bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of carbohydrate‐deficient transferrin in human serum by capillary zone electrophoresis: Evaluation of assay performance and quality assurance over a 10‐year period in the routine arena
Authors: Joneli Jeannine , Wanzenried Ursula , Schiess Jeannette , Lanz Christian , Caslavska Jitka , Thormann Wolfgang
Published: March 2013

The performance of high‐resolution CZE for determination of carbohydrate‐deficient transferrin (CDT) in human serum based on internal and external quality data gathered over a 10‐year period is reported. The assay comprises mixing of serum with a Fe(III) ion‐containing solution prior to analysis of the iron saturated mixture in a dynamically double‐coated capillary using a commercial buffer at alkaline pH. CDT values obtained with a human serum of a healthy individual and commercial quality control sera are shown to vary less than 10%. Values of a control from a specific lot were found to slowly decrease as function of time (less than 10% per year). Furthermore, due to unknown reasons, gradual changes in the monitored pattern around pentasialo‐transferrin were detected, which limit the use of commercial control sera of the same lot to less than 2 years. Analysis of external quality control sera revealed correct classification of the samples over the entire 10‐year period. Data obtained compare well with those of HPLC and CZE assays of other laboratories. The data gathered over a 10‐year period demonstrate the robustness of the high‐resolution CZE assay. This is the first account of a CZE‐based CDT assay with complete internal and external quality assessment over an extended time period.
Constraints on the composition of the Aleutian arc lower crust from VP/VS
Authors: Shillington Donna J. , Van Avendonk Harm J. A. , Behn Mark D. , Kelemen Peter B. , Jagoutz Oliver
Published: March 2013

Determining the bulk composition of island arc lower crust is essential for distinguishing between competing models for arc magmatism and assessing the stability of arc lower crust. We present new constraints on the composition of high P‐wave velocity (VP = 7.3–7.6 km/s) lower crust of the Aleutian arc from best‐fitting average lower crustal VP/VS ratio using sparse converted S‐waves from an along‐arc refraction profile. We find a low VP/VS of ~1.7–1.75. Using petrologic modeling, we show that no single composition is likely to explain the combination of high VP and low VP/VS. Our preferred explanation is a combination of clinopyroxenite (~50–70%) and alpha‐quartz bearing gabbros (~30–50%). This is consistent with Aleutian xenoliths and lower crustal rocks in obducted arcs, and implies that ~30–40% of the full Aleutian crust comprises ultramafic cumulates. These results also suggest that small amounts of quartz can exert a strong influence on VP/VS in arc crust.
Obscurins: Unassuming giants enter the spotlight
Authors: Perry Nicole A. , Ackermann Maegen A. , Shriver Marey , Hu Li‐Yen R. , Kontrogianni‐Konstantopoulos Aikaterini
Published: March 2013

Discovered about a decade ago, obscurin (∼720 kDa) is a member of a family of giant proteins expressed in striated muscle that are essential for normal muscle function. Much of what we understand about obscurin stems from its functions in cardiac and skeletal muscle. However, recent evidence has indicated that variants of obscurin (“obscurins”) are expressed in diverse cell types, where they contribute to distinct cellular processes. Dysfunction or abrogation of obscurins has also been implicated in the development of several pathological conditions, including cardiac hypertrophy and cancer. Herein, we present an overview of obscurins with an emphasis on novel findings that demonstrate their heretofore‐unsuspected importance in cell signaling and disease progression. © 2013 IUBMB Life, 65(6):479–486, 2013.
Multisite quantitative ultrasound for the prediction of fractures over 5 years of follow-up: The Canadian Multicentre Osteoporosis Study
Authors: Olszynski Wojciech P , Brown Jacques P , Adachi Jonathan D , Hanley David A , Ioannidis George , Davison Kenneth S ,   the CaMos Research Group
Published: March 2013

This study assessed the ability of multisite quantitative ultrasound (mQUS) to predict fracture over a 5-year follow-up. Participants were a subset of the Canadian Multicentre Osteoporosis Study. mQUS-assessed speed of sound (SOS in m/s) at three sites (distal radius, tibia, and phalanx) and extensive questionnaires were completed, after which participants were followed for 5 years and incident fractures recorded. Two survival analyses were completed for each site—a univariate analysis and an adjusted multivariate analysis controlling for age, antiresorptive use, femoral neck bone mineral density, number of diseases, previous fractures, body mass index (BMI), parental history of hip fracture, current smoking, current alcoholic drinks >3 per day, current use of glucocorticoids, and rheumatoid arthritis diagnosis (variables from the FRAX 10-year fracture risk assessment tool). The unit of change for regression analyses was one standard deviation for all measurement sites, specific to site and sex. Separate analyses were completed for all clinical fractures, nonvertebral fractures, and hip fractures by sex. There were 2633 women and 1108 men included, and they experienced 204 incident fractures over 5 years (5.5% fractured). Univariate models revealed statistically significant (p < 0.05) predictive ability of mQUS for all three measurement sites for women alone for all three fracture types (one standard deviation decrease in SOS was associated with a 52% to 130% increase in the risk of fracture), but not for the men's group. The adjusted model found that measures at the distal radius and tibia in the women's group could significantly (p < 0.05) predict all clinical fractures and nonvertebral fractures within the next 5 years (one standard deviation decrease in SOS was associated with a 25% to 31% increase in the risk of fracture). mQUS provided significant 5-year clinical fracture prediction in women, independent of bone mineral density and other significant risk factors for fracture, when measured at the distal radius and tibia sites.
The induction of cardiac ornithine decarboxylase by β2‐adrenergic agents is associated with calcium channels and phosphorylation of ERK1/2
Authors: López‐Contreras Andrés J. , de la Morena Maria Eugenia , Ramos‐Molina Bruno , Lambertos Ana , Cremades Asunción , Peñafiel Rafael
Published: March 2013

The role that the induction of cardiac ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, by beta‐adrenergic agents may have in heart hypertrophy is a controversial issue. Besides, the signaling pathways related to cardiac ODC regulation have not been fully elucidated. Here we show that in Balb C mice the stimulation of cardiac ODC activity by adrenergic agents was mainly mediated by β2‐adrenergic receptors, and that this induction was lower in the hypertrophic heart. Interestingly, this stimulation was abolished by the L‐calcium channel antagonists verapamil and nifedipine. In addition, whereas the treatment with β2‐adrenergic agents was associated to both the increases in ODC, ODC‐antizyme inhibitor 1 (AZIN1), c‐fos and c‐myc mRNA levels and the phosphorylation of CREB and MAP kinases ERK1 and ERK2 (ERK1/2), the co‐treatment with L‐calcium channel blockers differentially prevented most of these changes. These results suggest that the stimulation of cardiac ODC by β2‐adrenergic agents is associated with the activation of MAP kinases through the participation of L‐calcium channels, and that by itself p‐CREB does not appear to be sufficient for the transcriptional activation of ODC. In addition, post‐translational mechanisms related with the induction of AZIN1 appear to be related to the increase of cardiac ODC activity. J. Cell. Biochem. 114: 1978–1986, 2013. © 2013 Wiley Periodicals, Inc.
Cell‐cycle specific association of transcription factors and RNA polymerase ii with the human β‐globin gene locus
Authors: Rosenberg Michael , Fan Alex Xiucheng , Lin I‐Ju , Liang Shermi Y. , Bungert Jörg
Published: March 2013

The human β‐globin genes are regulated by a locus control region (LCR) and are expressed at extremely high levels in erythroid cells. How transcriptional fidelity of highly expressed genes is regulated and maintained during the cell cycle is not completely understood. Here, we analyzed the association of transcription factor USF, the co‐activator CBP, topoisomerase I (Topo I), basal transcription factor TFIIB, and RNA polymerase II (Pol II) with the β‐globin gene locus at specific cell‐cycle stages. The data demonstrate that while association of Pol II with globin locus associated chromatin decreased in mitotically arrested cells, it remained bound at lower levels at the γ‐globin gene promoter. During early S‐phase, association of CBP, USF, and Pol II with the globin gene locus decreased. The re‐association of CBP and USF2 with the LCR preceded re‐association of Pol II, suggesting that these proteins together mediate recruitment of Pol II to the β‐globin gene locus during S‐phase. Finally, we analyzed the association of Topo I with the globin gene locus during late S‐phase. In general, Topo I association correlated with the binding of Pol II. Inhibition of Topo I activity reduced Pol II binding at the LCR and intergenic regions but not at the γ‐globin gene promoter. The data demonstrate dynamic associations of transcription factors with the globin gene locus during the cell cycle and support previous results showing that specific components of transcription complexes remain associated with highly transcribed genes during mitosis. J. Cell. Biochem. 114: 1997–2006, 2013. © 2013 Wiley Periodicals, Inc.
Student Team Solutions to an Open‐Ended Mathematical Modeling Problem: Gaining Insights for Educational Improvement
Authors: Diefes‐Dux Heidi A. , Hjalmarson Margret A. , Zawojewski Judith S.
Published: March 2013

Background

When engineers and students engage in mathematical modeling, the models they create are representational systems of real‐world problem situations. These representational systems reveal modelers' interpretations of the relative importance of various real‐world aspects.

Purpose

This paper illustrates how interpretations of student teams' solution models (i.e., their representational systems) to a particular problem can be used to inform educational decisions.

Design/Method

First‐year engineering teams' iterative solution models to the Travel Mode Choice Model‐Eliciting Activity (MEA) were interpreted for the purpose of identifying patterns within and across teams' responses. This MEA requires the creation of a model for a client who wants to predict the mode of transportation an individual will likely take to a college campus. Teams were provided with the client's needs and sample data concerning individuals' actual travel mode and travel time, cost, and convenience for various travel modes (walk, bus, or drive).

Results

Student teams were required to submit their intermediate and final model descriptions in narrative form. Systematic study of their models resulted in identification of four different types of models. Patterns within and across model types were then used to suggest changes to the instructional system.

Conclusion

When instructors study student models as representations of their interpretation of a real‐world problem situation, insights gained can lead to practical proposals for improving instruction with authentic open‐ended problems including revisions to tasks, implementation strategies, formative assessment strategies, and course content.
Synthesis of New Indeno[1,2‐c]pyrazole‐Based Heterocycles and Evaluation of Their Protective Effect against DNA Damage Induced by Bleomycin–Iron
Authors: Hegazi Bahira , Abdel‐Gawad Hassan , Mohamed Hanan A. , Badria Farid A. , Farag Ahmad M.
Published: March 2013

image

Reaction of potassium 2‐(1‐phenyl‐1,4‐dihydroindeno[1,2‐c]pyrazole‐3‐carbonyl)hydrazine carbodithioate (2) with hydrazine hydrate, phenacyl bromides, and hydrazonoyl chlorides afforded the corresponding 1,2,4‐triazole, 1,3‐thiazole, and 1,3,4‐thiadiazole derivatives 3, 5, and 7, respectively. Reaction of 3‐mercapto‐4‐amino‐1,2,4‐triazole 3 with phenacyl bromides 4a–c and hydrazonoyl chlorides 6a,b afforded the corresponding 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives 10a–c and 13a,b, respectively, whereas its reaction with 2‐chloro‐N‐arylacetamide derivatives 11a–d afforded the corresponding 2‐(4‐amino‐5‐(1‐phenyl‐1,4‐dihydroindeno[1,2‐c]pyrazol‐3‐yl)‐4H‐1,2,4‐triazol‐3‐ylthio)‐N‐arylacetamide derivatives 12a–d. All of the new compounds were tested for their protection activity against DNA damage induced by bleomycin–iron complex. Compounds 7a and b showed the highest protection activity through diminishing chromogen formation between the damaged DNA and thiobarbituric acid.
High‐spatial and high‐temporal resolution dynamic contrast‐enhanced perfusion imaging of the liver with time‐resolved three‐dimensional radial MRI
Authors: Brodsky Ethan K. , Bultman Eric M. , Johnson Kevin M. , Horng Debra E. , Schelman William R. , Block Walter F. , Reeder Scott B.
Published: March 2013

Purpose

Detection, characterization, and monitoring the treatment of hepatocellular carcinomas (HCC) in patients with cirrhosis is challenging because of their variable and rapid arterial enhancement. Multiphase dynamic contrast‐enhanced MRI is used clinically for HCC assessment; however, the method suffers from limited temporal resolution and difficulty in coordinating imaging and breath‐hold timing within a narrow temporal window of interest. In this article, a volumetric, high‐spatial resolution, and high‐temporal resolution dynamic contrast‐enhanced liver imaging method for improved detection and characterization of HCC is demonstrated.

Methods

A time‐resolved three‐dimensional radial acquisition with iterative sensitivity‐encoding reconstruction images the entire abdomen and thorax with high spatial and temporal resolution, using real‐time three‐dimensional fluoroscopy to match the breath hold to contrast arrival. The sequence was tested on 17 subjects, including eight patients with HCC or other hypervascular focal lesions.

Results

This technique was successful in acquiring volumetric imaging of the entire liver with 2.1‐mm isotropic spatial and true 4‐s temporal resolution.

Conclusion

This technique may be suitable for detecting, characterizing, and monitoring the treatment of HCC. It also holds significant potential for perfusion modeling, which may provide a noninvasive means to rapidly determine the efficacy of chemotherapeutic agents in these tumors over the entire liver volume. Magn Reson Med 71:934–941, 2014. © 2013 Wiley Periodicals, Inc.
Reproducibility study for free‐breathing measurements of pyruvate metabolism using hyperpolarized 13C in the heart
Authors: Lau Angus Z. , Chen Albert P. , Barry Jennifer , Graham John J. , Dominguez‐Viqueira William , Ghugre Nilesh R. , Wright Graham A. , Cunningham Charles H.
Published: March 2013

Spatially resolved images of hyperpolarized 13C substrates and their downstream products provide insight into real‐time metabolic processes occurring in vivo. Recently, hyperpolarized 13C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig, but accurate and reproducible measurements remain challenging due to the limited period available for imaging as well as physiological motion. In this article, time‐resolved cardiac‐ and respiratory‐gated images of [1‐13C] pyruvate, [1‐13C] lactate, and 13C bicarbonate in the heart are acquired without the need for a breathhold. The robustness of these free‐breathing measurements is demonstrated using the time‐resolved data to produce a normalized metric of pyruvate dehydrogenase and lactate dehydrogenase activity in the heart. The values obtained are reproducible in a controlled metabolic state. In a 60‐min ischemia/reperfusion model, significant differences in hyperpolarized bicarbonate and lactate, normalized using the left ventricular pyruvate signal, were detected between scans performed at baseline and 45 min after reperfusion. The sequence is anticipated to improve quantitative measurements of cardiac metabolism, leading to feasible validation studies using fewer subjects, and potentially improved diagnosis, serial monitoring, and treatment of cardiac disease in patients. © 2013 Wiley Periodicals, Inc.
CD36 is important for adipocyte recruitment and affects lipolysis
Authors: Vroegrijk Irene O.C.M. , van Klinken Jan Bert , van Diepen Janna A. , van den Berg Sjoerd A.A. , Febbraio Maria , Steinbusch Laura K.M. , Glatz Jan F.C. , Havekes Louis M. , Voshol Peter J. , Rensen Patrick C.N. , van Dijk Ko Willems , van Harmelen Vanessa
Published: March 2013

Objective: The scavenger receptor CD36 facilitates the cellular uptake of long‐chain fatty acids. As CD36‐deficiency attenuates the development of high fat diet (HFD)‐induced obesity, the role of CD36‐deficiency in preadipocyte recruitment and adipocyte function was set out to characterize.

Design and Methods: Fat cell size and number were determined in gonadal, visceral, and subcutaneous adipose tissue of CD36−/− and WT mice after 6 weeks on HFD. Basal lipolysis and insulin‐inhibited lipolysis were investigated in gonadal adipose tissue.

Results: CD36−/− mice showed a reduction in adipocyte size in all fat pads. Gonadal adipose tissue also showed a lower total number of adipocytes because of a lower number of very small adipocytes (diameter <50 μm). This was accompanied by an increased pool of preadipocytes, which suggests that CD36‐deficiency reduces the capacity of preadipocytes to become adipocytes. Regarding lipolysis, in adipose tissue from CD36−/− mice, cAMP levels were increased and both basal and 8‐bromo‐cAMP stimulated lipolysis were higher. However, insulin‐mediated inhibition of lipolysis was more potent in CD36−/− mice.

Conclusions: These results indicate that during fat depot expansion, CD36‐deficiency negatively affects preadipocyte recruitment and that in mature adipocytes, CD36‐deficiency is associated with increased basal lipolysis and insulin responsiveness.
A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population
Authors: Verrijken A. , Beckers S. , Francque S. , Hilden H. , Caron S. , Zegers D. , Ruppert M. , Hubens G. , Van Marck E. , Michielsen P. , Staels B. , Taskinen M.‐R. , Van Hul W. , Van Gaal L.
Published: March 2013

Objective

Mechanisms explaining the relationship in non‐alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance are poorly understood. A genetic basis has been suggested. We studied the association between the genes patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients.

Design and Methods

Overweight and obese patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. APOC3 variant rs2854117 and PNPLA3 variant rs738409 were genotyped.

Results

Four hundred seventy patients were included (61.1% had liver biopsy). The percentage of patients with non‐alcoholic steatohepatitis (NASH) was significantly different according to the PNPLA3 variant. After adjustment for age and body mass index, the PNPLA3 variant was associated with alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P < 0.001). The PNPLA3 variant was associated with more severe features of steatohepatitis: steatosis (P < 0.001), lobular inflammation (P < 0.001), and ballooning (P = 0.002), but not with liver fibrosis, anthropometry, or insulin resistance. No significant difference in liver histology, anthropometric, or metabolic parameters was found between carriers and non‐carriers of the APOC3 variant.

Conclusions

PNPLA3 polymorphism rs738409 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD was found.
Reversal of dopamine system dysfunction in response to high‐fat diet
Authors: Carlin JesseLea , Hill‐Smith Tiffany E. , Lucki Irwin , Reyes Teresa M.
Published: March 2013

Objective

To test whether high‐fat diet (HFD) decreases dopaminergic tone in reward regions of the brain and evaluate whether these changes reverse after removal of the HFD.

Design and Methods

Male and female mice were fed a 60% HFD for 12 weeks. An additional group was evaluated 4 weeks after removal of the HFD. These groups were compared with control fed, age‐matched controls. Sucrose and saccharin preference was measured along with mRNA expression of dopamine (DA)‐related genes by Real Time‐quantitative PCR (RT‐qPCR). DA and 3,4‐dihydroxyphenylacetic acid (DOPAC) were measured using high‐performance liquid chromatography. DNA methylation of the dopamine transporter (DAT) promoter was measured by methylated DNA immunoprecipitation and RT‐qPCR.

Results

After chronic HFD, sucrose preference was reduced, and then normalized after removal of the HFD. Decreased expression of DA genes, decreased DA content and alterations in DAT promoter methylation, was observed. Importantly, response to HFD and the persistence of changes depended on sex and brain region.

Conclusions

These data identify diminished DA tone after early‐life chronic HFD with a complex pattern of reversal and persistence that varies by both sex and brain region. Central nervous system changes that did not reverse after HFD withdrawal may contribute to the difficulty in maintaining weight‐loss after diet intervention.
In vivo multi‐tissue efficacy of peroxisome proliferator‐activated receptor‐γ therapy on glucose and fatty acid metabolism in obese type 2 diabetic rats
Authors: Nemanich Samuel , Rani Sudheer , Shoghi Kooresh
Published: March 2013

Objective

To identify the disturbances in glucose and lipid metabolism observed in type 2 diabetes mellitus, we examined the interaction and contribution of multiple tissues (liver, heart, muscle, and brown adipose tissue) and monitored the effects of the Peroxisome Proliferator‐Activated Receptor‐γ (PPARγ) agonist rosiglitazone (RGZ) on metabolism in these tissues.

Design and Methods

Rates of [18F]fluorodeoxyglucose ([18F]FDG) and [11C]Palmitate uptake and utilization in the Zucker diabetic fatty (ZDF) rat were quantified using noninvasive positron emission tomography imaging and quantitative modeling in comparison to lean Zucker rats. Furthermore, we studied two separate groups of RGZ‐treated and untreated ZDF rats.

Results

Glucose uptake is impaired in ZDF brown fat, muscle, and heart tissues compared to leans, while RGZ treatment increased glucose uptake compared to untreated ZDF rats. Fatty acid (FA) uptake decreased, but FA flux increased in brown fat and skeletal muscle of ZDF rats. RGZ treatment increased uptake of FA in brown fat but decreased uptake and utilization in liver, muscle, and heart.

Conclusion

Our data indicate tissue‐specific mechanisms for glucose and FA disposal as well as differential action of insulin‐sensitizing drugs to normalize substrate handling and highlight the role that preclinical imaging may play in screening drugs for obesity and diabetes.
Modest fructose beverage intake causes liver injury and fat accumulation in marginal copper deficient rats
Authors: Song Ming , Schuschke Dale A. , Zhou Zhanxiang , Chen Theresa , Shi Xue , Zhang Jiayuan , Zhang Xiang , Pierce William M. , Johnson W. Thomas , Vos Miriam B. , McClain Craig J.
Published: March 2013

Objective

Dietary fructose and copper interaction may play an important role in the pathogenesis of nonalcoholic fatty liver disease. In this study, whether or not modest fructose consumption (3% fructose, w/v) (which is more closely related to the American lifestyle with regard to sugar beverage consumption) affects copper status, and causes liver injury and fat accumulation in marginal copper deficient rats was investigated.

Design and Methods

Male weanling Sprague‐Dawley rats were fed either an adequate copper (6ppm) or a marginally copper deficient (1.6ppm) diet for 4 weeks. Deionized water or deionized water containing 3% fructose (w/v) was given ad lib.

Results

Modest fructose consumption further impaired copper status in the marginal copper deficient rats and increased hepatic iron accumulation. Liver injury and fat accumulation were significantly induced in the marginal copper deficient rats exposed to fructose.

Conclusions

Our data suggest that modest fructose consumption can impair copper status and lead to hepatic iron overload, which in turn, may lead to liver injury and fatty liver in marginal copper deficient rats. This study provides important information on dietary fructose and copper interaction, suggesting that dietary fructose‐induced low copper availability might be an important mechanism underlying fructose‐induced fatty liver.
Validation of the TracmorD Triaxial Accelerometer to Assess Physical Activity in Preschool Children
Authors: Sijtsma Anna , Schierbeek Henk , Goris Annelies H.C. , Joosten Koen F.M. , van Kessel Imke , Corpeleijn Eva , Sauer Pieter J.J.
Published: March 2013

Objectives: To assess validity evidence of TracmorD to determine energy used for physical activity in 3‐4‐year‐old children.

Design and Methods: Participants were randomly selected from GECKO Drenthe cohort (n = 30, age 3.4 ± 0.3 years). Total energy expenditure (TEE) was measured using the doubly labeled water method. Sleeping metabolic rate (SMR) was measured by indirect calorimetry (Deltatrac). TEE and SMR were used to calculate physical activity level (PAL) and activity energy expenditure (AEE). Physical activity was monitored using a DirectLife triaxial accelerometer, TracmorD with activity counts per minute (ACM) and activity counts per day (ACD) as outcome measures.

Results: The best predictor for PAL was ACM with gender and weight, the best predictor for AEE was ACM alone (backward regression, R2 = 0.50, P = 0.010 and R2 = 0.31, P = 0.011, respectively). With ACD, the prediction model for PAL included ACD, height, gender, and sleep duration (R2 = 0.48, P = 0.033), the prediction model for AEE included ACD, gender and sleep duration (R2 = 0.39, P = 0.042). The accelerometer was worn for 5 days, but 3 days did not give a different estimated PAL.

Conclusion: TracmorD provides moderate‐to‐strong validity evidence that supports its use to evaluate energy used for physical activity in 3‐4‐year‐old children.
Body mass index, gender, and clinical outcome among hypertensive and diabetic patients with stage A/B heart failure
Authors: Ballo Piercarlo , Betti Irene , Barchielli Alessandro , Castelli Gabriele , De Luca Leonardo , Gheorghiade Mihai , Zuppiroli Alfredo
Published: March 2013

Objective

The existence of an “obesity paradox” in asymptomatic patients with preclinical heart failure (HF) has not been investigated. The prognostic value of BMI in a cohort of hypertensive and diabetic patients with stage A/B HF enrolled in the PROBE‐HF study was explored.

Design and Methods

BMI was measured in 1003 asymptomatic subjects (age 66.4 ± 7.8 years, 48% males) with hypertension and/or type 2 diabetes and no clinical evidence of HF. Predefined endpoints were all‐cause mortality and a composite of death and hospitalization for cardiac causes.

Results

During a follow‐up of 38.5 ± 4.1 months, 33 deaths were observed. Mortality in the normal BMI group (1.6 deaths per 100 patient‐years) did not differ to that in the overweight group (1.1 per 100 patient‐years, p = 0.31), but was higher than that in the obese group (0.4 per 100 patient‐years, p = 0.0089). In multivariable analysis, obesity (hazard ratio [HR] 0.27 [0.09‐0.85], p = 0.025) but not overweight (HR 0.68 [0.32‐1.45], p = 0.32) was associated with lower risk of death. Obesity was also independently associated with reduced risk of the composite endpoint (HR 0.54 [0.28‐0.99], p = 0.047).

Conclusion

In asymptomatic hypertensive and diabetic patients with preclinical HF, obesity is associated with better survival and reduced risk of events.
Relation of Food Intake Behaviors and Obesity Development in Young Common Marmoset Monkeys
Authors: Ross Corinna N. , Power Michael L. , Artavia Joselyn M. , Tardif Suzette D.
Published: March 2013

Objective: Increasing prevalence of childhood obesity and associated risks of adult type disease have led to worldwide concern. It remains unclear how genetic predisposition, environmental exposure to obesogenic food, and developmental programming interact to lead to overweight and obese children. The development of a nonhuman primate model of obesity, and particularly juvenile obesity, is an important step to elucidating the factors associated with obesity and evaluating intervention strategies.

Design and Methods: Infant marmosets were followed from birth to 12 months of age. Feeding phenotypes were determined through the use of behavioral observation, solid food intake trials, and liquid feeding trials monitored via lickometer.

Results: Marmosets found to be obese at 12 months of age (more than 14%body fat) start consuming solid food sooner and initiate more time off of care givers. These individuals developed stable feeding phenotypes that included being more efficient consumers during liquid intake trials, drinking more grams of diet per contact with the licksit.

Conclusions: The weaning process appears to be particularly important in the development of feeding phenotypes and the development of juvenile obesity for the marmosets, and thus this is the time that should be focused upon for intervention testing in both nonhuman primates and children.
Retinal vessel abnormalities as a possible biomarker of brain volume loss in obese adolescents
Authors: Tirsi Aziz , Duong Michelle , Tsui Wai , Lee Carol , Convit Antonio
Published: March 2013

Objective: Endothelial dysfunction in childhood obesity may precede cerebrovascular damage and cognitive impairment in adulthood. A noninvasive proxy of microvascular health is required to identify the risk for microvascular damage in obese children.

Design and Methods

The associations of hippocampal volumes and global cerebral atrophy were assessed with retinal vessel caliber in 40 normal BMI controls and 62 obese age‐matched nondiabetic adolescents and the contribution of inflammation, obesity, and insulin resistance to retinal vessel caliber was evaluated.

Results

Compared to controls, obese adolescents had smaller retinal arterioles (8.3% decrease, P < 0.05) and wider venules (5.4% increase, P < 0.01). Larger retinal arteriole diameters were associated with less global cerebral atrophy (B = −0.24 [95% confidence interval, CI: −0.48, −0.002]) and larger hippocampal volumes (B = 0.01 [95% CI: 0, 0.02]). Venule diameters (B = 84.2 [95% CI: 30.3, 138.1]) were predicted by inflammation (fibrinogen). Arteriolar diameters were predicted by insulin resistance, indicated by logHOMA (homeostatic model assessment, HOMA) values (B = −17.03 [95% CI: −28.25, −5.81)] and body mass index (BMI) (B = −.67 [95% CI: −1.09, −0.24)]. All analyses were adjusted for mean arterial pressure, sleep apnea, and vessel diameter.

Conclusions

Measures of brain health, BMI, and insulin resistance are associated with retinal vessel caliber. If confirmed in larger studies, retinal arteriolar caliber may serve as a possible noninvasive proxy for brain atrophy in obese adolescents, and the identification of elevated risk for cerebral microvascular disease in adulthood.
Gender Dimorphism and Lack of Day/Night Variation or Effects of Energy Deprivation on Undercarboxylated Osteocalcin Levels in Humans
Authors: Foo Joo‐Pin , Aronis Konstantinos N. , Chamberland John P. , Thakkar Bindiya , Hamnvik Ole‐Petter , Brinkoetter Mary , Zaichenko Lesya , Mantzoros Christos S.
Published: March 2013

Objective

Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short‐term and/or chronic energy deprivation alters ucOC levels, and whether leptin may mediate these changes in humans.

Design and Methods

Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels.

Results

Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short‐term and chronic energy deprivation or leptin administrations do not alter ucOC levels.

Conclusions

The hypothesis that ucOC plays a role in energy homeostasis or of leptin in regulating ucOC in humans is not supported.
High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women
Authors: Jakubowicz Daniela , Barnea Maayan , Wainstein Julio , Froy Oren
Published: March 2013

Objective

Few studies examined the association between time‐of‐day of nutrient intake and the metabolic syndrome. Our goal was to compare a weight loss diet with high caloric intake during breakfast to an isocaloric diet with high caloric intake at dinner.

Design and Methods

Overweight and obese women (BMI 32.4 ± 1.8 kg/m2) with metabolic syndrome were randomized into two isocaloric (∼1400 kcal) weight loss groups, a breakfast (BF) (700 kcal breakfast, 500 kcal lunch, 200 kcal dinner) or a dinner (D) group (200 kcal breakfast, 500 kcal lunch, 700 kcal dinner) for 12 weeks.

Results

The BF group showed greater weight loss and waist circumference reduction. Although fasting glucose, insulin, and ghrelin were reduced in both groups, fasting glucose, insulin, and HOMA‐IR decreased significantly to a greater extent in the BF group. Mean triglyceride levels decreased by 33.6% in the BF group, but increased by 14.6% in the D group. Oral glucose tolerance test led to a greater decrease of glucose and insulin in the BF group. In response to meal challenges, the overall daily glucose, insulin, ghrelin, and mean hunger scores were significantly lower, whereas mean satiety scores were significantly higher in the BF group.

Conclusions

High‐calorie breakfast with reduced intake at dinner is beneficial and might be a useful alternative for the management of obesity and metabolic syndrome.
Metabolic consequences of the early onset of obesity in common marmoset monkeys
Authors: Power Michael L. , Ross Corinna N. , Schulkin Jay , Ziegler Toni E. , Tardif Suzette D.
Published: March 2013

Objective

The common marmoset as a model of early obesity was assessed. The hypotheses that juvenile marmosets with excess adipose tissue will display higher fasting glucose, decreased insulin sensitivity, and decreased ability to clear glucose from the blood stream were tested.

Design and Methods

Normal and obese (body fat > 14%) common marmoset infants (N = 39) were followed up from birth until 1 year. Body fat was measured by quantitative magnetic resonance. Circulating glucose was measured by glucometer and insulin, adiponectin, and leptin by commercial assays. The quantitative insulin sensitivity check index (QUICKI; a measure of insulin sensitivity) was calculated for subjects with fasting glucose and insulin measures. Oral glucose tolerance tests (OGTTs) were conducted at 12 months on 35 subjects.

Results

At 6 months, obese subjects already had significantly lower insulin sensitivity (mean QUICKI = 0.378 ± 0.029 vs. 0.525 ± 0.019, N = 11, P = 0.003). By 12 months, obese subjects also had higher fasting glucose (129.3 ± 9.1 mg/dL vs. 106.1 ± 6.5 mg/dL, P = 0.042), and circulating adiponectin tended to be lower (P = 0.057). Leptin was associated with percent body fat; however, birth weight also influenced circulating leptin. The OGTT results demonstrated that obese animals had a decreased ability to clear glucose.

Conclusions

Early‐onset obesity in marmosets results in impaired glucose homeostasis by 1 year.
Indications and pregnancy outcomes when multidisciplinary centers for prenatal diagnosis refuse request for termination of pregnancy: a retrospective French study
Authors: Nguyen M. L. , Roman H. , Dommergues M. , Verspyck E.
Published: March 2013

Objectives

To report indications and risk factors for effective termination of pregnancy (TOP) when multidisciplinary prenatal diagnosis centers refuse request for TOP.

Methods

This is a retrospective study from a French national registry between 2005 and 2009. Indication groups for TOP refusal were created. Risk factors for pregnancy outcomes and effective TOP were determined by multinomial logistic regression model.

Results

The overall number of TOP refusals was 573. Indications were single malformations (37%), chromosomal abnormalities (16.6%), hygroma (5.2%), potential fetopathies (11%), maternal indications (17.4%), and other indications (12.7%). Pregnancy outcomes were live infants (35.1%), effective TOP (36.3%), intra‐uterine fetal death (5.4%), and lost to follow‐up (23.2%). Logistic regression model showed an increased likelihood of effective TOP in groups with single malformations [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.6–7.4], chromosomal abnormalities (OR 3, 95% CI 1.2–7.2), and hygromas (OR 19.6, 95% CI 2.3–16.8) compared with other groups. An increased likelihood of effective TOP was also reported when the request was made at first (OR 29.5, 95% CI 10–16.7) and second (OR 6.3, 95% CI 2.3–16.7) trimesters compared with the third trimester.

Conclusions

Effective TOP is particularly frequent when requested during the first trimester and in cases of structural anomalies of the fetus. © 2013 John Wiley & Sons, Ltd.
Drug safety data mining with a tree‐based scan statistic
Authors: Kulldorff Martin , Dashevsky Inna , Avery Taliser R. , Chan Arnold K. , Davis Robert L. , Graham David , Platt Richard , Andrade Susan E , Boudreau Denise , Gunter Margaret J. , Herrinton Lisa J. , Pawloski Pamala A. , Raebel Marsha A. , Roblin Douglas , Brown Jeffrey S.
Published: March 2013

Purpose

In post‐marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug–event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree‐based scan statistic data mining method to enhance drug safety surveillance.

Methods

We use a three‐million‐member electronic health records database from the HMO Research Network. Using the tree‐based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic.

Results

Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non‐overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation.

Conclusion

The tree‐based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug–event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.
LINKING SOCIAL–ENVIRONMENTAL RISK FACTORS WITH AGGRESSION IN SUBURBAN ADOLESCENTS: THE ROLE OF SOCIAL–COGNITIVE MEDIATORS
Authors: Bradshaw Catherine P. , Goldweber Asha , Garbarino James
Published: March 2013

Previous research suggests that social–cognitive factors mediate the association between social–environmental risk and aggression in high‐risk samples, but less is known about the relation among these factors in suburban youth. The present study examined whether such an association occurred for suburban youth exposed to low levels of social rejection and community violence. Using data from 184 adolescents (mean age = 14.97 years,SD= .84) and their homeroom teachers, analyses with structural equation modeling revealed a significant relation between relatively mild levels of social–environmental risk and aggression. This association was partially mediated by negatively biased social–cognitive factors (i.e., general knowledge structures and social information processing). Findings suggest that even relatively low levels of social rejection and community violence exposure characterizing suburban youth (in contrast to urban youth) put them at an increased risk for problems with aggression.
Microwave‐Assisted One‐Pot Synthesis of Metal‐Free Nitrogen and Phosphorus Dual‐Doped Nanocarbon for Electrocatalysis and Cell Imaging
Authors: Prasad K. Sudhakara , Pallela Ramjee , Kim Dong‐Min , Shim Yoon‐Bo
Published: March 2013

Metal‐free nitrogen and phosphorus dual‐doped, electrocatlytically active, functionalized nanocarbon (FNC) and photoluminescent carbon nanodots (PCNDs) are simultaneously synthesized using a facile one‐pot microwave‐assisted process. The successful incorporation of phosphorus and nitrogen to oxygen rich PCNDs and FNC are confirmed using surface morphological and spectral studies. The characterization studies of FNC further reveals the presence of edge‐plane‐like sites/defects and remarkable electrocatalytical activity. In addition to the electroctalytical activity, FNC shows attractive properties as a metal‐free oxygen reduction catalyst and is resistant to methanol crossover effects in alkaline media. The 5–10 nm PCNDs, which exhibit blue fluorescence under UV exposure, are successfully used for bioimaging applications.
Mott–Hubbard transition in V2O3 revisited
Authors: Hansmann P. , Toschi A. , Sangiovanni G. , Saha‐Dasgupta T. , Lupi S. , Marsi M. , Held K.
Published: March 2013

The isostructural metal‐insulator transition in Cr‐doped V2O3 is the textbook example of a Mott–Hubbard transition between a paramagnetic metal (PM) and a paramagnetic insulator. We review recent theoretical calculations as well as experimental findings which shed new light on this famous transition. In particular, the old paradigm of a doping‐pressure equivalence does not hold, and there is a microscale phase separation for Cr‐doped V2O3.
Confidential initial identification and other improvements for UMTS security
Authors: Caragata Daniel , El Assad Safwan , Shoniregun Charles , Akmayeva Galyna
Published: March 2013

One of the most important Universal Mobile Telecommunications System security breaches that were identified was the identity catching vulnerability. Whenever the user turns his mobile device on or if the service network fails, the International Mobile Subscriber Identity will be sent in clear over the radio link. This allows the International Mobile Subscriber Identity to be intercepted by an attacker who can use it for different purposes. In this paper, we present a Confidential Initial Identification Protocol that protects user identity and also offers the support for further Universal Mobile Telecommunications System security improvement, especially in the authentication and key agreement protocol and the security algorithms negotiation protocol. We show that these new protocols solve the identity catching vulnerability, limit the secret key exposure to cryptographic attacks, and increase the level of confidence of the user and the home network put in the service network. Copyright © 2013 John Wiley & Sons, Ltd.
Edge‐to‐Edge Assembled Graphene Oxide Aerogels with Outstanding Mechanical Performance and Superhigh Chemical Activity
Authors: Huang Huan , Chen Pengwan , Zhang Xuetong , Lu Yun , Zhan Wanchu
Published: March 2013

Aerogels, an extremely important aggregation state of various self‐assembled nanoscale building blocks, have great potential in fields ranging from energy storage to thermal insulation. However, the porosity of aerogels makes them mechanically weak in most cases, and the chemical activity of the resulting aerogel needs consideration. Herein, chemically crosslinked graphene oxide (GO) 3D aerogels with large specific surface areas (up to 850 m2 g−1), outstanding mechanical performance (up to 20 MPa Young's modulus, 1 MPa yield strength and 45 J g−1 specific energy adsorption), and superhigh chemical activity (toward some reducing gases such as H2S, HI, and SO2), are fabricated by assembling 2D GO sheets edge‐to‐edge into uniform, 3D hydrogel networks with subsequent supercritical fluid drying. These aerogels are superior to other 3D frameworks (e.g. graphene aerogels) assembled via partial overlapping of the basal planes of the 2D building blocks.
Reconstruction of Higgs bosons in the di-tau channel via 3-prong decay
Authors: Gripaios Ben , Nagao Keiko , Nojiri Mihoko , Sakurai Kazuki , Webber Bryan
Published: March 2013

Abstract

We propose a method for reconstructing the mass of a particle, such as the Higgs boson, decaying into a pair of τ leptons, of which one subsequently undergoes a 3-prong decay. The kinematics is solved using information from the visible decay products, the missing transverse momentum, and the 3-prong τ decay vertex, with the detector resolution taken into account using a likelihood method. The method is shown to give good discrimination between a 125 GeV Higgs boson signal and the dominant backgrounds, such as Z
0 decays to ττ and W
± plus jets production. As a result, we find an improvement, compared to existing methods for this channel, in the discovery potential, as well as in measurements of the Higgs boson mass and production cross section times branching ratio.
Production of avian influenza virus vaccine using primary cell cultures generated from host organs
Authors: Babar Mustafeez Mujtaba , Riaz Muhammad Suleman , Zaidi Najam-us-Sahar Sadaf , Afzal Farhan , Farooq Muhammad Sabir
Published: March 2013

The global availability of a therapeutically effective influenza virus vaccine during a pandemic remains a major challenge for the biopharmaceutical industry. Long production time, coupled with decreased supply of embryonated chicken eggs (ECE), significantly affects the conventional vaccine production. Transformed cell lines have attained regulatory approvals for vaccine production. Based on the fact that the avian influenza virus would infect the cells derived from its natural host, the viral growth characteristics were studied on chicken embryo-derived primary cell cultures. The viral propagation was determined on avian origin primary cell cultures, transformed mammalian cell lines, and in ECE. A comparison was made between these systems by utilizing various cell culture-based assays. In-vitro substrate susceptibility and viral infection characteristics were evaluated by performing hemagglutination assay (HA), 50 % tissue culture infectious dose (TCID50) and monitoring of cytopathic effects (CPE) caused by the virus. The primary cell culture developed from chicken embryos showed stable growth characteristics with no contamination. HA, TCID50, and CPE exhibited that these cell systems were permissive to viral infection, yielding 2–10 times higher viral titer as compared to mammalian cell lines. Though the viral output from the ECE was equivalent to the chicken cell culture, the time period for achieving it was decreased to half. Some of the prerequisites of inactivated influenza virus vaccine production include generation of higher vial titer, independence from exogenous sources, and decrease in the production time lines. Based on the tests, it can be concluded that chicken embryo primary cell culture addresses these issues and can serve as a potential alternative for influenza virus vaccine production.