bluuebunny/crossref_metadata_2025 huggingface dataset:
Maturation and long-term hypoxia-induced acclimatization responses in PKC-mediated signaling pathways in ovine cerebral arterial contractility
Authors: Goyal Ravi , Mittal Ashwani , Chu Nina , Arthur Rebecca Afiba , Zhang Lubo , Longo Lawrence D.
Published: August 2010

In the developing fetus, cerebral arteries (CA) show striking differences in signal transduction mechanisms compared with the adult, and these differences are magnified in response to high-altitude long-term hypoxia (LTH). In addition, in the mature organism, cerebrovascular acclimatization to LTH may be associated with several clinical problems, the mechanisms of which are unknown. Because PKC plays a key role in regulating CA contractility, in fetal and adult cerebral arteries, we tested the hypothesis that LTH differentially regulates the PKC-mediated Ca2+sensitization pathways and contractility. In four groups of sheep [fetal normoxic (FN), fetal hypoxic (FH), adult normoxic (AN), and adult hypoxic (AH)], we examined, simultaneously, responses of CA tension and intracellular Ca2+concentration and measured CA levels of PKC, ERK1/2, RhoA, 20-kDa myosin light chain, and the 17-kDa PKC-potentiated myosin phosphatase inhibitor CPI-17. The PKC activator phorbol 12,13-dibutyrate (PDBu) produced robust contractions in all four groups. However, PDBu-induced contractions were significantly greater in AH CA than in the other groups. In all CA groups except AH, in the presence of MEK inhibitor (U-0126), the PDBu-induced contractions were increased a further 20–30%. Furthermore, in adult CA, PDBu led to increased phosphorylation of ERK1, but not ERK2; in fetal CA, the reverse was the case. PDBu-stimulated ERK2 phosphorylation also was significantly greater in FH than FN CA. Also, although RhoA/Rho kinase played a significant role in PDBu-mediated contractions of FN CA, this was not the case in FH or either adult group. Also, whereas CPI-17 had a significant role in adult CA contractility, this was not the case for the fetus. Overall, in ovine CA, the present study demonstrates several important maturational and LTH acclimatization changes in PKC-induced contractile responses and downstream pathways. The latter may play a key role in the pathophysiologic disorders associated with acclimatization to high altitude.
Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet
Authors: Morris Jill K. , Bomhoff Gregory L. , Stanford John A. , Geiger Paige C.
Published: August 2010

Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.
Adenoviral inhibition of AT1areceptors in the paraventricular nucleus inhibits acute increases in mean arterial blood pressure in the rat
Authors: Northcott Carrie A. , Watts Stephanie , Chen Yanfang , Morris Mariana , Chen Alex , Haywood Joseph R.
Published: August 2010

Brain and peripheral renin-angiotensin systems are important in blood pressure maintenance. Circulating ANG II stimulates brain RAS to contribute to the increase mean arterial pressure (MAP). This mechanism has not been fully clarified, so it was hypothesized that reducing angiotensin type 1a (AT1a) receptors (AT1aRs) in the paraventricular nucleus (PVN) would diminish intravenous ANG II-induced increases in MAP. Adenoviruses (Ad) encoding AT1asmall hairpin RNA (shRNA) or Ad-LacZ (marker gene) were injected into the PVN [1 × 109plaque-forming units/ml, bilateral (200 nl/site)] of male Sprague-Dawley rats instrumented with radiotelemetry transmitters for MAP and heart rate measurements and with venous catheters for drug administration. No differences in weight gain or basal MAP were observed. ANG II (30 ng·kg−1·min−1iv, 15 μl/min for 60 min) was administered 3, 7, 10, and 14 days after PVN Ad injection to increase blood pressure. ANG II-induced elevations in MAP were significantly reduced in PVN Ad-AT1ashRNA rats compared with Ad-LacZ rats (32 ± 6 vs. 8 ± 9 mmHg at 7 days, 35 ± 6 vs. 10 ± 6 mmHg at 10 days, and 32 ± 2 vs. 1 ± 5 mmHg at 14 days; P < 0.05). These observations were confirmed by acute administration of losartan (20 nmol/l, 100 nl/site) in the PVN prior to short-term infusion of ANG II; the ANG II-pressor response was attenuated by 69%. In contrast, PVN Ad-AT1ashRNA treatment did not influence phenylephrine-induced increases in blood pressure (30 μg·kg−1·min−1iv, 15 μl/min for 30 min). Importantly, PVN Ad-AT1ashRNA did not alter superior mesenteric arterial contractility to ANG II or norepinephrine; ACh-induced arterial relaxation was also unaltered. β-Galactosidase staining revealed PVN Ad transduction, and Western blot analyses revealed significant reductions of PVN AT1protein. In conclusion, PVN-localized AT1Rs are critical for short-term circulating ANG II-mediated elevations of blood pressure. A sustained suppression of AT1aR expression by single administration of shRNA can interfere with short-term actions of ANG II.
Differential control of renal and lumbar sympathetic nerve activity during freezing behavior in conscious rats
Authors: Yoshimoto Misa , Nagata Keiko , Miki Kenju
Published: August 2010

The present study was designed to document changes in sympathetic nerve activity and cardiovascular function when conscious rats were challenged with a noise stressor to induce freezing behavior. The potential contribution of the arterial baroreceptors in regulating sympathetic nerve activity and cardiovascular adjustments during the freezing behavior was then examined. Wistar male rats were assigned to sham-operated (SO) and sinoaortic-denervated (SAD) groups and instrumented chronically with electrodes for measurements of renal (RSNA) and lumbar (LSNA) sympathetic nerve activity, electroencephalogram, electromyogram, and electrocardiogram and catheters for measurements of systemic arterial and central venous pressure. Both SO and SAD rats were exposed to 90 dB of white noise for 10 min, causing freezing behavior in both groups. In SO rats, freezing behavior was associated with an immediate and significant ( P < 0.05) increase in RSNA, no changes in LSNA or mean arterial pressure, and a significant ( P < 0.05) decrease in heart rate. SAD attenuated the magnitude of the immediate increase in RSNA and had no influence on the response in LSNA during freezing behavior compared with SO rats. Moreover, in SAD rats, mean arterial pressure increased significantly ( P < 0.05) while heart rate did not change during the freezing behavior. These data indicate that freezing behavior evokes regionally different changes in sympathetic outflows, which may be involved in generating the patterned responses of cardiovascular function to stressful or threatening sensory stimulation. Moreover, it is suggested that the arterial baroreceptors are involved in generating the differential changes in RSNA and LSNA and thus the patterned changes in cardiovascular functions observed during freezing behavior in conscious rats.
Nucleofection disrupts tight junction fence function to alter membrane polarity of renal epithelial cells
Authors: Mo Di , Potter Beth A. , Bertrand Carol A. , Hildebrand Jeffrey D. , Bruns Jennifer R. , Weisz Ora A.
Published: August 2010

Here, we compared the effects of nucleofection and lipid-based approaches to introduce siRNA duplexes on the subsequent development of membrane polarity in kidney cells. Nucleofection of Madin-Darby canine kidney (MDCK) cells, even with control siRNA duplexes, disrupted the initial surface polarity as well as the steady-state distribution of membrane proteins. Transfection using lipofectamine yielded slightly less efficient knockdown but did not disrupt membrane polarity. Polarized secretion was unaffected by nucleofection, suggesting a selective defect in the development of membrane polarity. Cilia frequency and length were not altered by nucleofection. However, the basolateral appearance of a fluorescent lipid tracer added to the apical surface of nucleofected cells was dramatically enhanced relative to untransfected controls or lipofectamine-treated cells. In contrast, [3H]inulin diffusion and transepithelial electrical resistance were not altered in nucleofected cells compared with untransfected ones. We conclude that nucleofection selectively hinders development of the tight junction fence function in MDCK cells.
Adaptation and Reintegration of Proprioceptive Information in Young and Older Adults' Postural Control
Authors: Doumas Michail , Krampe Ralf Th.
Published: August 2010

We investigated age-related changes in adaptation and sensory reintegration in postural control without vision. In two sessions, participants adapted their posture to sway reference and to reverse sway reference conditions, the former reducing (near eliminating) and the latter enhancing (near doubling) proprioceptive information for posture by means of support-surface rotations in proportion to body sway. Participants stood on a stable platform for 3 min (baseline) followed by 18 min of sway reference or reverse sway reference (adaptation) and finally again on a stable platform for 3 min (reintegration). Results showed that when inaccurate proprioception was introduced, anterior-posterior (AP) sway path length increased in comparable levels in the two age groups. During adaptation, young and older adults reduced postural sway at the same rate. On restoration of the stable platform in the reintegration phase, a sizeable aftereffect of increased AP path length was observed in both groups, which was greater in magnitude and duration for older adults. In line with linear feedback models of postural control, spectral analyses showed that this aftereffect differed between the two platform conditions. In the sway-referenced condition, a switch from low- to high-frequency COP sway marked the transition from reduced to normal proprioceptive information. The opposite switch was observed in the reverse sway referenced condition. Our findings illustrate age-related slowing in participants' postural control adjustments to sudden changes in environmental conditions. Over and above differences in postural control, our results implicate sensory reweighting as a specific mechanism highly sensitive to age-related decline.
Intrinsic Constraint of Asymmetry Acting as a Control Parameter on Rapid, Rhythmic Bimanual Coordination: A Study of Professional Drummers and Nondrummers
Authors: Fujii Shinya , Kudo Kazutoshi , Ohtsuki Tatsuyuki , Oda Shingo
Published: August 2010

Expert musicians show experience-dependent reduced asymmetry in the structure of motor-related brain areas and in the maximum tapping frequency between the hands. Therefore we hypothesized that a reduced hand-skill asymmetry is strongly related to rapid and rhythmical bimanual coordination and developed a dynamical model including a symmetry-breaking parameter Δω, for human bimanual coordination. We conducted unimanual and bimanual drumming experiments to test the following model predictions. 1) The asymmetry in the maximum tapping frequency is more pronounced in nondrummers than that in drummers. If so, 2) a larger number of phase wanderings (i.e., succession of taps by the same hand), 3) larger SD of the relative phase between the hands ( SD ϕ), and 4) larger deviation of mean relative phase (mean ϕ) from 180° would be observed in nondrummers than that in professional drummers during antiphase bimanual drumming at the maximum speed. In a unimanual tapping task, the asymmetry in maximum tapping frequency of nondrummers was more pronounced than that of professional drummers. In a bimanual coordination task, phase wanderings were observed only in nondrummers and SD ϕ of the nondrummers is significantly larger than that of professional drummers. On the other hand, there was no significant difference between the mean ϕ of the two groups. All these observations were successfully reproduced by changing Δω, which corresponded to the asymmetry in the maximum tapping frequency. These results support the hypothesis indicating that the prominent bimanual coordination pattern emerges spontaneously after a nonspecific change in Δω or symmetry restoration of the nonlinear dynamical systems.
Cardiovascular Risk Reduction with Renin-Angiotensin Aldosterone System Blockade
Authors: Houston Miller Nancy
Published: August 2010

This paper examines the evidence supporting treatments within the renin-angiotensin aldosterone system (RAS), the role cardioprotection plays within the management of hypertension, considerations around medication adherence, and the role of the nurse or nurse practitioner in guiding patients to achieve higher hypertension control rates. A large body of data now exists to support the use of angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) which act on RAS, in the management of hypertension and their effect on cardiovascular risk reduction. Current evidence suggests that inhibition of the RAS is an important target for cardioprotection. RAS inhibition controls blood pressure and also reduces target-organ damage. This is especially important in populations at high-risk for damage including patients with diabetes and those with chronic kidney disease. Both ARBs and ACEIs target the RAS offering important reductions in both BP and target organ damage.
Mechanical Evaluation of Polymer Composite Hip Protectors
Authors: Melo Jose Daniel Diniz , Barbosa Ayrles S. Gonçalves , Guerra Ricardo Oliveira
Published: August 2010

Hip fractures often result in serious health implications, particularly in the geriatric population, and have been related to long-term morbidity and death. In most cases, these fractures are caused by impact loads in the area of the greater trochanter, which are produced in a fall. This work is aimed at developing hip protectors using composite materials and evaluating their effectiveness in preventing hip fractures under high impact energy (120 J). The hip protectors were developed with an inner layer of energy absorbing soft material and an outer rigid shell of fiberglass-reinforced polymer composite. According to the experimental results, all tested configurations proved to be effective at reducing the impact load to below the average fracture threshold of proximal femur. Furthermore, an addition of Ethylene Vinyl Acetate (EVA) to the impacted area of the composite shell proved to be beneficial to increase impact strength of the hip protectors. Thus, composite hip protectors proved to be a viable alternative for a mechanically efficient and cost-effective solution to prevent hip fractures.
Synthetic Biology Guides Biofuel Production
Authors: Connor Michael R. , Atsumi Shota
Published: August 2010

The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges.
On the Recursive Sequence xn+1=max {xn,A}/xn2xn−1
Authors: Yalcinkaya Ibrahim , Cinar Cengiz , Gelisken Ali
Published: August 2010

We investigate the periodic nature of the solution of the max‐type difference equation ,n= 0,1, 2, …, where the initial conditions are and forA∈ (0,∞), and thatr1andr2are positive rational numbers. The results in this paper solve the Open Problem proposed by Grove and Ladas (2005).
Yarn Strength Prediction: A Practical Model Based on Artificial Neural Networks
Authors: Furferi Rocco , Gelli Maurizio
Published: August 2010

Yarn strength is one of the most significant parameters to be controlled during yarn spinning process. This parameter strongly depends on both the rovings' characteristics and the spinning process. On the basis of their expertise textile technicians are able to provide a raw and qualitative prediction of the yarn strength by knowing a series of fiber parameters like length, strength, and fineness. Nevertheless, they often need to perform many tests before producing a yarn with a desired strength. This paper describes a Feed Forward Back Propagation Artificial Neural Network-based model able to help the technicians in predicting the yarn strength without the need of physically spinning the yarn. The model performs a reliable prediction of the yarn strength on the basis of a series of roving parameters, commonly measured by the technicians before the yarn spinning process starts. The model has been trained with 98 training data and validated with 50 new tests. The mean error in prediction of yarn strength, using the validation set, is less than 4%. The results have been compared with the one obtained by means of a classical method: the multiple regression. Nowadays, the developed model is running in the laboratory of New Mill S.p.A., an important textile company that operates in Prato (Italy).
Short-Term Cardiac and Noncardiac Mortality Following Liver Transplantation
Authors: Eleid Mackram F. , Hurst R. Todd , Vargas Hugo E. , Rakela Jorge , Mulligan David C. , Appleton Christopher P.
Published: August 2010

Objectives. To determine the importance of acute cardiac events as a cause of mortality compared to non-cardiac events in the four month period following liver transplantation (LT) using current preoperative cardiac screening strategies.Patients and Methods. We retrospectively reviewed timing, type, and outcome of adverse cardiac events, and all cause mortality in the 4 month postoperative period in 393 consecutive LT patients from October 1999 to February 2008.Results. Of 30 total deaths (7.6% overall mortality rate), 27 (90%) were due to surgical or medical complications and 3 (10%) were primary cardiac deaths (0.8% cardiac mortality rate). Acute cardiac events occurred in 26 patients (6.6%), including 13 arrhythmias (50%), 7 new onset heart failures (27%), and 6 myocardial infarctions (23%). Twelve of 13 intraoperative events were arrhythmias (92%) including two of three cardiac deaths.Conclusions. Using current preoperative screening recommendations, deaths from primary cardiac events within four months of LT are very uncommon (0.8%), especially compared with deaths related to medical and surgical complications (6.9%).
Assessment of Acute and Chronic Pharmacological Effects on Energy Expenditure and Macronutrient Oxidation in Humans: Responses to Ephedrine
Authors: Napolitano Antonella , Murgatroyd Peter R. , Finer Nick , Hussey Elizabeth K. , Dobbins Robert , O'Rahilly Steve , Nunez Derek J. R.
Published: August 2010

Evidence of active brown adipose tissue in human adults suggests that this may become a pharmacological target to induce negative energy balance. We have explored whole-body indirect calorimetry to detect the metabolic effects of thermogenic drugs through administration of ephedrine hydrochloride and have assessed ephedrine's merits as a comparator compound in the evaluation of novel thermogenic agents. Volunteers randomly given ephedrine hydrochloride 15 mg QID(n=8)or placebo(n=6)were studied at baseline and after 1-2 and 14-15 days of treatment. We demonstrate that overnight or 23-hour, 2% energy expenditure (EE) and 5% fat (FO) or CHO oxidation effects are detectable both acutely and over 14 days. Compared to placebo, ephedrine increased EE and FO rates overnight (EE 63 kJ day 2, EE 105 kJ, FO 190 kJ, day 14), but not over 23 h. We conclude that modest energy expenditure and fat oxidation responses to pharmacological interventions can be confidently detected by calorimetry in small groups. Ephedrine should provide reliable data against which to compare novel thermogenic compounds.
A User-Friendly Method for Synthesizing High-QualityNaYF4:Yb,Er(Tm) Nanocrystals in Liquid Paraffin
Authors: Liang Sen , Liu Yi , Tang Yue , Xie Yue , Sun Haizhu , Zhang Hao , Yang Bai
Published: August 2010

Application of “green chemistry” concept to synthesize nanomaterials is the current goal in developing new techniques for producing materials in commercial scale. In this study, we reported a low-cost and convenient method for synthesizing high-qualityNaYF4:Yb,Er(Tm) nanocrystals (NCs) in liquid paraffin. Experimental results indicated that the as-prepared NCs possessed pureβ-phase structure, narrow size distribution, as well as strong up-conversion fluorescence. By varying the doped lanthanides, Er or Tm, the emission color of up-conversion fluorescence was tunable. In comparison to other high-boiling-point organic solvents, liquid paraffin is cheaper and prolific in oil industry. Besides,280∘C was the optimal temperature forNaYF4:Yb,Er(Tm) synthesis, which was lower than that in the previous reports using other high-boiling-point organic solvents. Accordingly, this user-friendly method will facilitate the synthesis of high-quality lanthanide-dopedNaYF4NCs in commercial scale.
Physical Activity Plays an Important Role in Body Weight Regulation
Authors: Chaput Jean-Philippe , Klingenberg Lars , Rosenkilde Mads , Gilbert Jo-Anne , Tremblay Angelo , Sjödin Anders
Published: August 2010

Emerging literature highlights the need to incorporate physical activity into every strategy intended to prevent weight gain as well as to maintain weight loss over time. Furthermore, physical activity should be part of any plan to lose weight. The stimulus of exercise provides valuable metabolic adaptations that improve energy and macronutrient balance regulation. A tight coupling between energy intake and energy expenditure has been documented at high levels of physical exercise, suggesting that exercise may improve appetite control. The regular practice of physical activity has also been reported to reduce the risk of stress-induced weight gain. A more personalized approach is recommended when planning exercise programs in a clinical weight loss setting in order to limit the compensatory changes associated to exercise-induced weight loss. With modern environment promoting overeating and sedentary behavior, there is an urgent need for a concerted action including legislative measures to promote healthy active living in order to curb the current epidemic of chronic diseases.
Size-Dependent Elastic Modulus and Vibration Frequency of Nanocrystals
Authors: Liang Lihong , Ma Hansong , Wei Yueguang
Published: August 2010

The elastic properties and the vibration characterization are important for the stability of materials and devices, especially for nanomaterials with potential and broad application. Nanomaterials show different properties from the corresponding bulk materials; the valid theoretical model about the size effect of the elastic modulus and the vibration frequency is significant to guide the application of nanomaterials. In this paper, a unified analytical model about the size-dependent elastic modulus and vibration frequency of nanocrystalline metals, ceramics and semiconductors is established based on the inherent lattice strain and the binding energy change of nanocrystals compared with the bulk crystals, and the intrinsic correlation between the elasticity and the vibration properties is discussed. The theoretical predictions for Cu, Ag, Si thin films, nanoparticles, andTiO2nanoparticles agree with the experimental results, the computational simulations, and the other theoretical models.
Experience (Mostly Negative) with the Use of Sympathomimetic Agents for Weight Loss
Authors: Inchiosa Mario A.
Published: August 2010

Sympathomimetic agents have a poor history of long-term success in the treatment of obesity. From earlier experiences with amphetamine and its analogs, to more recent drugs with direct effects on adrenergic receptors or indirect effects from release of catecholamines or inhibition of reuptake, cardiovascular toxicity (strokes and cardiac arrhythmias) has been the major concern. These concerns also extended to food supplements containing ephedra alkaloids and may require consideration for current supplements containing the sympathomimetic drug, synephrine.
Tumor Regression and Curability of Preclinical Neuroblastoma Models by PEGylated SN38 (EZN-2208), a Novel Topoisomerase I Inhibitor
Authors: Pastorino Fabio , Loi Monica , Sapra Puja , Becherini Pamela , Cilli Michele , Emionite Laura , Ribatti Domenico , Greenberger Lee M. , Horak Ivan D. , Ponzoni Mirco
Published: August 2010

Purpose: Treatment of neuroblastoma is successful in less than half of patients with high-risk disease. The antitumor activity of a water soluble pegylated SN38 drug conjugate, EZN-2208, was compared with CPT-11 (a prodrug for SN38) in preclinical models of human neuroblastoma.

Experimental Design: The in vitro cytotoxicity of EZN-2208 was tested by counting trypan blue dye– and Annexin V–positive cells, whereas its therapeutic efficacy was evaluated, in terms of survival, and antitumor and antiangiogenic activities, in s.c. luciferase-transfected, pseudometastatic, and orthotopic neuroblastoma animal models.

Results: EZN-2208 was about 100-fold more potent than CPT-11 in vitro, by inducing apoptosis/necrosis and p53 expression and by reducing hypoxia-inducible factor (HIF)-1α/HIF-2α expression. EZN-2208 gave superior antitumor effects compared with CPT-11 in neuroblastoma xenografts. EZN-2208 treatment always resulted in lack of tumor detection at the end of trials whereas only small therapeutic effects were observed with CPT-11, as assessed by luciferase assay or tumor size, or even by staining histologic sections of tumors with antibodies recognizing neuroblastoma cells and cell proliferation. In a neuroblastoma model resistant to doxorubicin, cisplatin, vincristine, fenretinide, and topotecan, EZN-2208 induced 100% curability. It also blocked tumor relapse after topotecan-vincristine-doxorubicin combined treatment. Mechanistic experiments showed statistically significantly enhanced terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and Histone H2ax staining as well as decreased vascular endothelial growth factor, CD31, matrix metalloproteinase (MMP)-2, and MMP-9 expression in tumors removed from EZN-2208–treated mice and radiating vessels invading the tumor implanted onto the chorioallantoic membranes.

Conclusions: EZN-2208 should be considered a most promising novel antineuroblastoma agent. An ongoing phase I study in pediatric patients should identify the optimal dose for a phase II study. Clin Cancer Res; 16(19); 4809–21. ©2010 AACR.
Caries Experience and Quantification of Streptococcus mutans and Streptococcus sobrinus in Saliva of Sudanese Schoolchildren
Authors: Nurelhuda N.M. , Al-Haroni M. , Trovik T.A. , Bakken V.
Published: August 2010

Streptococcus mutans and Streptococcus sobrinus are among the most commonly isolated bacterial species implicated as etiological agents of dental caries. Details of the composition of the oral microflora related to dental caries should aid in assessing the prevalence and risk of disease at an individual level. The aim of the present study was to determine the presence and relative amounts of S. mutans and S. sobrinus in the saliva samples obtained from schoolchildren in Khartoum State, the Sudan, and to study the association of the amounts of S. mutans and S. sobrinus with caries experience, socioeconomic status and sugar-sweetened snacks in this population. 140 samples, 30 of which were from individuals with caries experience, were examined using quantitative real-time polymerase chain reaction (qRT-PCR) with specific oligonucleotide primers. The mean ratio of fold differences of S. mutans to S. sobrinus was 0.77 (SD 5.4) and 2.29 (SD 6.0) for samples obtained from caries-free and caries-active individuals, respectively. This suggested that the proportion of S. sobrinus was higher than S.mutans in the caries-active group when compared to the caries-free group. An association was found between children with caries-active lesions and the frequent consumption of sticky desserts and higher socioeconomic status. S. sobrinus seems to be associated with caries experience in the studied population. A proposal of caries screening programs designed to test for S. sobrinus in this population may be developed.
Metabolic and Appetite Hormone Responses of Hyperinsulinemic Normoglycemic Males to Meals with Varied Macronutrient Compositions
Authors: El Khoury Dalia , Hwalla Nahla
Published: August 2010

Aims: The aim of this study was to investigate the appetite hormones and metabolic responses of hyperinsulinemic subjects to high-protein (HP) meals as compared to high-carbohydrate (HC) and high-fat (HF) meals. Design: Fifteen hyperinsulinemic normoglycemic men received, on 3 separate occasions, HP, HC, or HF meals in a randomized crossover design. Blood samples were collected before and after the ingestion of each meal. Postprandially, acylated ghrelin, PYY3–36, insulin, glucose, and triglycerides were measured. Results: While the HC meal induced an acutely greater postprandial ghrelin decrease below baseline, the HP meal maintained this decline significantly more than the HF meal at 240 min. Postprandial PYY3–36 responses did not significantly vary with time and meal composition. Postprandial insulin and glucose peaks were significantly lower following the HP and HF meals in comparison to the HC meal, whereas triglyceride responses were significantly higher following the HF meal. Significant correlations, negative between acylated ghrelin and insulin and positive between PYY3–36 and insulin, were observed. Conclusions: In hyperinsulinemic normoglycemic men, HP meals ensure a longer-lasting suppression of circulating ghrelin levels and result in more favorable metabolic responses, characterized by a lower surge of postprandial insulin and glucose and a reduced postprandial triglyceride response, as compared to both HC and HF meals.
Cinacalcet – Clinical and Laboratory Effectiveness, Concomitant Treatment Patterns and Treatment Cost: Could We Do Better and How?
Authors: Smržová Jana , Urbánek Tomáš
Published: August 2010

Background: The cost and effectiveness patterns in the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients in the Czech Republic are unknown. Methods: 52 dialysis patients from 17 centers were followed up in a multicenter prospective study of laboratory and clinical (hospitalization rate, clinical complaints questionnaire) responses to 12-month cinacalcet treatment. Treatment patterns and cost (including phosphate binders, vitamin D, and cinacalcet) were evaluated. Results: The mean s-Ca dropped significantly from 2.36 ± 0.24 to 2.21 ± 0.20 mmol/l, s-P from 2.45 ± 0.54 to 2.01 ± 0.53 mmol/l, Ca×P from 5.79 ± 1.25 to 4.42 ± 1.13 mmol2/l2, and iPTH dropped from 919.0 ± 465.6 to 372.1 ± 294.6 pg/ml. The mean cinacalcet dose reached 44.1 ± 23.0 mg/day after 12 months. Itching intensity decreased significantly. No change in hospitalization rate was observed. The direct cost of daily SHPT treatment rose significantly from EUR 8.77 ± 9.59 to 20.62 ± 9.22. Conclusions: Cinacalcet decreased elevated s-Ca, s-P, Ca×P, and iPTH, alleviated itching, and significantly raised the SHPT treatment cost. A minority of patients reached K/DOQI targets, especially due to poor phosphate control caused by insufficient phosphate binder treatment, cinacalcet underdosing, and advanced SHPT.
Acute Responses of Gastrointestinal Hormones to Both Oral and Parenteral Intradialytic Nutrition
Authors: Fernández-Reyes María José , Sánchez Rosa , García Laura , Grande Cristina , Codoceo Rosa , Heras Manuel , Iglesias Pedro , Velasco Sonia , Molina Alvaro , Gutierrez Carmen , Alvarez-Ude Fernando
Published: August 2010

Introduction: Intradialytic nutrition (IDN) has been used to improve the nutritional status of malnourished hemodialysis (HD) patients. Objective: To evaluate the different effects of parenteral IDN (IDPN) and oral IDN (IDON) on nutrition-related gastrointestinal hormones. Patients and Methods: Seven clinically stable HD patients with malnutrition were included. All patients were treated for 1 month with either IDPN or IDON, with a 4-week period of no nutritional support between each type of therapy. On the first day of each nutritional support (IDON or IDPN) we analyzed the acute responses of insulin, ghrelin, and glucagon-like peptide 1 (GLP-1). We compared the areas under the secretory curves (AUC) and the maximum peaks of serum glucose, insulin, ghrelin, and GLP-1. A group of 6 clinically stable HD patients without any type of IDN served as the control group. Results: The acute responses of glucose and insulin to IDN were significantly higher with IDPN than with IDON. The AUC of glucose (602 ± 81 vs. 495 ± 81 mg/dl/h, p < 0.01) and insulin (232 ± 103 vs. 73.8 ± 69 µU/ml/h, p < 0.01) as well as the maximum peaks of glucose (228 ± 41 vs. 177 ± 47 mg/dl, p < 0.05) and insulin (104 ± 46 vs. 29 ± 24 µU/ml, p < 0.01) were significantly higher after IDPN than after IDON. Ghrelin decreased after both IDPN and IDON; however, the decrease was significantly higher with IDPN compared to IDON. The ghrelin nadir was significantly lower in IDPN than in IDON (0.77 ± 0.5 vs. 1.5 ± 0.3, p < 0.05) although the AUC of ghrelin was not significantly different. GLP-1 was significantly increased at 1 h after starting both IDPN and IDON with no significant differences between the groups. Conclusion: IDPN induces a higher increase in serum glucose and insulin levels and a greater reduction in serum ghrelin concentrations compared with an equivalent orally administered nutritional supplement.
Do Differences in Dialysis Prescription Impact on KDOQI Bone Mineral Targets? The Pan Thames Renal Audit
Authors: Davenport Andrew , Gardner Carrie , Delaney Michael ,   on behalf of the Pan Thames Renal Audit Group
Published: August 2010

Background and Objectives:Patients achieving the Kidney Disease Outcomes Quality Initiative (KDOQI) bone mineral clinical practice guidelines have been reported to have improved survival. Many factors affecting calcium and phosphate control are not modifiable; however, we wished to determine whether differences in dialysis treatment could affect achievement of KDOQI clinical guideline targets. Methods: We audited pre-mid-week session calcium and phosphate levels in 5,324 adult patients receiving thrice weekly dialysis in the 14 Pan Thames centres: 60% male, mean age 62 ± 16 years, median dialysis vintage 29 months (14–58), 84% treated by haemodialysis, 16% by online haemodiafiltration, median session time 4.0 h (3.5–4.0). Results: Patients achieving the KDOQI guidelines varied between the centres: 23.4–60% for calcium, 31.7–56.7% for phosphate, 60–87.3% for calcium-phosphate product, 17.1–46.8% for parathyroid hormone (PTH) and 1.8–10.8% for all 4 targets. Those centres which used the highest dialysate calcium concentrations (1.5 mmol/l, 3 mEq/l) had more patients above the KDOQI serum calcium and more below the PTH target, than those centres using the lowest calcium dialysates (1 mmol/l, 2 mEq/l), with χ2 = 85.1 and χ2 = 52.4, p < 0.001, respectively. On logistic regression analysis, serum phosphate was negatively associated with duration of dialysis session time (F = 21.4, p = 0.000) and haemodiafiltration (F = 9.6, p = 0.000), respectively. Conclusions: Although many of the factors determining calcium and phosphate control in haemodialysis patients are unmodifiable, dialysate calcium concentration, the duration of the dialysis session and haemodiafiltration all had an impact on calcium, phosphate and PTH.
Increased Adipose Tissue Expression of Proinflammatory CD40, MKK4 and JNK in Patients with Very Severe Chronic Obstructive Pulmonary Disease
Authors: Tkacova Ruzena , Ukropec Jozef , Skyba Peter , Ukropcova Barbara , Pobeha Pavol , Kurdiova Timea , Joppa Pavol , Klimes Iwar , Tkac Ivan , Gasperikova Daniela
Published: August 2010

Background: CD40, a transmembrane receptor of the tumor necrosis factor gene superfamily, is activated in response to cellular stress, including hypoxia, and orchestrates the process of inflammation via secondary messengers such as mitogen-activated protein kinase kinase 4 (MKK4) and c-Jun NH2-terminal kinases (JNK). Objectives: We hypothesized that CD40, MKK4 and JNK expression is increased in the adipose tissue of patients with very severe chronic obstructive pulmonary disease (COPD). Methods: In 20 patients with stable COPD, lung function was assessed using body plethysmography, and samples of subcutaneous adipose tissue were analyzed using real-time PCR. Body composition, including fat mass index (FMI), was assessed by bioelectrical impedance. Results: 12 patients in GOLD stage I–III (age 61.6 ± 8.6 years, 4 females, mean partial pressure of oxygen in arterial blood, PaO2, 9.38 ± 0.21 kPa) were compared to 8 patients in GOLD stage IV (age 62.6 ± 6.3 years, all male, mean PaO2 7.70 ± 0.37 kPa). Compared to patients in GOLD stage I–III, patients in GOLD stage IV had lower FMI (p = 0.004), being associated with significantly higher adipose tissue expression of CD40, MKK4 and JNK [ΔΔCt: 2.55 (1.99, 4.40) vs. 1.87 (1.63, 2.23), p = 0.013; 5.19 (3.13, 5.96) vs. 2.98 (2.82, 3.86), p = 0.002; 9.01 (5.12, 11.41) vs. 4.65 (4.42, 6.26), p = 0.001, respectively]. Log-transformed CD40, MKK4 and JNK expression was significantly inversely related to PaO2, respectively. Conclusions: Upregulation of proinflammatory CD40, MKK4 and JNK gene expression in adipose tissue in very severe COPD raises the possibility of a role of chronic systemic hypoxia in the pathogenesis of adipose tissue inflammation in COPD.
Use of Competency-Based Metrics to Determine Effectiveness of a Postgraduate Thoracoscopy Course
Authors: Colt Henri G. , Davoudi Mohsen , Quadrelli Silvia , Zamanian Rohani Nazanin
Published: August 2010

Background: Despite the paradigm shift from process to competency-based education, no study has explored how competency-based metrics might be used to assess short-term effectiveness of thoracoscopy-related postgraduate medical education. Objectives: To assess the use of a single-group, pre-/post-test model comprised of multiple-choice questions (MCQ) and psychomotor skill measures to ascertain the effectiveness of a postgraduate thoracoscopy program. Methods: A 37-item MCQ test of cognitive knowledge was administered to 17 chest physicians before and after a 2-day continued medical education-approved program. Pre- and post-course technical skills were assessed using rigid videothoracoscopy simulation stations. Competency-based metrics (mean relative gain, mean absolute gain, and class-average normalized gain ) were calculated. A  >30% was used to determine curricular effectiveness. Results: Mean cognitive knowledge score improved significantly from 20.9 to 28.7 (7.8 ± 1.3 points, p < 0.001), representing a relative gain of 37% and an absolute gain of 21%. Mean technical skill score improved significantly from 5.20 to 7.82 (2.62 ± 0.33 points, p < 0.001), representing a relative gain of 50% and an absolute gain of 33%. Non-parametric testing confirmed t test results (p < 0.001). Class-average normalized gains were 48 and 92%, respectively. Conclusion: Competency-based metrics, including class-average normalized gain, can be used to assess course effectiveness and to determine if a program meets predesignated objectives of knowledge acquisition and psychomotor technical skill.
Resolvin E1 Regulates Adenosine Diphosphate Activation of Human Platelets
Authors: Fredman Gabrielle , Van Dyke Thomas E. , Serhan Charles N.
Published: August 2010

Objective—

To investigate the ability of resolvin E1 (RvE1) to regulate adenosine diphosphate (ADP) activation of platelets via specific receptors because RvE1 reduces platelet aggregation with certain agonists, including ADP.

Methods and Results—

RvE1 is an eicosapentaenoic acid–derived specialized proresolving mediator generated during the resolution of acute inflammation. RvE1 exhibits potent organ-protective actions in vivo and acts on specific cell types, including platelets. RvE1, 0.1 to 100 nmol/L, incubated with platelets gave reduced ADP-stimulated P-selectin mobilization (IC
50
, approximately 1.6×10
−12
mol/L) and polymerized actin content compared with control platelets. RvE1, 1 to 100 nmol/L, did not stimulate or block intracellular Ca
2+
mobilization. By using a new P2Y
12
–β-arrestin–coupled cell system, ADP-activated P2Y
12
with an EC
50
of 5×10
−6
mol/L and RvE1 did not directly stimulate P2Y
12
or block the ADP–P2Y
12
signals. In this system, another eicosanoid, leukotriene E
4
(LTE
4
) (EC
50
, 1.3×10
−11
mol/L), dose dependently activated P2Y
12
. When recombinant P2Y
12
–expressing cells were transiently transfected with an RvE1 receptor, human ChemR23 (present on human platelets), with the addition of RvE1 (0.1–10.0 nmol/L), blocked ADP signals (IC
50
, approximately 1.6×10
−11
mol/L) in P2Y
12
–ChemR23–expressing cells compared with mock transfections.

Conclusion—

RvE1’s regulatory actions (ie, reducing ADP-stimulated P-selectin mobilization and actin polymerization) are human (h)ChemR23-dependent. Moreover, specific platelet actions of RvE1 selectively engaged with ADP-activated platelets that illuminate a new cellular mechanism and affect ω-3 eicosapentaenoic acid, which may contribute to both resolution of vascular inflammation and ADP-dependent platelet activation relevant in pathological cardiovascular events.
An analysis of bias in supervisor narrative comments in performance appraisal
Authors: Wilson Kathlyn Y
Published: August 2010

This study explored supervisors’ explanations for performance ratings assigned to subordinates. It was suggested that supervisors may emphasize a different set of factors across groups in arriving at an overall evaluation that would reflect different implicit theories of performance for different ethnic groups. Operationally, these differences were predicted to be reflected as differences across groups in the factors cited by supervisors in justifying their performance ratings of subordinates. The study also examined the consistency between these assigned ratings and the written justifications. Using a sample of bank staff, supervisors’ written summaries of subordinate performance were content analyzed to identify the types of comments made across groups and the match or mismatch with overall ratings. Hypotheses received partial support.The results are interpreted in light of the literature on group differences in performance ratings, and implications for future research and practice are discussed.
Effect of heat and moisture transfer properties on microclimate and subjective thermal comfort of caps
Authors: Youngmin Jun  , Chung Hee Park  , Tae Jin Kang
Published: August 2010

The purpose of this research is to explore the effect of textile properties on the microclimate inside the cap and subjective wearing sensations in various environmental conditions, with/without radiation or air current. Heat and moisture transfer properties of cap fabrics were measured and their relationships with the microclimate inside caps and with the subjective wearing sensations in three different environmental conditions were analyzed. Principal component analysis and regression analysis were employed for the relationship of microclimatic temperature and thermal comfort. The most important fabric properties affecting the cap microclimate in a hot environment was found to be those related to liquid moisture transport and emission. Properties related to vapor transport and air permeability did not affect the microclimate much in a hot environment without radiation or air current. However, in the radiation environment, fabric with high thermal resistance generated a microclimate with low temperature and humidity, thereby giving good thermal comfort. In the environment with air current, air permeability and its related properties were the most critical fabric properties influencing the microclimate and subjective thermal comfort. According to the regression models obtained, thermal discomfort sensation starts at around 33°C, and becomes very high at 35°C.
Customer participating 3D garment design for mass personalization
Authors: Jin Wang  , Guodong Lu  , Long Chen  , Yulei Geng  , Weiyan Deng
Published: August 2010

This paper presents customer participating 3D garment design methods for mass personalization. Complex fashion design is separated into garment surface modeling, pattern designing and texture mapping. Based on the modularization of the garment, we propose a component option sheet to describe the Garment surface Style (GS). Customers can choose components flexibly to construct a basic GS fast. Individual GS can be further modeled by editing the contour curves. Thus, we encode contour curves to save GS information and construct a GS library. The user can drag a favorite GS onto a 3D mannequin model and recover it by decoding the contour curves as a prototype for individual surface design. The users can also draw or drag style curves freely on a 3D triangular garment surface to design individual 3D pattern styles. Total or partial style curves encoding/decoding methods are proposed to store the 3D Pattern Style (PS), and to form a library. Customers can also choose a favorite PS and decode them on another garment surface as a prototype for individual pattern design. Through flexible choices from the garment component library, GS library, PS library, and simply dragging or drawing of contour curves and style curves, customers can easily and conveniently participate in 3D garment design for mass personalization.