Comparison of two experimental models of pulmonary hypertension

Objective: To compare two models of pulmonary hypertension (monocrotaline and monocrotaline+pneumonectomy) regarding hemodynamic severity, structure of pulmonary arteries, inflammatory markers (IL-1 and PDGF), and 45-day survival. Methods: We used 80 Sprague-Dawley rats in two study protocols: structural analysis; and survival analysis. The rats were divided into four groups: control; monocrotaline (M), pneumonectomy (P), and monocrotaline+pneumonectomy (M+P). In the structural analysis protocol, 40 rats (10/group) were catheterized for the determination of hemodynamic variables, followed by euthanasia for the removal of heart and lung tissue. The right ventricle (RV) was dissected from the interventricular septum (IS), and the ratio between RV weight and the weight of the left ventricle (LV) plus IS (RV/LV+IS) was taken as the index of RV hypertrophy. In lung tissues, we performed histological analyses, as well as using ELISA to determine IL-1 and PDGF levels. In the survival protocol, 40 animals (10/group) were followed for 45 days. Results: The M and M+P rats developed pulmonary hypertension, whereas the control and P rats did not. The RV/LV+IS ratio was significantly higher in M+P rats than in M rats, as well as being significantly higher in M and M+P rats than in control and P rats. There were no significant differences between the M and M+P rats regarding the area of the medial layer of the pulmonary arteries; IL-1 and PDGF levels; or survival. Conclusions: On the basis of our results, we cannot conclude that the monocrotaline+pneumonectomy model is superior to the monocrotaline model.

Twinlike models for kinks and compactons in flat and warped spacetime

This work deals with the presence of twinlike models in scalar field theories. We show how to build distinct scalar field theories having the same extended solution, with the same energy density and linear stability. Here, however, we start from a given but generalized scalar field theory, and we construct the corresponding twin model, which also engenders generalized dynamics. We investigate how the twinlike models arise in both flat and curved spacetimes. In the curved spacetime, we consider a braneworld model with the warp factor controlling the spacetime geometry with a single extra dimension of infinite extent. In particular, we study linear stability in both flat and curved spacetimes, and in the case of curved spacetime-in both the gravity and the scalar field sectors-for the two braneworld models. DOI: 10.1103/PhysRevD.86.125021

Effective carrying capacity and analytical solution of a particular case of the Richards-like two-species population dynamics model

We consider a generalized two-species population dynamic model and analytically solve it for the amensalism and commensalism ecological interactions. These two-species models can be simplified to a one-species model with a time dependent extrinsic growth factor. With a one-species model with an effective carrying capacity one is able to retrieve the steady state solutions of the previous one-species model. The equivalence obtained between the effective carrying capacity and the extrinsic growth factor is complete only for a particular case, the Gompertz model. Here we unveil important aspects of sigmoid growth curves, which are relevant to growth processes and population dynamics. (C) 2011 Elsevier B.V. All rights reserved.

Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 +/- 1.1, 12.7 +/- 1.8, 8.4 +/- 0.8, and 11.1 +/- 3.3 s) and mechanical threshold in response to von Frey filaments (459 +/- 82.8, 447.5 +/- 91.7, 320.1 +/- 120, 126.43 +/- 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.

High-throughput sequencing of small RNA transcriptomes reveals critical biological features targeted by microRNAs in cell models used for squamous cell cancer research

Abstract Background The implication of post-transcriptional regulation by microRNAs in molecular mechanisms underlying cancer disease is well documented. However, their interference at the cellular level is not fully explored. Functional in vitro studies are fundamental for the comprehension of their role; nevertheless results are highly dependable on the adopted cellular model. Next generation small RNA transcriptomic sequencing data of a tumor cell line and keratinocytes derived from primary culture was generated in order to characterize the microRNA content of these systems, thus helping in their understanding. Both constitute cell models for functional studies of microRNAs in head and neck squamous cell carcinoma (HNSCC), a smoking-related cancer. Known microRNAs were quantified and analyzed in the context of gene regulation. New microRNAs were investigated using similarity and structural search, ab initio classification, and prediction of the location of mature microRNAs within would-be precursor sequences. Results were compared with small RNA transcriptomic sequences from HNSCC samples in order to access the applicability of these cell models for cancer phenotype comprehension and for novel molecule discovery. Results Ten miRNAs represented over 70% of the mature molecules present in each of the cell types. The most expressed molecules were miR-21, miR-24 and miR-205, Accordingly; miR-21 and miR-205 have been previously shown to play a role in epithelial cell biology. Although miR-21 has been implicated in cancer development, and evaluated as a biomarker in HNSCC progression, no significant expression differences were seen between cell types. We demonstrate that differentially expressed mature miRNAs target cell differentiation and apoptosis related biological processes, indicating that they might represent, with acceptable accuracy, the genetic context from which they derive. Most miRNAs identified in the cancer cell line and in keratinocytes were present in tumor samples and cancer-free samples, respectively, with miR-21, miR-24 and miR-205 still among the most prevalent molecules at all instances. Thirteen miRNA-like structures, containing reads identified by the deep sequencing, were predicted from putative miRNA precursor sequences. Strong evidences suggest that one of them could be a new miRNA. This molecule was mostly expressed in the tumor cell line and HNSCC samples indicating a possible biological function in cancer. Conclusions Critical biological features of cells must be fully understood before they can be chosen as models for functional studies. Expression levels of miRNAs relate to cell type and tissue context. This study provides insights on miRNA content of two cell models used for cancer research. Pathways commonly deregulated in HNSCC might be targeted by most expressed and also by differentially expressed miRNAs. Results indicate that the use of cell models for cancer research demands careful assessment of underlying molecular characteristics for proper data interpretation. Additionally, one new miRNA-like molecule with a potential role in cancer was identified in the cell lines and clinical samples.

Argon and Nd:YAG Lasers for Caries Prevention in Enamel

Objective: The aim of this study was to investigate the effect of Nd:YAG and argon laser irradiations on enamel demineralization after two different models to induce artificial caries. Background data: It is believed that the use of the high-intensity laser on the dental structure can lead to a more acid-resistant surface. Materials and methods: Twenty-one extracted human third molars were sectioned into tooth quarters. The quarters were distributed in three groups: Group I (control), untreated; Group II, Nd:YAG laser (60 mJ, 15 pps, 47.77 J/cm(2), 30 sec); and Group III, argon laser (250mW, 12 J/cm(2), 48 sec). Tooth quarters from each group were subjected to two different demineralization models: cycle 1, a 14 day demineralization (pH 4.5; 6 h) and remineralization (pH 7.0; 18 h) solutions, 37 degrees C and cycle 2, 48 h in demineralization solution (pH 4.5). Samples were prepared in slices (60-100 mu m thick) to be evaluated under polarized light microscopy. Demineralization areas were measured (mm(2)) (n = 11). Data were analyzed by ANOVA and Tukey's test (p < 0.05). Results: Means followed by different letters are significantly different: 0.25 A (control, cycle 48 h); 0.18 AB (control, cycle 14 days); 0.17 AB (Nd:YAG, cycle 14 days); 0.14 BC (argon, cycle 48 h); 0.09 BC (Nd:YAG, cycle 48 h), and 0.06 C (argon, cycle 14 days). Conclusions: The argon laser was more effective for caries preventive treatment than Nd: YAG laser, showing a smaller demineralization area in enamel.

Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development

Congenital heart disease (CHD) occurs in similar to 1% of newborns. CHD arises from many distinct etiologies, ranging from genetic or genomic variation to exposure to teratogens, which elicit diverse cell and molecular responses during cardiac development. To systematically explore the relationships between CHD risk factors and responses, we compiled and integrated comprehensive datasets from studies of CHD in humans and model organisms. We examined two alternative models of potential functional relationships between genes in these datasets: direct convergence, in which CHD risk factors significantly and directly impact the same genes and molecules and functional convergence, in which risk factors significantly impact different molecules that participate in a discrete heart development network. We observed no evidence for direct convergence. In contrast, we show that CHD risk factors functionally converge in protein networks driving the development of specific anatomical structures (e.g., outflow tract, ventricular septum, and atrial septum) that are malformed by CHD. This integrative analysis of CHD risk factors and responses suggests a complex pattern of functional interactions between genomic variation and environmental exposures that modulate critical biological systems during heart development.

Modelling shared attention through relational reinforcement learning

Shared attention is a type of communication very important among human beings. It is sometimes reserved for the more complex form of communication being constituted by a sequence of four steps: mutual gaze, gaze following, imperative pointing and declarative pointing. Some approaches have been proposed in Human-Robot Interaction area to solve part of shared attention process, that is, the most of works proposed try to solve the first two steps. Models based on temporal difference, neural networks, probabilistic and reinforcement learning are methods used in several works. In this article, we are presenting a robotic architecture that provides a robot or agent, the capacity of learning mutual gaze, gaze following and declarative pointing using a robotic head interacting with a caregiver. Three learning methods have been incorporated to this architecture and a comparison of their performance has been done to find the most adequate to be used in real experiment. The learning capabilities of this architecture have been analyzed by observing the robot interacting with the human in a controlled environment. The experimental results show that the robotic head is able to produce appropriate behavior and to learn from sociable interaction.

Protein quality control disruption by PKC beta II in heart failure: rescue by the selective PKC beta II inhibitor, beta IIV5-3

Myocardial remodeling and heart failure (HF) are common sequelae of many forms of cardiovascular disease and a leading cause of mortality worldwide. Accumulation of damaged cardiac proteins in heart failure has been described. However, how protein quality control (PQC) is regulated and its contribution to HF development are not known. Here, we describe a novel role for activated protein kinase C isoform beta II (PKC beta II) in disrupting PQC. We show that active PKC beta II directly phosphorylated the proteasome and inhibited proteasomal activity in vitro and in cultured neonatal cardiomyocytes. Importantly, inhibition of PKC beta II, using a selective PKC beta II peptide inhibitor (beta IIV5-3), improved proteasomal activity and conferred protection in cultured neonatal cardiomyocytes. We also show that sustained inhibition of PKC beta II increased proteasomal activity, decreased accumulation of damaged and misfolded proteins and increased animal survival in two rat models of HF. Interestingly, beta IIV5-3-mediated protection was blunted by sustained proteasomal inhibition in HF. Finally, increased cardiac PKC beta II activity and accumulation of misfolded proteins associated with decreased proteasomal function were found also in remodeled and failing human hearts, indicating a potential clinical relevance of our findings. Together, our data highlights PKC beta II as a novel inhibitor of proteasomal function. PQC disruption by increased PKC beta II activity in vivo appears to contribute to the pathophysiology of heart failure, suggesting that PKC beta II inhibition may benefit patients with heart failure. (218 words)

Agricultural commodities pricing model applied to the Brazilian sugar market

This article suggests a pricing model for commodities used to produce biofuel. The model is based on the concept that the deterministic component of the Wiener process is not constant and depends on time and exogenous variables. The model, which incorporates theory of storage, the convenience yield and the seasonality of harvests, was applied in the Brazilian sugar market. After predictions were made with the Kalman filter, the model produced results that were statistically more accurate than those returned by the two-factor model available in the literature.

A possible role to nitric oxide in the anti-inflammatory effects of amitriptyline

Antidepressants are reported to display anti-inflammatory effects. Nitric oxide (NO), in turn, has a key role in inflammation. The objective of the present study was to evaluate the effect of amitriptyline co-administered with L-NAME (a NO synthase inhibitor) on certain parameters of acute inflammatory response in rats, as a form to investigate a possible participation of NO in the anti-inflammatory effects of amitriptyline. For this, two animal models were used: carrageenan-induced paw edema and acute peritonitis. In the last one, peritoneal exudate, adhesion molecules expression by peripheral blood leukocytes and serum cytokines levels were evaluated. In a noninflammatory condition, serum levels of nitrates were determined. L-NAME induced a potentiation of the anti-inflammatory effects of amitriptyline (p < 0.05) in the paw edema model; however, these effects were not abrogated when L-NAME was substituted by L-arginine administration. A decrease in both leukocyte concentration and total number of cells in the peritoneal exudate and a reduction in the total serum levels of nitrates were observed with co-administration of L-NAME and amitriptyline (p < 0.05). No significant differences among groups were found concerning the expression of adhesion molecules by peripheral blood leukocytes (p > 0.05). There was a significant decrease on IL-1 beta and TNF-alpha serum levels in the experimental groups when compared to the control animals. Together the present results and the literature suggest that the anti-inflammatory effects of amitriptyline may be due to a decrease in NO production. A decrease in IL-1 beta/TNF-alpha serum levels may also be implicated in the results observed.

Psychometric properties of the Spanish version of the mindful attention awareness scale (MAAS) in patients with fibromyalgia

Background Mindful-based interventions improve functioning and quality of life in fibromyalgia (FM) patients. The aim of the study is to perform a psychometric analysis of the Spanish version of the Mindful Attention Awareness Scale (MAAS) in a sample of patients diagnosed with FM. Methods The following measures were administered to 251 Spanish patients with FM: the Spanish version of MAAS, the Chronic Pain Acceptance Questionnaire, the Pain Catastrophising Scale, the Injustice Experience Questionnaire, the Psychological Inflexibility in Pain Scale, the Fibromyalgia Impact Questionnaire and the Euroqol. Factorial structure was analysed using Confirmatory Factor Analyses (CFA). Cronbach's α coefficient was calculated to examine internal consistency, and the intraclass correlation coefficient (ICC) was calculated to assess the test-retest reliability of the measures. Pearson’s correlation tests were run to evaluate univariate relationships between scores on the MAAS and criterion variables. Results The MAAS scores in our sample were low (M = 56.7; SD = 17.5). CFA confirmed a two-factor structure, with the following fit indices [sbX2 = 172.34 (p < 0.001), CFI = 0.95, GFI = 0.90, SRMR = 0.05, RMSEA = 0.06. MAAS was found to have high internal consistency (Cronbach’s α = 0.90) and adequate test-retest reliability at a 1–2 week interval (ICC = 0.90). It showed significant and expected correlations with the criterion measures with the exception of the Euroqol (Pearson = 0.15). Conclusion Psychometric properties of the Spanish version of the MAAS in patients with FM are adequate. The dimensionality of the MAAS found in this sample and directions for future research are discussed.

Shear force and torsion in reinforced concrete beam elements: theoretical analysis based on Brazilian Standard Code ABNT NBR 6118:2007

Reinforced concrete beam elements are submitted to applicable loads along their life cycle that cause shear and torsion. These elements may be subject to only shear, pure torsion or both, torsion and shear combined. The Brazilian Standard Code ABNT NBR 6118:2007 [1] fixes conditions to calculate the transverse reinforcement area in beam reinforced concrete elements, using two design models, based on the strut and tie analogy model, first studied by Mörsch [2]. The strut angle θ (theta) can be considered constant and equal to 45º (Model I), or varying between 30º and 45º (Model II). In the case of transversal ties (stirrups), the variation of angle α (alpha) is between 45º and 90º. When the equilibrium torsion is required, a resistant model based on space truss with hollow section is considered. The space truss admits an inclination angle θ between 30º and 45º, in accordance with beam elements subjected to shear. This paper presents a theoretical study of models I and II for combined shear and torsion, in which ranges the geometry and intensity of action in reinforced concrete beams, aimed to verify the consumption of transverse reinforcement in accordance with the calculation model adopted As the strut angle on model II ranges from 30º to 45º, transverse reinforcement area (Asw) decreases, and total reinforcement area, which includes longitudinal torsion reinforcement (Asℓ), increases. It appears that, when considering model II with strut angle above 40º, under shear only, transverse reinforcement area increases 22% compared to values obtained using model I.