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Background: The CYP19A1 gene, which encodes the enzyme responsible for androgen aromatization into estrogens, may play an important role in breast cancer aggressiveness. However, no study has evaluated CYP19A1 gene expression in the peripheral blood of women with relapsed breast cancer., Methods: In this cross-sectional study, CYP19A1 gene expression was quantified by RT-PCR in the peripheral blood of 146 women with breast cancer who were first divided into two groups according to the expression of CYP19A1 (low and high); each group had 73 patients. Subsequently, women were divided into two groups: those without recurrence (control, n = 85) and those with recurrence (study, n = 61). Statistical analysis of the data was performed using ANOVA, the Mann-Whitney, Chi-square or Fisher's exact test (p <  0.05)., Results: There were no significant differences between the relative expression of CYP19A1 mRNA in the low expression group and the high expression group according to the variables studied. There were no significant differences in CYP19A1 gene expression in the study and control groups (p = 0.8461). In the relapse group, CYP19A1 gene expression was significantly higher in the hybrid luminal subtype than in the triple-negative subtype (p = 0.0321), whereas it was significantly lower in HER2-negative cases than in HER2-positive cases (p <  0.0376). Women with locoregional recurrence showed higher expression than women with distant recurrence (p <  0.0001)., Conclusions: The present study found no significant differences between women with high and low expression of the CYP19A1 gene mRNA or between those in the study group and the control group. However, in women with recurrence, there was increased expression of CYP19A1 mRNA in those who had the luminal hybrid subtype and locoregional relapse and decreased expression in those negative for HER2.

Background: Leprosy can be cured, but physical disability (PD) as a result of the infection can progress in the post-release from treatment phase. This study evaluated the likelihood of, and factors associated with, the progression of the PD grade post-release from treatment among leprosy patients treated in Cáceres-MT, Brazil in the period 2000 to 2017., Methods: A retrospective cohort study and survival analysis were performed in the hyperendemic municipality of Cáceres in the state of Mato Grosso. The study population consisted of newly diagnosed leprosy patients released from treatment between January 1, 2000 and December 31, 2017. The main outcome was the progression of the PD grade with regard to probability and time; and the evaluated covariates included clinical, operational and demographic variables. The Cox proportional risk model was used to estimate the risk ratio (Hazard Ratios) of the covariates. Both an univariate and a multivariate analysis were implemented, with 95% confidence intervals., Results: The mean time for progression of the PD grade was 162 months for PB and 151 months for MB leprosy patients. The survival curve showed that 15 years after the release from treatment, the probability of PD grade progression was 35%, with no difference between PB and MB or age groups. Leprosy reactions and registered medical complaints of any kind during treatment were identified as risk factors with Hazard Ratios of 1.6 and 1.8 respectively., Conclusions: People released from treatment as cured of leprosy are susceptible to worsening of the PD, especially those who have had complications during multi-drug therapy treatment. This indicates that leprosy patients should be periodically monitored, even after the successful completion of multidrug therapy.

Background: Cancer and fibroadenoma are the most common breast tumors in women of reproductive age. Nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappaB (NF-κB) transcription factor play an important role in the inflammatory process and in cell proliferation. However, few studies have analyzed these markers in breast cancer and fibroadenoma in women of reproductive age. Results: Light microscopy showed a higher concentration of anti-Nrf2 and anti-NF-κB-stained nuclei in breast cancer than in fibroadenoma. The mean percentage of stained nuclei for Nrf2 was 7.12 ± 5.2 and 43.21 ± 19.83 in the control and study groups, respectively (p < 0.0001). The mean percentage of anti-NF-κB was 10.75 ± 7.09 and 56.14 ± 21.19 (mean ± standard deviation) in the control and study groups, respectively (p < 0.0001). Histological grade 3 tumors showed a significantly higher expression of Nrf2 and NF-κB than grade 1 tumors (p < 0.05). Material and methods: This study was approved by the Institutional Review Board of Federal University of Piaui and all patients assigned an inform consent term prior to the study initiation. Nrf2 and NF-κB expression was evaluated by immunohistochemistry in 66 patients, divided into two groups, control (fibroadenoma, n = 36) and study (cancer, n = 30). The data were analyzed using ANOVA test and the statistical significance was established at p < 0.05. Conclusion: Nrf2 and NF-κB expression was significantly higher in breast cancer than in fibroadenoma, in addition to having a greater association with more aggressive tumors., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests., (Copyright: © 2020 Simplicio-Revoredo et al.)

Context: Biochemical markers correlate positively with the development and severity of obesity, depression, and anxiety, and can be modulated by changes in intestinal microbiota composition., Objective: A systematic review and meta-analysis was conducted to determine the effects of prebiotics or synbiotics on blood biomarkers of obesity, depression, and anxiety (including: ACTH [adrenocorticotropic hormone], cortisol, leptin, ghrelin, TSH [thyroid-stimulating hormone], PTH [parathyroid hormone], vitamin D, BDNF [brain-derived neurotrophic factor], and PCR [polymerase chain reaction]) in individuals with overweight or obesity., Data Sources: MEDLINE, Web of Science, Scopus, and CENTRAL databases were searched, along with the reference lists of included articles. Authors were contacted for unpublished data., Study Selection: RCT in individuals with overweight or obesity, supplemented with prebiotics or synbiotics, assessing any of the outcomes of interest., Data Extraction: Data were extracted independently by three researchers., Results: Thirteen studies were identified up to March 7, 2018. Regarding outcomes, 1 study assessed leptin, 4 studies assessed ghrelin, and 10 studies assessed CRP (C-reactive protein). Meta-analysis showed reduction in serum concentrations of ghrelin (-37.17 pg/mL; 95%CI = -69.62, -4.73; P = 0.025) and CRP (SMD [standardized mean difference] = -0.31; 95%CI = -0.58, -0.04; P = 0.027) after supplementation of inulin-type fructans., Conclusions: Prebiotics may help regulate blood concentrations of ghrelin and CRP in overweight or obese individuals., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study evaluated the rose bengal- and erythrosine-mediated photoinactivation against Salmonella Typhimurium and Staphylococcus aureus planktonic and sessile cells using green LED as a light source. The free-living or 2-day-old biofilm cells were treated with different concentrations of the photosensitizing agents and subjected to irradiation. Only 5 min photosensitization with rose bengal at 25 nmol L -1 and 75 μmol L -1 completely eliminated S. aureus and S. Typhimurium planktonic cells, respectively. Erythrosine at 500 nmol L -1 and 5 min of light exposure also reduced S. aureus planktonic cells to undetectable levels. Eradication of S. aureus biofilms was achieved when 500 μmol L -1 of erythrosine or 250 μmol L -1 of rose bengal was combined with 30 min of irradiation. Scanning electron microscopy allowed the observation of morphological changes in planktonic cells and disruption of the biofilm architecture after photodynamic treatment. The overall data demonstrate that rose bengal and erythrosine activated by green LED may be a targeted strategy for controlling foodborne pathogens in both planktonic and sessile states., (© 2019 American Society for Photobiology.)

The difficulties encountered and the numerous side effects present in the treatment of cutaneous leishmaniasis have encouraged the research for new compounds that can complement or replace existing treatment. The growing scientific interest in the study of plants, which are already used in folk remedies, has led our group to test Endlicheria bracteolata essential oil against Leishmania amazonensis . Several species of the Lauraceae family, or their compounds, have relevant antiprotozoal activities Therefore, the biological potential on L. amazonensis forms from the essential oil of Endlicheria bracteolata leaves was verified for the first time in that work. The antileishmanial activity was evaluated against promastigotes and intracellular amastigotes, and cytotoxicity were performed with J774.G8, which were incubated with different concentrations of E. bracteolata essential oil. Transmission electron microscopy and flow cytometry were performed with E. bracteolata essential oil IC 50 . Promastigote forms showed E. bracteolata essential oil IC 50 of 7.945 ± 1.285 µg/mL (24 h) and 6.186 ± 1.226 µg/mL (48 h), while for intracellular amastigote forms it was 3.546 ± 1.184 µg/mL (24 h). The CC 50 was 15.14 ± 0.090 µg/mL showing that E. bracteolata essential oil is less toxic to macrophages than to parasites. Transmission electron microscopy showed that E. bracteolata essential oil treatment is capable of inducing mitochondrial damage to promastigote and intracellular amastigote forms, while flow cytometry showed ΔѰm disruption in treated parasites. These results could bring about new possibilities to develop products based on E. bracteolata essential oil to treat cutaneous leishmaniasis, especially for people who cannot receive the conventional therapy.

The toxic effects of thyroxine (T 4 F), levothyroxine (L-T 4 ), and thyroxine complexed into β-cyclodextrin (β-CD-T 4 ) on the biological parameters of tambaqui (Colossoma macropomum) were evaluated. The animals were exposed to a chronic toxicity test based on concentrations of influent (60 ng/L) for 2 months. Weight, total length, animal behavior, oxygen consumption, photopic electroretinogram (ERG), and the Flicker exam were evaluated. No significant differences were observed (p > 0.05) on the weight and total length measurements between all groups studied. Behavioral observations of the animals exposed to L-T 4 and β-CD-T 4 complex showed a reduction (p < 0.05) in slow swimming and an increase in staying motionless events. The animals exposed to the β-CD-T 4 complex presented the highest O 2 consumption. L-T 4 and β-CD-T 4 promoted a reduction in the ability of the animals to respond to stimuli in the photoreceptors according to the photopic ERG examination. Data from the experimental Flicker exam showed no significant differences (p > 0.05) in all groups studied. It can be concluded that the complexation of T 4 into β-CD and L-T 4 modified the toxicity of this hormone, promoting changes in the behavior, oxygen consumption, and electrophysiological responses of the exposed animals, suggesting that inclusion complexes should be submitted to new toxicity tests to ensure higher safety.

Weather phenomena El Niño and La Niña are observed by meteorological variables, which allows you to track climate change and its possible effects in certain regions. The objective of this study was to analyze the behavior of rainfall, temperature and evapotranspiration in the Amazon river basin (Latitudes 5° N to 20° S and Longitudes 50° W to 80° W), comparing them with the occurrence of El Niño and La Niña phenomena, from January 2000 to December 2016. The values referring to the meteorological variables were obtained from the TRMM and MODIS orbital sensors. After data pre-processing, the data were separated into monthly and annual scales and per period according to the presence or absence of El Niño and La Niña phenomena. Based on the results obtained, it was observed that the studied variables were affected by modification of both phenomena. The modifications are more noticeable in the distinction between the more and less rainy periods. Among the variables studied, the evapotranspiration was severely affected in the rainiest months, the La Niña phenomenon, and the least rainy months, El Niño. Thus, it was possible to conclude that, in general, the presence of La Niña increased precipitation values in comparison to the Neutral period, but the inverse occurs in the presence of El Niño. The methodology applied in the present study was adequate for the analysis of the modifications of the meteorological variables coming from the El Niño and La Niña phenomena, being able to be adapted to other variables and regions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Half of invasive fungal infections lead to death. Amongst pathogenic fungi, the most widespread species belong to the Candida genus and vary in their susceptibility to antifungal drugs. The emergence of antifungal resistance has become a major clinical problem. Therefore, the definition of susceptibility patterns is crucial for the survival of patients and the monitoring of resistance epidemiology. Although, most routinely used methods of AntiFungal Susceptibility Testing (AFST) have reached their limits, the rediscovery of Matrix Associated Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) in the field of mycology provides a promising alternative for the study of antifungal resistance. MALDI-TOF MS is already used in mycology for fungal identification, which permits to highlight inherent antifungal resistance. However, the main concern of clinicians is the rise of acquired antifungal resistance and the time needed for their detection. For this purpose, MALDI-TOF MS has been shown to be an accurate tool for AFST, presenting numerous advantages in comparison to commonly used techniques. Finally, MALDI-TOF MS could be used directly to detect resistance mechanisms through typing. Consequently, MALDI-TOF MS offers new perspectives in the context of healthcare associated outbreaks of emerging multi-drug resistant fungi, such as C. auris . As a proof of concept, we will illustrate the current and future benefits in using and adapting MALDI-TOF MS-based assays to define the susceptibility pattern of C. auris , by species identification, AFST, and typing.

Infection with human papillomavirus (HPV) is the main cause of cervical cancer. Viral persistence is considered the main risk factor for neoplastic progression and evidence suggests that regulatory T cells (Treg) play an important role in the failure of viral elimination. The aim of this study was to detect phenotypic markers of Treg and cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β, in the cervical microenvironment of HPV-infected patients. One hundred and one samples of uterine cervix embedded in paraffin were analyzed. We used immunohistochemistry to examine the coexpression of the CD25/FOXP3 and CD4/TGF-β markers, and the expression of GITR and IL-10 in cells present in the cervical stroma. We detected a microenvironment composed of high proportions of CD25 + FOXP3 + , CD4 + TGFβ + , IL-10 + , and GITR + cells in samples with high viral loads and severe lesions of HPV-infected patients. The abundance of these markers, indicative of the presence of Treg cells and immunosuppressive cytokines, was significantly associated with severe lesions and elevated viral loads in the examined samples. These results suggest that Treg cells may be involved in maintaining a microenvironment favorable for viral persistence and neoplastic progression. Our findings support those of previous studies that suggested that these markers could be used to predict HPV persistence and neoplastic progression, and as potential targets for immune response modulation., (© 2018 Wiley Periodicals, Inc.)

The extensive use of pesticides in agricultural practices has been associated with human health problems and environmental contamination worldwide. Brazil is the largest consumer of pesticides in the world and Espírito Santo State stands out as the second Brazilian producer of coffee. However, there is no information about environmental impact of coffee producing at Itapemirim River Basin (IRB) region, Espírito Santo State, Brazil; hence a simple and quick method using open access softwares (AGROSCRE and ARAquá Web) to estimate surface entrainment and pesticide leaching potential was carried out. AGROSCRE evaluates the contamination risk of superficial and groundwater by Active Ingredients (AIs), using GOSS Method, GUS index and US EPA criteria, while ARAquá Web estimates AI concentrations in water resources, indicating their suitability based on water quality requirements for different uses. Regarding pesticides used in coffee plantations, there is 44.7% chance of surface water and 23.7% chance of groundwater contamination. Results showed that ametryne, cyproconazole, diuron, epoxiconazole, flutriafol, triadimenol and triazophos pose contamination risk to both surface water and groundwater in the IRB region. Of these, 10.5% of the total AIs are triazoles and fall under environmental classes II and III (Product Very/Dangerous to the Environment). The AIs ametryne, thiamethoxam, iprodione, flutriafol, triazophos, endosulfan, triadimenol, cyproconazole, diuron, pendimethalin, chlorpyrifos, copper II hydroxide, etion, epoxiconazole and paraquat dichloride, were found to be potentially toxic, presenting environmental concentrations ranging from 123.40 μg L -1 to 0.14 μg L -1 , which are higher than the safety standard for potable water (0.1 μg L -1 ). With respect to these AIs, chlorpyrifos, ethion and triazophos showed concentrations higher than EC 50 values for aquatic invertebrates and ametryne and diuron for algae. Thus, local residents and environment may be at high risk of pesticide exposure, when these AIs are used in coffee plantations next to surface water or groundwater., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Skull base tumors, such as large olfactory groove meningiomas (OGMs), are a challenge for neurosurgeons. However, the tendency to reduce invasive surgeries is gaining more adepts. We describe a minimally invasive interhemispheric approach with a falx window for microsurgical resection of the giant OGM as a technical note., Methods: A minimal medial frontal craniotomy measuring 3-5 cm in size is performed, and an interhemispheric approach is combined with an opening in the falx to improve microsurgical resection of the giant OGM. The technique and more details are described., Results: A minimally invasive interhemispheric approach with a falx window was performed in this case. Gross total resection of the OGM was possible with minimal brain retraction. Simpson grade I was achieved, and there was a good outcome on the postoperative recovery period of the patient, with vision improvement, preservation of olfaction, and no other complications., Conclusions: The minimally invasive interhemispheric approach with a falx window is effective and safe for giant OGM with a good outcome for the patient. The opening in the falx improves the interhemispheric pathway and allows gross total resection with minimal brain retraction and low morbidity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Over the past few years, many sectors such as energy generation, industry, domestic supply, and agriculture have encountered serious environmental problems due to the lack of rainfall. Thus, the purpose of this paper is to review the current methodology of royalties distribution from Itaipu hydroelectric plant. In the proposed approach, two criteria were considered to establish the division of Itaipu royalties: (1) the relative percentage of the water flow in the generation of electricity and, (2) the relative percentage of the drop in the height of water. 62 hydroelectric plants were evaluated in this study. In 52 plants the water flow was the factor that most contributed to the generation of electricity. In 2013, 346 municipalities benefited the Itaipu royalties. With the proposed methodology, 1,327 municipalities will receive the resource, what would increase the revenue of each of these municipalities by, on average, US$ 87,436.91 per year. The methodology presented herein proposes a reduction in the environmental disparity that now exists in Brazil, through improvement to Government instruments and environmental policies. The distribution of royalties throughout the watershed can provide additional resources to support payment programs for environmental services at the state and municipality levels., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims: The aim of this study was evaluate the effect of photodynamic inactivation mediated by eosin Y in Salmonella enterica serotype Typhimurium ATCC 14028, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 and Bacillus cereus ATCC 11778., Methods and Results: Bacteria (10 7 CFU per ml) were incubated with eosin Y at concentrations ranging from 0·1 to 10 μmol l -1 , irradiated by green LED (λ max 490-570 nm) for 5, 10 and 15 min and the cellular viability was determined. Pseudomonas aeruginosa was completely inactivated when treated with 10 μmol l -1 eosin Y for 10 min. Treatments reduced B. cereus and Salm. Typhimurium counts to 2·7 log CFU per ml and 1·7 log CFU per ml, respectively. Escherichia coli counts were slightly reduced. Staphylococcus aureus presented the highest sensitivity, being completely inactivated by eosin Y at 5 μmol l -1 and 5 min of illumination. The reduction of cellular viability of photoinactivated Staph. aureus was also demonstrated by flow cytometry and morphological changes were observed by scanning electron microscopy., Conclusions: Eosin Y in combination with LED produced bacterial inactivation, being a potential candidate for photodynamic inactivation., Significance and Impact of the Study: This study evidenced the efficacy of photodynamic inactivation as a novel and promising alternative to bacterial control., (© 2018 The Society for Applied Microbiology.)

Models of individual trees are composed of sub-models that generally estimate competition, mortality, and growth in height and diameter of each tree. They are usually adopted when we want more detailed information to estimate forest multiproduct. In these models, estimates of growth in diameter at 1.30m above the ground (DBH) and total height (H) are obtained by regression analysis. Recently, artificial intelligence techniques (AIT) have been used with satisfactory performance in forest measurement. Therefore, the objective of this study was to evaluate the performance of two AIT, artificial neural networks and adaptive neuro-fuzzy inference system, to estimate the growth in DBH and H of eucalyptus trees. We used data of continuous forest inventories of eucalyptus, with annual measurements of DBH, H, and the dominant height of trees of 398 plots, plus two qualitative variables: genetic material and site index. It was observed that the two AIT showed accuracy in growth estimation of DBH and H. Therefore, the two techniques discussed can be used for the prognosis of DBH and H in even-aged eucalyptus stands. The techniques used could also be adapted to other areas and forest species., (Copyright © 2017 Elsevier B.V. All rights reserved.)

N-Heptane and 2,2,4-trimethylpentane (isooctane) are the key species in the modeling of ignition of hydrocarbon-based fuel formulations. Isooctane is knock-resistant whereas n-heptane is a very knock-prone hydrocarbon. It has been suggested that interconversion of their associated alkylperoxy and hydroperoxyalkyl species via hydrogen-transfer isomerization reaction is the key step to understand their different knocking behavior. In this work, the kinetics of unimolecular hydrogen-transfer reactions of n-heptylperoxy and isooctylperoxy are determined using canonical variational transition-state theory and multidimensional small curvature tunneling. Internal rotation of involved molecules is taken explicitly into account in the molecular partition function. The rate coefficients are calculated in the temperature range 300-900 K, relevant to low-temperature autoignition. The concerted HO 2 elimination is an important reaction that competes with some H-transfer and is associated with chain termination. Thus, the branching ratio between these reaction channels is analyzed. We show that variational and multidimensional tunneling effects cannot be neglected for the H-transfer reaction. In particular, the pre-exponential Arrhenius fitting parameter derived from our rate constants shows a strong dependence on the temperature, because tunneling increases quickly at temperatures below 500 K. On the basis of our results, the existing qualitative model for the reasons for different knock behavior observed for n-heptane and isooctane is quantitatively validated at the molecular level.

The effect of cinnamaldehyde against biofilm cells of Salmonella Typhimurium ATCC 14028 was evaluated. We also assessed differential protein patterns that were expressed by biofilms compared with planktonic cells and protein expression by cinnamaldehyde-treated biofilms cells. This compound decreased biofilm biomass and metabolic activity of biofilms at both concentrations tested. Cinnamaldehyde treatment reduced the number of attached cells in polypropylene, reflected by colony count and scanning electron microscopy. The proteomic analysis of biofilms compared with planktonic cells indicated that several proteins were upregulated or downregulated, especially proteins that are involved in energy metabolism. Peroxiredoxin, ATP synthase alpha chain protein, conjugal transfer nickase/helicase TraI and elongation factor G were upregulated in untreated-biofilm cells, and their expression decreased as a function of cinnamaldehyde treatment. Cinnamaldehyde had antibiofilm activity, and several differentially expressed proteins identified provide potential and interesting targets to explore new control strategies for S. Typhimurium biofilms., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The formation of an urban heat island (UHI) is one of the most common impacts of the urbanization process. To mitigate the effects of UHI, the planning of urban forests (e.g., creation of parks, forests and afforestation streets) has been the major tool applied in this context. Thus, the aim of this study is to evaluate the spatial and temporal distribution of heat islands in Vila Velha, ES, Brazil using the mono-window algorithm. The study followed these methodological steps: 1) mapping of urban green areas through a photointerpretation screen; 2) application of the mono-window algorithm to obtain the spatial and temporal patterns of land surface temperature (LST); 3) correlation between LST and the normalized difference vegetation index (NDVI) and normalized difference build-up index (NDBI); 4) application of ecological evaluation index. The results showed that the mean values of LST in urban areas were at least 2.34 to 7.19°C higher than undeveloped areas. Moreover, the positive correlation between LST and NDBI showed an amplifying effect of the developed areas for UHI, while areas with a predominance of vegetation attenuated the effect of UHI. Urban centers, clustered in some parts of the city, received the worst ecological assessment index. Finally, the adoption of measures to guide the urban forest planning within urban centers is necessary to mitigate the effect of heat islands and provide thermal comfort in urban areas., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aerobic exercise (AE) reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during the sensitization remains unclear. Therefore, we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge. Mice were divided into 4 groups: mice non-sensitized and not submitted to exercise (Sedentary, n=10); mice non-sensitized and submitted to exercise (Exercise, n=10); mice sensitized and exposed to ovalbumin (OVA, n=10); and mice sensitized, submitted to exercise and exposed to OVA (OVA+Exercise, n=10). 24 h after the OVA/saline exposure, we counted inflammatory cells from bronchoalveolar fluid (BALF), lung levels of total IgE, IL-4, IL-5, IL-10 and IL-1ra, measurements of OVA-specific IgG1 and IgE, and VEGF and NOS-2 expression via western blotting. AE reduced cell counts from BALF in the OVA group (p<0.05), total IgE, IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers (p<0.05). There was an increase of NOS-2 expression, IL-10 and IL-1ra lung levels in the OVA groups (p<0.05). Our results showed that AE attenuated the acute lung inflammation, suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma., Competing Interests: Conflict of interest: The authors have no conflict of interest to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)

Prospecting for suitable areas for forestry operations, where the objective is a reduction in production and transportation costs, as well as the maximization of profits and available resources, constitutes an optimization problem. However, fuzzy logic is an alternative method for solving this problem. In the context of prospecting for suitable areas for the installation of wood panel industries, we propose applying fuzzy logic analysis for simulating the planting of different species and eucalyptus hybrids in Espírito Santo State, Brazil. The necessary methodological steps for this study are as follows: a) agriclimatological zoning of different species and eucalyptus hybrids; b) the selection of the vector variables; c) the application of the Euclidean distance to the vector variables; d) the application of fuzzy logic to matrix variables of the Euclidean distance; and e) the application of overlap fuzzy logic to locate areas for installation of wood panel industries. Among all the species and hybrids, Corymbia citriodora showed the highest percentage values for the combined very good and good classes, with 8.60%, followed by Eucalyptus grandis with 8.52%, Eucalyptus urophylla with 8.35% and Urograndis with 8.34%. The fuzzy logic analysis afforded flexibility in prospecting for suitable areas for the installation of wood panel industries in the Espírito Santo State can bring great economic and social benefits to the local population with the generation of jobs, income, tax revenues and GDP increase for the State and municipalities involved. The proposed methodology can be adapted to other areas and agricultural crops., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Pramipexole (PPX), a dopamine D2/3 receptor preferring agonist, is currently in use for the treatment of Parkinson's disease symptoms and restless legs syndrome. Recently, anti-inflammatory properties of PPX have been shown in an autoimmune model of multiple sclerosis, and case reports indicate PPX ameliorates depressive symptoms. Since peripheral inflammation is known to induce depression-like behavior in rodents, we assessed the potential antidepressant effect of PPX in an inflammatory model of depression induced by LPS. Repeated (daily for 7days, 1mg/kg, i.p.), but not acute (1h before LPS) treatment with PPX abolished the depression-like behavior induced by LPS (0.1mg/kg, i.p.) in the forced swim test, and the anhedonic behavior in the splash test. Interestingly, PPX per se decreased interleukin 1β levels and reversed LPS-induced increase in its content in mice hippocampus⋅ Repeated PPX treatment also prevented the increase in hippocampal levels of the 3-nitrotyrosine protein adducts induced by LPS. Haloperidol (0.2mg/kg, i.p.) and sulpiride (50mg/kg, i.p.) were unable to prevent the antidepressant-like effect of PPX in LPS-treated mice. Altogether, these results suggest that the observed antidepressant-like effect of PPX in LPS-treated mice may be dependent on its anti-inflammatory properties and may not be related to dopamine D2 receptor activation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Methylmalonic acid (MMA) accumulates in tissues in methylmalonic acidemia, a heterogeneous group of inherited childhood diseases characterized by neurological dysfunction, oxidative stress and neuroinflammation; it is associated with degeneration of striatal neurons and cerebral cortical atrophy. It is presently unknown, however, whether transient exposure to MMA in the neonatal period is sufficient to trigger inflammatory and apoptotic processes that lead to brain structural damage. Here, newborn mice were given a single intracerebroventricular dose of MMA at 12 hours after birth. Maze testing of 21- and 40-day-old mice showed that MMA-injected animals exhibited deficit in the working memory test but not in the reference test. MMA-injected mice showed increased levels of the reactive oxygen species marker 2',7'-dichlorofluorescein diacetate, tumor necrosis factor, interleukin-1β, caspases 1, 3, and 8, and increased acetylcholinesterase activity in the cortex, hippocampus and striatum. This was associated with increased astrocyte and microglial immunoreactivity in all brain regions. These findings suggest that transient exposure to MMA may alter the redox state and cause neuroinflammatory/apoptotic processes and glial activation during critical periods of brain development. Similar processes may underlie brain dysfunction and cognitive impairment in patients with methylmalonic acidemia., (© 2017 American Association of Neuropathologists, Inc. All rights reserved.)

Astyanax has been the subject of extensive cytogenetic studies due to its wide karyotypic diversity. This genus comprises species complexes, namely groups of fish of difficult morphological differentiation, such as the bimaculatus complex, which includes the characids with a rounded humeral spot. Thence, the present study proposed to accomplish a cytogenetic characterization of two species of this complex: A. asuncionensis and A. altiparanae, aiming to find chromosomal markers that differentiate these species, as well as achieve a better understanding of the karyotype evolution in the genus. For this we used different techniques of chromosome banding as C-banding, impregnation by silver nitrate, fluorochrome staining and FISH with 18S rDNA probe. This is the first cytogenetic study in A. asuncionensis, from Miranda river, which presented 2n = 50 and 18 m + 22sm + 6st + 4a (FN = 96) and single NORs. The populations of A. altiparanae also presented 2n = 50, but with different karyotypic formulae: the population of the Quexada river presented 16 m + 24sm + 4st + 6a (FN = 94) and the Esperança stream and Jacutinga river showed 16 m + 20sm + 4st + 10a (FN = 90). All analyzed populations showed an interindividual variation in the number and location of the nucleolar organizer regions (NORs). Single and multiple NORs were detected either by impregnation with silver nitrate or by FISH with 18S rDNA probe. After C-banding, the two species differed in relation to the composition and heterochromatin distribution. The meiotic cells of A. altiparanae male individuals were also analyzed, showing that, despite the high karyotype variability, chromosome pairing occurs normally. The data show that A. altiparanae and A. asuncionensis share some characteristics with other species of the bimaculatus complex, suggesting a close phylogenetic relationship among those species. However, some features can be used as differentiation chromosomal markers in altiparanae/asuncionensis morphotypes, which could result from a natural speciation process.

Background: Some plants had been used in the treatment of cancer and one of these has attracted scientific interest, the Euphorbia tirucalli (E. tirucalli), used in the treatment of asthma, ulcers, warts has active components with activities scientifically proven as antimutagenic, anti-inflammatory and anticancer., Methods: We evaluate the influence of the antitumoral fraction of the E. tirucalli latex in the larynx squamous cell carcinoma (Hep-2), on the morphology, cell proliferation and gene expression. The Hep-2 cells were cultivated in complete medium (MEM 10 %) and treated with E. tirucalli latex for 1, 3, 5 and 7 days. After statistically analyzing the proliferation of the tested cells, the cells were cultivated again for RNA extraction and the Rapid Subtractive Hybridization (RaSH) technique was used to identify genes with altered expression. The genes found using the RaSH technique were analyzed by Gene Ontology (GO) using Ingenuity Systems., Results: The five genes found to have differential expression were validated by real-time quantitative PCR. Though treatment with E. tirucalli latex did not change the cell morphology in comparison to control samples, but the cell growth was significantly decreased. The RaSH showed change in the expression of some genes, including ANXA1, TCEA1, NGFRAP1, ITPR1 and CD55, which are associated with inflammatory response, transcriptional regulation, apoptosis, calcium ion transport regulation and complement system, respectively. The E. tirucalli latex treatment down-regulated ITPR1 and up-regulated ANXA1 and CD55 genes, and was validated by real-time quantitative PCR., Conclusions: The data indicate the involvement of E. tirucalli latex in the altered expression of genes involved in tumorigenic processes, which could potentially be applied as a therapeutic indicator of larynx cancer.

A forest fire risk map is a basic element for planning and protecting forested areas. The main goal of this study was to develop a statistical model for preparing a forest fire risk map using GIS. Such model is based on assigning weights to nine variables divided into two classes: physical factors of the site (terrain slope, land-use/occupation, proximity to roads, terrain orientation, and altitude) and climatic factors (precipitation, temperature, water deficit, and evapotranspiration). In regions where the climate is different from the conditions of this study, the model will require an adjustment of the variables weights according to the local climate. The study area, Espírito Santo State, exhibited approximately 3.81% low risk, 21.18% moderate risk, 30.10% high risk, 41.50% very high risk, and 3.40% extreme risk of forest fire. The areas classified as high risk, very high and extreme, contemplated a total of 78.92% of heat spots., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: This study evaluated the tissue and inflammatory responses to the use of simvastatin and poly(lactic-co-glycolic acid) + hydroxyapatite + β-tricalcium phosphate (PLGA+HA+βTCP) scaffold for bone repair., Materials and Methods: Two defects of 5 mm in diameter were made in the calvaria of rats, which were shared into the following 6 groups: naive, sham, vehicle, PLGA+HA+βTCP scaffold, simvastatin (4 mg/mL), and simvastatin with the scaffold. Tissue samples were collected at 1, 7, 15, 30, and 60 days after surgery. Inflammation was evaluated by interleukin-1 beta and tumor necrosis factor alpha quantification and by a hemogram, whereas bone repair was evaluated using densitometry and scanning electron microscopy. Data were statistically analyzed using ANOVA followed by post hoc tests (P < 0.05)., Results: There was an increased cytokine expression in the scaffold and simvastatin groups (P < 0.001 and P < 0.05, respectively) 1 day after surgery but no alterations on the hemogram were observed. It was found on bone tissue samples that 60 days after surgery all groups presented similar densitometry values and morphology characteristics, despite the occurrence of bone formation delay in the simvastatin group (P < 0.01)., Conclusion: The use of simvastatin and PLGA+HA+βTCP scaffold, associated or not, did not lead to improvement in bone repair.

Many countries have environmental legislation to protecting natural resources on private property. In Brazil, the Brazilian Forestry Code determines specific areas to maintain with natural vegetation cover, known as areas of permanent preservation (APP). Currently, there are few studies that relate topographic variables on APP. In this context, we sought to evaluate the influence of relief on the conservation of areas of permanent preservation (APP) in the areas surrounding Caparaó National Park, Brazil. By using the chi-squared statistical test, we verified that the presence of forest cover is closely associated with altitude. The classes of APP in better conservation status are slopes in addition to hilltops and mountains, whereas APP streams and springs are among the areas most affected by human activities. The most deforested areas are located at altitudes below 1100.00 m and on slopes less than 45°. All orientations of the sides were significant for APP conservation status, with the southern, southeastern, and southwestern sides showing the lower degrees of impact. The methodology can be adjusted to environmental legislation to other countries.

Searches related to global warming have provided important insights into the response of terrestrial ecosystems, but few have examined the impacts on agricultural crops, particularly those associated with the monitoring of agrotoxin residues. In this context, the agriclimatological zoning is an important tool in the planning and consolidation of crops and should be considered in any initiative that involves such planning. This tool is particularly important in the analysis of agrotoxin residues and may be applied by the Program Analysis of Agrotoxin Residues in Food (PARA) created by the National Health Vigilance Agency of Brazil (ANVISA), which enables greater food security and contributes to the improvement of human health. The aim of this study was to elaborate the current and future agriclimatological zoning for the tomato crop, relating it with the monitoring of samples collected by PARA in Espírito Santo State, Brazil. The results indicate that a temperature increase of 5 °C creates a decrease in apt areas from 37.3% to 4.3%, for a total reduction of 33 percentage points (-88.5%). It is noted that of the 41 producing municipalities, only 26 have apt areas greater than 50%, highlighting the municipalities with apt areas greater than 90%, represented by Mantenópolis (100%), Guaçuí (98.5%), São José do Calçado (97.8%), Irupi (94.4%), Santa Teresa (92.3%), and Marechal Floriano (91.4%). The veracity of agriclimatological zoning is proved by a Kendall rank correlation coefficient of 0.876, indicating that the distribution of the variables of apt areas and productivity are similar at the significance level of 0.05 with a confidence interval 95%. After validation of the agriclimatological zoning for the tomato crop, it is recommended that the PARA should monitor 36 municipalities rather than the current 18, representing an increase of 100%. The methodology can be adjusted to agricultural crops of other countries., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The Cerrado is a wide Neotropical savanna with tremendously high endemic diversity. Yet, it is not clear what the prevalent processes leading to such diversification are. We used the Cerrado-endemic lizard Norops meridionalis to investigate the main abiotic factors that promoted genetic divergence, the timings of these divergence events, and how these relate to cryptic diversity in the group. We sequenced mitochondrial and nuclear genes from 21 sites of N. meridionalis to generate species tree, divergence time estimations, and estimate species limits. We also performed population-level analysis and estimated distribution models to test the roles of niche conservatism and divergence in the group diversification. We found that N. meridionalis is composed by at least five cryptic species. Divergence time estimations suggest that the deepest branches split back into the early-mid Miocene, when most of the geophysical activity of the Cerrado took place. The deep divergences found in N. meridionalis suggest that beta anoles invaded South America much earlier than previously thought. Recent published evidence supports this view, indicating that the Panama gap closed as early as 15 mya, allowing for an early invasion of Norops into South America. The spatial pattern of diversification within N. meridionalis follows a northwest-southeast direction, which is consistent across several species of vertebrates endemic to the Cerrado. Also, we found evidence for non-stationary isolation by distance, which occurs when genetic differentiation depends on space. Our preliminary data in two out of five lineages suggest that niche conservatism is an important mechanism that promoted geographic fragmentation in the group., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Melanotic neuroectodermal tumor of infancy frequently affects the maxilla. A communication between the oral and nasal cavities can be created by surgery. The authors rehabilitated a young patient with obturator prostheses to correct feeding. The association of the obturators with orthodontic devices provided proper maxillary growth and eruption of teeth. The outcomes were very satisfactory after a 3-year follow-up, and dental implants are planned.

Ethnopharmacological Relevance: Cedrus atlantica essential oil (CaEO) presents analgesic and anti-inflammatory sedative properties. However, it remains unknown whether CaEO alleviates acute postoperative pain., Materials and Methods: Here, we investigated the effect of CaEO on postoperative pain and its mechanisms related to the descending pain control in Swiss males mice induced by a plantar incision surgery (PIS) in the hindpaw., Results: Inhalation of CaEO (5', 30' or 60') markedly reduced mechanical hypersensitivity. This effect was prevented by pre-treatment with naloxone or p-chlorophenylalanine methyl ester (PCPA, 100mg/kg, i.p.)-induced depletion of serotonin. In addition, p-alpha-methyl-para-tyrosin (AMPT, 100mg/kg, i.p.)-induced depletion of norepinephrine, intraperitoneal injection of the α2-adrenergic receptor antagonist yohimbine (0.15 mg/kg, i.p.) or haloperidol (1mg/kg, i.p.) an antagonist of dopaminergic (D1 and D2) receptors prevented the effect of CaEO on hypersensitivity., Conclusions: These findings suggest that CaEO alleviates postoperative pain by activating the descending pain modulation pathways on the opioidergic, serotonergic, noradrenergic (α2-adrenergic) and dopaminergic (dopamine D1 and D2 receptors) systems., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Cervical cancer is the second most frequent cancer in women worldwide and is associated with genetic alterations, infection with human papilloma virus (HPV), angiogenesis and inflammatory processes. The idea that inflammation is involved in tumorigenesis is supported by the frequent appearance of cancer in areas of chronic inflammation. On the other hand, the inflammatory response is controlled by the action of anti-inflammatory mediators, among these mediators, annexin A1 (ANXA1), a 37 kDa protein was detected as a modulator of inflammatory processes and is expressed by tumor cells. The study was carried out on the epithelial cancer cell line (SiHa) treated with the peptide of annexin A1 (ANXA1Ac2-26). We combined subtraction hybridization approach, Ingenuity Systems software and quantitative PCR, in order to evaluate gene expression influenced by ANXA1. We observed that ANXA1Ac2-26 inhibited proliferation in SiHa cells after 72h. In these cells, 55 genes exhibited changes in expression levels in response to peptide treatment. Six genes were selected and the expression results of 5 up-regulated genes (TPT1, LDHA, NCOA3, HIF1A, RAB13) and one down-regulated gene (ID1) were research by real time quantitative PCR. Four more genes (BMP4, BMPR1B, SMAD1 and SMAD4) of the ID1 pathway were investigated and only one (BMPR1B) shows the same down regulation. The data indicate the involvement of ANXA1Ac2-26 in the altered expression of genes involved in tumorigenic processes, which could potentially be applied as a therapeutic indicator of cervical cancer., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Road mortality is the leading source of biodiversity loss in the world, especially due to fragmentation of natural habitats and loss of wildlife. The survey of the main species victims of roadkill is of fundamental importance for the better understanding of the problem, being necessary, for this, the correct species identification. The aim of this study was to verify if DNA barcodes can be applied to identify road-killed samples that often cannot be determined morphologically. For this purpose, 222 vertebrate samples were collected in a stretch of the BR-101 highway that crosses two Discovery Coast Atlantic Forest Natural Reserves, the Sooretama Biological Reserve and the Vale Natural Reserve, in Espírito Santo, Brazil. The mitochondrial COI gene was amplified, sequenced and confronted with the BOLD database. It was possible to identify 62.16% of samples, totaling 62 different species, including Pyrrhura cruentata, Chaetomys subspinosus, Puma yagouaroundi and Leopardus wiedii considered Vulnerable in the National Official List of Species of Endangered Wildlife. The most commonly identified animals were a bat (Molossus molossus), an opossum (Didelphis aurita) and a frog (Trachycephalus mesophaeus) species. Only one reptile was identified using the technique, probably due to lack of reference sequences in BOLD. These data may contribute to a better understanding of the impact of roads on species biodiversity loss and to introduce the DNA barcode technique to road ecology scenarios.

The effect of 3β-hidroxihop-22(29)ene (3-BHO) on insulin and glucagon-like peptide 1 (GLP-1) secretion as well as the mechanism of action of the compound in pancreatic islet on glucose homeostasis was investigated. The data from in vivo treatment show that 3-BHO significantly reduces the hyperglycemia by increasing the insulin and GLP-1 secretion, as well as by accumulating hepatic glycogen in hyperglycemic rats. In rat pancreatic β-cell, 3-BHO stimulates the glucose uptake, insulin vesicles translocation to the plasma membrane and thus the insulin secretion through the involvement of potassium channels (ATP- and Ca(2+)-dependent K(+) channels) and calcium channels (L-type voltage-dependent calcium channels (L-VDCC)). Furthermore, this study also provides evidence for a crosstalk between intracellular high calcium concentration, PKA and PKC in the signal transduction of 3-BHO to stimulate insulin secretion. In conclusion, 3-BHO diminishes glycaemia, stimulates GLP-1 secretion and potentiates insulin secretion and increase hepatic glycogen content. Moreover, this triterpene modulates calcium influx characterizing ATP-K(+), Ca(2+)-K(+) and L-VDCC channels-dependent pathways as well as PKA and PKC activity in pancreatic islets underlying the signaling of 3-BHO for the secretory activity and contribution on glucose homeostasis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Previous studies have demonstrated that myofibroblasts in the adjacent stroma are involved in the development and progression of malignant tumors. The aim of this study was to investigate the involvement of myofibroblasts in the progression of oral squamous cell carcinomas (OSCCs) by determining myofibroblast density in potentially malignant and malignant oral lesions. A total of 69 potentially malignant oral lesions (leukoplakias with mild, moderate or severe dysplasia), 90 OSCCs (well-, moderately and poorly differentiated), eight oral verrucous carcinomas and 29 fibrous hyperplasias were examined for the presence of myofibroblasts using immunohistochemical detection of isoform α of smooth muscle actin. Myofibroblasts were not identified in the adjacent stroma of fibrous hyperplasias and potentially malignant oral lesions, whereas 59.8% of the oral carcinomas exhibited myofibroblasts in various densities. The density was significantly higher in moderately and poorly differentiated OSCCs when compared with well-differentiated tumors (P=0.04 and P=0.007, respectively). In verrucous carcinomas, the specific variant of well-differentiated OSCC, stromal myofibroblasts were not detected. The results of the present study demonstrated that immunodetection of myofibroblasts does not aid with the determination of the malignant transformation potential of oral dysplasias, although moderately and poorly differentiated tumors exhibited a significantly higher density of myofibroblasts. The results reinforce the hypothesis that myofibroblasts may contribute to oral tumorigenesis, indicating that verification and monitoring of such may serve as a putative marker of OSCC behavior.

Essential oil of Cymbopogon citratus collected from Brazil and Cuba was tested to a chemical characterization and then was tested on the post-embryonic development of Musca domestica. The chemical composition analysis by GC-MS of the oils from Brazil/Cuba allowed the identification of 13 and 12 major constituents respectively; nine of them common to both. In the both oils, the main components were the isomers geranial and neral, which together form the compound citral. This corresponds to a total of 97.92%/Brazil and 97.69%/Cuba of the compounds identified. The monoterpene myrcene, observed only in the sample of Cuba, presented a large relative abundance (6.52%). The essential oil of C. citratus (Brazil/Cuba) was dissolved in DMSO and tested at concentrations of 5, 10, 25, 50, 75 and 100% and citral was prepared by mixing 16.8 mg with 960 µL DMSO. Both essential oils and monoterpene citral were applied topically to newly-hatched larvae (1µL/larva). The results showed a lethal concentration (LC50) of 4.25 and 3.24% for the Brazilian and Cuban essential oils, respectively. Mortalities of larval and newly-hatched larvae to adult periods were dose-dependent for the two both oils as for monoterpene citral, reaching 90%. Both essential oils and citral caused morphological changes in adult specimens.

Unlabelled: MicroRNAs (miRNAs) are small non-coding nucleotide sequences between 17 and 25 nucleotides in length that primarily function in the regulation of gene expression. A since miRNA has thousand of predict targets in a complex, regulatory cell signaling network. Therefore, it is of interest to study multiple target genes simultaneously. Hence, we describe a web tool (developed using Java programming language and MySQL database server) to analyse multiple targets of pre-selected miRNAs. We cross validated the tool in eight most highly expressed miRNAs in the antrum region of stomach. This helped to identify 43 potential genes that are target of at least six of the referred miRNAs. The developed tool aims to reduce the randomness and increase the chance of selecting strong candidate target genes and miRNAs responsible for playing important roles in the studied tissue., Availability: http://lghm.ufpa.br/targetcompare.

Background: Fasciolosis affects different ruminant species and leads to great economic losses for cattle farmers worldwide. Thus, the current study aimed to evaluate bovine fasciolosis prevalence in the state of Espírito Santo, Brazil, using slaughter maps provided by slaughterhouses and verifying the origin of cattle., Methods: A map was created based on analysis of epidemiological data. The ArcGIS/ArcINFO 10.1 software was employed in order to elaborate updated bioclimatic maps that displayed the fasciolosis prevalence within the state - per city- between 2009 and 2011., Results: According to the bioclimatic map it was clear that 52.24% of the state's total area comprise regions considered favorable for the development and survival of Fasciola hepatica. According to the data provided by slaughterhouses, the parasite was more frequent in the cities of Atílio Vivácqua, Itapemirim and Anchieta with respective prevalence of 28.41, 25.50 and 24.95%. Although the northern portion of the state is also favorable for the disease maintenance (reaching rates above 90%), several cities presented prevalence of only 0.99 and 1.94% respectively. These findings indicate that climatic and environmental factors only cannot be considered preponderant to fasciolosis occurrence. Regarding the slaughterhouse located in Anchieta city, the higher prevalence was registered in the cities of Jerônimo Monteiro, Alegre and Cachoeiro de Itapemirim, with mean prevalence of 1.21, 1.07 and 2.09% respectively., Conclusion: Although the present findings suggest a pattern for the prevalence of fasciolosis, records of the cities for the occurrence of the disease usually do not reflect the true origin of animals.

Rationale: There are evidences indicating the role of kinins in pathophysiology of traumatic brain injury, but little is known about their action on memory deficits., Objectives: Our aim was to establish the role of bradykinin receptors B₁ (B₁R) and B₂ (B₂R) on the behavioral, biochemical, and histologic features elicited by moderate lateral fluid percussion injury (mLFPI) in mice., Methods: The role of kinin B₁ and B₂ receptors in brain damage, neuromotor, and cognitive deficits induced by mLFPI, was evaluated by means of subcutaneous injection of B₂R antagonist (HOE-140; 1 or 10 nmol/kg) or B₁R antagonist (des-Arg9-[Leu8]-bradykinin (DAL-Bk; 1 or 10 nmol/kg) 30 min and 24 h after brain injury. Brain damage was evaluated in the cortex, being considered as lesion volume, inflammatory, and oxidative damage. The open field and elevated plus maze tests were performed to exclude the nonspecific effects on object recognition memory test., Results: Our data revealed that HOE-140 (10 nmol/kg) protected against memory impairment. This treatment attenuated the brain edema, interleukin-1β, tumor necrosis factor-α, and nitric oxide metabolites content elicited by mLFPI. Accordingly, HOE-140 administration protected against the increase of nicotinamide adenine dinucleotide phosphate oxidase activity, thiobarbituric-acid-reactive species, protein carbonylation generation, and Na⁺ K⁺ ATPase inhibition induced by trauma. Histologic analysis showed that HOE-140 reduced lesion volume when analyzed 7 days after brain injury., Conclusions: This study suggests the involvement of the B₂ receptor in memory deficits and brain damage caused by mLFPI in mice.

Objectives: In this study, we evaluated the effect of the proanthocyanidins-rich fraction (PRF) obtained from Croton celtidifolius bark in an experimental animal model of spinal cord injury and cell death induced by glutamate., Methods: Experiments were conducted using adult male Wistar rats (10 weeks old and weighing 270-300g). Experimental groups were randomly allocated into the following groups: spinal cord injury (SCI) + vehicle group: rats were subjected to SCI plus intraperitoneal administration of vehicle (saline 10 ml/kg); SCI + PRF: rats were subjected to SCI plus intraperitoneal administration of PRF (10 mg/kg) at 1 and 6 h after injury and sham operated., Key Findings: The treatment with the proanthocyanidin-rich fraction significantly improved not only motor recovery and grip force but also H2 O2 or glutamate-induced cell death and reactive oxygen species generation induced by glutamate in dorsal root ganglion cells. In this study we demonstrate that the neuroprotective effect triggered by the proanthocyanidins-rich fraction appears to be mediated in part by the inhibition of N-methyl-D-aspartate-type glutamate receptors., Conclusions: Taken together, our results demonstrate that PRF treatment ameliorates spinal cord injury and glutamatergic excitotoxicity and could have a potential therapeutic use., (© 2014 Royal Pharmaceutical Society.)

Objectives: The aim of this study was to evaluate the accuracy of virtual three-dimensional (3D) reconstructions of human dry mandibles, produced from two segmentation protocols ("outline only" and "all-boundary lines")., Materials and Methods: Twenty virtual three-dimensional (3D) images were built from computed tomography exam (CT) of 10 dry mandibles, in which linear measurements between anatomical landmarks were obtained and compared to an error probability of 5 %., Results: The results showed no statistically significant difference among the dry mandibles and the virtual 3D reconstructions produced from segmentation protocols tested (p = 0,24)., Conclusions: During the designing of a virtual 3D reconstruction, both "outline only" and "all-boundary lines" segmentation protocols can be used., Clinical Relevance: Virtual processing of CT images is the most complex stage during the manufacture of the biomodel. Establishing a better protocol during this phase allows the construction of a biomodel with characteristics that are closer to the original anatomical structures. This is essential to ensure a correct preoperative planning and a suitable treatment.

Background: The factors influencing variation in the clinical forms of Chagas disease have not been elucidated; however, it is likely that the genetics of both the host and the parasite are involved. Several studies have attempted to correlate the T. cruzi strains involved in infection with the clinical forms of the disease by using hemoculture and/or PCR-based genotyping of parasites from infected human tissues. However, both techniques have limitations that hamper the analysis of large numbers of samples. The goal of this work was to identify conserved and polymorphic linear B-cell epitopes of T. cruzi that could be used for serodiagnosis and serotyping of Chagas disease using ELISA., Methodology: By performing B-cell epitope prediction on proteins derived from pair of alleles of the hybrid CL Brener genome, we have identified conserved and polymorphic epitopes in the two CL Brener haplotypes. The rationale underlying this strategy is that, because CL Brener is a recent hybrid between the TcII and TcIII DTUs (discrete typing units), it is likely that polymorphic epitopes in pairs of alleles could also be polymorphic in the parental genotypes. We excluded sequences that are also present in the Leishmania major, L. infantum, L. braziliensis and T. brucei genomes to minimize the chance of cross-reactivity. A peptide array containing 150 peptides was covalently linked to a cellulose membrane, and the reactivity of the peptides was tested using sera from C57BL/6 mice chronically infected with the Colombiana (TcI) and CL Brener (TcVI) clones and Y (TcII) strain., Findings and Conclusions: A total of 36 peptides were considered reactive, and the cross-reactivity among the strains is in agreement with the evolutionary origin of the different T. cruzi DTUs. Four peptides were tested against a panel of chagasic patients using ELISA. A conserved peptide showed 95.8% sensitivity, 88.5% specificity, and 92.7% accuracy for the identification of T. cruzi in patients infected with different strains of the parasite. Therefore, this peptide, in association with other T. cruzi antigens, may improve Chagas disease serodiagnosis. Together, three polymorphic epitopes were able to discriminate between the three parasite strains used in this study and are thus potential targets for Chagas disease serotyping.

The methylmalonic acidemia is an inborn error of metabolism (IEM) characterized by methylmalonic acid (MMA) accumulation in body fluids and tissues, causing neurological dysfunction, mitochondrial failure and oxidative stress. Although neurological evidence demonstrate that infection and/or inflammation mediators facilitate metabolic crises in patients, the involvement of neuroinflammatory processes in the neuropathology of this organic acidemia is not yet established. In this experimental study, we used newborn Wistar rats to induce a model of chronic acidemia via subcutaneous injections of methylmalonate (MMA, from 5th to 28th day of life, twice a day, ranged from 0.72 to 1.67 μmol/g as a function of animal age). In the following days (29th-31st) animal behavior was assessed in the object exploration test and elevated plus maze. It was performed differential cell and the number of neutrophils counting and interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the blood, as well as levels of IL-1β, TNF-α, inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in the cerebral cortex were measured. Behavioral tests showed that animals injected chronically with MMA have a reduction in the recognition index (R.I.) when the objects were arranged in a new configuration space, but do not exhibit anxiety-like behaviors. The blood of MMA-treated animals showed a decrease in the number of polymorphonuclear and neutrophils, and an increase in mononuclear and other cell types, as well as an increase of IL-1β and TNF-α levels. Concomitantly, MMA increased levels of IL-1β, TNF-α, and expression of iNOS and 3-NT in the cerebral cortex of rats. The overall results indicate that chronic administration of MMA increased pro-inflammatory markers in the cerebral cortex, reduced immune system defenses in blood, and coincide with the behavioral changes found in young rats. This leads to speculate that, through mechanisms not yet elucidated, the neuroinflammatory processes during critical periods of development may contribute to the progression of cognitive impairment in patients with methylmalonic acidemia., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Acute intermittent porphyria is the most common acute porphyria caused by a decrease in hepatic porphobilinogen deaminase activity, resulting in an accumulation of delta-aminolevulinic acid and porphobilinogen. This disease shows nonspecific signs and symptoms that can be confused with other diseases, thereby making the diagnosis difficult. We report a case of acute intermittent porphyria, reviewing clinical and laboratory aspects, highlighting the hematological and biochemical parameters during and after the crisis. A female patient, aged 28 years, suffered two crises, both presenting gastrointestinal disorders. The second presented neuropsychiatric symptoms. The analysis of hematological and biochemical parameters during the second crisis showed anemia, leukocytosis, hyponatremia, mild hypokalemia, uremia and elevated C-reactive protein. The initial treatment included glucose infusion, a diet rich in carbohydrates and interruption of porphyrinogenic drugs. Subsequently, treatment was maintained with oral contraceptive use. According to the observed data, signs and symptoms of gastrointestinal, neurological and psychiatric disorders, associated with laboratory results presented in this paper can be applied to screen acute porphyria, contributing to early diagnosis.

Although attempts have been made to unveil protein-protein and host-pathogen interactions based on molecular insights of important biological events and pathogenesis in various organisms, these efforts have not yet been reported in Corynebacterium pseudotuberculosis (Cp), the causative agent of Caseous Lymphadenitis (CLA). In this study, we used computational approaches to develop common conserved intra-species protein-protein interaction (PPI) networks first time for four Cp strains (Cp FRC41, Cp 316, Cp 3/99-5, and Cp P54B96) followed by development of a common conserved inter-species bacterial PPI using conserved proteins in multiple pathogens (Y. pestis, M. tuberculosis, C. diphtheriae, C. ulcerans, E. coli, and all four Cp strains) and E. Coli based experimentally validated PPI data. Furthermore, the interacting proteins in the common conserved inter-species bacterial PPI were used to generate a conserved host-pathogen interaction (HP-PPI) network considering human, goat, sheep, bovine, and horse as hosts. The HP-PPI network was validated, and acetate kinase (Ack) was identified as a novel broad spectrum target. Ceftiofur, penicillin, and two natural compounds derived from Piper betel were predicted to inhibit Ack activity. One of these Piper betel compounds found to inhibit E. coli O157:H7 growth similar to penicillin. The target specificity of these betel compounds, their effects on other studied pathogens, and other in silico results are currently being validated and the results are promising.

New sequencing platforms have enabled rapid decoding of complete prokaryotic genomes at relatively low cost. The Ion Torrent platform is an example of these technologies, characterized by lower coverage, generating challenges for the genome assembly. One particular problem is the lack of genomes that enable reference-based assembly, such as the one used in the present study, Corynebacterium pseudotuberculosis biovar equi, which causes high economic losses in the US equine industry. The quality treatment strategy incorporated into the assembly pipeline enabled a 16-fold greater use of the sequencing data obtained compared with traditional quality filter approaches. Data preprocessing prior to the de novo assembly enabled the use of known methodologies in the next-generation sequencing data assembly. Moreover, manual curation was proved to be essential for ensuring a quality assembly, which was validated by comparative genomics with other species of the genus Corynebacterium. The present study presents a modus operandi that enables a greater and better use of data obtained from semiconductor sequencing for obtaining the complete genome from a prokaryotic microorganism, C. pseudotuberculosis, which is not a traditional biological model such as Escherichia coli., (© 2012 The Authors. Published by Society for Applied Microbiology and Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Fragments of mitochondrial (COI and rRNA 16S) and nuclear (Tmo-4C4) genes were sequenced to evaluate the phylogenetic relationships among 15 genera of the western South Atlantic Sciaenidae, two freshwater genera and the northwest Pacific Larimichthys crocea. Our results suggest a great diversification for the western Atlantic assemblage; the monophyly of Macrodon, Menticirrhus and Plagioscion genera; the distinctiveness of Bardiella, Stellifer and Ophioscion as belonging to the same clade; the possible existence of two distinct groups in Stellifer; the closer relationship between Lonchurus and Paralonchurus; the non-monophyly of Cynoscion; and the remarkable diversification of Larimus breviceps populations in the Brazilian coast. This is the most comprehensive study evaluating the phylogenetic relationships of the western Atlantic sciaenid and provides a guide for future studies within this family., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

Background: Although the molecular pathogenesis of pituitary adenomas has been assessed by several different techniques, it still remains partially unclear. Ribosomal proteins (RPs) have been recently related to human tumorigenesis, but they have not yet been evaluated in pituitary tumorigenesis., Objective: The aim of this study was to introduce serial analysis of gene expression (SAGE), a high-throughput method, in pituitary research in order to compare differential gene expression., Methods: Two SAGE cDNA libraries were constructed, one using a pool of mRNA obtained from five GH-secreting pituitary tumors and another from three normal pituitaries. Genes differentially expressed between the libraries were further validated by real-time PCR in 22 GH-secreting pituitary tumors and in 15 normal pituitaries., Results: Computer-generated genomic analysis tools identified 13,722 and 14,993 exclusive genes in normal and adenoma libraries respectively. Both shared 6497 genes, 2188 were underexpressed and 4309 overexpressed in tumoral library. In adenoma library, 33 genes encoding RPs were underexpressed. Among these, RPSA, RPS3, RPS14, and RPS29 were validated by real-time PCR., Conclusion: We report the first SAGE library from normal pituitary tissue and GH-secreting pituitary tumor, which provide quantitative assessment of cellular transcriptome. We also validated some downregulated genes encoding RPs. Altogether, the present data suggest that the underexpression of the studied RP genes possibly collaborates directly or indirectly with other genes to modify cell cycle arrest, DNA repair, and apoptosis, leading to an environment that might have a putative role in the tumorigenesis, introducing new perspectives for further studies on molecular genesis of somatotrophinomas.