinical attachment compared to the placebo group (P <0.05). Decrease in IL‐6 in the SDD group was significantly higher compared to the placebo group at 6 and 9 months in deep pockets (P <0.05), whereas tumor necrosis factor‐α was significantly reduced in moderately deep pockets (P <0.05). SDD resulted in a stable IL‐4 and IL‐10 response while reducing the monocyte chemoattractant protein 1 levels at 3 months (P <0.05).

Conclusions: These results show that SDD, as an adjunct to non‐surgical periodontal therapy, stabilizes the inflammatory response by promoting the suppression of proinflammatory cytokines and increasing the anti‐inflammatory cytokines. The chemokine activity would account for the regulation of the inflammatory response to SDD therapy.
The Welfare Implications of Rent Control: A Rent-Seeking Contest Approach
Authors: Chang Yang-Ming , Sanders Shane D.
Published: October 2010

This paper uses a contest approach to characterize a probabilistic, non-price contest between potential consumers of rent-controlled apartments. The model extends upon the rent control model of Glaeser and Luttmer (2003) as well as the rent-seeking contributions of Hurley (1998), Dixit (1987), and Hirshleifer (1989) to consider the roles of chance and endogenously-chosen efforts in the allocation of rent-controlled apartments. Nash equilibrium effort levels for each consumer-type imply that the effort-inducing cost of rent control is greater than the misallocative cost. Further, misallocative costs are lower under the effort contest interpretation than under random allocation, as high willingness to pay consumers allocates more effort. The relationship between effort contest and misallocation influences the policys overall social cost.
Direct Recruitment of Insulin Receptor and ERK Signaling Cascade to Insulin-Inducible Gene Loci
Authors: Nelson Joel D. , LeBoeuf Renée C. , Bomsztyk Karol
Published: October 2010

OBJECTIVE

Insulin receptor (IR) translocates to the nucleus, but its recruitment to gene loci has not been demonstrated. Here, we tested the hypothesis that IR and its downstream mitogenic transducers are corecruited to two prototypic insulin-inducible genes: early growth response 1 (egr-1), involved in mitogenic response, and glucokinase (Gck), encoding a key metabolic enzyme.

RESEARCH DESIGN AND METHODS

We used RNA and chromatin from insulin-treated rat hepatic tumor cell line expressing human insulin receptor (HTC-IR) and livers from lean and insulin-resistant ob/ob glucose-fed mice in quantitative RT-PCR and chromatin immunoprecipitation studies to determine gene expression levels and associated recruitment of RNA polymerase II (Pol II), insulin receptor, and cognate signaling proteins to gene loci, respectively.

RESULTS

Insulin-induced egr-1 mRNA in HTC-IR cells was associated with corecruitment of IR signaling cascade (IR, SOS, Grb2, B-Raf, MEK, and ERK) to this gene. Recruitment profiles of phosphorylated IR, B-Raf, MEK, and Erk along egr-1 transcribed region were similar to those of elongating Pol II. Glucose-feeding increased Gck mRNA expression in livers of lean but not ob/ob mice. In lean mice, there was glucose feeding-induced recruitment of IR and its transducers to Gck gene synchronized with elongating Pol II. In sharp contrast, in glucose-fed ob/ob mice, the Gck recruitment patterns of active MEK/Erk, IR, and Pol II were asynchronous.

CONCLUSIONS

IR and its signal transducers recruited to genes coupled to elongating Pol II may play a role in maintaining productive mRNA synthesis of target genes. These studies suggest a possibility that impaired Pol II processivity along genes bearing aberrant levels of IR/signal transducers is a previously unrecognized facet of insulin resistance.
Pharmacological Treatment of the Pathogenetic Defects in Type 2 Diabetes
Authors: Gram Jeppe , Henriksen Jan Erik , Grodum Ellen , Juhl Henning , Hansen Tony Bill , Christiansen Christian , Yderstræde Knud , Gjessing Hans , Hansen Henrik M. , Vestergaard Vibe , Hangaard Jørgen , Beck-Nielsen Henning
Published: October 2010

OBJECTIVE

To determine the effect of treatment with insulin aspart compared with NPH insulin, together with metformin/placebo and rosiglitazone/placebo. The hypothesis was that combined correction of major pathogenetic defects in type 2 diabetes would result in optimal glycemic control.

RESEARCH DESIGN AND METHODS

This study was a 2-year investigator-driven randomized partly placebo-controlled multicenter trial in 371 patients with type 2 diabetes on at least oral antiglycemic treatment. Patients were assigned to one of eight treatment groups in a factorial design with insulin aspart at mealtimes versus NPH insulin once daily at bedtime, metformin twice daily versus placebo, and rosiglitazone twice daily versus placebo. The main outcome measurement was change in A1C.

RESULTS

A1C decreased more in patients treated with insulin aspart compared with NPH (−0.41 ± 0.10%, P < 0.001). Metformin decreased A1C compared with placebo (−0.60 ± 0.10%, P < 0.001), as did rosiglitazone (−0.55 ± 0.10%, P < 0.001). Triple therapy (rosiglitazone, metformin, and any insulin) resulted in a greater reduction in A1C than rosiglitazone plus insulin (−0.50 ± 0.14%, P < 0.001) and metformin plus insulin (−0.45 ± 0.14%, P < 0.001). Aspart was associated with a higher increase in body weight (1.6 ± 0.6 kg, P < 0.01) and higher incidence of mild daytime hypoglycemia (4.9 ± 7.5 vs. 1.7 ± 5.4 number/person/year, P < 0.001) compared with NPH.

CONCLUSIONS

Insulin treatment of postprandial hyperglycemia results in lower A1C than treatment of fasting hyperglycemia, at the expense of higher body weight and hypoglycemic episodes. However, insulin therapy has to be combined with treatment of both peripheral and liver insulin resistance to normalize blood glucose, and in this case, the insulin regimen is less important.
Improving Epinephrine Responses in Hypoglycemia Unawareness With Real-Time Continuous Glucose Monitoring in Adolescents With Type 1 Diabetes
Authors: Ly Trang T. , Hewitt Jacqueline , Davey Raymond J. , Lim Ee Mun , Davis Elizabeth A. , Jones Timothy W.
Published: October 2010

OBJECTIVE

To determine whether real-time continuous glucose monitoring (CGM) with preset alarms at specific glucose levels would prove a useful tool to achieve avoidance of hypoglycemia and improve the counterregulatory response to hypoglycemia in adolescents with type 1 diabetes with hypoglycemia unawareness.

RESEARCH DESIGN AND METHODS

Adolescents with type 1 diabetes with hypoglycemia unawareness underwent hyperinsulinemic hypoglycemic clamp studies at baseline to determine their counterregulatory hormone responses to hypoglycemia. Subjects were then randomized to either standard therapy or real-time CGM for 4 weeks. The clamp study was then repeated.

RESULTS

The epinephrine response during hypoglycemia after the intervention was greater in the CGM group than in the standard therapy group.

CONCLUSIONS

A greater epinephrine response during hypoglycemia suggests that real-time CGM is a useful clinical tool to improve hypoglycemia unawareness in adolescents with type 1 diabetes.
(lnP)5/(Ga0.47In0.53As)5 superlattice confined 1.5 µm multiquantum well laser grown by all-solid source atomic layer molecular beam epitaxy.
Authors: Dotor M. L. , Huertas P. , Postigo P. A. , Golmayo D. , Briones F.
Published: October 2010

Room temperature laser emission near 1.55 µm is obtained in compressive strained multiquantum well separate confinement heterostructure grown at 340°C by solid source Atomic Layer Molecular Beam Epitaxy, where (lnP)5/(Ga0.47In0.53As)5, lattice-matched short period superlattices have been used as pseudoquaternary barrier to confine Ga0.27In0.73As wells. These preliminary results show that solid source Atomic Layer Molecular Beam Epitaxy is well adapted to fabricate advanced optoelectronic components including pseudoquaternary material.