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Background/objectives: Breast cancer is the most common cancer among women globally, and it negatively impacts diet and quality of life, increasing the risk of recurrence. Adhering to World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) lifestyle guidelines, such as healthy eating habits and nutritional status, can help in primary and secondary cancer prevention. However, no questionnaire was found for self-assessment of these guidelines for the Brazilian population. The aim of this study is to carry out content validity, pilot, and usability testing of the self-administered digital instrument "PrevCancer" assessing adherence to the WCRF/AICR recommendations in Brazilian female breast cancer survivors., Methods: We conducted a psychometric study that involved the development of an instrument based on WCRF/AICR recommendations. Assessment of content validity involved the Content Validity Index (CVI) based on expert assessments (n = 7). The pilot study involved the System Usability Scale (SUS) after applying the developed instrument (n = 65) and anthropometric assessment for convergent validity by female participants (n = 55). The final usability test consisted of evaluating the satisfaction with the instrument of women with breast cancer (n = 14)., Results: The "PrevCancer" instrument demonstrated good content (CVI = 1.0) as well as good usability and acceptability in the pilot study (mean SUS score = 88.1). The convergent validity stage demonstrated positive associations between the PrevCancer parameters and anthropometric parameters ( p < 0.001). In the final usability study (mean SUS score = 90.3), participants' receptivity to the instrument was excellent., Conclusions: The PrevCancer instrument had valid content and great usability by the target population, proving to be a useful tool for future cancer research.

The bone-muscle unit refers to the reciprocal regulation between bone and muscle by mechanical interaction and tissue communication via soluble factors. The RANKL stimulation induces mitochondrial biogenesis and increases the oxidative capacity in osteoclasts and adipocytes. RANKL may bind to the membrane bound RANK or to osteoprotegerin (OPG), a decoy receptor that inhibits RANK-RANKL activation. RANK is highly expressed in skeletal muscle, but the contribution of RANKL to healthy skeletal muscle fiber remains elusive. Here we show that RANKL stimulation in C2C12-derived myotubes induced activation of mitochondrial biogenesis pathways as detected by RNA-seq and western blot. RANKL expanded the mitochondrial reticulum, as shown by mitochondrial DNA quantification and MitoTracker staining, and boosted the spare respiratory capacity. Using MEK and MAPK inhibitors, we found that RANKL signals via ERK and p38 to induce mitochondrial biogenesis. The soleus from OPG-/- and OPG+/- mice showed higher respiratory rates compared to C57BL6/J WT mice, which correlates with high serum RANKL levels. RANKL infusion using a mini-osmotic pump in WT mice increased the number of mitochondria, boosted the respiratory rate, increased succinate dehydrogenase activity in skeletal muscle, and improved the fatigue resistance of gastrocnemius. Therefore, our findings reveal a new role of RANKL as an osteokine-like protein that impacts muscle fiber metabolism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Many antimicrobial peptides directly disrupt bacterial membranes yet can also damage mammalian membranes. It is therefore central to their therapeutic use that rules governing the membrane selectivity of antimicrobial peptides be deciphered. However, this is difficult even for short peptides owing to the large combinatorial space of amino acid sequences. Here we describe a method for measuring the loss or maintenance of antimicrobial-peptide activity for thousands of peptide-sequence variants simultaneously, and its application to Protegrin-1, a potent yet toxic antimicrobial peptide, to determine the positional importance and flexibility of residues across its sequence while identifying variants with changes in membrane selectivity. More bacterially selective variants maintained a membrane-bound secondary structure while avoiding aromatic residues and cysteine pairs. A machine-learning model trained with our datasets accurately predicted membrane-specific activities for over 5.7 million Protegrin-1 variants, and identified one variant that showed substantially reduced toxicity and retention of activity in a mouse model of intraperitoneal infection. The high-throughput methodology may help elucidate sequence-structure-function relationships in antimicrobial peptides and inform the design of peptide-based synthetic drugs., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The development of novel phytotoxic compounds has been an important aim of weed control research. In this study, we synthesized fluorinated chalcone derivatives featuring both electron-donating and electron-withdrawing groups. These compounds were evaluated both as inhibitors of the photosystem II (PSII) electron chain as well as inhibitors of the germination and seedling growth of Amaranthus plants. Chlorophyll a (Chl a) fluorescence assay was employed to evaluate their effects on PSII, while germination experiments were conducted to assess their impact on germination and seedling development. The results revealed promising herbicidal activity for (E)-3-(4-bromophenyl)-1-(4-fluorophenyl)prop-2-en-1-one (7 a) and (E)-1-(4-fluorophenyl)-3-phenylprop-2-en-1-one (7 e). Compounds 7 a and 7 e exhibited a reduction in Chl a parameters associated with performance indexes and electron transport per reaction center. This reduction suggests a decrease in PSII activity, attributed to the blockage of electron flow at the quinone pool. Molecular docking analyses of chalcone derivatives with the D1 protein of PSII revealed a stable binding conformation, wherein the carbonyl and fluorine groups interacted with Phe265 and His215 residues, respectively. Additionally, at a concentration of 100 μM, compound 7 e demonstrated pre- and post-emergent herbicidal activity, resulting in a reduction of the seed germination index, radicle and hypocotyl lengths of Amaranthus weeds., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Objective: to evaluate the patient safety climate in Primary Health Care from the perspective of nurses working in the services., Method: a quantitative and cross-sectional study conducted with 148 nurses from a municipality in the state of São Paulo. The Brazilian version of the Primary Care Safety Questionnaire Survey and personal, professional, and organizational performance variables (intention to stay at work, job satisfaction, care quality, and frequency of incidents) were used. Parametric and non-parametric comparison tests and Spearman's correlation coefficient were performed, considering a 5% significance level., Results: the safety climate was positive, varying from 4.52 to 5.33 and differing across districts for workload (p=0.0214) and leadership (p=0.0129). The safety climate professional variables and dimensions differed in relation to the frequency of incidents. Teamwork and safety and learning system were strongly correlated with job satisfaction and moderately with perceived care quality., Conclusion: teamwork and safety and learning system stood out for their positive correlations with job satisfaction and care quality. A positive safety climate favors the involvement of Primary Care nurses to develop improvement plans aligned with the National Patient Safety Program., Background: (1) The safety climate is perceived differently across health districts. (2) There is a correlation between the climate dimensions and professional satisfaction. (3) Workload and leadership exert an influence on the safety climate perception. (4) There is a relationship between the safety climate and reporting of care-related incidents. (5) The safety climate is perceived differently among nurses regarding their role.

Background: Trichoderma reesei is an organism extensively used in the bioethanol industry, owing to its capability to produce enzymes capable of breaking down holocellulose into simple sugars. The uptake of carbohydrates generated from cellulose breakdown is crucial to induce the signaling cascade that triggers cellulase production. However, the sugar transporters involved in this process in T. reesei remain poorly identified and characterized., Results: To address this gap, this study used temporal membrane proteomics analysis to identify five known and nine putative sugar transporters that may be involved in cellulose degradation by T. reesei. Docking analysis pointed out potential ligands for the putative sugar transporter Tr44175. Further functional validation of this transporter was carried out in Saccharomyces cerevisiae. The results showed that Tr44175 transports a variety of sugar molecules, including cellobiose, cellotriose, cellotetraose, and sophorose., Conclusion: This study has unveiled a transporter Tr44175 capable of transporting cellobiose, cellotriose, cellotetraose, and sophorose. Our study represents the first inventory of T. reesei sugar transportome once exposed to cellulose, offering promising potential targets for strain engineering in the context of bioethanol production., (© 2024. The Author(s).)

Freshwater ecosystems are essential to human and wildlife survival. They harbor a wide biodiversity that contributes to ecosystem services. In the ecosystem of the Brazilian Savanna, anthropic activities related to environmental pollution that includes mercury (Hg) is of concern. We studied total mercury concentrations ([THg]) in bottom sediments and macrophytes to assess its short-term (2012 and 2019) impact on a natural lake. Temporal changes in [Hg] were assessed with the geoaccumulation index (I geo ) and the sediment quality guidelines (SQG). The land use index (LUI) was used to assess differences in anthropogenic activities and the Normalized Difference Aquatic Vegetation Index (NDAVI) was used to assess macrophyte biomass density. The bioaccumulation factor (BAF) was used to assess Hg accumulation in macrophytes relative to sediments. The LUI showed an increase in the intensity of agricultural activities in the vicinities of the lake. The NDAVI indicated an increase in the density of macrophytes in the evaluated period. The I geo indicated that in all sampling sites, pollution levels in sediments increased in 2019 (I geo > 0), with concentrations exceeding the SQG in 2019. In 2012, [THg] in sediments ranged from 20.7 to 74.6 ng g -1 , and in 2019 they ranged from 129.1 to 318.2 ng g -1 . In macrophytes, [THg] ranged from 14.0 to 42.1 ng g -1 in 2012, to 53.0 and 175.3 ng g -1 in 2019. [THg] in bottom sediments and macrophytes were significantly higher in the second collection period (p < 0.05). There was no significant difference in BAF values between the periods and no significant bioaccumulation in macrophytes (BAF <1). Our results demonstrated that the macrophytes are not sensitive indicators of Hg pollution in lentic environments of the Brazilian Savanna; however, the increased land use intensity (agriculture, automotive traffic, and urban infrastructure) could increase Hg accumulation in sediments and macrophytes in a short time interval., 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 Ltd. All rights reserved.)

Tebuthiuron (TBU), a phenylurea herbicide, is widely applied in agricultural and non-agricultural soils. Because TBU resists degradation, it can contaminate water and reach the biota once it is released into the environment. However, the potential toxic effects of TBU on aquatic developing organisms have been poorly studied. By taking advantage of the early-life stages of zebrafish (Danio rerio), we have combined morphological, biochemical, behavioural, and molecular approaches to investigate the developmental toxicity triggered by environmentally relevant concentrations (from 0.1 to 1000 μg/L) of TBU. Exposure to TBU did not elicit morphological abnormalities but it significantly delayed hatching. In addition, TBU altered the frequency of tail coils in one-day post-fertilization (dpf) old embryos. Moreover, TBU exposure during four days significantly inhibited the whole body AChE activity of larvae. At the molecular level, TBU did not significantly affect the mRNA levels of four genes (elavl3, gfap, gap43, and shha) that play key roles during the neurodevelopment of zebrafish. By assessing the motor responses to repeated light-dark stimuli, 6 dpf larvae exposed to TBU displayed hyperactivity, showing greater travelling distance during the dark periods. Our categorization of swimming speed revealed an interesting finding - after the light was turned off, the exposed larvae abandoned the freezing mode (<2 mm/s) and travelled mainly at cruising speed (2-20 mm/s), showing that the larval hyperactivity did not translate into higher swimming velocity. Overall, our results offer new insights into the TBU toxicity to developing organisms, namely effects in AChE activity and hyperactivity, providing support data for future studies considering environmental risk assessment of this herbicide., 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 Ltd. All rights reserved.)

Objective: To evaluate the perception of the patient safety climate in primary health care associated with professional categories, health centers, and previous experience of participation in the National Program for the Improvement of Access and Quality of Primary Care., Method: Cross-sectional study with 119 health professionals in a city in the interior of the state of São Paulo, between August 2019 and February 2020, using the Brazilian version of the Primary Care Safety Questionnaire., Results: The safety climate was favorable, with better evaluation for communication and leadership and worse evaluation for workload. There were differences among health centers regarding teamwork (p=0.0010), workload (p=0.0001) and total score (p=0.0185). Professionals with previous experience participating in the improvement program have a better perception of the climate., Conclusion: The perception of climate did not differ between professional categories but differed between health centers.

The most highly expressed genes in microbial genomes tend to use a limited set of synonymous codons, often referred to as "preferred codons." The existence of preferred codons is commonly attributed to selection pressures on various aspects of protein translation including accuracy and/or speed. However, gene expression is condition-dependent and even within single-celled organisms transcript and protein abundances can vary depending on a variety of environmental and other factors. Here, we show that growth rate-dependent expression variation is an important constraint that significantly influences the evolution of gene sequences. Using large-scale transcriptomic and proteomic data sets in Escherichia coli and Saccharomyces cerevisiae, we confirm that codon usage biases are strongly associated with gene expression but highlight that this relationship is most pronounced when gene expression measurements are taken during rapid growth conditions. Specifically, genes whose relative expression increases during periods of rapid growth have stronger codon usage biases than comparably expressed genes whose expression decreases during rapid growth conditions. These findings highlight that gene expression measured in any particular condition tells only part of the story regarding the forces shaping the evolution of microbial gene sequences. More generally, our results imply that microbial physiology during rapid growth is critical for explaining long-term translational constraints., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

•Most data on the natural history of portal hypertension come from studies in adults. •The morbidity rate of upper gastrointestinal bleeding in children with portal hypertension tend to be underestimated. •This study showed the relevance of morbidity rates after variceal hemorrhage in pediatric patients, especially those with cirrhosis. •Patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications secondary to upper gastrointestinal bleeding and should be closely monitored. Background - Most data on the natural history of portal hypertension come from studies in adults. The morbidity rate of upper gastrointestinal bleeding (UGIB) in children with portal hypertension has not been systematically characterized. Objective - To describe the morbidity and mortality of UGIB in pediatric patients with portal hypertension and identify predictive factors for the occurrence of its main complications. Methods - This retrospective study included pediatric patients with cirrhotic portal hypertension or with extrahepatic portal vein obstruction (EHPVO). Mortality and UGIB complications within a period of up to 6 weeks of the bleeding were investigated. To determine the predictive factors of morbidity, a multivariate analysis was performed using logistic regression; all results were considered significant at P<0.05. Results - A total of 86 patients (51.2% with EHPVO and 48.8% with cirrhosis) had 174 bleeding events. Ascites was the most common complication (43.1% of all cases), being more prevalent in patients with cirrhosis (P<0.001). Cirrhosis was a predictor of the occurrence of any morbidity (OR 20.3). The need for blood transfusion was predictor of at least one complication (OR 5.8), ascites (OR 7.2) and infections (OR 3.8) in the general group and at least one complication (OR 11.3) and ascites (OR 5.8) in cirrhotic patients. The need for expansion was a predictor of any morbidity (OR 4.6) and infections (OR 3.9) in the general group, in addition to being predictor of infection in cirrhotic patients (OR 5.4). There were no deaths from UGIB in the six weeks post-bleeding. Conclusion - The study showed the relevance of morbidity after UGIB in pediatric patients with portal hypertension, especially in those with cirrhosis. The patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications related to upper gastrointestinal bleeding and should be closely monitored.

Concentrative nucleoside transporters (Cnts) are unidirectional carriers that mediate the energy-costly influx of nucleosides driven by the transmembrane sodium gradient. Cnts are transmembrane proteins that share a common structural organization and are found in all phyla. Although there have been studies on Cnts from a biochemical perspective, no deep research has examined their role at the organismal level. Here, we investigated the role of the Drosophila melanogaster cnt1 gene, which is specifically expressed in the testes. We used the CRISPR/Cas9 system to generate a mutation in the cnt1 gene. The cnt1 mutants exhibited defects in the duration of copulation and spermatid maturation, which significantly impaired male fertility. The most striking effect of the cnt1 mutation in spermatid maturation was an abnormal structure of the sperm tail, in which the formation of major and minor mitochondrial derivatives was disrupted. Our results demonstrate the importance of cnt1 in male fertility and suggest that the observed defects in mating behavior and spermatogenesis are due to alterations in nucleoside transport and associated metabolic pathways., 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., (Copyright © 2022 Maaroufi, Pauchova, Lin, Wu, Rouhova, Kucerova, Vieira, Renner, Sehadova, Hradilova and Zurovec.)

The main goal of this study was to assess alternatives to the current challenges on environmental quality and circular economy. The former is here addressed by the treatment of radioactively contaminated solutions, and the latter by using abundant and low-cost biomass. In this paper, we examine the biosorption of hexavalent uranium (U(VI)) in a batch system using the macrophytes Limnobium laevigatum and Azolla sp. by three operational parameters: biomass dose, metal ion concentration, and contact time. Simulated solutions were firstly addressed with two biomasses, followed by studies with real liquid organic radioactive waste (LORW) with Azolla sp. The batch experiments were carried out by mixing 0.20 g biomass in 10 mL of the prepared solution or LORW. The total contact time employed for the determination of the equilibrium times was 240 min, and the initial U(VI) concentration was 0.63 mmol L -1 . The equilibrium times were 15 min for L. laevigatum and 30 min for Azolla sp. respectively. A wide range of initial U(VI) concentrations (0.25-36 mmol L -1 ) was then used to assess the adsorption capacity of each macrophyte. Isotherm models validated the adsorption performance of the biosorption process. Azolla sp. presented a much higher U(VI) uptake (0.474 mmol g -1 ) compared to L. laevigatum (0.026 mmol g -1 ). When in contact with LORW, Azolla sp. removed much less uranium, indicating an adsorption capacity of 0.010 mmol g -1 . In conclusion, both biomasses, especially Azolla sp., can be used in the treatment of uranium-contaminated solutions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The ER membrane protein complex (EMC) is required for the biogenesis of a subset of tail anchored (TA) and polytopic membrane proteins, including Rhodopsin-1 (Rh1) and the TRP channel. To understand the physiological implications of EMC-dependent membrane protein biogenesis, we perform a bioinformatic identification of Drosophila TA proteins. From 254 predicted TA proteins, screening in larval eye discs identified two proteins that require EMC for their biogenesis: fan and Xport-A. Fan is required for male fertility in Drosophila and we show that EMC is also required for this process. Xport-A is essential for the biogenesis of both Rh1 and TRP, raising the possibility that disruption of Rh1 and TRP biogenesis in EMC mutants is secondary to the Xport-A defect. We show that EMC is required for Xport-A TMD membrane insertion and that EMC-independent Xport-A mutants rescue Rh1 and TRP biogenesis in EMC mutants. Finally, our work also reveals a role for Xport-A in a glycosylation-dependent triage mechanism during Rh1 biogenesis in the endoplasmic reticulum., (© 2021 The Authors.)

Abstract: The use of hyaluronic acid (HA) fillers in lip augmentation represents today 1 of the most widely used nonsurgical aesthetic procedures in the world. Regarding the severe complications are rare, insufficient professional experience for recognizing signs of vascular impairment and inadequate technique could lead to severe lip skin necrosis complications. Several of existing treatment protocols in the literature to treat vascular complication are mainly based on the use of hyaluronidase. Nevertheless, there is no consensus on dosage, interval between doses and complementary protocol among the aforementioned studies. This case aims to present a conservative approach for the clinical management of serious vasculature complications with HA injection. A high dose of hyaluronidase(11500 IU) with additional multimodal treatment was performed to the upper lip, nasolabial fold, and nose that successfully reversed a vascular complication process. The present findings suggest that the use of high doses of hyaluronidase with the complementary protocol used herein might be a promising approach in the treatment of severe vascular complication in the lips caused by HA filling., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Different biological groups can be used for monitoring aquatic ecosystems because they can respond to variations in the environment. However, the evaluation of different bioindicators may demand multiple financial resources and time, especially when abundance quantification and species-level identification are required. In this study, we evaluated whether taxonomic, numerical resolution and cross-taxa can be used to optimize costs and time for stream biomonitoring in Central Brazil (Cerrado biome). For this, we sampled different biological groups (fish, zooplankton, phytoplankton, and periphyton) in stream stretches distributed in a gradient of land conversion dominated by agriculture and livestock. We used the Mantel and Procrustes analyses to test the association among different taxonomic levels (species to class), the association between incidence and abundance data (numerical resolution), and biological groups. We also assessed the relative effect of local environmental and spatial predictors on different groups. The taxonomic levels and numerical resolutions were strongly correlated in all taxonomic groups (r > 0.70). We found no correlations among biological groups. Different sets of environmental variables were the most important to explain the variability in species composition of distinct biological groups. Thus, we conclude that monitoring the streams in this region using bioindicators is more informative through higher taxonomic levels with occurrence data than abundance. However, different biological groups provide complementary information, reinforcing the need for a multi-taxa approach in biomonitoring., Competing Interests: The authors have declared that no competing interests exist.

The aim of this pilot study was to evaluate the cardioprotective effects of carvedilol in dogs receiving doxorubicin chemotherapy and provide suggestions to future studies based on results and limitations of our study. Thirteen dogs were randomized into two experimental groups: 6 dogs in carvedilol group and 7 dogs in placebo group. In carvedilol group, 0.39 mg/kg ± 0.04 twice-daily oral carvedilol was started on the day of the first doxorubicin treatment and continued throughout the chemotherapy protocol until the final cardiological evaluation. Cardiological evaluations were performed before the first doxorubicin administration and then 10 to 15 days after each subsequent dose. Troponin I and oxidative stress tests were performed with serum collected from dogs at the initial and final cardiological evaluation. Carvedilol produced some echocardiographic and electrocardiographic changes (reduced E velocity and E/IVRT ratio, as well reduced heart rate and increased PR and QT interval) due to its beta-block effect. In placebo group Doppler study showed a significant increase in mitral flow deceleration time (EDT), as well increased amplitude of the S wave in the right, and R wave in the left, precordial chest leads. There were significant difference in the EDT, E/IVRT and A' velocity, as well heart rate, PR interval and R wave in V4/CV6LU precordial chest lead between groups. In conclusion, some indexes of diastolic function and in precordial chest leads were less affected by doxorubicin in carvedilol than in control group. This suggests that carvedilol may have a beneficial effect in canine cancer patients receiving doxorubicin., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Non-infectious uveitis, an ocular inflammatory condition that affects the iris, ciliary body, choroid, and adjacent tissues (retina, optic nerve, and vitreous), is an important cause of blindness worldwide. Sirolimus (SRL), a potent immunomodulatory drug, has shown promising results in the treatment of inflammatory ocular diseases. Despite this therapeutic potential, its clinical use is a major challenge due to low bioavailability and poor solubility. Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer commonly used for ophthalmic drug delivery due to its suitable characteristics such as biocompatibility, good mechanical properties, and improvement of the pharmacokinetic profile of the drug. In the present study, we investigated the effects of SRL-PLGA implant on experimental autoimmune uveitis in rabbits. Clinical and histopathological examinations were performed, followed by assessment of protein levels and determination of myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activity in the aqueous humor/vitreous. As a result, treated eyes had decreased average inflammatory scores, protein significant decreases in treated eyes, assessed after 35 days. Histopathological examination showed less severe intraocular inflammation and decreased tissue damage in treated eyes. According to these results, the SRL-PLGA implant evaluated in this study was apparently safe, reducing inflammation in treated eyes, with an extended effect possibly associated with prolonged release of SRL in the posterior segment of the eye. Therefore, intravitreal SRL-PLGA implant could be a promising alternative for treatment of non-infectious uveitis.

Background: The expansion of Aedes aegypti (Diptera: Culicidae) population has increased the number of cases of arboviruses, in part due to the inefficiency and toxicity of the chemical control methods available to control this vector. We synthesized 19 chalcone derivatives and examined their activity against Ae. aegypti larvae in order to select larvicidal compounds that are non-toxic to other organisms., Results: Seven chalcone derivatives (3a, 3e, 3f, 6a, 6c, 6d, and 6f) had lethal concentrations of substituted chalcones capable of killing 50% (LC 50 ) values lower than 100 mg mL -1 at 24 h post-treatment, which is the dose that the World Health Organization recommends for the selection of promising larvicides. The type of substituent added to (E)-1,3-diphenylprop-2-en-1-one (3a) markedly affected the larvicidal activity. Addition of chlorine, bromine and methoxy groups to the aromatic rings reduced the larvicidal activity, while replacement of the B-ring (phenyl) by a furan ring significantly increased the larvicidal activity. The furan-chalcone (E)-3-(4-bromophenyl)-1-(furan-2-yl)prop-2-en-1-one (6c) killed Ae. aegypti larvae (LC 50 = 6.66 mg mL -1 ; LC 90 = 9.97 mg mL -1 ) more effectively than the non-substituted chalcone (3a) (LC 50 = 14.43 mg mL -1 ; LC 90 = 20.96 mg mL -1 ), and was not toxic to the insect Galleria mellonella, to the protozoan Tetrahymena pyriformis, and to the algae Chorella vulgaris., Conclusions: The substitution pattern of chalcones influenced their larvicidal activity. In the set of compounds tested, (E)-3-(4-bromophenyl)-1-(furan-2-yl)prop-2-en-1-one (6c) was the most effective larvicide against Ae. aegypti, with no clear signs of toxicity to other animal models. Its mechanism of action and effectiveness under field conditions remain to be determined., (© 2020 Society of Chemical Industry.)

Rosmarinic acid, a plant-derived compound with antiangiogenic activity, can be applied for the treatment of ocular diseases related to neovascularization, such as diabetic retinopathy, macular edema, and age-related macular degeneration. These diseases represent the leading causes of blindness worldwide if they are not properly treated. Intravitreal devices allow for localized drug delivery to the posterior segment, increasing the drug bioavailability and promoting extended release, thus, reducing side effects and enhancing the patient's compliance to the treatment. In this work, rosmarinic acid-loaded poly lactic-co-glycolic acid intraocular implants were developed with a view for the treatment of ocular neovascularization. Physical-chemical, biocompatibility, and safety studies of the implants were carried out in vitro and in vivo as well as an evaluation of the antiangiogenic activity in a chorioallantoic membrane assay. Data obtained showed that rosmarinic acid released from the implants was quantified in the vitreous for 6 weeks, while when it was in the solution formulation, after 24 h, no drug was found in the vitreous. The delivery device did not show any sign of toxicity after clinical evaluation and in electroretinographic findings. Histological analysis showed normal eye tissue. Rosmarinic acid released from implants reduced 30% of new vessel's formation. The intravitreal implant successfully allowed for the prolonged release of rosmarinic acid, was safe to rabbits eyes, and demonstrated activity in vessel reduction, thus demonstrating potential in preventing neovascularization in ophthalmic diseases., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aim: Eight coumarin derivatives ( 1a-h ) obtained from natural (-)-mammea A/BB ( 1 ) and 13 synthetic coumarins ( 2-14 ) had their cytotoxicity and biological activity evaluated against Mycobacterium tuberculosis H 37 Rv reference strain and multidrug-resistant clinical isolates. Materials & methods: Anti- M. tuberculosis activity was evaluated by resazurin microtiter assay plate, and the cytotoxicity of natural and synthetic products using J774A.1 macrophages by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Results: Compounds 1g , 5 , 6 , 12 and 14 were more active against M. tuberculosis H 37 Rv and multidrug-resistant clinical isolates with MIC values ranging from 15.6 to 62.5 μg/ml. Conclusion: These results demonstrate that the coumarin derivatives were active against multidrug-resistant clinical isolates, becoming potential candidates to be used in the treatment of resistant tuberculosis.

Uveitis encompasses a heterogeneous and complex group of conditions characterized by intraocular inflammation, frequently affecting young individuals and representing an important cause of irreversible blindness worldwide. Animal models have been critical to understand etiology and pathogenesis of uveitis, being also employed to assess new therapeutic strategies, preceding human studies. However, there is still a need of developing and studying different models, due to the difficulties in recapitulating all forms of human uveitis effectively. Although corticosteroids are usually the first-line therapy for non-infectious uveitis, their long-term use is limited by potentially serious side effects in all possible delivery routes. Thus, thalidomide, a drug with anti-inflammatory and antiangiogenic properties, was investigated in a novel experimental model of uveitis, induced by Mycobacterium bovis Calmette-Guérin Bacillus (BCG), in rabbits. The experimental protocol consisted of two subcutaneous injections of BCG, followed by two intravitreal injections of the same antigen, inducing panuveitis. Animals were treated with a single intravitreal injection of thalidomide suspension or PBS. Clinical manifestations of uveitis improved after intravitreal thalidomide, involving both anterior and posterior segments. Protein content, N-acetyl-b-glucosaminidase (NAG) and myeloperoxidase (MPO) activities were elevated in ocular tissues after disease induction, further decreasing post-treatment with intravitreal thalidomide. This therapeutic response was also confirmed on ocular electrophysiology, as well as histopathology. This experimental model induced panuveitis in rabbits using a low-cost mycobacterial antigen, with intraocular inflammation subsequently improving after treatment. Intravitreal thalidomide may be a potential alternative to treat intraocular inflammation in corticosteroid-sparing therapies., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cockatiels are popular pets. Still, despite medical and surgical relevance, the radiographic anatomy of the cockatiel (Nymphicus hollandicus) skeleton, like that of different wild and exotic bird species, has seldom been described. This study set out to describe the radiographic anatomy of the cockatiel skeleton. Twelve adult male and nine adult female specimens were radiographed using a digital X-ray system and different views. The radiographic anatomy of these birds was similar to that of other Psittacidae. However, some particularities inherent to the target species were detected, such as the presence of four flexion zones in the skull (craniofacial, nasal, jugal arch and palatine), complete bony orbit comprising a suborbital arch, 34-38 vertebrae (10 or 11 cervical, 8 or 9 thoracic, 9 or 10 lumbosacral, 5 or 6 caudal vertebrae and a pygostyle comprising 2 fused vertebrae), eight or nine pairs of ribs and a notarium made up of fused T2-T6 vertebrae. Poor radiopacity of the notarium, ribs and respective uncinate processes, and synsacral vertebrae made demarcation of these structures difficult. The appendicular skeleton of the cockatiel was very similar to that of other Psittacidae, and there were no gender-related differences., (© 2019 Blackwell Verlag GmbH.)

Gradual environmental changes are determining factors in the disposition of plants and associated organisms, such as arbuscular mycorrhizal fungi (AMF). The objective of this study was to evaluate the AMF species communities in a tropical semi-arid region of NE Brazil under decreasing clay content at a mountain top area forming a vegetative mosaic of dry forests, savanna-like shrubland and humid montane forests. Through field and trap culture samples, 80 species of AMF were identified belonging to 25 genera, of which Acaulospora and Glomus were the most representative. In general, representatives of the order Gigasporales were indicators of sites with lower clay content and showed greater abundance in these sites. As expected, less richness was found in the site with higher clay content, but there was no variation in the Shannon-Weaver index in the gradient studied. The areas showed different assemblies of AMF among the sites with higher and lower clay content, and the main factors structuring the species were carbon, clay and potential acidity. In addition, field samples and trap cultures showed different assemblies; through the use of cultures it was possible to detect additional species. Soil properties have been found to be determinants for the distribution of these microorganisms and further studies in different vegetation types can help to understand the ecological preferences of AMF species., Competing Interests: The authors declare no conflict of interest.

Changes in relief in montane areas, with increasing altitude, provide different biotic and abiotic conditions, acting on the species of arbuscular mycorrhizal fungi (AMF). The objective of this work was to determine the influence of altitude, edaphic factors, and vegetation on the AMF species in a mountainous area. The list of AMF species was obtained from morphological identification of the spores, with 72 species recovered from field samples and trap cultures. Lower levels of Shannon's diversity occurred only at lower altitude; however, there was no difference in AMF richness. The structure of the AMF assembly between the two highest altitudes was similar and differed in relation to the lower altitude. There was variation in the distribution of AMF species, which was related to soil texture and chemical factors along the altitude gradient. Some species, genera, and families were indicative of a certain altitude, showing the preference of fungi for certain environmental conditions, which may aid in decisions to conserve montane ecosystems.

Biosorption-based technologies have been proposed for the removal of radionuclides from radioactive liquid waste containing organic compounds. Nevertheless, pytoremediation potential of uranium (U) by nonliving aquatic macrophytes Lemna sp. and Pistia stratiotes has not been previously addressed. In this study, uranium biosorption capacity by Pistia stratiotes and Lemna sp. was evaluated by equilibrium and kinetics experiments. The biomasses were added to synthetic and real waste solutions. The assays were tested in polypropylene vials containing 10 mL of uranium nitrate solution and 0.20 g of biomass. Solutions ranging from 0.25 to 84.03 mmol l -1 were employed for the assessment of uranium concentration in each macrophyte. The equilibrium time was 1 h for both macrophytes. Lemna sp. achieved the highest sorption capacity with the use of the synthetic solution, which was 0.68 mmol g -1 for the macrophyte. Since Lemna sp. exhibit a much higher adsorption capacity, only this biomass was exposed to the actual waste solution, being able to adsorb 9.24 × 10 -3  mmol g -1 U (total). The results show that these materials are potentially applicable to the treatment of liquid radioactive waste., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This research aimed to find main users, frequent utilized tasks, major usability problems, and the context of use of a neonatal incubator (NI) present in a neonatal intensive care unit from a Brazilian hospital and to find out the problems faced by a new user. The chosen methods were the heuristics analysis, contextual investigation, and usability test (UT). Nurses and technicians are the main users of NIs. The predominant contexts of use are the admission of newborns and the replacement of the equipment. Eight selected tasks were performed in the UT, and the most significant problems refer to alarms and configuration of the Air and Skin Modes, because the interface is not intuitive to novice users. Therefore, mitigating errors should be an investment in human factor engineering methods from the beginning of the product development process to the training of the main users.

The [ 18 F]Fluorocholine ([ 18 F]FCH) tracer for PET imaging has been proven to be effective for several malignances. However, there are only a few studies related to its breast tumor applicability and they are still limited. The aim of this study was investigate the efficacy of [ 18 F]FCH/PET compared to [ 18 F]FDG/PET in a murine 4T1 mammary carcinoma model treated and nontreated. [ 18 F]FCH/PET showed its applicability for primary tumor and lung metastasis detection and their use for response monitoring of breast cancer therapeutics at earlier stages., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Acute kidney injury (AKI) is an important health problem and can be caused by number of factors. The use of aminoglycosides, such as gentamicin, is one of these factors. Recently, an effort has been made to find biomarkers to guide treatment protocols. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to estimate the contents of Ca, Cu, Fe, K, Mg, Mn, Na, P, and Zn in serum and urine of the healthy, AKI, and spontaneous recovery (SR) groups of animals. The animal model of AKI and SR was validated by measuring serum and urinary urea and creatinine. The quantitative determination of the elements showed a decrease in serum levels of Ca, and Fe in the AKI group (P<0.01 vs. healthy), with a return to normal levels in the SR group, without a significant difference between the healthy and SR groups. In the urine samples, there was a decrease in P and Na levels in the AKI group (P<0.001 and P<0.01 vs. healthy), but Ca levels were increased in this group compared with the healthy and SR groups (P<0.01). These findings indicate that mineral elements might be useful as biomarkers for AKI.

Parvoviruses (family Parvoviridae ) are small, single-stranded DNA viruses. Many parvoviral pathogens of medical, veterinary and ecological importance have been identified. In this study, we used high-throughput sequencing (HTS) to investigate the diversity of parvoviruses infecting wild and domestic animals in Brazil. We identified 21 parvovirus sequences (including twelve nearly complete genomes and nine partial genomes) in samples derived from rodents, bats, opossums, birds and cattle in Pernambuco, São Paulo, Paraná and Rio Grande do Sul states. These sequences were investigated using phylogenetic and distance-based approaches and were thereby classified into eight parvovirus species (six of which have not been described previously), representing six distinct genera in the subfamily Parvovirinae . Our findings extend the known biogeographic range of previously characterized parvovirus species and the known host range of three parvovirus genera ( Dependovirus , Aveparvovirus and Tetraparvovirus ). Moreover, our investigation provides a window into the ecological dynamics of parvovirus infections in vertebrates, revealing that many parvovirus genera contain well-defined sub-lineages that circulate widely throughout the world within particular taxonomic groups of hosts., Competing Interests: The authors declare no conflict of interest.

Objective: To assess light irradiance (LI) delivered by two light-curing units (LCU's) and to measure the degree of conversion (DC) of three composite cements, when cured through different thicknesses of two novel CAD-CAM block materials., Methods: 100-μm-thick films of a dual-curable composite cement (G-CEM LinkAce, GC), a light-curable flowable resin-based composite (RBC) (G-ænial Universal Flo, GC) and a micro-hybrid RBC (G-ænial Posterior, GC) were investigated as luting agents. Two 'polymer-ceramic' CAD-CAM blocks (Cerasmart, GC; Enamic, Vita Zahnfabrik) were sectioned in slabs with different thicknesses (1, 3 and 5mm). LI at the bottom of the specimens was measured using a calibrated spectrometer, while being light-cured through the CAD-CAM block slabs for 40s with a low- (±500mW/cm 2 ) or high- (±1,600mW/cm 2 ) irradiance LCU (n=5). After light-curing, micro-Raman spectra of the composite films were acquired to determine DC at 5min, 10min, 1h and 24h. LI data were statistically analyzed by Kruskal-Wallis followed by post-hoc comparisons, while a linear mixed-effect model was applied for the DC analysis. In addition, the CAD-CAM blocks ultrastructure was characterized upon argon-ion slicing using scanning transmission electron microscopy (STEM). Finally, light transmission (LT) through each CAD-CAM block material was assessed using a spectrophotometer., Results: Curing-light attenuation and DC were significantly influenced by thickness and type of the overlying material. LCU only had a significant effect on DC of the micro-hybrid RBC. DC significantly increased over time for all composite cements. CAD-CAM block structural analysis revealed a relatively small and homogenous filler configuration (mean filler size of 0.2-0.5μm) for Cerasmart, while Enamic contained ceramic grains varying in shape and size (1-10μm), which were interconnected by the polymer-based network. LT was much higher at a wavelength range of 300-800nm for Cerasmart than for Enamic., Significance: Light-curable composite cements can be cured through a restoration up to 2.7-mm thickness, depending on the kind of CAD-CAM material. A high-irradiance LCU only has a limited effect on the maximum thickness of the polymer-ceramic CAD-CAM material that can be cured through., (Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Uncontrolled angiogenesis is directly associated with ocular diseases such as macular degeneration and diabetic retinopathy. Implantable polymeric drug delivery systems have been proposed for intravitreal applications and in the present work, we evaluated the antiangiogenic potential of PLGA ocular implants loaded with the triterpene lupeol using in vitro and in vivo models. The drug/polymer physiochemical properties of the lupeol-loaded PLGA were validated as functionally similar using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Interestingly, in an in vitro culture system, lupeol (100μg/mL and 250μg/mL) was capable to inhibited the proliferation as well as the migration of Human Umbilical Vein Endothelial Cells (HUVEC), without interfering in cell viability, promoting a significant reduction in the percentage of vessels (39.41% and 44.12%, respectively), compared with the control group. In vivo test, by using the chorioallantoic membrane (CAM) model, lupeol-loaded PLGA ocular implants showed antiangiogenic activity comparable to the FDA-approved anti-VEGF antibody Bevacizumab. Overall, our results suggest lupeol-loaded PLGA ocular implants were able to inhibit the angiogenic process by impairing both proliferation and migration of endothelial cells., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate the effect of restoration design ('2.5-mm deep endocrown', '5-mm deep endocrown' or '5-mm deep post&crown') and CAD/CAM material type (composite or lithium disilicate glass-ceramic) on the load-to-failure of endodontically treated premolars in absence of any ferrule., Methods: The crowns of 48 single-rooted premolars were cut and the roots were endodontically treated. Teeth were randomly divided into six groups (n=8); teeth in each group were restored using one of the two tested materials with standardized CAD/CAM fabricated endocrowns (with either 2.5-mm or 5-mm deep intra-radicular extension) or conventional crowns (5-mm deep post&crown). After cementation using luting composite, the specimens were immersed in distilled water and subjected to 1,200,000 chewing cycles with a load of 50N applied parallel to the long axis of the tooth (0°). After cyclic loading, a compressive load was applied at 45° to the tooth's long axis using a universal testing machine until failure. Load-to-failure was recorded (N) and the specimens were examined under a stereomicroscope with 3.5x magnification to determine the mode of failure., Results: All specimens survived the 1,200,000 chewing cycles. A significant interaction between restoration design and CAD/CAM material was found using two-way ANOVA. In the '2.5-mm deep endocrown' groups, the composite achieved a significantly higher load-to-failure than the lithium disilicate glass-ceramic, while no differences between materials were found in the '5-mm deep endocrown' and '5-mm deep post&crown' groups. More unfavorable failures (root fractures) were observed for higher load-to-failure values., Conclusions: Only following a '2.5-mm deep endocrown' design, composite appeared more favorable than lithium disilicate glass-ceramic as crown material; this may be explained by their difference in elastic modulus., Clinical Significance: Shallow endocrown preparations on premolars present less surface for adhesive luting and a difference in crown material becomes apparent in terms of load-to-failure. The use of a more flexible composite crown material appeared then a better option., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The genus Phlebovirus includes the sandfly fever viruses and tick-transmitted uukuviruses. Sandfly fever group viruses have been isolated from various vertebrate species and from phlebotomines and occasionally alternative arthropods, e.g. mosquitoes, or ceratopogonids of the genus Culicoides. Uukuniemi serogroup viruses have been isolated from various vertebrate species and from ticks. Despite the public health importance of some viruses of the genus, the genomic diversity of phleboviruses that could be incriminated as causative of human or veterinary diseases remains underestimated. Here we describe the nearly complete sequences and genomic characterization of two phleboviruses belonging to the Bujaru antigenic complex: the prototype species and the Munguba virus. Furthermore, six previously unclassified phleboviruses isolated in Brazil were also sequenced and characterized: Ambe, Anhanga, Joa, Uriurana, Urucuri and Tapara viruses. The results of the phylogenetic analysis indicated that these viruses group with viruses of three antigenic complexes (Bujaru, Tapara and frijoles clades), with two unclassified phleboviruses. We also performed genomic reassortment analysis and confirmed that there were no events for the viruses described in this study, but we found a new potential reassortment in Medjerda Valley virus, which contains S and L segments of Arbia virus, and probably a unique M segment, both viruses circulate in the same geographic region, indicating these two isolates represent two distinct viruses. This study provides insights into the genetic diversity, classification and evolution of phleboviruses.

Purpose: To evaluate the antiangiogenic activity of bevacizumab-loaded polyurethane using two animal models of neovascularization., Methods: The percentage of blood vessels was evaluated in a chicken chorioallantoic membrane model (n=42) and in the rabbit cornea (n=24) with neovascularization induced by alkali injury. In each model, the animals were randomly divided into the groups treated with the bevacizumab-loaded polyurethane device, phosphate-buffered-saline (negative control) and bevacizumab commercial solution (positive control). Clinical examination, as well as histopathological and immunohistochemical evaluation, were performed in the rabbit eyes. Microvascular density in hot spot areas was determined in semi-thin sections of corneal tissue by hematoxylin-eosin staining and factor VIII immunohistochemistry. Immunohistochemical analysis was also performed to evaluate VEGF expression., Results: In the evaluated models, the use of bevacizumab (Avastin ® ) and the bevacizumab-loaded polyurethane device led to similar results with regard to inhibition of neovascularization. In the chorioallantoic membrane model, the bevacizumab-loaded polyurethane device reduced angiogenesis by 50.27% when compared to the negative control group. In the rabbit model of corneal neovascularization, the mean density of vessels/field was reduced by 46.87% on analysis of factor VIII immunohistochemistry photos in the bevacizumab-loaded polyurethane device group as compared to the negative control (PBS) sections. In both models, no significant difference could be identified between the bevacizumab-loaded polyurethane device and the positive control group, leading to similar results with regard to inhibition of neovascularization., Conclusions: The present study shows that the bevacizumab-loaded polyurethane device may release bevacizumab and inhibit neovascularization similarly to commercial bevacizumab solution in the short-term., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The contamination, passivation, or fouling of the detection electrodes is a serious problem undermining the analytical performance of electroanalytical devices. The methods to regenerate the electrochemical activity of the solid electrodes involve mechanical, physical, or chemical surface treatments that usually add operational time, complexity, chemicals, and further instrumental requirements to the analysis. In this paper, we describe for the first time a reproducible method for renewing solid electrodes whenever their morphology or composition are nonspecifically changed without any surface treatment. These renewable electrodes are the closest analogue to the mercury drop electrodes. Our approach was applied in microfluidics, where the downsides related to nonspecific modifications of the electrode are more critical. The renewal consisted in manually sliding metal-coated microwires across a channel with the sample. For this purpose, the chip was composed of a single piece of polydimethylsiloxane (PDMS) with three parallel channels interconnected to one perpendicular and top channel. The microwires were inserted in each one of the parallel channels acting as working, counter, and pseudoreference electrodes for voltammetry. This assembly allowed the renewal of all the three electrodes by simply pulling the microwires. The absence of any interfaces in the chips and the elastomeric nature of the PDMS allowed us to pull the microwires without the occurrence of leakages for the electrode channels even at harsh flow rates of up to 40.0 mL min -1 . We expect this paper can assist the researchers to develop new microfluidic platforms that eliminate any steps of electrode cleaning, representing a powerful alternative for precise and robust analyses to real samples.

Mosquito-borne alphaviruses are widely distributed throughout the world, causing important human illnesses. Therefore, the development of methods to enable early diagnosis of infections by alphavirus is essential. We show here the development and evaluation of a quantitative real-time RT-PCR using genus-specific primers to the nsP1 viral gene of all mosquito-borne alphaviruses. The specificity and sensitivity of the assay were tested using seven alphaviruses and RNA transcribed from Venezuelan equine encephalitis virus. The detection limits of real-time RT-PCR ranged from 10 to 76 copies per ml. The melting temperature (TM) values for amplification of the alphavirus genomes were 83.05 °C and 85.28 °C. Interestingly, the assay suggested the possibility the arthritogenic alphaviruses with TM peaks of 84.83 to 85.28 °C and encephalitic alphaviruses of 83.34 °C to 84.68 °C could be discriminated both diseases. Real-time RT-PCR may prove very useful for the screening and preliminary diagnosis in outbreaks and surveillance studies as well as for measuring the viral load in pathogenesis studies.

Chlorophyll-a (Chl-a) has been widely used in the assessment and monitoring of aquatic environments. Local and regional factors can influence Chl-a concentrations; moreover, the connection between terrestrial and aquatic ecosystems is a major paradigm within aquatic ecology. Here, we investigate the spatial distribution of Chl-a concentrations in a tropical savannah floodplain in Central Brazil using a broad spatial data set (a 900-km north-south transect; 30 lakes). We determine the relative importance of local environmental variables (limnological and morphometric) and regional (land use) and spatial distances (spatial eigenvector) on Chl-a concentrations using partial linear regression. We evaluate the direct and indirect effects of local and regional variables on Chl-a with a path analysis. Our results indicate spatially autocorrelated patterns wherein lakes in closer proximity showed more similar levels of Chl-a than more distant lakes. Local environmental factors explained most variance in Chl-a (R 2 adj  = 0.28; P = 0.02); more specifically, both lake area and total nitrogen significantly (P < 0.05) explained Chl-a concentrations (direct effects). Meanwhile, regional factors neither directly nor indirectly predicted Chl-a. Thus, internal processes, such as the resuspension of sediment (which is frequent in tropical floodplains), rather than external influences, were the main factors that explained Chl-a concentrations in this study. The importance of local variables in structuring Chl-a concentration may be used to guide the conservation of the aquatic ecosystems in these tropical floodplain lakes.

This paper addresses an important breakthrough in the deployment of ultra-high adhesion strength microfluidic technologies to provide turbulence at harsh flow rate conditions. This paper is only, to our knowledge, the second reporting on the generation of high flow rate-assisted turbulence in microchannels. This flow solves a crucial bottleneck in microfluidics: the generation of high throughput homogeneous mixings. We focused on the fabrication of bulky polydimethylsiloxane (PDMS) microchips (without any interfaces) rather than the laborious surface modifications that were employed in the first reporting about turbulence-assisted microfluidics. The fabrication is cleanroom-free, simple, low-cost, fast, solventless, and bondless requiring only a laboratory oven. More specifically, our method relies on the shaping of a nylon scaffold, cure of PDMS with embedded nylon, and removal of this scaffold. The scaffold was obtained by manually wrapping nylon threads. The withdrawing out of the scaffold was completed in few seconds using only a plier. Such microchannels endured flow rates of up to 60.0 mL min(-1) with a strikingly low elastic deformation. The importance in producing turbulence into microscale channels was successfully shown in liquid-liquid extractions. The great energy dissipation rate relative to the turbulence created high throughput and efficient extractions in microfluidics for the first time. The residence time was only 0.01 s at 25.0 mL min(-1) (total flow rate of the immiscible phases). In addition, the partition coefficient determined in a single run was similar to that obtained by the conventional batch shake-flask method that was realized in triplicate., (Copyright © 2016 Elsevier B.V. All rights reserved.)