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Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.
The increase of sheep meat competitiveness in international markets can be attributed to the rise of the quantity and the improvement of the quality of the edible portion of sheep carcasses. Usually, carcass yield is established after the slaughter of the animals. Yet, when carcass yield is determined in vivo, it can be both a costly and subjective method. This study proposes models for predicting the physical characteristics of lamb carcass using bioimpedance analysis (BIA) in live animals. Thirty-one Texel × Ile de France crossbreed ram lambs were slaughtered at 20, 26, 32 or 38 kg of BW. Before the slaughter, values of resistance (Rs) and reactance (Xc) were collected using a single-frequency BIA equipment (Model RJL Quantum II Bioelectrical Body Composition Analyzer). Then, BIA main variables such as body bioelectrical volume (V), phase angle (PA), resistive density (RsD) and reactive density (XcD) were calculated. After slaughter, cold carcass weight (CCW), cold carcass yield (CCY), subcutaneous fat thickness (SFT), soft tissue weight (STW) and soft tissue yield (STY) were also measured. Multiple regression analyses were carried out using the physical characteristics as dependent variables and the bioimpedance values as independent variables. Predictive performance of the models was assessed using leave-one-out cross-validation. The prediction model of CCW was obtained using the V, PA and RsD (R2 = 0.97), STW through the V, RsD and XcD (R2 = 0.97), CCY by Rs, Z and XcD (R2 = 0.69), STY by V and XcD (R2 = 0.67), and SFT only for XcD (R2 = 0.84). The results indicated that BIA has the potential to predict carcass characteristics of lambs at different body masses.
The use of forage legumes has been proposed as a means of generating sustainable grazing environments. Their limited use, particularly in tropical pastures, is partially due to the limited knowledge regarding the efficiency of utilization by animals. The present study characterized the sward structure, nutritive value and ingestive behaviour of dairy heifers in pastures of peanut cv. Belmonte under continuous stocking management. Treatments corresponded to sward heights of 5, 10, 15 and 20 cm, according to a randomized complete block design, with four replications. The following response variables were evaluated: vertical distribution of the morphological components within the sward, forage mass, nutritive value (simulated grazing), bite rate (BR), bite mass (BM) and short-term herbage intake rate (STIR). The top half of the sward height was mainly composed of leaves and the bottom half mainly of stolon and dead material regardless of management height. Greater values of neutral detergent fibre and acid detergent fibre were recorded during autumn, while higher values of in-vitro dry matter (DM) digestibility (0·85) occurred during spring regardless of management height for the grazed stratum. In relation to treatments, greater values of crude protein were recorded on swards managed at 5 cm (0·27) and 10 cm (0·26). Bite rate, BM and STIR varied with sward height, but not with a season of the year. The STIR followed a broken line response to sward height, with increasing values up to 13·1 cm (106 g DM/kg body weight). Sward structure played an important role in determining the STIR. To maximize the STIR of dairy heifers under continuous stocking management, swards should be managed at heights of not <13·1 cm.
Cepheids are excellent stellar tracers: they are bright enough to be observed even at large distances; their distances can be accurately determined via period-luminosity relations; their spectra contain numerous lines that enable us to derive abundances for many α, iron-peak or neutron-capture elements. Classical Cepheids are yellow supergiants that trace the young populations (⩽ 300 Myr); Type II Cepheids are post Horizontal Branch, low-mass, Population II stars (⩾ 10 Gyr). Both can be used for many purposes in Milky Way archaeology.
Several studies have shown that maternal low-protein (LP) diet induces detrimental effects in cardiovascular system and oxidative stress in male animals. Additional studies suggested that female has lower incidence of cardiovascular disease. However until present data, the possible effects of estradiol on the undernutrition during gestational and lactation periods are not discussed. The present study was conducted to evaluate the effects of a maternal LP diet during gestational and lactation period on oxidative balance in the female rat hearts ventricles at two ages. Dams were fed with normal protein (NP) or a LP diet during the gestational and lactation period, and their female offspring were divided into age groups (22 or 122 days, corresponding to a low or high estrogen level) composing four experimental groups. Evaluating the nutritional effect showed an increase in oxidative stress biomarkers and decrease in enzymatic defense in LP-22D compared with NP-22D. In contrast, no changes were observed in malondialdehyde and carbonyls, but an increase in glutathione-S-transferase (GST) activity in the LP-122D compared with NP-122D. The global oxy-score in the LP-22D group indicated a predominance of oxidative damage when compared with NP-22D, while in LP-122D group the global oxy-score was restored to NP-122D levels. Evaluating the estradiol effect, our data show a significant decrease in oxidative stress with increase in CAT and GST activity, associated with increase in intracellular thiols. Our data suggest that in situation with low levels of estradiol, hypoproteic diet during gestation and lactation period has detrimental effects on heart, however when estradiol levels raise, the detrimental effects induced are mitigated.
In this paper we formulate answers to three important questions related to Givetian carbonate records and their use for reconstructing million-year-scale past palaeoenvironmental changes. First, we provide detailed illustrations of the fascinating diversity that shaped a significant shallow reefal platform during early to late Givetian time in the Rhenohercynian Ocean; secondly we improve the sedimentological model of the extensive Givetian carbonate platform in the Dinant Basin; and thirdly we evaluate the application of magnetic susceptibility as a tool for long-term trend correlations and palaeoenvironmental reconstructions. These goals are reached by making a sedimentological, geophysical and geochemical study of the La Thure section. Through the early–late Givetian interval we discerned 18 microfacies ranging from a homoclinal ramp to a discontinuously rimmed shelf and then a drowning shelf. The comparison of these sedimentological results with those published for the south of the Dinant Syncline allowed us to provide an up to date model of the vertical and lateral environmental development of one of the largest Givetian carbonate platforms in Europe. This comparison also increased the knowledge on the distribution of facies belts in the Dinant Basin and allowed us to highlight the Taghanic Event. Palaeoredox proxies reveal a substantial change in the oxygenation level, from oxygen-depleted to more oxic conditions, between middle and late Givetian time. We demonstrated the relationship between variation in magnetic susceptibility values and proxies for siliciclastic input (such as Si, Al). The La Thure section is considered a key section for the understanding of internal shelf settings bordering Laurussia's southeastern margin.
We analyse the behavior of the projected rotational velocity vsin i for a sample of 20 lithium-rich evolved stars. Most of these stars show normal rotational velocity with respect to the typical lithium-normal evolved stars of the same spectral type. Stars presenting enhanced rotation show also high activity level. No sign of binarity was found for these lithium-rich evolved stars.
This paper studies the performance of (U, Pu)C fuel in a hexagonal assembly of a GFR (Gas Fast Reactor). The SCALE 6.0 (Standardized Computer Analysis for Licensing Evaluation version 6.0) code was used in the calculation. The goal is to evaluate the behavior of the infinite multiplication factor (kinf) for a heterogeneous assembly model using four nuclear data libraries: V6-238, V7-238, ENDF/B-VI.8 and ENDF/B-VII.0. The burnup of (U, Pu)C was performed by the TRITON-6 module, and the isotopic concentrations were evaluated during the cycle. The present work comprises calculations at Zero Power and Full Power condition. This study intends to achieve more information about different Fast Reactors.
Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL−1 concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0·05 mg mL−1. The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.
Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.
The aim of this study was analyzed if the flour or flaxseed oil treatment contributes to body composition in male rats subjected to early weaning. Pups were weaned for separation from mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, part of the pups was evaluated (C21 v. EW21). After 21 days, control (C60) was fed with control diet. EW was divided in control (EWC60); flaxseed flour (EWFF60); flaxseed oil (EWFO60) diets until 60 days. Body mass, length and body composition by dual-energy X-ray absorptiometry were determined. EW21 (v. C21) and EWC60 (v. C60 and EWFF60) showed lower (P<0.05) mass, length and body composition. EWFO60 (v. C60 and EWFF60) showed lower (P<0.05) body mass and length, body and trunk lean mass, bone mineral density and content and bone area. Flaxseed flour, in comparison with flaxseed oil, contributes to recovery of body composition after early weaning.
The precocious interruption of lactation is a prime factor for developmental plasticity. Here we analyzed whether flour or flaxseed oil treatment contributes to body and brain mass in male rats subjected to early weaning. Pups were weaned for separation from their mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, some of the pups were evaluated (C21 v. EW21). After 21 days, control pups (C60) were fed a control diet. EW pups were divided into those fed a control diet (EWC60), those given flaxseed flour (EWFF60), and those given flaxseed oil (EWFO60) until 60 days. EW21 showed lower body and absolute brain mass and higher relative brain mass. At 60 days, EWC60 and EWFO60 had lower body mass. With regard to relative brain mass, EWC60 was heavier; EWFO60 had lower values compared with EWC60 and higher values compared with C60 and EWFF60. These results indicated that flaxseed flour, in comparison with flaxseed oil, contributes to brain development after EW.
Course and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment.
A 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence.
Retention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms [odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54–25.45, p < 0.001], number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04–1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20–8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12–11.47, p = 0.03).
Despite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults.
We describe the preliminary design of a magnetograph and visible-light imager instrument to study the solar dynamo processes through observations of the solar surface magnetic field distribution. The instrument will provide measurements of the vector magnetic field and of the line-of-sight velocity in the solar photosphere. As the magnetic field anchored at the solar surface produces most of the structures and energetic events in the upper solar atmosphere and significantly influences the heliosphere, the development of this instrument plays an important role in reaching the scientific goals of The Atmospheric and Space Science Coordination (CEA) at the Brazilian National Institute for Space Research (INPE). In particular, the CEA's space weather program will benefit most from the development of this technology. We expect that this project will be the starting point to establish a strong research program on Solar Physics in Brazil. Our main aim is acquiring progressively the know-how to build state-of-the-art solar vector magnetograph and visible-light imagers for space-based platforms to contribute to the efforts of the solar-terrestrial physics community to address the main unanswered questions on how our nearby Star works.
The study of the evolution of organic matter subjected to space conditions, and more specifically to Solar photons in the vacuum ultraviolet range (120–200 nm) has been undertaken in low-Earth orbit since the 1990s, and implemented on various space platforms. This paper describes a photochemistry experiment called AMINO, conducted during 22 months between 2009 and 2011 on the EXPOSE-R ESA facility, outside the International Space Station. Samples with relevance to astrobiology (connected to comets, carbonaceous meteorites and micrometeorites, the atmosphere of Titan and RNA world hypothesis) have been selected and exposed to space environment. They have been analysed after return to the Earth. This paper is not discussing the results of the experiment, but rather gives a general overview of the project, the details of the hardware used, its configuration and recent developments to enable long-duration exposure of gaseous samples in tight closed cells enabling for the first time to derive quantitative results from gaseous phase samples exposed in space.
Direct numerical simulations of statistically steady homogeneous isotropic turbulence in viscoelastic fluids described by the FENE-P model, such as those laden with polymers, are presented. It is shown that the strong depletion of the turbulence dissipation reported by previous authors does not necessarily imply a depletion of the nonlinear energy cascade. However, for large relaxation times, of the order of the eddy turnover time, the polymers remove more energy from the large scales than they can dissipate and transfer the excess energy back into the turbulent dissipative scales. This is effectively a polymer-induced kinetic energy cascade which competes with the nonlinear energy cascade of the turbulence leading to its depletion. It is also shown that the total energy flux to the small scales from both cascade mechanisms remains approximately the same fraction of the kinetic energy over the turnover time as the nonlinear energy cascade flux in Newtonian turbulence.
Epigenetic studies suggest that diseases that develop in adulthood are related to certain conditions to which the individual is exposed during the initial stages of life. Experimental evidence has demonstrated that offspring born to mothers maintained on high-Na diets during pregnancy have higher mean arterial pressure (MAP) in adulthood. Although these studies have demonstrated the importance of prenatal phases to hypertension development, no evidence regarding the role of high Na intake during postnatal phases in the development of this pathology has been reported. Therefore, in the present study, the effects of Na overload during childhood on induced water and Na intakes and on cardiovascular parameters in adulthood were evaluated. Experiments were carried out in two groups of 21-d-old rats: experimental group, maintained on hypertonic saline (0·3 m-NaCl) solution and food for 60 d, and control group, maintained on tap water and food. Later, both groups were given water and food for 15 d (recovery period). After the recovery period, chronic cannulation of the right femoral artery was performed in unanaesthetised rats to record baseline MAP and heart rate (HR). The experimental group was found to have increased basal MAP (98·6 (sem 2·6) v. 118·3 (sem 2·7) mmHg, P< 0·05) and HR (365·4 (sem 12·2) v. 398·2 (sem 7·5) beats per min, P< 0·05). There was a decrease in the baroreflex index in the experimental group when compared with that in the control group. A water and Na intake test was performed using furosemide. Na depletion was found to induce an increase in Na intake in both the control and experimental groups (12·1 (sem 0·6) ml and 7·8 (sem 1·1), respectively, P< 0·05); however, this increase was of lower magnitude in the experimental group. These results demonstrate that postnatal Na overload alters behavioural and cardiovascular regulation in adulthood.
Lightweight steel-framed (LSF) structural elements in building construction provide a way
of increasing building sustainability. These structural elements present great potential
for recycling and reuse, allowing the conservation of natural resources and the
environment. When compared with other materials, these construction components also
provide other advantages: reduced weight with simultaneous high mechanical strength;
easier prefabrication, allowing modular elements and higher quality control; shorter
periods for assembling the building on-site; no dimensional variations caused by moisture;
and low cost. The high thermal conductivity of steel could be a drawback, leading to
thermal bridges if not well designed and executed. In the case of LSF components (e.g.
walls and slabs) it is necessary to take special care with the elements’ design
optimisation, with it being essential to use continuous thermal insulation. The building
envelope thermal performance is crucial to provide good thermal behaviour and energy
efficiency, allowing a reduction of operational energy. In this paper, the LSF
construction system is analysed in order to show its main advantages and drawbacks. The
assessment of embodied and operational energy is essential to perform a life cycle
analysis. The reduction of both energies’ consumption is crucial to increase the
sustainability label. Special focus will be given to the mitigation strategies of
operational energy in LSF construction.
This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg−1, intraperitoneally [i.p.]) and C-LNCs (10 mg kg−1, i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0·05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.
Euclid is the next ESA mission devoted to cosmology. It aims at observing most of the extragalactic sky, studying both gravitational lensing and clustering over ~15,000 square degrees. The mission is expected to be launched in year 2020 and to last six years. The sheer amount of data of different kinds, the variety of (un)known systematic effects and the complexity of measures require efforts both in sophisticated simulations and techniques of data analysis. We review the mission main characteristics, some aspects of the the survey and highlight some of the areas of interest to this meeting.