A magnetoencephalography study of first-time mothers listening to infant cries.

Studies using magnetoencephalography (MEG) have identified the orbitofrontal cortex (OFC) to be an important early hub for a "parental instinct" in the brain. This complements the finding from functional magnetic resonance imaging studies linking reward, emotion regulation, empathy, and mentalization networks to the "parental brain." Here, we used MEG in 43 first-time mothers listening to infant and adult cry vocalizations to investigate the link with mother-infant postpartum bonding scores and their level of sleep deprivation (assessed using both actigraphy and sleep logs). When comparing brain responses to infant versus adult cry vocalizations, we found significant differences at around 800-1,000 ms after stimuli onset in the primary auditory cortex, superior temporal gyrus, hippocampal areas, insula, precuneus supramarginal gyrus, postcentral gyrus, and posterior cingulate gyrus. Importantly, mothers with weaker bonding scores showed decreased brain responses to infant cries in the auditory cortex, middle and superior temporal gyrus, OFC, hippocampal areas, supramarginal gyrus, and inferior frontal gyrus at around 100-300 ms after the stimulus onset. In contrast, we did not find correlations with sleep deprivation scores. The significant decreases in brain processing of an infant's distress signals could potentially be a novel signature of weaker infant bonding in new mothers and should be investigated in vulnerable populations.

Surface charge and dynamic mechanoelectrical stimuli improves adhesion, proliferation and differentiation of neuron-like cells.

Neuronal diseases and trauma are among the current major health-care problems. Patients frequently develop an irreversible state of neuronal disfunction that lacks treatment, strongly reducing life quality and expectancy. Novel strategies are thus necessary and tissue engineering research is struggling to provide alternatives to current treatments, making use of biomaterials capable to provide cell supports and active stimuli to develop permissive environments for neural regeneration. As neuronal cells are naturally found in electrical microenvironments, the electrically active materials can pave the way for new and effective neuroregenerative therapies. In this work the influence of piezoelectric poly(vinylidene fluoride) with different surface charges and dynamic mechanoelectrical stimuli on neuron-like cells adhesion, proliferation and differentiation was addressed. It is successfully demonstrated that both surface charge and electrically active dynamic microenvironments can be suitable to improve neuron-like cells adhesion, proliferation, and differentiation. These findings provide new knowledge to develop effective approaches for preclinical applications.

Evaluation of Information Theoretic Network Meta-analysis to Rank First-Line Anticancer Regimens for Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer.

Importance: Hormone receptor-positive, ERBB2 (formerly HER2/neu)-negative metastatic breast cancer (HR-positive, ERBB2-negative MBC) is treated with targeted therapy, endocrine therapy, chemotherapy, or combinations of these modalities; however, evaluating the increasing number of treatment options is challenging because few regimens have been directly compared in randomized clinical trials (RCTs), and evidence has evolved over decades. Information theoretic network meta-analysis (IT-NMA) is a graph theory-based approach for regimen ranking that takes effect sizes and temporality of evidence into account. Objective: To examine the performance of an IT-NMA approach to rank HR-positive, ERBB2-negative MBC treatment regimens. Data Sources: HemOnc.org, a freely available medical online resource of interventions, regimens, and general information relevant to the fields of hematology and oncology, was used to identify relevant RCTs. Study Selection: All primary and subsequent reports of RCTs of first-line systemic treatments for HR-positive, ERBB2-negative MBC that were referenced on HemOnc.org and published between 1974 and 2019 were included. Additional RCTs that were evaluated by a prior traditional network meta-analysis on HR-positive, ERBB2-negative MBC were also included. Data Extraction and Synthesis: RCTs were independently extracted from HemOnc.org and a traditional NMA by separate observers. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for NMA with several exceptions: the risk of bias within individual studies and inconsistency in the treatment network were not assessed. Main Outcomes and Measures: Regimen rankings generated by IT-NMA based on clinical trial variables, including primary end point, enrollment number per trial arm, P value, effect size, years of enrollment, and year of publication. Results: A total of 203 RCTs with 63 629 patients encompassing 252 distinct regimens were compared by IT-NMA, which resulted in 151 rankings as of 2019. Combinations of targeted and endocrine therapy were highly ranked, especially the combination of endocrine therapy with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. For example, letrozole plus palbociclib was ranked first and letrozole plus ribociclib, third. Older monotherapies that continue to be used in RCTs in comparator groups, such as anastrozole (251 of 252) and letrozole (252), fell to the bottom of the rankings. Many regimens gravitated toward indeterminacy by 2019. Conclusions and Relevance: In this network meta-analysis study, combination therapies appeared to be associated with better outcomes than monotherapies in the treatment of HR-positive, ERBB2-negative MBC. These findings suggest that IT-NMA is a promising method for longitudinal ranking of anticancer regimens from RCTs with different end points, sparse interconnectivity, and decades-long timeframes.

Morfogênese de braquiárias sob estresse hídrico / Morphogenesis of Brachiarias species under water stress

Objetivou-se avaliar Urochloa spp. submetida a duas situações de estresse hídrico: déficit e alagamento. As forrageiras estudadas foram: U. humidicola cv. Tully, U. humidicola cv. Llanero, U. brizantha cv. BRS Piatã, U. brizantha cv. Xaraés, U. decumbens cv. Basilisk e U. ruziziensis cv. Kenedy, e os parâmetros avaliados foram relacionados às características estruturais e morfogênicas. O trabalho foi desenvolvido em casa de vegetação pertencente à Unidade Universitária de Aquidauana. Os tratamentos consistiram em diferentes condições de umidade do solo: 50 e 80% da capacidade de retenção de umidade do solo, e lâminas de 0cm, 1cm e 5cm de água acima do solo, com quatro repetições, em delineamento inteiramente ao acaso. O modelo considerou o efeito de umidade do solo para cada espécie forrageira a 5% de significância. As características estruturais e morfogênicas do capim-tully não foram afetadas pelas diferentes condições hídricas aqui avaliadas. O capim-llanero não reagiu ao alagamento. O capim-piatã foi tolerante às condições de déficit hídrico e apresentou mecanismos de adaptação ao alagamento. A U. decumbens cv. Basilisk apresentou respostas adaptativas que melhoram sua tolerância ao alagamento. A U. ruziziensis cv. Kenedy apresentou-se inapta às condições de alagamento e de déficit hídrico.(AU)

The aim of this study was to evaluate braquiarias submitted to two situations of water stress: deficit and flood. The studied forages were: U. humidicola cv. Tully, U. humidicola cv. Llanero, U. brizantha cv. BRS Piatã, U. brizantha cv. Xaraés, U. decumbens cv. Basilisk and U. ruziziensis cv. Kenedy, and the parameters evaluated were related to the structural and morphogenic characteristics. The work was carried out in a greenhouse at the University Unit of Aquidauana. The treatments consisted of different soil moisture conditions: 50 and 80% of the moisture retention capacity of the soil, and slides of 0cm, 1cm and 5cm of water above the soil, with four replications, in a completely randomized design. The model considered the effect of soil moisture for each forage species at 5% of significance. The structural and morphogenic characteristics of grass-tully were not affected by the different water conditions evaluated here. The grass-llanero did not react to flooding. The grass-piatã was tolerant to water deficit conditions and presented adaptation to flooding. The U. decumbens cv. Basilisk presented adaptive responses that improved its tolerance to flooding. The U. ruziziensis cv. Kenedy was unfit for flood and water deficit conditions.(AU)

Effects of 16-weeks of Pilates on health perception and sleep quality among elderly women.

The objective of this study was to determine the effect of 16 weeks of mat-based Pilates training on health perception and sleep quality among elderly women. A randomized and controlled trial was conducted in Caxias do Sul, Brazil, in 2015, in which 61 healthy older women were divided into two groups: experimental group (EG; n=31, average of 64.25 years old, SD 0.14) and control group (CG; n=30, average of 63.75 years old, SD 0.08). The EG participants performed mat-based Pilates exercises twice a week in 60-min sessions, whereas the CG did not train. All participants completed Brazilian-adapted and validated versions of the Pittsburgh Sleep Quality Index (PSQI-BR) and General Health Questionnaire (GHQ-12) at baseline and after 16 weeks. Significant time x group interaction effects were found for the GHQ-12 total score (p<0.001, η2=0.19), and the depression (p=0.002, η2=0.15) and social dysfunction subscales (p=0.001, η2=0.18), as well as the PSQI-BR total score (p=0.017, η2=0.09), and the sleep latency (p=0.023, η2=0.09) and use of sleeping medication subscales (p=0.019, η2=0.09), indicating better improvements (reductions) in these outcome variables for the Pilates EG when compared to the CG. All significant effects were classified as moderate to high. These results indicate that 16 weeks of mat-based Pilates training significantly improves the perceived health status and some sleep quality indices among elderly women. However, more studies are needed to assess the effectiveness of equipment-based Pilates exercises among this population.

HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication.

The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per µl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.

Effects of hydroxychloride sources of copper, zinc, and manganese on measures of supplement intake, mineral status, and pre- and postweaning performance of beef calves.

Our objective was to evaluate the effect of Cu, Zn, and Mn source on measures of 1) preferential intake of mineral-concentrated supplements and 2) mineral status and pre- and postweaning performance of beef calves. In Exp. 1, 4 trials were conducted to assess the effect of source of Cu (750 mg/kg; Trial 1), Zn (2,000 mg/kg; Trial 2), Mn (3,000 mg/kg; Trial 3), and all 3 elements (Trial 4) on preferential intake of mineral-concentrated supplements. Supplements differed only by source of Cu, Zn, and Mn, which included hydroxychloride (hydroxy), sulfate, and organic options. In each trial, the 3 supplements were simultaneously offered to 8 pens of early-weaned calves (2 calves/pen; 126 ± 8.0 kg average BW) for a 4-h period and preferential intake was determined. When offered the opportunity to select among 3 supplement options, calves consumed more ( < 0.001) supplement containing hydroxy vs. organic or sulfate sources of Cu (Trial 1), Zn (Trial 2), and Mn (Trial 3). In Trial 4, when all 3 elements were combined within a single supplement, calves almost exclusively selected ( < 0.001) the hydroxy vs. organic or sulfate sources (82.9, 10.4, and 6.7% of total supplement intake, respectively [SEM 3.16]). In Exp. 2, calves were supplemented at a rate of 114 g/calf daily for 84 d before weaning (2 calves/pasture; 10 and 12 pastures in yr 1 and 2, respectively). Supplements were formulated to contain no supplemental minerals (control); hydroxy Cu, Zn, and Mn; or copper sulfate, zinc sulfate, and manganese oxide (sulfate/oxide). Total supplement intake was greater ( = 0.01) for calves consuming the hydroxy vs. the sulfate/oxide sources of Cu, Zn, and Mn (9.0 vs. 7.2 kg [SEM 0.45]). Preweaning calf BW gain did not differ ( ≥ 0.15) among treatments; however, calves provided mineral-fortified supplements had greater ( = 0.003) liver concentrations of Co and Se and tended ( = 0.07) to have greater liver concentrations of Cu at weaning compared with the controls. Calves provided mineral-fortified vs. control supplements had greater ( ≤ 0.05) peak concentrations of ceruloplasmin and haptoglobin and less BW gain during in the 16-d postweaning period. These data demonstrate greater voluntary intake of mineral-concentrated supplements among calves offered hydroxy vs. sulfate or organic sources of Cu, Zn, and Mn. Preweaning mineral-fortified supplementation increased calf mineral status, heightened inflammatory responsiveness, and decreased BW gain during the immediate postweaning period.

Nonequilibrium critical dynamics of the two-dimensional Ashkin-Teller model at the Baxter line.

We investigate the short-time universal behavior of the two-dimensional Ashkin-Teller model at the Baxter line by performing time-dependent Monte Carlo simulations. First, as preparatory results, we obtain the critical parameters by searching the optimal power-law decay of the magnetization. Thus, the dynamic critical exponents θ_{m} and θ_{p}, related to the magnetic and electric order parameters, as well as the persistence exponent θ_{g}, are estimated using heat-bath Monte Carlo simulations. In addition, we estimate the dynamic exponent z and the static critical exponents ß and ν for both order parameters. We propose a refined method to estimate the static exponents that considers two different averages: one that combines an internal average using several seeds with another, which is taken over temporal variations in the power laws. Moreover, we also performed the bootstrapping method for a complementary analysis. Our results show that the ratio ß/ν exhibits universal behavior along the critical line corroborating the conjecture for both magnetization and polarization.

How structure sculpts function: Unveiling the contribution of anatomical connectivity to the brain's spontaneous correlation structure.

Intrinsic brain activity is characterized by highly organized co-activations between different regions, forming clustered spatial patterns referred to as resting-state networks. The observed co-activation patterns are sustained by the intricate fabric of millions of interconnected neurons constituting the brain's wiring diagram. However, as for other real networks, the relationship between the connectional structure and the emergent collective dynamics still evades complete understanding. Here, we show that it is possible to estimate the expected pair-wise correlations that a network tends to generate thanks to the underlying path structure. We start from the assumption that in order for two nodes to exhibit correlated activity, they must be exposed to similar input patterns from the entire network. We then acknowledge that information rarely spreads only along a unique route but rather travels along all possible paths. In real networks, the strength of local perturbations tends to decay as they propagate away from the sources, leading to a progressive attenuation of the original information content and, thus, of their influence. Accordingly, we define a novel graph measure, topological similarity, which quantifies the propensity of two nodes to dynamically correlate as a function of the resemblance of the overall influences they are expected to receive due to the underlying structure of the network. Applied to the human brain, we find that the similarity of whole-network inputs, estimated from the topology of the anatomical connectome, plays an important role in sculpting the backbone pattern of time-average correlations observed at rest.

Toxicity of two effluents from agricultural activity: Comparing the genotoxicity of sugar cane and orange vinasse.

Vinasse, produced by several countries as a by-product of agricultural activity, has different alternatives for its reuse, mainly fertirrigation. Several monocultures, such as sugar cane and orange crops, produce this effluent. Sugar cane vinasse is already widely used in fertirrigation and orange vinasse has potential for this intention. However, its use as a fertilizer has caused great concern. Thus, ecotoxicological evaluation is extremely important in order to assess the possible effects on the environment. Therefore, the aim of this study was to evaluate the potential toxicity of vinasse of two different crops: sugar cane and orange. For this purpose, bioassays with Allium cepa as a test organism were performed with two vinasse dilutions (2.5% and 5%) to detect chromosomal aberrations and micronucleus induction. The results showed that both types of vinasse are able to induce chromosomal aberrations in meristematic cells, mainly nuclear and anaphasic bridges, suggesting genotoxic potential. The induction of micronuclei in cells of the F1 region suggests that the two residues have mutagenic potential. Thus, caution is advised when applying these effluents in the environment.

Brain fingerprints of olfaction: a novel structural method for assessing olfactory cortical networks in health and disease.

Olfactory deficits are a common (often prodromal) symptom of neurodegenerative or psychiatric disorders. As such, olfaction could have great potential as an early biomarker of disease, for example using neuroimaging to investigate the breakdown of structural connectivity profile of the primary olfactory networks. We investigated the suitability for this purpose in two existing neuroimaging maps of olfactory networks. We found problems with both existing neuroimaging maps in terms of their structural connectivity to known secondary olfactory networks. Based on these findings, we were able to merge the existing maps to a new template map of olfactory networks with connections to all key secondary olfactory networks. We introduce a new method that combines diffusion tensor imaging with probabilistic tractography and pattern recognition techniques. This method can obtain comprehensive and reliable fingerprints of the structural connectivity underlying the neural processing of olfactory stimuli in normosmic adults. Combining the novel proposed method for structural fingerprinting with the template map of olfactory networks has great potential to be used for future neuroimaging investigations of olfactory function in disease. With time, the proposed method may even come to serve as structural biomarker for early detection of disease.

Bioglass implant-coating interactions in synthetic physiological fluids with varying degrees of biomimicry.

Synthetic physiological fluids are currently used as a first in vitro bioactivity assessment for bone grafts. Our understanding about the interactions taking place at the fluid-implant interface has evolved remarkably during the last decade, and does not comply with the traditional International Organization for Standardization/final draft International Standard 23317 protocol in purely inorganic simulated body fluid. The advances in our knowledge point to the need of a true paradigm shift toward testing physiological fluids with enhanced biomimicry and a better understanding of the materials' structure-dissolution behavior. This will contribute to "upgrade" our vision of entire cascades of events taking place at the implant surfaces upon immersion in the testing media or after implantation. Starting from an osteoinductive bioglass composition with the ability to alleviate the oxidative stress, thin bioglass films with different degrees of polymerization were deposited onto titanium substrates. Their biomineralization activity in simulated body fluid and in a series of new inorganic-organic media with increasing biomimicry that more closely simulated the human intercellular environment was compared. A comprehensive range of advanced characterization tools (scanning electron microscopy; grazing-incidence X-ray diffraction; Fourier-transform infrared, micro-Raman, energy-dispersive, X-ray photoelectron, and surface-enhanced laser desorption/ionization time-of-flight mass spectroscopies; and cytocompatibility assays using mesenchymal stem cells) were used. The information gathered is very useful to biologists, biophysicists, clinicians, and material scientists with special interest in teaching and research. By combining all the analyses, we propose herein a step forward toward establishing an improved unified protocol for testing the bioactivity of implant materials.

Eslicarbazepine acetate as adjunctive therapy in clinical practice: ESLADOBA study.

OBJECTIVE: To assess seizure control and tolerability of eslicarbazepine acetate (ESL) as adjunctive therapy to one baseline antiepileptic drug (AED), in adults with partial-onset seizures (POS) with or without secondary generalization. METHODS: Multicenter, non-interventional, prospective cohort study conducted between March 2012 and September 2014 at 12 neurology departments in Portugal. Adults with POS not controlled with one AED who had initiated ESL as adjunctive treatment were enrolled. Retention rate was defined at the final visit (Vfinal) 6-9 months of follow-up. Proportion of responders, seizure-free, changes in seizure frequency were evaluated using patients' diaries. Clinical Global Impression of Change (CGI-C) and Clinical Global Impression of Severity (CGI-S) were assessed by the neurologist. RESULTS: Fifty-two patients (48.1% male) were included with mean age 41.5±13.3 years. Mean epilepsy duration was 18.5±14.8 years; mean seizure frequency in the four previous weeks to baseline was 7.5±12.7. At Vfinal, retention rate was 73.0%; responder rate and seizure-free rates were 71.1% and 39.5%, respectively. The median relative reduction in seizure frequency between baseline and Vfinal was 82.2%. A reduction in epilepsy severity (CGI-S) was observed in 42.1%. According to CGI-C, 73.6% patients had their epilepsy "much improved" or "very much improved". Twelve patients (23.1%) had at least one adverse event (AE), two (3.9%) had one serious AE, and five (9.6%) discontinued due to AE. CONCLUSIONS: Eslicarbazepine acetate showed good retention rates, elicited a significant reduction in seizure frequency, and was well tolerated when used in the clinical practice.

TGF-ß1 activation in human hamstring cells through growth factor binding peptides on polycaprolactone surfaces.

The administration of soluble growth factors (GFs) to injured tendons and ligaments (T/L) is known to promote and enhance the healing process. However, the administration of GFs is a complex, expensive and heavily-regulated process and only achieved by employing supraphysiological GF concentrations. In addition, for proper healing, specific and spatial immobilization of the GFs (s) is critical. We hypothesized that biomaterials functionalized with GF-binding peptides can be employed to capture endogenous GFs in a spatially-controlled manner, thus overcoming the need for the exogenous administration of supraphysiological doses of GFs. Here we demonstrate that the modification of films of polycaprolactone (PCL) with transforming growth factor ß1 (TGF-ß1)-binding peptides allows GFs to be captured and presented to the target cells. Moreover, using a TGF-ß reporter cell line and immunocytochemistry, we show that the GFs retained their biological activity. In human primary tendon cells, the immobilized TGF-ß1 activated TGF-ß target genes ultimately lead to a 2.5-fold increase in total collagen matrix production. In vivo implantation in rats clearly shows an accumulation of TGF-ß1 on the polymer films functionalized with the TGF-ß1-binding peptide when compared with the native films. This accumulation leads to an increase in the recruitment of inflammatory cells at day 3 and an increase in the fibrogenic response and vascularization around the implant at day 7. The results herein presented will endow current and future medical devices with novel biological properties and by doing so will accelerate T/L healing. STATEMENT OF SIGNIFICANCE: Our study describes the possibility to deliver hTGF-ß1 to human derived hamstring cells using a non-covalent bioactive strategy. The significance of our results in vivo with our functionalized biomaterial with TGF-ß1-binding peptides lies in the fact that these materials can now be employed to capture endogenous TGF-ß1 in a spatially-controlled manner, overcoming the need for exogenous administration of supra-physiological TGF-ß1 doses. Our method is different from current solutions that rely on global TGF-ß1 administration, soaking the devices with TGF-ß1, etc. Therefore we believe that our method is a significant change from current state-of-the-art in the types of devices that are used for ligament/tendon repair and that following our method can endow current and future medical devices with TGF-ß1 binding properties.

Statistics, distillation, and ordering emergence in a two-dimensional stochastic model of particles in counterflowing streams.

In this paper, we propose a stochastic model which describes two species of particles moving in counterflow. The model generalizes the theoretical framework that describes the transport in random systems by taking into account two different scenarios: particles can work as mobile obstacles, whereas particles of one species move in the opposite direction to the particles of the other species, or particles of a given species work as fixed obstacles remaining in their places during the time evolution. We conduct a detailed study about the statistics concerning the crossing time of particles, as well as the effects of the lateral transitions on the time required to the system reaches a state of complete geographic separation of species. The spatial effects of jamming are also studied by looking into the deformation of the concentration of particles in the two-dimensional corridor. Finally, we observe in our study the formation of patterns of lanes which reach the steady state regardless of the initial conditions used for the evolution. A similar result is also observed in real experiments involving charged colloids motion and simulations of pedestrian dynamics based on Langevin equations, when periodic boundary conditions are considered (particles counterflow in a ring symmetry). The results obtained through Monte Carlo simulations and numerical integrations are in good agreement with each other. However, differently from previous studies, the dynamics considered in this work is not Newton-based, and therefore, even artificial situations of self-propelled objects should be studied in this first-principles modeling.

Amino acid deprivation using enzymes as a targeted therapy for cancer and viral infections.

INTRODUCTION: Amino acid depletion in the blood serum is currently being exploited and explored for therapies in tumors or viral infections that are auxotrophic for a certain amino acid or have a metabolic defect and cannot produce it. The success of these treatments is because normal cells remain unaltered since they are less demanding and/or can synthesize these compounds in sufficient amounts for their needs by other mechanisms. Areas covered: This review is focused on amino acid depriving enzymes and their formulations that have been successfully used in the treatment of several types of cancer and viral infections. Particular attention will be given to the enzymes L-asparaginase, L-arginase, L-arginine deiminase, and L-methionine-γ-lyase. Expert opinion: The immunogenicity and other toxic effects are perhaps the major limitations of these therapies, but they have been successfully decreased either through the expression of these enzymes from other organisms, recombination processes, pegylation of the selected enzymes or by specific mutations in the proteins. In 2006, FDA has already approved the use of L-asparaginase in the treatment of acute lymphoblastic leukemia. Other enzymes and in particular L-arginase, L-arginine deiminase, and L-methioninase have been showing promising results in vitro and in vivo studies.

Exigências de energia de borregas mestiças alimentadas com níveis crescentes de concentrado na dieta / Energy requirements of crossbreed ewe lambs fed with increasing dietary levels of concentrate

Objetivou-se estimar as exigências energéticas de borregas mestiças confinadas, alimentadas com níveis crescentes de concentrado na dieta. Foram avaliadas 36 borregas, com peso corporal inicial de 23,7±3,67kg. Seis animais foram abatidos no início do experimento para obtenção dos valores do grupo referência. Os demais (30 animais) foram distribuídos em cinco tratamentos: mantença (alimentação restrita com feno de capim Tifton) e suplementados com níveis crescentes de concentrado (20, 40, 60 e 80%) em base de matéria seca (seis animais por tratamento). As borregas foram abatidas quando atingiram 37,70±9,89kg. Os níveis de concentrado influenciaram a eficiência de utilização da energia metabolizável para mantença (km) e consequentemente as exigências diárias de energia metabolizável para mantença. A exigência de energia líquida para mantença de borregas mestiças em crescimento é 57 kcal/PCJ0,75/dia, em que PCJ é o peso corporal em jejum. As borregas com 20kg apresentaram exigência de energia líquida para 100g de ganho de peso diário de 465kcal/dia. As borregas com 40kg de peso corporal exigiram 930kcal/dia de energia líquida para o mesmo ganho. A exigência líquida para mantença de borregas pode ser estimada pela equação: ELm (Mcal/dia) = 0,057* PCJ0,75. A exigência líquida de energia para ganho de borregas mestiças (Mcal/dia) pode ser estimada a partir da equação: ELg = 0,524 x PVJ0,75 x GPCVZ1,21, em que GPCVZ é o ganho de peso do corpo vazio. As dietas influenciam as eficiências de usos da energia metabolizável para mantença (km) e ganho (kg).(AU)

The aim of this study was to estimate the energy requirements of crossbreed ewe lambs in a feedlot fed with increasing levels of concentrate in the diet. 36 ewe lambs were evaluated with initial body weight of 23.7±3.67kg. Six animals were slaughtered at the beginning of the experiment to obtain the reference group values. Animals (30) were distributed in five treatments: maintenance (feed restricted with Tifton grass hay) and those supplemented with increasing dietary levels of concentrate (20, 40, 60 and 80%) on a dry matter basis (six animals per treatment). The ewe lambs were slaughtered when they reached 37.70±9.89kg. The concentrate levels influenced the utilization efficiency of metabolizable energy for maintenance (km) and consequently the daily requirements of metabolizable energy for maintenance. The net energy requirements for maintenance of crossbred lambs in growth is 57kcal/FCW 0.75/day, where FCW is body weight on fasting. The ewe lambs with 20kg presented net energy requirement for 100g daily weight gain of 465kcal/day. The ewe lambs with 40kg of body weight required 930 kcal/day of net energy for the same gain. The net energy requirement for maintenance of ewe lambs can be estimated by the equation: NEm (Mcal/day) = 0.057 * FCW0.75. The net energy requirement for crossbred ewe lambs gain (Mcal/day) can be estimated from the equation: NEg (Mcal/day) = 0.524*FCW 0.75*GEBW1.21, where GEBW represented gain empty body weight. Diets affect the efficiencies of uses of metabolizable energy for maintenance (km) and gain (kg).(AU)

Antimitotic and antimutagenic action of the Hymenaea stigonocarpa bark on dividing cells / Ação antimitótica e antimutagênica do ritidoma de Hymenaea stigonocarpa Mart ex Hayne na divisão celular

Abstract The objective of this study was to evaluate the action of Hymenaea stigonocarpa bark hydroalcoholic extract against a mutagenic compound using A. cepa meristematic root cells as a test system. The treatment groups were: Negative Control (NC) – distilled water; Positive Control (PC) – paracetamol at a concentration of 0.008 mg/mL, Jatoba Control (JC) – aqueous fraction jatobá-do-cerrado at 0.5 or 1.0 or 1.5 mg/mL, and Simultaneous Treatment (ST) - jatobá-do-cerrado aqueous fraction at a concentration of 0.5 or 1.0 or 1.5 mg/mL associated with paracetamol solution at a concentration of 0.008 mg/mL. All groups were analyzed at 24 and 48 h. Five onion bulbs (five replications) were used for each treatment group. The root tips were fixed in Carnoy and slides prepared by the crush technique. Cells were analyzed throughout the cell cycle, totaling 5,000 for each treatment group at each exposure time. Mitotic indices were subjected to statistical analysis using the chi-square test (p<0.05). From the results it was found that the ST group, at the three concentrations, significantly potentiated the antiproliferative effect of the test system cells when compared to PC, NC and TJ at the three concentrations. Furthermore, the three ST concentrations significantly reduced the number of cell aberrations when compared to the number of aberrant cells obtained for the PC, demonstrating antimutagenic action on the A. cepa test system cells.

Resumo O objetivo do presente trabalho foi avaliar a ação do extrato hidroalcólico do ritidoma de Hymenaea stigonocarpa frente a um composto mutagênico, utilizando como sistema teste as células meristemáticas de raízes de A. cepa. Os grupos tratamentos avaliados foram: Controle Negativo (CN) – água destilada; Controle Positivo (CP) – paracetamol na concentração de 0,008 mg/mL, Controle Jatobá (CJ) – fração aquosa de jatobá-do-cerrado na concentração de 0,5 ou 1,0 ou 1,5 mg/mL, e Tratamento Simultâneo (TS) – fração aquosa de jatobá-do-cerrado na concentração de 0,5 ou 1,0 ou 1,5 mg/mL associada a solução de paracetamol na concentração de 0,008 mg/mL. Todos os grupos foram analisados nos tempos de 24 e 48 h. Para cada grupo tratamento cinco bulbos de cebolas (cinco repetições) foram utilizados. As radículas foram fixadas em Carnoy e as lâminas preparadas pela técnica de esmagamento. Analisaram-se células em todo ciclo celular, totalizando 5.000 para cada grupo tratamento em cada tempo de exposição. Os índices mitóticos obtidos foram submetidos à análise estatística do Qui-quadrado (p<0,05). A partir dos resultados verificou-se que o grupo TS, nas três concentrações, potencializou o efeito antiproliferativo significativo as células do sistema teste quando comparado ao CP, CN e TJ nas três concentrações. Ainda, o TS nas três concentrações reduziu de forma significativa o número de aberrações celulares quando comparado com o número de células aberrantes obtidas para o CP, demonstrando ação antimutagênica as células do sistema teste A. cepa.