Complex, 3D strain patterns in a synkinematic tonalite batholith from the Aracuai Neoproterozoic orogen (Eastern Brazil): Evidence from combined magnetic and isotopic chronology studies

This work combines structural and geochronological data to improve our understanding of the mechanical behaviour of continental crust involving large amount of magma or partially melted material in an abnormally hot collisional belt. We performed a magnetic and geochronological (U/Pb) study on a huge tonalitic batholith from the Neoproterozoic Aracual belt of East Brazil to determine the strain distribution through space and time. Anisotropy of magnetic susceptibility, combined with rock magnetism investigations, supports that the magnetic fabric is a good proxy of the structural fabric. Field measurements together with the magnetic fabrics highlight the presence in the batholith of four domains characterized by contrasted magmatic flow patterns. The western part is characterized by a gently dipping, orogen-parallel (similar to NS) magmatic foliation that bears down-dip lineations, in agreement with westward thrusting onto the Sao Francisco craton. Eastward, the magmatic foliation progressively turns sub-vertical with a lineation that flips from sub-horizontal to sub-vertical over short distances. This latter domain involves an elongated corridor in which the magmatic foliation is sub-horizontal and bears an orogen-parallel lineation. Finally the fourth, narrow domain displays sub-horizontal lineations on a sub-vertical magmatic foliation oblique (similar to N150 degrees E) to the trend of the belt. U/Pb dating of zircons from the various domains revealed homogeneity in age for all samples. This, together with the lack of solid-state deformation suggests that: 1) the whole batholith emplaced during a magmatic event at similar to 580 Ma, 2) the deformation occurred before complete solidification. and 3) the various fabrics are roughly contemporaneous. The complex structural pattern mapped in the studied tonalitic batholith suggests a 3D deformation of a slowly cooling, large magmatic body and its country rock. We suggest that the development of the observed 3D flow field was promoted by the low viscosity of the middle crust that turned gravitational force as an active tectonic force combining with the East-West convergence between the Sao Francisco and Congo cratons. (C) 2012 Elsevier Ltd. All rights reserved.

Effects of a combined strengthening, stretching and functional training program versus usual-care on gait biomechanics and foot function for diabetic neuropathy: a randomized controlled trial

Background: Polyneuropathy is a complication of diabetes mellitus that has been very challenging for clinicians. It results in high public health costs and has a huge impact on patients' quality of life. Preventive interventions are still the most important approach to avoid plantar ulceration and amputation, which is the most devastating endpoint of the disease. Some therapeutic interventions improve gait quality, confidence, and quality of life; however, there is no evidence yet of an effective physical therapy treatment for recovering musculoskeletal function and foot rollover during gait that could potentially redistribute plantar pressure and reduce the risk of ulcer formation. Methods/Design: A randomised, controlled trial, with blind assessment, was designed to study the effect of a physiotherapy intervention on foot rollover during gait, range of motion, muscle strength and function of the foot and ankle, and balance confidence. The main outcome is plantar pressure during foot rollover, and the secondary outcomes are kinetic and kinematic parameters of gait, neuropathy signs and symptoms, foot and ankle range of motion and function, muscle strength, and balance confidence. The intervention is carried out for 12 weeks, twice a week, for 40-60 min each session. The follow-up period is 24 weeks from the baseline condition. Discussion: Herein, we present a more comprehensive and specific physiotherapy approach for foot and ankle function, by choosing simple tasks, focusing on recovering range of motion, strength, and functionality of the joints most impaired by diabetic polyneuropathy. In addition, this intervention aims to transfer these peripheral gains to the functional and more complex task of foot rollover during gait, in order to reduce risk of ulceration. If it shows any benefit, this protocol can be used in clinical practice and can be indicated as complementary treatment for this disease.

Broad combined orange-red emissions from Eu2+- and Eu3+-doped low-silica calcium aluminosilicate glass

In this paper, a broad combined orange-red emission from Eu2+- and Eu3+-doped low-silica calcium aluminosilicate (LSCAS) glass is reported. Spectroscopic results demonstrate that it is possible to tune the emission wavelength by changing the excitation wavelength in the UV-Vis region. The color coordinates for the emission spectra were calculated, and using the Commission Internationale de l'Eclairage 1931 and 1976 chromatic diagrams, it is possible to note that they are dependent on the excitation wavelength. In addition, the (u', v') color coordinates for the investigated LSCAS samples are close to the Planckian spectrum in the cold region between 2000 and 2600K. Our results show that the Eu:LSCAS system can be used in a white light phosphor when mixed in aggregate with phosphors using green-yellow luminescent ions. (c) 2012 Optical Society of America

Acrodermatitis due to zinc deficiency after combined vertical gastroplasty with jejunoileal bypass: case report

CONTEXT: Nutritional complications may occur after bariatric surgery, due to restriction of food intake and impaired digestion or absorption of nutrients. CASE REPORT: After undergoing vertical gastroplasty and jejunoileal bypass, a female patient presented marked weight loss and protein deficiency. Seven months after the bariatric surgery, she presented dermatological features compatible with acrodermatitis enteropathica, as seen from the plasma zinc levels, which were below the reference values (34.4 mg%). The skin lesions improved significantly after 1,000 mg/day of zinc sulfate supplementation for one week. CONCLUSIONS: The patient's evolution shows that the multidisciplinary team involved in surgical treatment of obesity should take nutritional deficiencies into consideration in the differential diagnosis of skin diseases, in order to institute early treatment.

Three-dimensional solitons in cross-combined linear and nonlinear optical lattices

The existence and stability of three-dimensional (3D) solitons, in cross-combined linear and nonlinear optical lattices, are investigated. In particular, with a starting optical lattice (OL) configuration such that it is linear in the x-direction and nonlinear in the y-direction, we consider the z-direction either unconstrained (quasi-2D OL case) or with another linear OL (full 3D case). We perform this study both analytically and numerically: analytically by a variational approach based on a Gaussian ansatz for the soliton wavefunction and numerically by relaxation methods and direct integrations of the corresponding Gross-Pitaevskii equation. We conclude that, while 3D solitons in the quasi-2D OL case are always unstable, the addition of another linear OL in the z-direction allows us to stabilize 3D solitons both for attractive and repulsive mean interactions. From our results, we suggest the possible use of spatial modulations of the nonlinearity in one of the directions as a tool for the management of stable 3D solitons.

Leucine supplementation combined with resistance exercise improves the plasma lipid profile of dexamethasone-treated rats

The impact of leucine supplementation and resistance exercise (RE) on plasma lipid profile was evaluated in adult rats treated with dexamethasone, an experimental model of dyslipidemia. Total cholesterol did not differ among groups. Furthermore, leucine supplementation did not promote improvement in the plasma total cholesterol and LDL-c of the animals. However, plasma TG and VLDL-c were significantly decreased and HDL-c increased after 7 days of leucine supplementation combined with RE. In conclusion, leucine supplementation combined with RE, but not isolated, improved the plasma lipid profile of dexamethasone-induced dyslipidemic rats.

Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX plus Tumor Necrosis Factor Inhibitor Combined Therapy

Objective. We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-alpha (anti-TNF) combined therapy. Methods. We evaluated 25 patients with RA taking MTX 15-20 mg/week as a monotherapy (8 responders and 17 nonresponders). All MTX nonresponders received intliximab and were reassessed after 20 weeks to evaluate their anti-TNF responsiveness using the European League Against Rheumatism response criteria. A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program. Results. Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti-TNF responders from nonresponders. The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders. In MTX plus anti-TNF nonresponders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders. Conclusion. Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1 CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti-TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study. (First Release July 1 2012; J Rheumatol 2012;39:1524-32; doi:10.3899/jrheum.120092)

In vitro evaluation of combined hyperthermia and photodynamic effects using magnetoliposomes loaded with cucurbit[7]uril zinc phthalocyanine complex on melanoma

The aims of this study were two fold; to develop magnetoliposomes (MLs) loaded with zinc phthalocyanine (ZnPc) complexed with cucurbituril (CB) (CB:ZnPc-MLs) and to evaluate their in vitro photodynamic (PD) and/or hyperthermia (HT) effects while using melanoma cells (B16-F10) as model. The liposomal formulations were characterized by both average diameter and zeta potential. The vesicle average size ranged from 150 to 200 nm and the polydispersity index (PdI) from 0.093 to 0.230. The zeta potential was significantly positive with values between 48 and 57 mV. The cell viability (CV) after PD and HT treatments was assessed by colorimetric MTI method. Melanoma cells were initially treated with the liposome formulation without light and magnetic field application, revealing cell viability not different from the control cells (p > 0.05). Photodynamic and hyperthermia assays were also applied separately, demonstrating that PD is more effective than HT in reducing the CV of the neoplastic cells. Combined application of both PD and HT treatments was even more effective in reducing the CV of B16-F10 cells. At the highest light dose (2 J/cm(2)) and under magnetic field activation the CV was about half than PD applied alone. Therefore, the use of the photosensitizer-loaded magnetoliposome for combined photodynamic therapy (PDT) and magnetohyperthermia (MHT) application can be considered as a potential tool to treat malignant melanoma. (C) 2012 Elsevier B.V. All rights reserved.

Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

Abuse of cocaine and androgenic-anabolic steroids has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous illicit use of these substances, potential toxic interactions between cocaine and androgenic-anabolic steroids in the cardiovascular system are unknown. In the present study, we investigated the effect of single or combined administration of testosterone and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreflex activity, and hemodynamic responses to vasoactive agents in unanesthetized rats. Ten-day combined administration of testosterone and cocaine increased baseline arterial pressure. Changes in arterial pressure were associated with altered baroreflex activity and impairment of both hypotensive response to intravenous sodium nitroprusside and pressor effect of intravenous phenylephrine. Chronic single administration of either testosterone or cocaine did not affect baseline arterial pressure. However, testosterone-treated animals presented rest bradycardia, cardiac hypertrophy, alterations in baroreflex activity, and enhanced response to sodium nitroprusside. Repeated administration of cocaine affected baroreflex activity and impaired vascular responsiveness to both sodium nitroprusside and phenylephrine. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present results suggest a potential interaction between toxic effects of cocaine and testosterone on the cardiovascular activity. Changes in baseline arterial pressure after combined administration of these 2 drugs may result from alterations in baroreflex activity and impairment of vascular responsiveness to vasoactive agents.

Antioxidant defenses and biochemical changes in the neotropical fish pacu, Piaractus mesopotamicus: Responses to single and combined copper and hypercarbia exposure

This study investigated the potentially detrimental effects of copper and elevated aquatic CO2 (hypercarbia), alone or in combination, on pacu, Piaractus mesopotamicus. Fish were exposed for 48 h to control (no copper addition in normocarbia), to 400 mu g Cu2+L-1, to hypercarbic (1% CO2; PCO2=6.9 mm Hg) water and to 400 mu g Cu2+L-1+ hypercarbia. In liver the single factors caused an increase in lipid hydroperoxide concentration that was not observed when the factors were combined. Copper exposure elicited increased hepatic superoxide dismutase activity, irrespective of aquatic CO2 level. On the other hand, the effects of copper on hepatic glutathione peroxidase activity were dependent on water CO2 levels. The two stressors combined did not affect hepatic catalase activity. Hypercarbic water caused a decline in plasma glucose concentration, but this was not observed when hypercarbia was combined with copper exposure. Copper caused a decrease in branchial Na+/K+-ATPase activity that was independent of water CO2 level. Copper caused an increase in branchial metallothionein concentration that was independent of water CO2 level. Thus, branchial metallothionein and Na+/K+-ATPase were effective biomarkers of copper exposure that were not affected by water CO2 level. (C) 2012 Elsevier Inc. All rights reserved.

Post-breakup tectonics in southeast Brazil from thermochronological data and combined inverse-forward thermal history modeling

The continental margin of southeast Brazil is elevated. Onshore Tertiary basins and Late Cretaceous/Paleogene intrusions are good evidence for post breakup tectono-magmatic activity. To constrain the impact of post-rift reactivation on the geological history of the area, we carried out a new thermochronological study. Apatite fission track ages range from 60.7 +/- 1.9 Ma to 129.3 +/- 4.3 Ma, mean track lengths from 11.41 +/- 0.23 mu m to 14.31 +/- 0.24 mu m and a subset of the (U-Th)/He ages range from 45.1 +/- 1.5 to 122.4 +/- 2.5 Ma. Results of inverse thermal history modeling generally support the conclusions from an earlier study for a Late Cretaceous phase of cooling. Around the onshore Taubate Basin, for a limited number of samples, the first detectable period of cooling occurred during the Early Tertiary. The inferred thermal histories for many samples also imply subsequent reheating followed by Neogene cooling. Given the uncertainty of the inversion results, we did deterministic forward modeling to assess the range of possibilities of this Tertiary part of the thermal history. The evidence for reheating seems to be robust around the Taubate Basin, but elsewhere the data cannot discriminate between this and a less complex thermal history. However, forward modeling results and geological information support the conclusion that the whole area underwent cooling during the Neogene. The synchronicity of the cooling phases with Andean tectonics and those in NE Brazil leads us to assume a plate-wide compressional stress that reactivated inherited structures. The present-day topographic relief of the margin reflects a contribution from post-breakup reactivation and uplift.

Combined oral contraceptives and increasing cardiovascular risk: thromboembolism and hypertension

Background: Hormonal contraceptive pills are the most used reversible method for familiar planning in Brazil. The combined pill, with synthetic analogs of estrogen and progestin, is employed by 25% of Brazilian female population. Its use provokes an increase of blood pressure levels, takes patient to a hipercoagulability state and predisposes her to thromboembolic events. Purposes: We aimed to describe mechanisms of hypercoagulability promoted by oral combined contraceptives, to analyze the relative risk of cardiovascular events within users and to list the most common circulatory pathologies in these patients. Methods: Three virtual medical databases were surveyed (Pubmed/Medline, BVS/LILACS and Scielo). Twelve studies were selected: clinical trials, case reports and articles of indexed medical periodic originally published in Portuguese and English about synthetic hormones, oral contraception, coagulation disorders and cardiovascular morbimortality. Results: Synthetic estrogen promotes an increase of some clotting factors' levels (VII, VIII, IX, X, XII, XIII and fibrinogen), such as a reduction of their inhibitors (S protein and antithrombin). Because of this, etinilestradiol is the component most related to venous thrombosis and ischemic diseases of brain and heart. It also improves the releasing of hepatic angiotensinogen, taking to a increase of blood pressure levels. Conclusions: The prescription of oral combined contraceptives needs criteria, notably due to adverse effects of etinilestradiol. It is recommended to avoid the administration of these drugs for patients elder than 35 year-old or with risk factors. For these patients, the use of progestagen-only pills seems to be safer.

Gene Expression Profile in Response to Doxorubicin-Rapamycin Combined Treatment of HER-2-Overexpressing Human Mammary Epithelial Cell Lines

HER-2-positive breast cancers frequently sustain elevated AKT/mTOR signaling, which has been associated with resistance to doxorubicin treatment. Here, we investigated whether rapamycin, an mTOR inhibitor, increased the sensitivity to doxorubicin therapy in two HER-2-overexpressing cell lines: C5.2, which was derived from the parental HB4a by transfection with HER-2 and SKBR3, which exhibits HER-2 amplification. The epithelial mammary cell line HB4a was also analyzed. The combined treatment using 20 nmol/L of rapamycin and 30 nmol/L of doxorubicin arrested HB4a and C5.2 cells in S to G(2)-M, whereas SKBR3 cells showed an increase in the G(0)-G(1) phase. Rapamycin increased the sensitivity to doxorubicin in HER-2-overexpressing cells by approximately 2-fold, suggesting that the combination displayed a more effective antiproliferative action. Gene expression profiling showed that these results might reflect alterations in genes involved in canonical pathways related to purine metabolism, oxidative phosphorylation, protein ubiquitination, and mitochondrial dysfunction. A set of 122 genes modulated by the combined treatment and specifically related to HER-2 overexpression was determined by finding genes commonly regulated in both C5.2 and SKBR3 that were not affected in HB4a cells. Network analysis of this particular set showed a smaller subgroup of genes in which coexpression pattern in HB4a cells was disrupted in C5.2 and SKBR3. Altogether, our data showed a subset of genes that might be more robust than individual markers in predicting the response of HER-2-overexpressing breast cancers to doxorubicin and rapamycin combination. Mol Cancer Ther; 11(2); 464-74. (C) 2011 AACR.

A Combined Study Using Ligand-Based Design, Synthesis, and Pharmacological Evaluation of Analogues of the Acetaminophen Ortho-Regioisomer with Potent Analgesic Activity

A ligand-based drug design study was performed to acetaminophen regioisomers as analgesic candidates employing quantum chemical calculations at the DFT/B3LYP level of theory and the 6-31G* basis set. To do so, many molecular descriptors were used such as highest occupied molecular orbital, ionization potential, HO bond dissociation energies, and spin densities, which might be related to quench reactivity of the tyrosyl radical to give N-acetyl-p-benzosemiquinone-imine through an initial electron withdrawing or hydrogen atom abstraction. Based on this in silico work, the most promising molecule, orthobenzamol, was synthesized and tested. The results expected from the theoretical prediction were confirmed in vivo using mouse models of nociception such as writhing, paw licking, and hot plate tests. All biological results suggested an antinociceptive activity mediated by opioid receptors. Furthermore, at 90 and 120 min, this new compound had an effect that was comparable to morphine, the standard drug for this test. Finally, the pharmacophore model is discussed according to the electronic properties derived from quantum chemistry calculations.

Quantification of Short and Medium Range Order in Mixed Network Former Glasses of the System GeO2-NaPO3: A Combined NMR and X-ray Photoelectron Spectroscopy Study

Glasses in the system xGeO(2)-(1-x)NaPO3 (0 <= x <= 0.50) were prepared by conventional melting quenching and characterized by thermal analysis, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and P-31 nuclear magnetic resonance (MAS NMR) techniques. The deconvolution of the latter spectra was aided by homonuclear J-resolved and refocused INADEQUATE techniques. The combined analyses of P-31 MAS NMR and O-1s XPS lineshapes, taking charge and mass balance considerations into account, yield the detailed quantitative speciations of the phosphorus, germanium, and oxygen atoms and their respective connectivities. An internally consistent description is possible without invoking the formation of higher-coordinated germanium species in these glasses, in agreement with experimental evidence in the literature. The structure can be regarded, to a first approximation, as a network consisting of P-(2) and P-(3) tetrahedra linked via four-coordinate germanium. As implied by the appearance of P-(3) units, there is a moderate extent of network modifier sharing between phosphate and germanate network formers, as expressed by the formal melt reaction P-(2) + Ge-(4) -> P-(3) + Ge-(3). The equilibrium constant of this reaction is estimated as K = 0.52 +/- 0.11, indicating a preferential attraction of network modifier by the phosphorus component. These conclusions are qualitatively supported by Raman spectroscopy as well as P-31{Na-23} and P-31{Na-23} rotational echo double resonance (REDOR) NMR results. The combined interpretation of O-1s XPS and P-31 MAS NMR spectra shows further that there are clear deviations from a random connectivity scenario: heteroatomic P-O-Ge linkages are favored over homoatomic P-O-P and Ge-O-Ge linkages.