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Objectives: to analyze the use of spirituality/religiosity by oncology nurse residents in caring for patients with cancer., Methods: a census, descriptive, sectional study, with 46 nurse residents from three public hospitals in Rio de Janeiro. Data collection took place between August 2020 and January 2021, using a sociodemographic questionnaire, including a question about the use of spirituality/ religiosity to deal with work situations. Descriptive analysis was carried out using SPSS software version 22.0., Results: participants stated that they use religiosity/spirituality in work situations related to patients or themselves. In relation to patients, death was the most mentioned situation among professionals, and for themselves, everyday situations and emotional vulnerability were the most mentioned., Final Considerations: spirituality and religiosity are dimensions that guide oncology nurse residents' attitudes.

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 M pro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for M pro , ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and M pro , with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with M pro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments., Competing Interests: The authors declare no conflicts of interest.

Objective: To investigate the association between body mass index (BMI), obesity, clinical outcomes, and mortality following coronary artery bypass grafting (CABG) in Brazil using a large sample with one year of follow-up from the Brazilian Registry of Cardiovascular Surgeries in Adults (or BYPASS) Registry database., Methods: A multicenter cohort-study enrolled 2,589 patients submitted to isolated CABG and divided them into normal weight (BMI 20.0-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI > 30.0 kg/m2) groups. Inpatient postoperative outcomes included the most frequently described complications and events. Collected post-discharge outcomes included rehospitalization and mortality rates within 30 days, six months, and one year of follow-up., Results: Sternal wound infections (SWI) rate was higher in obese compared to normal-weight patients (relative risk [RR]=5.89, 95% confidence interval [CI]=2.37-17.82; P=0.001). Rehospitalization rates in six months after discharge were higher in obesity and overweight groups than in normal weight group (χ=6.03, P=0.049); obese patients presented a 2.2-fold increase in the risk for rehospitalization within six months compared to normal-weight patients (RR=2.16, 95% CI=1.17-4.09; P=0.045). Postoperative complications and mortality rates did not differ among groups during time periods., Conclusion: Obesity increased the risk for SWI, leading to higher rehospitalization rates and need for surgical interventions within six months following CABG. Age, female sex, and diabetes were associated with a higher risk of mortality. The obesity paradox remains controversial since BMI may not be sufficient to assess postoperative risk in light of more complex and dynamic evaluations of body composition and physical fitness.

The carambola fruit fly Bactrocera carambolae Drew and Hancock (Diptera: Tephritidae) is an invasive fruit fly reported in North Brazil that threatens Brazilian fruit culture. Assessing the potential risk of establishing this pest is necessary to reduce the threat of B. carambolae dispersion to other countries and Brazilian regions and to avoid damage to the fruit trade. In this study, the CLIMEX model was used to understand the response of B. carambolae to climate change and to determine its potential global distribution with and without irrigation practices. Based on ecophysiological parameters, the model simulates factors limiting species distribution concerning the climate. To assess the seasonal variation in the density of B. carambolae, monitoring data in Uiramutã municipality, Roraima, from 2013 to 2019 was used. According to the CLIMEX forecast, large parts of America, Africa, and Asia, mainly in areas closest to the equator, are highly suitable for the survival of B. carambolae. Brazil is a good part of its territory with high suitability for B. carambolae, especially the North, South, and Southeast regions and the entire coastal area. The periods of the highest climatic suitability in the five Brazilian regions were January-May and October-December. The potential distribution area expands under irrigation and is highly suitable for most areas without cold stress. The CLIMEX model for B. carambolae generated in the present study provides important information for the Brazilian eradication program and other surveillance activities established in pest-free areas., (© 2023. Sociedade Entomológica do Brasil.)

Staphylococcus aureus is a microorganism with high morbidity and mortality due to antibiotic-resistant strains, making the search for new therapeutic options urgent. In this context, computational drug design can facilitate the drug discovery process, optimizing time and resources. In this work, computational methods involving ligand- and structure-based virtual screening were employed to identify potential antibacterial agents against the S. aureus MRSA and VRSA strains. To achieve this goal, tetrahydroxybenzofuran, a promising antibacterial agent according to in vitro tests described in the literature, was adopted as the pivotal molecule and derivative molecules were considered to generate a pharmacophore model, which was used to perform virtual screening on the Pharmit platform. Through this result, twenty-four molecules were selected from the MolPort ® database. Using the Tanimoto Index on the BindingDB web server, it was possible to select eighteen molecules with greater structural similarity in relation to commercial antibiotics (methicillin and oxacillin). Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the eighteen most similar molecules, showed that only three exhibited desired properties (LB255, LB320 and LB415). In the molecular docking study, the promising molecules LB255, LB320 and LB415 showed significant values in both molecular targets. LB320 presented better binding affinity to MRSA (-8.18 kcal/mol) and VRSA (-8.01 kcal/mol) targets. Through PASS web server, the three molecules, specially LB320, showed potential for antibacterial activity. Synthetic accessibility (SA) analysis performed on AMBIT and SwissADME web servers showed that LB255 and LB415 can be considered difficult to synthesize and LB320 is considered easy. In conclusion, the results suggest that these ligands, particularly LB320, may bind strongly to the studied targets and may have appropriate ADME/Tox properties in experimental studies.

The scale mealybug, Diaspis echinocacti (Bouché, 1833) (Hemiptera: Diaspididae), is one of the main pests of the cactus pear in Brazil. The objective was to study biological aspects of D. echinocacti at the constant temperatures of 25, 28, 30, 33 and 35 °C with relative humidity of 60 ± 10% and photoperiod of 12 hours in the laboratory on the cactus pear cultivar, "Orelha de Elefante Mexicana", Opuntia stricta [Haw.] Haw. The development period (22 to 35 days) and survival in the egg (92 to 100%) and nymph (21.8 to 100%) stages and of the egg-adult cycle (20 to 100%), longevity (34.1 to 59.6 days) and fecundity (33 to 112 eggs) of D. echinocacti females with the different temperature and absence of males at the highest temperatures (> 30°C), indicated that the range between 25 °C and 30°C is the most favorable for this scale mealybug. This information may help to improve integrated management programs for D. echinocacti, in areas subject to seasonal temperature changes in the Brazilian regions where cactus pear is cultivated.

The mango weevil, Sternochetus mangiferae (Fabricius) (Curculionidae), pest present in Brazil and is restricted to some municipalities in the Rio de Janeiro State. This curculionid attacks the mango crop exclusively and puts mango production globally at risk, especially those destined for export. Using ecological modeling tools, this study is the first to map the potential risk of S. mangiferae in Brazil. We aimed to identify the potential distribution of this pest in Brazilian states, drawing up thematic maps of regions that present suitable and unsuitable climatic conditions for the establishment of the pest using the MaxEnt ecological niche model. The average annual temperature, the annual precipitation, the average daytime temperature range, and the annual temperature range were the variables that contributed most to the selected model. The MaxEnt model predicted highly suitable areas for S. mangiferae throughout the Brazilian coast, especially on the northeast coast. The region responsible for more than 50% of mango production in Brazil, the São Francisco Valley, was classified by the model with suitability for the pest; it can impacts exportations due to the imposition of phytosanitary barriers. This information can be used in strategies to prevent the introduction and establishment of this pest in new areas and monitor programs in areas with recent occurrence. In addition, the model results can be used in future research plans on S. mangiferae in worldwide modeling studies and climate change scenarios., (© 2023. Sociedade Entomológica do Brasil.)

The MutS homolog 6 (MSH6) is a nuclear DNA mismatch repair (MMR) gene that encodes the MSH6 protein. MSH6 interacts with MSH2 to form the MutSα heterodimer. MutSα corrects DNA mismatches and unpaired nucleotides arising during DNA replication, deamination of 5-methylcytosine, and recombination between non-identical DNA sequences. In addition to correcting DNA biosynthetic errors, MutSα also recognizes chemically damaged DNA bases. Here, we show that inactivation of MSH6 affects the basal susceptibility of Arabidopsis thaliana to Pseudomonas syringae pv tomato DC3000. The msh6 T-DNA insertional mutant exhibited a reduced susceptibility to the bacterial invasion. This heightened basal resistance of msh6 mutants appears to be dependent on an increased stomatal closure, an accumulation of H 2 O 2 and double-strand breaks (DSBs) and a constitutive expression of pathogenesis-related (NPR1 and PR1) and DNA damage response (RAD51D and SOG1) genes. Complementation of this mutant with the MSH6 wild type allele under the control of its own promoter resulted in reversal of the basal bacterial resistance phenotype and the stomatal closure back to wild type levels. Taken together, these results demonstrate that inactivation of MSH6 increases Arabidopsis basal susceptibility to the bacterial pathogen and suggests a link between DNA repair and stress signaling in plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

When an epidemic started in the Chinese city of Wuhan in December 2019, coronavirus was identified as the cause. Infection by the virus occurs through the interaction of viral S protein with the hosts' angiotensin-converting enzyme 2. By leveraging resources such as the DrugBank database and bioinformatics techniques, ligands with potential activity against the SARS-CoV-2 spike protein were designed and identified in this investigation. The FTMap server and the Molegro software were used to determine the active site of the Spike-ACE2 protein's crystal structure. Virtual screening was performed using a pharmacophore model obtained from antiparasitic drugs, obtaining 2000 molecules from molport ® . The ADME/Tox profiles were used to identify the most promising compounds with desirable drug characteristics. The binding affinity investigation was then conducted with selected candidates. A molecular docking study showed five structures with better binding affinity than hydroxychloroquine. Ligand_003 showed a binding affinity of -8.645 kcal·mol -1 , which was considered an optimal value for the study. The values presented by ligand_033, ligand_013, ligand_044, and ligand_080 meet the profile of novel drugs. To choose compounds with favorable potential for synthesis, synthetic accessibility studies and similarity analyses were carried out. Molecular dynamics and theoretical IC 50 values (ranging from 0.459 to 2.371 µM) demonstrate that these candidates are promising for further tests. Chemical descriptors showed that the candidates had strong molecule stability. Theoretical analyses here show that these molecules have potential as SARS-CoV-2 antivirals and therefore warrant further investigation.

The common bed bug, Cimex lectularius L., is a difficult urban pest to control. A simulated field study was conducted to compare the efficacy of steam application and an insecticide mixture spray (0.05% acetamiprid and 0.06% bifenthrin mixture) against C. lectularius. Three types of furniture (desk chair, upholstered armchair, and wooden table) were treated in the laboratory. The efficacy of the treatments was evaluated by visual inspection and placement of interceptor traps under the legs of the furniture. One hundred mixed stages of an insecticide-resistant population of C. lectularius were released onto each furniture item. After a 10-day acclimation period, each furniture item received steam treatment, insecticide spray, or no treatment. The second application of treatment was conducted 14 d later. Bed bug counts from interceptors and visual inspections were recorded at 13 d and 28 d after the initial treatment. At 28 d, the mean (± SE) live bed bug count in the steam, spray, and control group was 1 ± 0, 2 ± 1, and 83 ± 10, respectively. Both treatment methods were highly effective in controlling bed bugs on furniture. The mean bed bug count from interceptors in the steam, spray, and control groups were 0.3 ± 0.2, 11 ± 7, and 47 ± 9, respectively. There was no significant difference in the efficacy between steam and spray treatments based on either visual inspection or bed bug counts from interceptors. However, based on interceptor counts, the steam treatment caused faster bed bug population reduction than insecticide sprays., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Skin Cancer (SC) is among the most common type of cancers worldwide. The search for SC therapeutics using molecular modeling strategies as well as considering natural plant-derived products seems to be a promising strategy. The phytochemical Rocaglamide A (Roc-A) and its derivatives rise as an interesting set of reference compounds due to their in vitro cytotoxic activity with SC cell lines. In view of this, we performed a hierarchical virtual screening study considering Roc-A and its derivatives, with the aim to find new chemical entities with potential activity against SC. For this, we selected 15 molecules (Roc-A and 14 derivatives) and initially used them in docking studies to predict their interactions with Checkpoint kinase 1 (Chk1) as a target for SC. This allowed us to compile and use them as a training set to build robust pharmacophore models, validated by Pearson's correlation ( p ) values and hierarchical cluster analysis (HCA), subsequentially submitted to prospective virtual screening using the Molport ® database. Outputted compounds were then selected considering their similarities to Roc-A, followed by analyses of predicted toxicity and pharmacokinetic properties as well as of consensus molecular docking using three software. 10 promising compounds were selected and analyzed in terms of their properties and structural features and, also, considering their previous reports in literature. In this way, the 10 promising virtual hits found in this work may represent potential anti-SC agents and further investigations concerning their biological tests shall be conducted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation, though no other collaboration, with several of the authors GS, CS at the time of the review., (Copyright © 2022 dos Santos, Borges, Silva, de Lima, Bastos, Ramos, Silva, da Silva and dos Santos.)

This study aimed to identify potential inhibitors and investigate the mechanism of action on SARS-CoV-2 ACE2 receptors using a molecular modeling study and theoretical determination of biological activity. Hydroxychloroquine was used as a pivot structure and antimalarial analogues of 1,2,4,5 tetraoxanes were used for the construction and evaluation of pharmacophoric models. The pharmacophore-based virtual screening was performed on the Molport ® database (~7.9 million compounds) and obtained 313 structures. Additionally, a pharmacokinetic study was developed, obtaining 174 structures with 99% confidence for human intestinal absorption and penetration into the blood-brain barrier (BBB); posteriorly, a study of toxicological properties was realized. Toxicological predictions showed that the selected molecules do not present a risk of hepatotoxicity, carcinogenicity, mutagenicity, and skin irritation. Only 54 structures were selected for molecular docking studies, and five structures showed binding affinity (ΔG) values satisfactory for ACE2 receptors (PDB 6M0J), in which the molecule MolPort-007-913-111 had the best ΔG value of -8.540 Kcal/mol, followed by MolPort-002-693-933 with ΔG = -8.440 Kcal/mol. Theoretical determination of biological activity was realized for 54 structures, and five molecules showed potential protease inhibitors. Additionally, we investigated the Mpro receptor (6M0K) for the five structures via molecular docking, and we confirmed the possible interaction with the target. In parallel, we selected the TopsHits 9 with antiviral potential that evaluated synthetic accessibility for future synthesis studies and in vivo and in vitro tests.

Plasmodium the causative agent of malaria is a member of the phylum Apicomplexa, where all invasive forms have a substrate-dependent motility called gliding, key to malaria transmission. Gliding allows parasite host-cell recognition, binding, cell entry and trespassing the cytoplasm. In this process Plasmodium releases molecules from micronemes and the cell surface that are deposited on trails left behind on the substratum as the parasite progresses. Previously we identified the heat shock protein 70-1 (HSP 70-1) on the surface and micronemes of P. berghei ookinetes, the parasite form that invades the mosquito midgut. To investigate if this protein is shed of from the parasite during invasion, we searched HSP 70-1 in gliding trails deposited on a solid surface by P. berghei ookinetes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chrysodeixis includens is a polyphagous pest restricted to the American continent. The occurrence of C. includens is allied, among other factors, by favorable conditions such as temperature, humidity, presence of hosts, and migratory behavior. In this work, we built spatiotemporal species distribution models at continental and global levels for the distribution of C. includens using CLIMEX to determine times and regions favorable for year-round survival and migration of this species and in case of invasion on other continents to apply timely and right phytosanitary measures. Our models estimated high climate suitability for C. includens in Central and large proportions of South America throughout the year. Moreover, there is suitability for C. includens growth in all months of the year in Central and northern part of South America. In the northern hemisphere, these conditions range from April to October, while in mid-southern parts of South America, favorable periods comprise October through June. The countries with the highest suitability for C. includens outside the American continent are located on the African and Asian continents. Our results show variable climate suitability for C. includens during the year that help to understand likely migration pattern in North America. This information would direct efforts for appropriate C. includens management during warm and moist periods of the year. Furthermore, our models notify the need for the development of strategies for the inspection and interception of C. includens especially in central Africa, India, South and Southeast Asia, and Northeast Australia.

Purpose: Lung cancer is a global health problem, with more than 220,000 new cases and 150,000 deaths per year in the United States. Likewise, in Brazil, lung cancer is the most lethal cancer with 30,200 new cases expected in 2020. Regarding treatment types, radiation therapy (RT) represents an important approach, since 60%-70% of the patients will receive this modality of treatment during the course of their disease. However, access to RT remains challenging because of the socioeconomic inequalities in the Brazilian population, where approximately 100,000 patients/year die without access to RT. This work provides an overview on the availability of high technology RT in Brazil., Methods: A retrospective study was performed using the Brazilian Radiotherapy Census, local public and private databases, and the current literature published in 2019., Results: The Brazilian radiotherapy network relies on approximately 363 linear accelerators and 20 cobalt machines that remain operational. Most of these machines are installed at public health facilities. Regarding high technology, intensity-modulated RT is available in 53.7% (n = 130) and volumetric modulated arc therapy in 28.5% (n = 69) of the institutions, although only 19.8% (n = 48) of those facilities are capable of performing image-guided RT using cone beam computed tomography. Considering only the public health care system, the scenario is more restricted, with 40.1% (n = 65) of the institutions offering intensity-modulated RT, 21% (n = 34) volumetric modulated arc therapy, and 14.8% (n = 24) using cone beam computed tomography. Because of these scare resources, only 16% of Radiation Departments offer stereotactic body RT., Conclusion: Brazil still needs to improve and provide high and safer RT technologies to patients with lung cancer across all Brazilian regions to attend the population needs and obtain better patient outcomes., Competing Interests: Arthur Accioly RosaEmployment: Grupo OncoclinicasHonoraria: RocheConsulting or Advisory Role: AstraZenecaTravel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

Background: In precision integrated pest management, management tactics are implemented only where and when needed, by identifying the sites where the pest population has reached economic thresholds. Tomato, Solanum lycopersicum (Linn.), is a vegetable cultivated worldwide, but its production is reduced by insect pests such as the whitefly, Bemisia tabaci (Genn.). To improve management, there is a need to understand B. tabaci spatial dynamics in tomato fields, which will elucidate colonization patterns and may improve management of this pest. Thus, this study was conducted to assess the spatial autocorrelation, distribution, and colonization patterns of B. tabaci in 19 commercial tomato fields through the growing season., Results: A total of 69 isotropic variograms were fit for B. tabaci. The insect distribution was aggregated with a strong level of spatial dependence. Ranges of spatial dependence varied from 0.53 to 19.05 m and 0.5 to 20 m for adults and nymphs, respectively. Overall, densities of adults and nymphs were higher and reached the economic threshold mainly at the field edges., Conclusion: Our results suggest a colonization pattern for B. tabaci starting at the edges and spreading inwards in to the tomato fields. This study can improve B. tabaci management in tomato fields, especially scouting and decision-making to treat fields. Scouting for this pest should be directed to the field edges, with sample points at least 20 m apart from each other for independent insect counts. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

Plant ribosomal proteins play universal roles in translation, although they are also involved in developmental processes and hormone signaling pathways. Among Arabidopsis RPL10 family members, RPL10A exhibits the highest expression during germination and early development, suggesting that RPL10A is the main contributor to these processes. In this work, we first analyzed RPL10A expression pattern in Arabidopsis thaliana using transgenic RPL10A pro :GUS plants. The gene exhibits a ubiquitous expression pattern throughout the plant, but it is most strongly expressed in undifferentiated tissues. Interestingly, gene expression was also detected in stomatal cells. We then examined protein function during seedling establishment and abscisic acid (ABA) response. Heterozygous rpl10A mutant plants show decreased ABA-sensitivity during seed germination, are impaired in early seedling and root development, and exhibit reduced ABA-inhibition of stomatal aperture under light conditions. Overexpression of RPL10A does not affect the germination and seedling growth, but RPL10A -overexpressing lines are more sensitive to ABA during early plant development and exhibit higher stomatal closure under light condition both with and without ABA treatment than wild type plants. Interestingly, RPL10A expression is induced by ABA. Together, we conclude that RPL10A could act as a positive regulator for ABA-dependent responses in Arabidopsis plants., (Copyright © 2020 Ramos, Casati, Spampinato and Falcone Ferreyra.)

Background: Raoiella indica Hirst (Acari: Tenuipalpidae) is the most critical coconut and banana pest recently introduced in Brazil. Once the mite pests are introduced, it is essential to understand their dynamics in important crops under open-field climatic conditions to implement strategies for their management and determine the periods when species populations may increase in the field. Modelling tools have been used to determine the potential distribution of species and implications for the management of invasive species. Thus, our aim in this study was to determine the seasonal variation in R. indica and the influence of the monthly climate using CLIMEX modelling. We adjusted the CLIMEX model for R. indica based on distribution data, additional biological characteristics, and fluctuations in the R. indica population in a commercial coconut plantation., Results: The model for the current climate shows a good match between the ecoclimatic index and the global distribution of R. indica. The model results demonstrate that most states of Brazil and several regions worldwide include areas with highly suitable climatic conditions for R. indica. We observed variations in the density of R. indica in commercial coconut crops, with the highest incidence occurring during the first months of the year., Conclusion: Our results showed different alterations in seasonal suitability for R. indica that may provide information for the implementation of methods for time management, such as strategies for sampling and control during periods with a high degree of suitability for R. indica. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

The heat shock protein family 70 (Hsp70) comprises chaperone proteins that play major multiple roles in Plasmodium asexual and sexual development. In this study, we analyzed the expression of Hsp70-1 in gametocytes, gametes, zygotes, and its participation in ookinete formation and their transition into oocysts. A monoclonal antibody against recombinant Hsp70-1 revealed its presence in zygotes and micronemes of ookinetes. Compared to wild type parasites, Hsp70-1 knockout ookinetes produced fewer oocysts in Plasmodium-susceptible Anopheles albimanus mosquitoes. This may indicate a defective transformation of ookinetes into oocysts in the absence of Hsp70-1. The presence of this protein in micronemes suggests its participation in mosquito infection, probably aiding to the adequate structural conformation of proteins in charge of motility, recognition and invasion of the insect midgut epithelium., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: This study assessed the linearity of pharmacokinetics (PK) of trimetazidine (TMZ) modified-release tablets (indicated in adults as an add-on therapy for stable angina pectoris) and measured its renal elimination, safety, and tolerability in healthy subjects., Methods: This was a randomized, open-label, single-ascending dose study in healthy subjects. Subjects were administered with a single dose of 35, 70, or 105 mg TMZ-modified release tablets (six subjects each). Pharmacokinetic evaluations and safety analysis were performed before the first dose and till 48 h post-first dose., Results: Following administration of 35, 70, and 105 mg TMZ-modified release; the C max (mean±SD) was 79.32 (±23.08), 153.17 (±23.08), and 199.67 (±23.08) ng/mL, the T max was 5.42 (±0.49), 4.51 (±1.27), and 4.57 (±0.96) h, t 1/2 was 7.75 (±1.62), 6.40 (±1.23), and 6.50 (±1.18) h, AUC (0-inf) was 1116.89 (±378.35), 1838.39 (±284.50), and 2504.84 (±348.35) ng.h/mL, CL R was 13.70 (±2.24), 14.80 (±5.91), and 19.58 (±6.24) L·h -1 and CL/F was 33.69 (±8.51), 38.85 (±6.15), and 42.74 (±7.10) L·h -1 , respectively. Slope estimates for AUC (0-inf) , AUC (0-t) , and C max were less than 1. Corresponding 95% CI of the slope for the AUC parameters excluded 1, indicating that the deviation from dose-proportionality was statistically significant. Corresponding 95% CI of the slope for C max included 1, indicating that the less than dose-proportional increase in C max was not statistically significant. No significant adverse events were observed., Conclusion: Substantial deviation from a dose-proportional increase in AUC (0-inf) and AUC (0-t) suggested a non-linear PK for TMZ-modified release. Single dose of TMZ-modified release was well tolerated and safe., Competing Interests: Abdus Samad, Deepa Arora, and Shashank Jain are employees of Lupin Limited, India. Sigal Kaplan is an employee of Teva Pharmaceutical Industries Ltd, Israel. Mónika Domahidy is an employee of Gedeon Richter Plc., Hungary. Hanka de Voogd is an employee of Mylan EPD, The Netherlands. Stella Böhmert is an employee of Sandoz International GmbH, Germany. Rita Silveira Ramos is an employee of Generis® Farmacêutica, Portugal., (Thieme. All rights reserved.)

Models validation in QSAR, pharmacophore, docking and others can ensure the accuracy and reliability of future predictions in design and selection of molecules with biological activity. In this study, pyriproxyfen was used as a pivot/template to search the database of the Maybridge Database for potential inhibitors of the enzymes acetylcholinesterase and juvenile hormone as well. The initial virtual screening based on the 3D shape resulted in 2000 molecules with Tanimoto index ranging from 0.58 to 0.88. A new reclassification was performed on the overlapping of positive and negative charges, which resulted in 100 molecules with Tanimoto's electrostatic score ranging from 0.627 to 0.87. Using parameters related to absorption, distribution, metabolism and excretion and the pivot molecule, the molecules selected in the previous stage were evaluated regarding these criteria, and 21 were then selected. The pharmacokinetic and toxicological properties were considered and for 12 molecules, the DEREK software not fired any alert of toxicity, which were thus considered satisfactory for prediction of biological activity using the Web server PASS. In the molecular docking with insect acetylcholinesterase, the Maybridge3_002654 molecule had binding affinity of -11.1 kcal/mol, whereas in human acetylcholinesterase, the Maybridge4_001571molecule show in silico affinity of -10.2 kcal/mol, and in the juvenile hormone, the molecule MCULE-8839595892 show in silico affinity value of -11.6 kcal/mol. Subsequent long-trajectory molecular dynamics studies indicated considerable stability of the novel molecules compared to the controls.AbbreviationsQSARquantitative structure-activity relationshipsPASSprediction of activity spectra for substancesCommunicated by Ramaswamy H. Sarma.

Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase-2 (COX-2) that were developed in order to avoid the side effects of non-selective inhibitors of COX-1. Thus, the present study aims to identify new selective chemical entities for the COX-2 enzyme via molecular modeling approaches. The best pharmacophore model was used to identify compounds within the ZINC database. The molecular properties were determined and selected with Pearson's correlation for the construction of quantitative structure-activity relationship (QSAR) models to predict the biological activities of the compounds obtained with virtual screening. The pharmacokinetic/toxicological profiles of the compounds were determined, as well as the binding modes through molecular docking compared to commercial compounds (rofecoxib and celecoxib). The QSAR analysis showed a fit with R = 0.9617, R 2 = 0.9250, standard error of estimate (SEE) = 0.2238, and F = 46.2739, with the tetra-parametric regression model. After the analysis, only three promising inhibitors were selected, Z-964 , Z-627 , and Z-814 , with their predicted pIC 50 (-log IC 50 ) values, Z-814 = 7.9484, Z-627 = 9.3458, and Z-964 = 9.5272. All candidates inhibitors complied with Lipinski's rule of five, which predicts a good oral availability and can be used in in vitro and in vivo tests in the zebrafish model in order to confirm the obtained in silico data.

This study evaluated the effect of age and renal impairment on pharmacokinetics of trimetazidine (TMZ) in healthy elderly and renally impaired subjects and assess safety and tolerability. In this open-label, multi-dose study, 73 subjects were divided into six treatment groups: (1) 55-65 years; (2) 66-75 years; (3) >75 years (dosing for groups 1-3 [healthy]: B.D. for 4 days), (4) mild renally impaired (dosed B.D. for 8 days); (5) moderate renally impaired (dosed O.D. for 8 days); and (6) severe renally impaired-no dialysis (dosed once every 48 h for 8 days). Blood and urine samples were collected and analyzed. The geometric least squares mean ratios for; Group 2 and 1 of AUC (0-τ)ss was 112.2 (90% CI; 92.0-136.8) and C max,ss was 109.9 (89.6-134.8), Group 3 and 1 of AUC (0-τ),ss was 140.5 (115.9-170.3) and C max,ss was 137.8 (112.9-168.2), Group 4 and 1 of AUC (0-τ),ss was 114.2 (90.3-144.4) and C max,ss was 120.8 (92.5-157.8), Group 5 and 1 of; AUC (0-τ),ss was 213.0 (153.1-296.3) and C max,ss was 123.3 (92.2-164.7) and Group 6 and 1 of AUC (0-τ),ss was 247.4 (197.8-309.6) and C max,ss was 95.6 (73.0-125.1). Significant increase in systemic exposure of TMZ was observed in subjects; over 75 year's age and renally impaired compared to healthy subjects. TMZ was safe and well-tolerated., (© 2020 Wiley Periodicals, Inc.)

Pest populations are mostly regulated by climate, intra- and interspecific competition, natural enemies, and host plant quality. Myzus persicae (Sulzer) (Hemiptera: Aphididae) is a widely adapted aphid in the agroecosystems and is one of the main bell pepper pests. In the present study, we determined the spatial and temporal dynamics and the regulatory factors of M. persicae populations in bell pepper crops. The number of aphids and their natural enemies were evaluated during 2 years in four commercial bell pepper fields. Myzus persicae density data were related to temperature, rainfall, and natural enemies by multiple regression analysis and were then submitted to geostatistical analysis. The density of M. persicae was higher during the plant's reproductive growth stage. Rainfall, Chrysoperla spp., and Toxomerus spp. regulate M. persicae populations. Initial infestations of this pest occur along the edges of the fields and subsequently spread towards the center. This information is useful for integrated management programs aimed at anticipating periods of higher abundance of M. persicae and identifying arthropods to be prioritized in biological control.

Nigella sativa ( N. sativa ) is a medicinal plant used for its therapeutic pharmacological effects such as anti-inflammatory, antioxidant, anticancer, antidiabetic, and immunomodulation. This study explored the anti-cytotoxic and anti-genotoxic effect of N. sativa through a micronucleus test (MNT) of BALB/c mice peripheral blood. Using 6-to-8-week-old healthy male BALB/c mice, four groups were formed: (1) Control (sterile water), single-dose 2 mg/kg/intraperitoneal (i.p); (2) N. sativa oil, 500 mg/kg/24 h/7 days/i.p; (3) Cisplatin (CP), single-dose 2 mg/kg/subcutaneous (s.c); (4) N. sativa + CP with their respective dosage. When evaluating polychromatic erythrocytes (PCE), a biomarker of cytotoxicity, the group treated with N. sativa + CP experienced an increase in the frequency of PCE, which demonstrated the recovery of bone marrow and modulation of cell proliferation. The analysis of micronucleated polychromatic erythrocytes (MNPCE), an acute genotoxicity biomarker, showed similar frequency of MNPCE within the groups except in CP, but, in the N. sativa + CP group, the frequency of MNPCE decreased and then regulated. Finally, the frequency of micronucleated erythrocytes (MNE), a biomarker of genotoxicity, the supplementation of N. sativa oil did not induce genotoxic damage in this model. Thus, we conclude that N. sativa has both cytoprotective, genoprotective effects and modulates cell proliferation in BALB/c mice.

Adenosine Receptor Type 2A (A 2A AR) plays a role in important processes, such as anti-inflammatory ones. In this way, the present work aimed to search for compounds by pharmacophore-based virtual screening. The pharmacokinetic/toxicological profiles of the compounds, as well as a robust QSAR, predicted the binding modes via molecular docking. Finally, we used molecular dynamics to investigate the stability of interactions from ligand-A 2A AR. For the search for A 2A AR agonists, the UK-432097 and a set of 20 compounds available in the BindingDB database were studied. These compounds were used to generate pharmacophore models. Molecular properties were used for construction of the QSAR model by multiple linear regression for the prediction of biological activity. The best pharmacophore model was used by searching for commercial compounds in databases and the resulting compounds from the pharmacophore-based virtual screening were applied to the QSAR. Two compounds had promising activity due to their satisfactory pharmacokinetic/toxicological profiles and predictions via QSAR (Diverset 10002403 pEC 50 = 7.54407; ZINC04257548 pEC 50 = 7.38310). Moreover, they had satisfactory docking and molecular dynamics results compared to those obtained for Regadenoson (Lexiscan ® ), used as the positive control. These compounds can be used in biological assays (in vitro and in vivo) in order to confirm the potential activity agonist to A 2A AR.

Rice is one of the most important socioeconomic crops in the world. The tarsonemid mite Steneotarsonemus spinki is one of the most destructive pests for this crop and is restricted to some regions of Asia and America. The aim of this work was to map the risk of S. spinki invasion in rice-growing areas in the world. Presence data of Oryza sativa and S. spinki obtained from the literature and bioclimatic parameters from WorldClim were analyzed in the MaxEnt program to generate suitability indices and distribution maps for each species and for the two species together. High annual mean temperature associated with low temperature annual range were the most important environmental variables for the occurrence of O. sativa and S. spinki, and low rainfall favoring S. spinki. The model indicates that there are climatic conditions for the establishment of S. spinki in important rice-producing regions, such as western and central Africa, Oceania, Asia, and North, Central, and South America. Our results are useful for the efficient establishment of phytosanitary measures to prevent the dispersal of S. spinki to new rice-producing areas.

Studying the spatial dynamics of pests allows the determination of abiotic and biotic factors affecting time and locations of pest attack to the crops. Such abiotic and biotic factors mainly include 1) climatic elements, 2) natural enemies, 3) phenological stage of plants, and 4) surrounding vegetation. Melon (Cucumis melo L. [Cucurbitales: Cucurbitaceae]) is among the most consumed fruit in the world, and the whitefly Bemisia tabaci (Gennadius) is among the main pests of this crop. This work aimed to determine the effects of surrounding vegetation, natural enemies, climatic elements, and stages of plants on the spatial dynamics of B. tabaci in commercial melon fields. Adult whitefly densities were monitored on four melon fields in a tropical climate region. Sampling location in crops was georeferenced. Experimental data were submitted to geostatistical analysis. The highest densities of B. tabaci occurred during hot periods experiencing lower rainfall, and when the surrounding area presented crops hosting B. tabaci, especially other melon farms. The density ratio of the predators (i.e., spiders and Geocoris sp.) were dependent on pest density. The pattern of field colonization by B. tabaci varies according to its density. Therefore, the surrounding vegetation, air temperature, and predators influence the spatial distribution of B. tabaci in melon fields. These results provide important information to melon farmers, assisting them to improve the management of B. tabaci in the field., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The pea leafminer, Liriomyza huidobrensis (Blanchard), is an important pest of tomato crops worldwide. Conventional sampling plans are the starting point for the development of pest control decision-making. The present study aimed to develop a conventional sampling plan for L. huidobrensis during the vegetative and reproductive stages of tomato (Solanum Lycopersicum L.). The best sampling unit for vegetative and reproductive stages of tomato crops was determined. The frequency distributions of L. huidobrensis densities in tomato crops were assessed, and the ideal number of samples to constitute the sampling plan was determined. The basal leaf of the middle section of the plant canopy was the best plant part for sampling. Pea leafminer densities were fitted to the negative binomial distribution with a common aggregation parameter (Kcommon = 0.7289) that represents all tomato fields. The sampling plan consists of 73 samples per field, irrespective of field size (1, 5, or 10 ha). Evaluations using this sampling plan were performed in 47 min, 1 h 9 min, and 1 h 25 min at a cost of US$1.74, US$2.54, and US$3.12 per sampling in fields of 1, 5, and 10 ha, respectively. The sampling plan developed in this study may lead to more well-informed decision-making for controlling L. huidobrensis in tomato fields up to 10 ha. Additionally, it is inexpensive (up to US$3.12 per sampling area), fast (up to 1 h 25 min per sampling area), and practical (it can be used in tomato crops at the vegetative and reproductive stages)., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bell pepper [Capsicum annuum L. (Solanales: Solanaceae)] is cultivated worldwide, and the consumption of its fruits has increased because this plant is a functional food rich in antioxidants. Frankliniella schultzei (Trybom) is an important bell pepper pest worldwide. Sampling plans are essential components of integrated pest management programs. Thus, we developed a conventional sampling plan for F. schultzei in bell pepper. The work was conducted during 2 yr in commercial bell pepper fields in the vegetative, flowering, and fruiting stages. Our results indicated that the sample and the ideal technique for the evaluation of F. schultzei populations in bell pepper were the apical canopy and the beating of this part of the plant in a white plastic tray, respectively. The densities of F. schultzei were adjusted to a negative binomial distribution, and they presented a common aggregation parameter (Kcommon = 0.3176), which made it possible to generate a sampling plan that could be used in bell pepper plantations at all plant growth stages. The developed sampling plan consisted of an evaluation of 61 plants per field that took 23 and 38 min to run on 1 and 5 ha fields, respectively. In the 1 and 5 ha fields, US$1.27 and US$1.92 were spent per sampling, respectively. Thus, the plan developed in this work can be incorporated into integrated management programs for F. schultzei in bell pepper crops by facilitating the accurate, representative and feasible sampling of this pest at all stages of the plant., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The whitefly, Bemisia tabaci, is considered one of the most important pests for tomato Solanum lycopersicum. The population density of this pest varies throughout the year in response to seasonal variation. Studies of seasonality are important to understand the ecological dynamics and insect population in crops and help to identify which seasons have the best climatic conditions for the growth and development of this insect species. In this research, we used CLIMEX to estimate the seasonal abundance of a species in relation to climate over time and species geographical distribution. Therefore, this research is designed to infer the mechanisms affecting population processes, rather than simply provide an empirical description of field observations based on matching patterns of meteorological data. In this research, we identified monthly suitability for Bemisia tabaci, with the climate models, for 12 commercial tomato crop locations through CLIMEX (version 4.0). We observed that B. tabaci displays seasonality with increased abundance in tomato crops during March, April, May, June, October and November (first year) and during March, April, May, September and October (second year) in all monitored areas. During this period, our model demonstrated a strong agreement between B. tabaci density and CLIMEX weekly growth index (GIw), which indicates significant reliability of our model results. Our results may be useful to design sampling and control strategies, in periods and locations when there is high suitability for B. tabaci.

Plant natural products can attenuate the myonecrosis caused by Bothrops snake venom and their phospholipases A₂ (PLA₂). In this study, we evaluated the effects of two fractions (F4 and F6) from Swietenia macrophylla and purified catechin on the muscle damage caused by a myotoxic PLA₂ from Colombian Bothrops asper venom (BaColPLA₂) in mice and by Bothrops marmoratus venom from Brazil in mouse phrenic nerve-diaphragm muscle (PND) preparations in vitro. Male mice were injected with PLA₂ (50 µg) in the absence or presence of F4, F6, and catechin, in the gastrocnemius muscle and then killed 3, 7, 14, and 28 h later for histopathological analysis of myonecrosis, leukocyte infiltration, and the presence of collagen. Fractions F4 and F6 (500 µg) and catechin (90 µg) significantly reduced the extent of necrosis at all-time intervals. These two fractions and catechin also attenuated the leukocyte infiltration on day 3, as did catechin on day 14. There was medium-to-moderate collagen deposition in all groups up to day 7, but greater deposition on days 14 and 28 in the presence of F6 and catechin. Bothrops marmoratus venom (100 µg/mL) caused slight (~25%) muscle facilitation after 10 minutes and weak neuromuscular blockade (~64% decrease in contractile activity after a 120-minute incubation). Pre-incubation of venom with F4 or F6 abolished the facilitation, whereas catechin, which was itself facilitatory, did not. All three fractions attenuated the venom-induced decrease in muscle contractions. These findings indicate that fractions and catechin from S. macrophylla can reduce the muscle damage caused by Bothrops venom and PLA₂. These fractions or their components could be useful for treating venom-induced local damage., Competing Interests: The authors declare no potential conflicts of interest regarding this manuscript. The funding sponsors had no role in the design of the study, in the collection, analysis or interpretation of the data, in the writing of the manuscript, or in the decision to publish the results.

A drug design for safer phenylbutazone was been explored by reactivity and docking studies involving single electron transfer mechanism, as well as toxicological predictions. Several approaches about its structural properties were performed through quantum chemistry calculations at the B3LYP level of theory, together with the 6-31+G(d,p) basis sets. Molecular orbital and ionization potential were associated to electron donation capacity. The spin densities contribution showed a preferential hydroxylation at the para -positions of phenyl ring when compared to other positions. In addition, on electron abstractions the aromatic hydroxylation has more impact than alkyl hydroxylation. Docking studies indicate that six structures 1 , 7 , 8 and 13 ⁻ 15 have potential for inhibiting human as well as murine COX-2, due to regions showing similar intermolecular interactions to the observed for the control compounds (indomethacin and refecoxib). Toxicity can be related to aromatic hydroxylation. In accordance to our calculations, the derivatives here proposed are potentially more active as well safer than phenylbutazone and only structures 8 and 13 ⁻ 15 were the most promising. Such results can explain the biological properties of phenylbutazone and support the design of potentially safer candidates.

Purpose: In 2012, the Committee for Medicinal Products for Human Use (CHMP) restricted prescription of trimetazidine (TMZ) to "add-on therapy for patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line therapies." TMZ was no longer indicated for ophthalmology and otolaryngology. Risk minimization measure (RMM) was communicated to physicians. The survey presented here evaluated effectiveness of the RMM and assessed physicians knowledge and compliance with RMM. It also analyzed actual prescribing pattern of TMZ., Methods: A cross sectional, web-based survey was developed and conducted among prescribing physicians of TMZ across 12 European countries. Physicians' samples were weighted to account for the actual proportion of specialties within and across countries., Results: Using weighted samples, data from 1123 physicians and 8332 prescriptions were analyzed. Most (74.0%) of the physicians assumed stable angina pectoris to be an indication for TMZ. Three quarter of (75.7%) of these physicians were aware of the approved indication. Vertigo (62.1%), tinnitus (42.5%), declined visual acuity, and visual field disturbances (45.1%) were also presumed to be approved indications for TMZ, and physicians actually prescribed for these indications. Only 29.8% of the physicians remembered receiving RMM communications regarding TMZ. Most (90.5%) of the physicians expressed their interest to know and comply with the safety communications. Of all prescriptions, 33.9% were issued for add-on therapy for patients with stable angina pectoris., Conclusions: RMM for TMZ prescription have been moderately effective. Improvement in physician's compliance with safety information of TMZ is necessary for patient's safety., (© 2018 John Wiley & Sons, Ltd.)

Background: A major, unresolved issue is how the uterine microenvironment determines pregnancy success in cattle. Before implantation, conceptus development depends on the uterine secretome (i.e., histotroph). Despite its pivotal role, little is known about the dynamics of histotroph synthesis and changes in composition throughout the early diestrus and the relevance to pregnancy establishment. We hypothesize that disturbances on histotroph composition affect the establishment of pregnancy. Aim was to disturb histotroph composition at early diestrus and verify the effects on: (Exp. 1) timing to restore its composition; and (Exp. 2) pregnancy rate after multiple-embryo transfer. Estrous cycle of multiparous Nelore cows were synchronized and estrus was considered d 0 (D0) of the experiments. Disturbance was through flushing each uterine horn with 30 mL of DMPBS and collecting the resulting uterine luminal flushing (ULF) on D1; D4; D7; D1 + D4 + D7. Control group remained not-collected. In Exp. 1, ULF was collected on D7.5 from all animals and used for quantification of total protein concentration and abundance of albumin. In Exp. 2, three in vitro-produced embryos were transferred to the uterine horn ipsilateral to the ovary containing the CL on D7.5 and pregnancy was checked on D25 by ultrasound., Results: In Exp. 1, ULF collection on D4 or D7 increased (1.5- to 2.2-folds) the total protein concentration and albumin abundance. ULF collection on D1 did not alter ( P  > 0.10) these endpoints. In Exp. 2, ULF collected on D4 or D7 decreased pregnancy rates to approximately half of that measured in the remaining groups., Conclusions: Subtle perturbations imposed to the native intrauterine milieu, such as those caused by a single, low-volume collection of ULF, profoundly disturbs intrauterine composition and pregnancy success. At least 4 d were necessary for the uterus to recover its composition and the functional capacity to carry post-implantation gestation., Competing Interests: Animal procedures were approved by the Ethics and Animal Handling Committee of the University of São Paulo (CEUA-FMVZ/USP; n° 9,585,220,316). The experiments were conducted at the University of São Paulo, Pirassununga, Brazil.Not applicable.The authors declare that they have no competing interests.

The whitefly, Bemisia tabaci, is a major threat to tomato Solanum lycopersicum and ranks as one of the world's 100 most invasive pests. This is the first study of B. tabaci (Biotype B and Q) global distribution, focusing on risk levels of this invasive pest, in areas projected to be suitable for open field S. lycopersicum cultivation under climate change. This study aims to identify levels of risk of invasive B. tabaci for areas of suitability for open field S. lycopersicum cultivation for the present, 2050 and 2070 using MaxEnt and the Global Climate Model, HadGEM2_ES under RCP45. Our results show that 5% of areas optimal for open field S. lycopersicum cultivation are currently at high risk of B. tabaci. Among the optimal areas for S. lycopersicum, the projections for 2050 compared to the current time showed an extension of 180% in areas under high risk, and a shortening of 67 and 27% in areas under medium and low risk of B. tabaci, respectively, while projections for 2070 showed an extension of 164, and a shortening of 49 and 64% under high, medium and low risk, respectively. The basis of these projections is that predicted temperature increases could affect the pest, which has great adaptability to different climate conditions, but could also impose limitations on the growth of S. lycopersicum. These results may be used in designing strategies to prevent the introduction and establishment of B. tabaci for open-field tomato crops, and assist the implementation of pest management programs., Competing Interests: The authors have declared that no competing interests exist.

Copidosoma truncatellum (Hymenoptera: Encyrtidae) is an important parasitoid wasp of the soybean looper, Chrysodeixis includens, but its effectiveness can be severely curtailed by the application of certain insecticides. Therefore, to identify insecticides that are potentially compatible with C. truncatellum, the lethal and behavioral effects of nine chemicals used to control the soybean looper were evaluated for their toxicity to the wasp. Chlorantraniliprole, chlorfenapyr, flubendiamide, and indoxacarb were the least toxic insecticides to the parasitoid, resulting in mortalities of less than 25%. In contrast, cartap, deltamethrin, and methomyl caused 100% mortality, and acephate and spinosad caused 76% and 78% mortality, respectively. At least one of the detoxifying enzymes (monooxygenase, glutathione S-transferase, and/or esterases) may be involved in the mechanisms underlying the selectivity of chlorantraniliprole, chlorfenapyr, flubendiamide, and indoxacarb for the parasitoid based on the results for the insecticide plus synergist treatment. Changes in the behavioral patterns (walking time and resting time) of the parasitoid were found with exposure to acephate, flubendiamide, indoxacarb and methomyl, but behavioral avoidance was not observed. Our results indicate that the insecticides chlorantraniliprole and chlorfenapyr are the most suitable for inclusion in integrated pest management strategies for the control of C. includens., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The building of multivariate calibration models using near-infrared spectroscopy (NIR) and partial least squares (PLS) to estimate the lignin content in different parts of sugarcane genotypes is presented. Laboratory analyses were performed to determine the lignin content using the Klason method. The independent variables were obtained from different materials: dry bagasse, bagasse-with-juice, leaf, and stalk. The NIR spectra in the range of 10 000-4000 cm -1 were obtained directly for each material. The models were built using PLS regression, and different algorithms for variable selection were tested and compared: iPLS, biPLS, genetic algorithm (GA), and the ordered predictors selection method (OPS). The best models were obtained by feature selection with the OPS algorithm. The values of the root mean square error prediction (RMSEP), correlation of prediction ( R P ), and ratio of performance to deviation (RPD) were, respectively, for dry bagasse equal to 0.85, 0.97, and 2.87; for bagasse-with-juice equal to 0.65, 0.94, and 2.77; for leaf equal to 0.58, 0.96, and 2.56; for the middle stalk equal to 0.61, 0.95, and 3.24; and for the top stalk equal to 0.58, 0.96, and 2.34. The OPS algorithm selected fewer variables, with greater predictive capacity. All the models are reliable, with high accuracy for predicting lignin in sugarcane, and significantly reduce the time to perform the analysis, the cost and the chemical reagent consumption, thus optimizing the entire process. In general, the future application of these models will have a positive impact on the biofuels industry, where there is a need for rapid decision-making regarding clone production and genetic breeding program.

There is increasing demand for new products for vegetable pest management. Thus, the aim of this study was to assess the toxicity of pyrethroids with acid moiety modifications to measure the insecticidal activity of these compounds on the lepidopteran vegetable pests Diaphania hyalinata (L.) (Lepidoptera: Pyralidae) and Asciamonuste (Latreille) (Lepidoptera: Pieridae) and evaluate their selectivity for the predatory ant Solenopsis saevissima (F. Smith) (Hymenoptera: Formicidae) and pollinator Tetragonisca angustula (Latreille) (Hymenoptera: Apidae: Meliponinae). Racemic mixtures of five new pyrethroids (30 µg molecule mg -1 insect body weight) resulted in high (100%) and rapid (stable LD 50 after 12 h) mortality in D. hyalinata and A. monuste. In A. monuste, the trans-pyrethroid [12] isomer showed similar toxicity to permethrin. For D. hyalinata, the trans-pyrethroid [9] isomer and cis-pyrethroid [10] isomer were as toxic as permethrin. Due to their low selectivity, these new pyrethroids should be applied on the basis of ecological selectivity principles to minimize impacts on nontarget organisms S. saevissima and T. angustula.

The objectives of the present investigation were to evaluate the pregnancy diagnosis by detection of either the allantochorion membrane (FMS) or amniotic sac (ASP) by per rectum palpation (PRP) during late embryonic or early fetal period on pregnancy loss (PRL) at reexamination, calving rates, and abnormalities in newborn calves. A controlled randomized blind design with 800 lactating dairy pregnant cows diagnosed by transrectal ultrasonography (TRUS) between Days 35 and 57 of gestation from one dairy farm were included. The cows were randomly divided according to detection of allantochorion membrane (FMS group; n = 264), detection of amniotic sac (ASP group; n = 266), and TRUS (control [CON] group; n = 270). TRUS was considered as the criterion standard method of comparison. The entire PRP was performed by one experienced veterinarian. Then, all the cows were reexamined only by TRUS between 2 and 4 weeks later by two independent veterinarians to assess PRL. The calving rate one (number of cows calved divided by the number of cows initially pregnant) and calving rate two (number of cows calved divided by the number of cows pregnant at reexamination) for each group was calculated. All abortions and stillborns were necropsied, and calves alive were followed for 5 days. The overall initial PRL (between initial pregnant cows and reexamination) for FMS, ASP, and CON groups was 7.4% (19/258), 8.8% (23/262), and 9.2% (24/260), respectively (P = 0.75). The overall late PRL (between reexamination and calving) for FMS, ASP, and CON groups was 4.2% (9/213), 5.7% (12/209), and 4.2% (9/216), respectively (P = 0.71). The calving rate one for FMS, ASP, and TRUS groups was 79.1% (204/258), 75.2% (197/262), and 79.6% (207/260), respectively (P = 0.63). The calving rate two for the same groups was 85.4% (204/239), 82.4% (197/239), and 87.7% (207/236), respectively (P = 0.27). The number of fetuses aborted late, premature, and mature dead from FMS, ASP, and CON groups was 6, 4, and 5, respectively (P = 0.85), and no abnormalities at necropsy were detected. One stillborn male calf with atresia coli after 281 days of gestation from a cow examined by ASP at Day 51 was diagnosed. It was concluded that the use of either FMS or ASP for pregnancy diagnosis during late embryonic or early fetal period did not increase the PRL, affect calving rates, or produce calves with congenital abnormalities., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The objective of the present study is to evaluate the acute effects of low-level laser therapy (LLLT) on functional capacity, perceived exertion, and blood lactate in hospitalized patients with heart failure (HF). Patients diagnosed with systolic HF (left ventricular ejection fraction <45 %) were randomized and allocated prospectively into two groups: placebo LLLT group (n = 10)-subjects who were submitted to placebo laser and active LLLT group (n = 10)-subjects who were submitted to active laser. The 6-min walk test (6MWT) was performed, and blood lactate was determined at rest (before LLLT application and 6MWT), immediately after the exercise test (time 0) and recovery (3, 6, and 30 min). A multi-diode LLLT cluster probe (DMC, São Carlos, Brazil) was used. Both groups increased 6MWT distance after active or placebo LLLT application compared to baseline values (p = 0.03 and p = 0.01, respectively); however, no difference was observed during intergroup comparison. The active LLLT group showed a significant reduction in the perceived exertion Borg (PEB) scale compared to the placebo LLLT group (p = 0.006). In addition, the group that received active LLLT showed no statistically significant difference for the blood lactate level through the times analyzed. The placebo LLLT group demonstrated a significant increase in blood lactate between the rest and recovery phase (p < 0.05). Acute effects of LLLT irradiation on skeletal musculature were not able to improve the functional capacity of hospitalized patients with HF, although it may favorably modulate blood lactate metabolism and reduce perceived muscle fatigue.

The objectives of the present study were to evaluate the effect of per rectal amniotic sac palpation (ASP) for pregnancy diagnosis during the late embryonic period on pregnancy loss, calving rates, and abnormalities in newborn calves. A controlled, randomized, blocked, blind experiment containing 680 lactating pregnant dairy cows with a viable embryo diagnosed by transrectal ultrasonography was performed. Two dairy operation sites (farm A and farm B) were selected. At each farm, the cows were randomly divided into control (CON) and ASP groups. The CON group was not subjected to pregnancy diagnosis via per rectum palpation. The ASP examinations were performed by one experienced veterinarian between Days 34 and 45 after breeding. All cows were reevaluated by transrectal ultrasonography only between 2 and 4 weeks later. Two calving rates were calculated: calving rate 1 (cows that calved from the initial number of pregnant cows) and calving rate 2 (cows that calved from cows pregnant at reexamination). In farm A, the percentages of early pregnancy loss were 11.5% (19 of 165) and 13.2% (24 of 182) for the CON and the ASP groups, respectively (P = 0.64). In farm B, the percentage of early pregnancy loss was 11.2% (19 of 170) for the CON group and 8.8% (14 of 159; P = 0.48) for the ASP group. In farm A, the percentage of late pregnancy loss was 7.6% (11 of 145) for the CON group and 5.5% (8 of 155; P = 0.39) for the ASP group. In farm B, the percentage of late pregnancy loss was 3.7% (5 of 137) for the CON group and 6.3% (8 of 127; P = 0.32) for the ASP group. In farm A, early pregnancy loss was higher than late pregnancy loss (12.4% vs. 6.3%; P = 0.01), and in farm B, the same tendency was detected (10.0% vs. 4.9%, for early and late pregnancy loss, respectively; P = 0.02). In farm A, calving rate 1 was 81.2% (134 of 165) for the CON group and 80.8% (147 of 182; P = 0.92) for the ASP group. Calving rate 2 for the same groups was 92.4% (134 of 145) and 94.8% (147 of 155), respectively (P = 0.68). In farm B, calving rate 1 was 77.7% (132 of 170) for the CON group and 74.8% (119 of 159; P = 0.55) for the ASP group. Calving rates 2 for the same groups were 87.4% (132 of 151) and 82.1% (119 of 145), respectively (P = 0.20). Two female calves with atresia coli were diagnosed only in the CON group. It was concluded that ASP during the late embryonic period for pregnancy diagnosis did not increase the pregnancy loss, affect calving rates, or produce abnormalities in calves., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Studying the multitude of molecular networks and pathways that are potentially involved in a complex trait such as fertility requires an equally complex and broad strategy. Here, we used Next-Generation Sequencing for the characterization of the transcriptional signature of the bovine endometrial tissue. Periovulatory endocrine environments were manipulated to generate two distinctly different fertility phenotypes. Cycling, non-lactating, multiparous Nelore cows were manipulated to ovulate larger (> 13 mm; LF group; high fertility phenotype) or smaller (< 12 mm; SF group) follicles. As a result, greater proestrus estrogen concentrations, corpora lutea and early diestrus progesterone concentrations were also observed in LF group in comparison to SF group. Endometrial cell proliferation was estimated by the protein marker MKI67 on tissues collected 4 (D4) and 7 (D7) days after induction of ovulation. Total RNA extracts from D7 were sequenced and compared according to the transcriptional profile of each experimental group (LF versus SF). Functional enrichment analysis revealed that LF and SF endometria were asynchronous in regards to their phenotype manifestation. Major findings indicated an LF endometrium that was switching phenotypes earlier than the SF one. More specifically, a proliferating SF endometrium was observed on D7, whereas the LF tissue, which expressed a proliferative phenotype earlier at D4, seemed to have already shifted towards a biosynthetically and metabolically active endometrium on D7. Data on MKI67 support the transcriptomic results. RNA-Seq-derived transcriptional profile of the endometrial tissue indicated a temporal effect of the periovulatory endocrine environment, suggesting that the moment of the endometrial exposure to the ovarian steroids, E2 and P4, regulates the timing of phenotype manifestation. Gene expression profiling revealed molecules that may be targeted to elucidate ovarian steroid-dependent mechanisms that regulate endometrial tissue receptivity. Data was deposited in the SRA database from NCBI (SRA Experiment SRP051330) and are associated with the Bio-Project (PRJNA270391). An overview of the gene expression data has been deposited in NCBI's Gene Expression Omnibus (GEO) and is accessible through GEO Series accession number GSE65450. Further assessment of the data in combination with other data sets exploring the transcriptional profile of the endometrial tissue during early diestrus may potentially identify novel molecular mechanisms and/or markers of the uterine receptivity.

This study aimed to characterize the endometrial transcriptome and functional pathways overrepresented in the endometrium of cows treated to ovulate larger (≥13 mm) versus smaller (≤12 mm) follicles. Nelore cows were presynchronized prior to receiving cloprostenol (large follicle [LF] group) or not (small follicle [SF] group), along with a progesterone (P4) device on Day (D) -10. Devices were withdrawn and cloprostenol administered 42-60 h (LF) or 30-36 h (SF) before GnRH agonist treatment (D0). Tissues were collected on D4 (experiment [Exp.] 1; n = 24) or D7 (Exp. 2; n = 60). Endometrial transcriptome was obtained by RNA-Seq, whereas proliferation and apoptosis were assessed by immunohistochemistry. Overall, LF cows developed larger follicles and corpora lutea, and produced greater amounts of estradiol (D-1, Exp. 1, SF: 0.7 ± 0.2; LF: 2.4 ± 0.2 pg/ml; D-1, Exp. 2, SF: 0.5 ± 0.1; LF: 2.3 ± 0.6 pg/ml) and P4 (D4, Exp. 1, SF: 0.8 ± 0.1; LF: 1.4 ± 0.2 ng/ml; D7, Exp. 2, SF: 2.5 ± 0.4; LF: 3.7 ± 0.4 ng/ml). Functional enrichment indicated that biosynthetic and metabolic processes were enriched in LF endometrium, whereas SF endometrium transcriptome was biased toward cell proliferation. Data also suggested reorganization of the extracellular matrix toward a proliferation-permissive phenotype in SF endometrium. LF endometrium showed an earlier onset of proliferative activity, whereas SF endometrium expressed a delayed increase in glandular epithelium proliferation. In conclusion, the periovulatory endocrine milieu regulates bovine endometrial transcriptome and seems to determine the transition from a proliferation-permissive to a biosynthetic and metabolically active endometrial phenotype, which may be associated with the preparation of an optimally receptive uterine environment., (© 2015 by the Society for the Study of Reproduction, Inc.)

Background: In cattle, recent studies have shown positive associations between pre-ovulatory concentrations of estradiol (E2), progesterone (P4) at early diestrus and fertility. However, information on cellular and molecular mechanisms through which sex steroids regulate uterine function to support early pregnancy is lacking. Based on endometrial transcriptome data, objective was to compare function of the redox system in the bovine uterus in response to different periovulatory endocrine milieus., Methods: We employed an animal model to control growth of the pre-ovulatory follicle and subsequent corpus luteum (CL). The large follicle-large CL group (LF-LCL, N=42) presented greater levels of E2 on the day of GnRH treatment (D0; 2.94 vs. 1.27 pg/mL; P=0.0007) and P4 at slaughter on D7 (3.71 vs. 2.62 ng/mL, P=0.01), compared with the small follicle-small CL group (SF-SCL, N=41). Endometrium and uterine washings (N=9, per group) were collected for analyses of variables associated with the uterine redox system., Results: The SF-SCL group had lower endometrial catalase (0.5 vs. 0.79 U/mg protein, P<0.001) and glutathione peroxidase (GPx; 2.0 vs. 2.43 nmol β-nicotinamide adenine dinucleotide phosphate reduced/min/mg protein, P=0.04) activity, as well as higher lipid peroxidation (28.5 vs. 17.43 nmol malondialdehyde/mg of protein, P<0.001) and superoxide dismutase (SOD) activity (44.77 vs. 37.76 U; P=0.04). There were no differences in the endometrial reactive species (RS) or glutathione (GSH) concentrations between the groups. The uterine washing samples showed no differences in the concentrations of RS or GSH or in total SOD activity (P>0.1). Additionally, catalase, GPx4, SOD1 and SOD2 gene expression was lower in the SF-SCL group than in the LF-LCL group., Conclusions: We concluded that the intrauterine environment of cows from the LF-LCL group exhibited higher antioxidant activity than that of the cows from the SF-SCL group. We speculate that uterine receptivity and fertility are associated with an optimal redox environment, such as that present in the animals in the LF-LCL group.

The functional response and predation parameters of three species of predatory pirate bugs Amphiareus constrictus (Stal), Blaptostethus pallescens Poppius, and Orius tristicolor (White) (Hemiptera: Anthocoridae) were evaluated at four different densities of eggs of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). Experiments were conducted in Petri dishes containing a tomato leaf disk infested with the pest eggs, and maintained inside growth chamber with environmental conditions of 25 ± 2 °C, 70 ± 10% relative humidity, and a photoperiod of 12:12 (L:D) h. A. constrictus and B. pallescens showed a type III functional response where predation increased at a decreasing rate after egg density was higher than 12 per leaf disk, reaching an upper plateau of 18.86 and 25.42 eggs per 24 hours, respectively. By contrast, O. tristicolor showed a type II functional response where the number of eggs preyed upon increased at a decreasing rate as egg density increased, reaching an upper limit of 15.20 eggs per 24 hours. The predator equations used in this study estimated handling time of 1.25, 0.87, 0.96 h for A. constrictus, B. pallescens, and O. tristicolor, respectively. The lower handling time and possible higher attack rate of B. pallescens suggests a higher efficiency and probably greater impact on the pest population. If conservation or classical biological control of T. absoluta is to be implemented, then prioritizing which natural enemy species is the most efficient is an important first step., (© The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)