Assessment of in vitro digestibility and postdigestion peptide release of mare milk in relation to different management systems and lactation stages.

Mare milk has a unique protein composition that makes it a preferred option for adult and infant nutrition. Several functional properties have been attributed to this milk, but with little current evidence. In fact, knowledge on mare milk composition is still limited. In particular, studies addressing the performance of mare milk proteins during human gastrointestinal digestion are scarce, which limits the understanding of mare milk nutritional quality and functionality. For this reason, the present study describes the digestibility of mare milk proteins and the release of peptides as affected by management and lactation stage, factors which are known to affect milk composition. Mare milk samples from 3 different farms collected during 6 mo of lactation (n = 54) were subjected to a static in vitro gastrointestinal model to measure peptide release and protein digestibility. In the present study, a detailed description of protein and individual amino acid behavior during the digestion process was given. For the first time, digestion of the 2 equine ß-lactoglobulin isoforms (I and II) was described individually. In addition, it was found that lactation stage and management system can significantly affect protein digestibility and peptide release during gastrointestinal digestion of mare milk. Presumably, differences in the composition of mare milk influence the protein structure and enzyme accessibility, which might have an impact on digestion behavior. Although no specific bioactive peptides were identified, several precursors of previously described bioactive peptides were found. These findings could support the idea of mare milk as a food with added value.

Synthesis of 6,8-diaminopurines via acid-induced cascade cyclization of 5-aminoimidazole precursors and preliminary anticancer evaluation.

Inspired by the pharmacological interest generated by 6-substituted purine roscovitine for cancer treatment, 5-aminoimidazole-4-carboxamidine precursors containing a cyanamide unit were prepared by condensation of 5-amino-N-cyanoimidazole-4-carbimidoyl cyanides with a wide range of primary amines. When these amidine precursors were combined with acids, a fast cascade cyclization occurred at room temperature, affording new 6,8-diaminopurines with the N-3 and N-6 substituents changed relatively to the original positions they occupied in the amidine and imidazole moieties of precursors. The efficacy and wide scope of this method was well demonstrated by an easy and affordable synthesis of 22 6,8-diaminopurines decorated with a wide diversity of substituents at the N-3 and N-6 positions of the purine ring. Preliminary in silico and in vitro assessments of these 22 compounds were carried out and the results showed that 13 of these tested compounds not only exhibited IC50 values between 1.4 and 7.5 µM against the colorectal cancer cell line HCT116 but also showed better binding energies than known inhibitors in docking studies with different cancer-related target proteins. In addition, good harmonization observed between in silico and in vitro results strengthens and validates this preliminary evaluation, suggesting that these novel entities are good candidates for further studies as new anticancer agents.

Cerebral Venous Thrombosis in Pediatric Age: Risk Factors and Prognosis.

INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare but potentially fatal disease in pediatric age with an important morbimortality. In adults several factors have been associated with worse outcomes, however there are still few studies in children. This study aims to identify risk factors associated with clinical manifestations and long-term sequelae in pediatric CVT. METHODS: Retrospective analysis of pediatric inpatients admitted to a tertiary-care hospital due to CVT between 2008 and 2020. RESULTS: Fifty-four children were included, 56% male, median age of 6.5 years (9 months-17.3 years). Permanent risk factors were identified in 13 patients (malignancy, 8; hematologic condition, 5) and transient risk factors in 47, including head and neck infections (57%) and head trauma (15%). Multiple venous sinuses involvement was present in 65% and the deep venous system was affected in four patients. Seventeen percent had intracranial hemorrhage and 9% cerebral infarction. Sixty-four percent of patients with multiple venous sinuses involvement presented with severe clinical manifestations: impaired consciousness, intracranial hypertension, acute symptomatic seizures or focal deficits. Regarding long-term prognosis, six patients had major sequelae: epilepsy (n = 3), sensory motor deficits (n = 2), and cognitive impairment (n = 3). Permanent risk factors were associated with severe clinical manifestations (p = 0.043). Cerebral infarction and intracranial hemorrhage were associated with major sequelae (p = 0.006 and p = 0.03, respectively, adjusted for age and sex). CONCLUSION: Permanent risk factors, involvement of multiple venous sinuses, intracranial hemorrhage, and cerebral infarction, were related to worse prognosis. Detection and early management of risk factors may limit CVT extension and reduce its morbimortality.

Explainability agreement between dermatologists and five visual explanations techniques in deep neural networks for melanoma AI classification.

Introduction: The use of deep convolutional neural networks for analyzing skin lesion images has shown promising results. The identification of skin cancer by faster and less expensive means can lead to an early diagnosis, saving lives and avoiding treatment costs. However, to implement this technology in a clinical context, it is important for specialists to understand why a certain model makes a prediction; it must be explainable. Explainability techniques can be used to highlight the patterns of interest for a prediction. Methods: Our goal was to test five different techniques: Grad-CAM, Grad-CAM++, Score-CAM, Eigen-CAM, and LIME, to analyze the agreement rate between features highlighted by the visual explanation maps to 3 important clinical criteria for melanoma classification: asymmetry, border irregularity, and color heterogeneity (ABC rule) in 100 melanoma images. Two dermatologists scored the visual maps and the clinical images using a semi-quantitative scale, and the results were compared. They also ranked their preferable techniques. Results: We found that the techniques had different agreement rates and acceptance. In the overall analysis, Grad-CAM showed the best total+partial agreement rate (93.6%), followed by LIME (89.8%), Grad-CAM++ (88.0%), Eigen-CAM (86.4%), and Score-CAM (84.6%). Dermatologists ranked their favorite options: Grad-CAM and Grad-CAM++, followed by Score-CAM, LIME, and Eigen-CAM. Discussion: Saliency maps are one of the few methods that can be used for visual explanations. The evaluation of explainability with humans is ideal to assess the understanding and applicability of these methods. Our results demonstrated that there is a significant agreement between clinical features used by dermatologists to diagnose melanomas and visual explanation techniques, especially Grad-Cam.

Child Neurology: Anti-Hu Encephalitis in an Adolescent With a Mediastinal Seminoma.

Anti-Hu antibodies are associated with autoimmune syndromes, mainly limbic encephalitis, encephalomyelitis, and painful sensory polyneuropathy (Denny-Brown). We report the case of a 15-year-old boy presenting with epilepsia partialis continua (EPC) found to have a right middle frontal gyrus brain lesion without atrophy or contralateral involvement. After partial resection, neuropathology revealed neuronal loss, reactive gliosis and astrocytosis, and perivascular mononuclear inflammatory infiltrate and features of neuronophagia resembling Rasmussen encephalitis. Suboptimal response to antiseizure drugs and surgery prompted further workup with identification of positive serum anti-Hu antibodies and a mediastinal seminoma. The patient was treated with immunotherapy including steroids, IV immunoglobulin, azathioprine, rituximab, plasmapheresis, and mediastinal lesion resection. However, he continued to experience EPC and psychomotor impairment along with left hemiparesis and dysarthria. Given clinical progression with failure to respond to immunotherapy and antiseizure polytherapy, hemispherotomy was attempted and seizure freedom achieved. A review of the literature found only 16 cases of neurologic presentations associated with anti-Hu antibodies in children, confirming the rarity of EPC in these cases. Thus, this report provides a new observation of germ cell mediastinal tumor associated with anti-Hu antibodies in children, broadening the spectrum of anti-Hu-associated neurologic disorders in children and highlighting the importance of considering antineuronal antibody testing in children presenting with EPC and brain lesions suggestive of Rasmussen encephalitis.

An In Vivo Assessment of the Effect of Hexane Extract from Endlicheria paniculata Branches and Its Main Compound, Methyldehydrodieugenol B, on Murine Sponge-Induced Inflammation.

The present study aims to explore the anti-inflammatory potential activity of the hexane extract from branches (HEB) of Endlicheria paniculata (Lauraceae) and its main compound, methyldehydrodieugenol B, in the inflammatory response induced by a murine implant sponge model. HPLC-ESI/MS analysis of HEB led to the identification of six chemically related neolignans, with methyldehydrodieugenol B as the main compound. An in silico analysis of the pharmacokinetic parameters of the identified compounds suggested moderate solubility but good absorption and biodistribution in vivo. Thus, the treatment of mice with HEB using in vivo assays indicated that HEB promoted pro-inflammatory, antiangiogenic, and antifibrogenic effects, whereas treatment with methyldehydrodieugenol B caused anti-inflammatory, antifibrogenic, and antiangiogenic effects. The obtained results shown the therapeutic potential of HEB and methyldehydrodieugenol B in the treatment of pathologies associated with inflammation and angiogenesis, including chronic wounds.

The role of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) - ratio in clinical practice in obstetrics: diagnostic and prognostic value.

OBJECTIVES: Analyze the diagnostic and prognostic value of the sFlt-1/PlGF ratio in pregnant women with at least one sign/symptom of suspected/diagnosed pre-eclampsia. METHODS: This retrospective observational study included 170 pregnant women with at least one sign/symptom of pre-eclampsia, who had sFlt-1/PlGF ratio values. The following information was evaluated: pregnant women's demographic data and clinical history; laboratory data (urine protein/creatinine ratio; sFlt-1/PlGF ratio); signs and symptoms presented; clinical outcome; fetal complications; data related to childbirth. Statistical analysis was performed by R Software Version 3.5.2. RESULTS: Among the 170 patients, 78 presented pre-eclampsia. The median sFlt-1/PlGF ratio was significantly higher [143.1 (2.2-2,927.1)] for women who presented pre-eclampsia than for women without pre-eclampsia [33.5 (0.8-400.2)]. The negative predictive value of sFlt-1/PlGF ratio <38 was 83.9 % (95 % CI, 71.7-92.4 %) and the positive predictive value of sFlt-1/PlGF ratio >85 or 110 (for late onset pre-eclampsia) was 76.4 % (95 % CI, 66.2-84.8 %). sFlt-1/PlGF >85 or 110 was associated with pre-eclampsia clinical development, fetal complications, shorter gestational age at birth, higher number of caesarean deliveries and lower birth weight. CONCLUSIONS: The sFlt-1/PlGF ratio, together with the standard diagnostic criteria, can be used to rule out pre-eclampsia, identify high-risk patients and predict the occurrence of adverse outcomes.

Pediatric neuromyelitis optica spectrum disorders in Portugal: A multicentre retrospective study.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) are more prevalent in adulthood, with few cases reported in pediatric age (<18 years). In this group, anti-aquaporin 4 (AQP4) antibodies are less frequent, while antibodies against myelin oligodendrocyte glycoprotein (MOG) are more commonly detectable than in adults. OBJECTIVE AND METHODS: Description of pediatric NMOSD cases identified in a national multicentric NMOSD Portuguese registry. RESULTS: Twenty (11.1%) NMOSD cases were diagnosed in pediatric age. Twelve (60%) were female, with a median age of onset of 12.5 (6.8-16.5) years. The presenting feature was transverse myelitis in 10 (50%), 4 of which with simultaneous optic neuritis and 2 with concomitant brainstem syndrome. Nine patients (45%) had pleocytosis in the CSF. Six (30.0%) exhibited anti-AQP4 antibodies, 13 (65.0%) anti-MOG antibodies, and one was seronegative for both. Four anti-AQP4 antibodies-positive patients had ≥1 relapse. Most anti-MOG-positive cases were monophasic (53.8%). In the acute phase, all patients received IV methylprednisolone, nine received IVIg and four plasma exchange. One anti-AQP4-positive patient died. Ten patients (5 anti-AQP4-positive/5 anti-MOG-positive) were on maintenance immunosuppressive therapy at the time of data collection. CONCLUSION: NMOSD may present in pediatric age. It is essential to establish the diagnosis and promptly start therapy to improve the prognosis.

Implementation of artificial intelligence algorithms for melanoma screening in a primary care setting.

Skin cancer is currently the most common type of cancer among Caucasians. The increase in life expectancy, along with new diagnostic tools and treatments for skin cancer, has resulted in unprecedented changes in patient care and has generated a great burden on healthcare systems. Early detection of skin tumors is expected to reduce this burden. Artificial intelligence (AI) algorithms that support skin cancer diagnoses have been shown to perform at least as well as dermatologists' diagnoses. Recognizing the need for clinically and economically efficient means of diagnosing skin cancers at early stages in the primary care attention, we developed an efficient computer-aided diagnosis (CAD) system to be used by primary care physicians (PCP). Additionally, we developed a smartphone application with a protocol for data acquisition (i.e., photographs, demographic data and short clinical histories) and AI algorithms for clinical and dermoscopic image classification. For each lesion analyzed, a report is generated, showing the image of the suspected lesion and its respective Heat Map; the predicted probability of the suspected lesion being melanoma or malignant; the probable diagnosis based on that probability; and a suggestion on how the lesion should be managed. The accuracy of the dermoscopy model for melanoma was 89.3%, and for the clinical model, 84.7% with 0.91 and 0.89 sensitivity and 0.89 and 0.83 specificity, respectively. Both models achieved an area under the curve (AUC) above 0.9. Our CAD system can screen skin cancers to guide lesion management by PCPs, especially in the contexts where the access to the dermatologist can be difficult or time consuming. Its use can enable risk stratification of lesions and/or patients and dramatically improve timely access to specialist care for those requiring urgent attention.

Formulation Effects in the Antioxidant Activity of Extract from the Leaves of Cymbopogon citratus (DC) Stapf.

Cymbopogon citratus DC (Stapf.) is a perennial grass and it is distributed around the world. It is used as a condiment for food and beverage flavouring in the form of infusions and decoctions of its dried leaves. Our previous studies have shown antioxidant, anti-inflammatory and gastroprotective activities for the infusion and its phenolic fractions. The aim of the present work was to develop oral dosage forms from a Cymbopogon citratus extract to be used as a functional food with antioxidant properties. Initially, an essential oil-free infusion was prepared, lyophilized and characterized by HPLC-PDA. Total phenols were quantified with the Folin-Ciocalteu method and the antioxidant activity was assessed by DPPH assay. Gelatine capsules containing the extract with different excipients, selected after DSC and IR trials, were prepared. A formulation exhibiting better antioxidant behaviour in a gastric environment was attained. These results suggest that the proposed formulation for this extract could be a valuable antioxidant product and, consequently, make an important contribution to "preventing" and minimizing diseases related to oxidative stress conditions.

Aproximações do Campo-tema Juventude e Violência na Periferia de Fortaleza / Approaches of the Youth and Violence Field in the Periphery of Fortaleza / Aproximaciones del Campo-tema Juventud y Violencia en la Periferia de Fortaleza

Este artigo tem o propósito de trazer reflexões sobre violência urbana e violação de diretos fundamentais como acontecimentos que têm marcado o cotidiano de adolescentes e jovens residentes na periferia de Fortaleza. Também traz uma discussão sobre os desafios metodológicos das pesquisas participativas com esse público. O Estado do Ceará e, principalmente, sua capital têm apresentado os maiores índices de homicídios de adolescentes nos últimos anos, e os índices estão crescendo entre as meninas. Embora tenham ocorrido intervenções dos órgãos nacionais e latino-americanos de Direitos Humanos, com ações judiciais interpostas por entidades que atuam na defesa de direitos de crianças, adolescentes e jovens, os poderes executivo, judiciário e legislativo se mobilizam, quase sempre, oferecendo respostas paliativas à população, e propõem ações de controle e repressão para o fortalecimento do projeto político neoliberal. Nesse cenário, importa refletir sobre os efeitos da dinâmica territorial da violência na vida de jovens da periferia, os dispositivos que compõem a rede de controle/enfrentamento à violência e seus impactos na construção de lentes teórico-metodológicas que instrumentalizem os/as pesquisadores/as ao manejo da produção de conhecimento no campo-tema juventude-violência. (AU)

This article aims to bring reflections on urban violence and violation of fundamental rights as events that have marked the daily lives of adolescents and young people living in the outskirts of Fortaleza. It also brings a discussion about the methodological challenges of participatory research with this audience. The state of Ceará and, especially, its capital, has had the highest rates of homicide among adolescents in recent years, and rates are growing among girls. Although interventions by national and Latin American Human Rights bodies have taken place, the judicial and legislative powers are mobilized, based on lawsuits filed by entities that defend and guarantee the rights of children, adolescents and youth, offering palliative responses to the population, and, mainly, they to propose measures of control and repression, which ensure the strengthening of the neoliberal political project. In this scenario, it is important to reflect on the effects of the territorial dynamics of violence on the life of young people from the periphery, the devices that make up the network of control / coping with violence and its impacts on the construction of theoretical and methodological lenses, that equip the researchers to manage knowledge production in the youth-violence field. (AU)

Este artículo tiene el propósito de traer reflexiones sobre violencia urbana y violación de derechos fundamentales como acontecimientos que marcan el cotidiano de adolescentes y jóvenes residentes en la periferia de Fortaleza. También trae un debate sobre los desafíos metodológicos de la investigación participativa con este público. El Estado de Ceará y, principalmente su capital, ha presentado los mayores índices de homicidios de adolescentes en los últimos años, las cifras continúan creciendo. Aunque se han producido intervenciones de los órganos nacionales y latinoamericanos de Derechos Humanos, con acciones judiciales interpuestas por entidades que actúan en la defensa de derechos de niños, adolescentes y jóvenes, los poderes ejecutivo, judicial y legislativo se movilizan en la perspectiva de ofrecer respuestas paliativas a la población, y se empeñan en proponer acciones de control y represión, que aseguren el fortalecimiento del proyecto político neoliberal. En este escenario, es importante reflexionar sobre los efectos de la dinámica territorial de la violencia en la vida de jóvenes periféricos, los dispositivos que componen la red de control/enfrentamiento a la violencia y sus impactos en la construcción de lentes teórico-metodológicas que instrumentalicen adecuadamente a los/las investigadores/as para el manejo de la producción de conocimiento en el campo-tema juventud-violencia. (AU)

Essential oil from leaves of Eugenia calycina Cambes: Natural larvicidal against Aedes aegypti.

BACKGROUND: Eugenia calycina is an endemic species in the Brazilian savannah (the Cerrado) and it is threatened with extinction. Several species of Eugenia are used as insecticides or insect repellents. No data are available on the larvicidal activity of E. calycina. The chemical composition of the essential oil (EO) from leaves of Eugenia calycina was analyzed by gas chromatography coupled to mass spectrometry (GC-MS) and the larvicidal activity against Aedes aegypti larvae in the third stage of development was studied. RESULTS: Oxygenated and non-oxygenated sesquiterpenes were identified, and the main compounds were bicyclogermacrene, spathulenol, and ß-caryophyllene. The EO was fractionated in a chromatographic column and three compounds were isolated and identified: spathulenol, aromadendrane-4ß,10α-diol, and 1ß-11-dihydroxy-5-eudesmene. It is the first time that the last two compounds have been identified in E. calycina. The exposure times in the larvicidal test were 24 h and 48 h and the LC50 values obtained were 199.3 and 166.4 µg mL-1 . The cytotoxicity of the EO in mammalian cells (HeLa and Vero) was evaluated for 24 and 48 h of incubation. The cytotoxic concentrations of the EO for HeLa and Vero cells (266.8 ± 46.5 and 312.1 ± 42.5 µg mL-1 , respectively) in 48 h of exposure were higher than the LC50 , showing low cytotoxicity at the concentration exhibiting larvicidal activity, resulting in a positive selectivity index. CONCLUSION: These results indicate that the EO of E. calycina showed high activity against the A. aegypti larvae but lower cytotoxicity to mammalian cells. The leaves of E. calycina are therefore a very promising source of natural larvicidal products. © 2020 Society of Chemical Industry.

Chemical and toxicological evaluation along with unprecedented transformation products during photolysis and heterogeneous photocatalysis of chloramphenicol in different aqueous matrices.

As the presence of antibiotics in environmental waters enhances antimicrobial resistance, photolysis and heterogeneous photocatalysis of chloramphenicol (CAP) were evaluated in deionized water (DW) and in sewage treatment plant (STP) effluent under black light and solar irradiation. Processes were compared in terms of CAP degradation, reaction kinetics, and electrical energy per order, as well as regarding theoretical toxicity, biodegradability, carcinogenicity, and mutagenicity of transformation products (TPs). Rate constants obtained under photolysis (0.008 min-1) and heterogeneous photocatalysis (0.18 min-1) only differed in DW. This is due to the generation of photo-active reactive oxygen species (HO· and HO2·-/O2·-) under photolysis in STP effluent, as verified by experiments in the presence of 2-propanol and chloroform. Natural organic matter and HCO3- were the main responsible for reducing CAP degradation in STP effluent. Fifteen TPs were identified during both processes in DW, 13 of which are unprecedented. TPs were formed mainly via HO· preferential attack on the aromatic ring and on the α-carbon, and some of them were classified as persistent and toxic, genotoxic, or carcinogenic by Toxtree software. Results confirm that solar photocatalysis is less costly than to photocatalysis under black light for wastewater treatment.

Part II: Accuracy of Teledermatology in Skin Neoplasms.

Teledermatology has been proving to be of great help for delivering healthcare, especially now, during the SARS-CoV-2 pandemic. It is crucial to assess how accurate this method can be for evaluating different dermatoses. Such knowledge can contribute to the dermatologists' decision of whether to adhere to teledermatology or not. Our objective was to determine the accuracy of teledermatology in the 10 most frequent skin neoplasms in our population, comparing telediagnosis to histopathological report and in-person dermatologists' diagnosis. A retrospective cohort study was conducted in São Paulo, Brazil, where a store-and-forward teledermatology project was implemented under primary-care attention to triage surgical, more complex, or severe dermatoses. A total of 30,976 patients presenting 55,012 lesions took part in the project. Thirteen teledermatologists who participated in the project had three options to refer the patients: send them directly to biopsy, to the in-person dermatologist, or back to the general physician with the most probable diagnosis and management. In the groups referred to the in-person dermatologist and biopsy, we looked for the 10 most frequent International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) of skin neoplasms, which resulted in 289 histopathologic reports and 803 in-person dermatologists' diagnosis. We were able to compare the ICD-10 codes filled by teledermatologists, in-person dermatologists, and from histopathological reports. The proportion of complete, partial, and no agreement rates between the in-person dermatologist's, histopathologic report, and the teledermatologist's diagnosis was assessed. We also calculated Cohen's kappa, for complete and complete plus partial agreement. The mean complete agreement rate comparing telediagnosis to histopathological report was 54% (157/289; kappa = 0.087), being the highest for malign lesions; to in-person dermatologists was 61% (487/803; kappa = 0.213), highest for benign lesions. When accuracy of telediagnosis for either malign or benign lesions was evaluated, the agreement rate with histopathology was 70% (kappa = 0.529) and with in-person dermatologist, 81% (kappa = 0.582). This study supports that teledermatology for skin neoplasms has moderate accuracy. This result reassures that it can be a proper option for patient care, especially when the goal is to differentiate benign from malign lesions.

Part I: Accuracy of Teledermatology in Inflammatory Dermatoses.

Teledermatology is assuming a progressively greater role as a healthcare delivery method, especially now, during this pandemic time. It is important to know how accurate this tool is for different skin diseases. Most of the studies have focused on skin neoplasms or general dermatology. Studies based on a large number of inflammatory dermatoses have not yet been performed. Such knowledge can help dermatologists to decide whether endorsing this method or not. Our objective was to determine the accuracy of teledermatology in inflammatory dermatoses in a robust number of cases. A retrospective cohort study was conducted in São Paulo, Brazil, from July 2017-18, where a store-and-forward Teledermatology project was implemented under primary-care attention to triage surgical, more complex, or severe dermatoses. A total of 30,976 patients presenting 55,012 lesions took part in the project. Thirteen participating teledermatologists had three options to refer the patients: directly to biopsy, to the in-person dermatologist or back to the general physician with most probable diagnosis and management. In the group referred to the in-person dermatologist, we looked for the 20 most frequent International Classification of Diseases and Related Health Problems- 10th revision (ICD-10) of inflammatory dermatoses, which resulted in 739 patients and 739 lesions. As patients had been triaged by teledermatology previously, we were able to compare ICD-10 codes filled both by teledermatogists and by in-person dermatologists. The proportion of complete, partial, and no agreement rates between the in-person dermatologist's and the teledermatologist's diagnoses was used for accuracy. We also calculated Cohen's kappa, a statistical measure of inter-rater agreement, for complete agreement. The mean complete agreement rate for all twenty dermatoses was 78% (31-100%) and kappa = 0.743; partial agreement 8%; and no agreement 14%, presenting variability according to the disease. Our study showed that teledermatology for inflammatory dermatoses has a high accuracy. This result reassures that it can be a proper option for patient care.

Dehydrodieugenol B and hexane extract from Endlicheria paniculata regulate inflammation, angiogenesis, and collagen deposition induced by a murine sponge model.

The present study reports the evaluation of hexane extract from Endlicheria paniculata and its main metabolite dehydrodieugenol B in the inflammatory response induced by a murine implant sponge model. As a result, a reduction in the inflammatory markers (myeloperoxidase and N-acetyl-ß-D-glucosaminidase) and number of mast cells were observed in comparison to the control group. All doses were also able to reduce angiogenic parameters evaluated in fibrovascular tissue. In implants treated with dehydrodieugenol B a reduction in total collagen deposition and types I and III collagen fibers were observed, while an increased in total collagen deposition and types I and III collagen fibers were observed in the treatment with hexane extract. Docking studies into cyclooxygenase-2 active site revealed that the dehydrodieugenol B had binding modes and energies comparable with celecoxib, diclofenac and ibuprofen. Therefore, dehydrodieugenol B was able to alter key components of chronic inflammation, resulting in a reduced inflammatory response and also presenting antifibrogenic and antiangiogenic effects. However, treatment with hexane extract resulted in a reduced inflammatory response with antiangiogenic effects, but caused fibrogenic effects.

Produção científica sobre letramento: mapeamento bibliométrico das teses da bdtd (1997-2016) / Constitution of the scientific field of literacy: bibliometric mapping of the bdtd theses (1997-2016) / Production scientifique sur la littératie: cartographie bibliométrique des thèses de la bdtd (1997-2016) / Producción científica sobre letramiento: mapeo bibliométrico de las tesis de la bdtd (1997-2016)

Resumo A fim de identificar a constituição do campo científico do letramento no Brasil, foram analisadas 237 teses defendidas entre 1997 e 2016 disponíveis na Biblioteca Digital Brasileira de Teses e Dissertações, o que permitiu a realização de um mapeamento bibliométrico enfocando as variáveis: a) evolução temporal; b) distribuição geográfica e institucional; e c) orientação e gênero. Observou-se crescimento de pesquisas de doutorado sobre o tema, com 88,6% tendo sido defendidas entre 2007 e 2016. Percebeu-se uma discrepância geográfica, com 51,48% de teses desenvolvidas no Sudeste e nenhum trabalho realizado no Norte. A frente de orientadores apontou para um grupo de 10 docentes com mais orientações. Verificou-se que 74% das orientações, 82,28% da autoria e 100% da frente de orientadores são formados por pesquisadores do gênero feminino. Os indicadores lançam luz à compreensão do campo científico sobre letramento no Brasil pela identificação de algumas de suas raízes históricas.

Abstract In order to identify the constitution of the scientific field of literacy in Brazil, 237 theses defended between 1997and 2016 available at the Biblioteca Digital Brasileira de Teses e Dissertações [Brazilian Digital Library of Theses and Dissertations] were analyzed, which allowed the realization of a bibliometric mapping focusing on the variables: a) temporal evolution; b) geographical and institutional distribution; and c) orientation and gender. There was an increase in doctoral research on the topic, 88.6% of which were defended between 2007 and 2016. A geographic discrepancy can be seen, with 51.48% of theses developed in the Southeast and no work carried out in the North. The research front shows a group of 10 teachers with more guidance. It was found that 74% of the guidelines, 82.28% of the authorship and 100% of the supervisors' front are formed by female researchers. The indicators shed light on the understanding of the scientific field on literacy in Brazil by identifying some of its historical roots.

Résumé Afin d'identifier la constitution du champ scientifique de la littératie au Brésil, cette étude a analysé 237 thèses, soutenues entre 1997 et 2016, disponibles dans la Biblioteca Digital Brasileira de Teses e Dissertações [Bibliothèque Numérique Brésilienne de Thèses]. Ce travail a permis de réaliser une cartographie bibliométrique axée sur les variables suivantes: a) l'évolution temporelle; b) la distribution géographique et institutionnelle; et c) la direction de thèse et genre. Une augmentation de la recherche doctorale sur le sujet a pu être observée, avec la realisation de 88,6% des soutenances entre 2007 et 2016. Une disparité géographique a aussi été constatée, 51,48 % des thèses dans le Sud-Est et aucune dans le Nord du pays. La variable directeurs de thèse a mis en évidence l'existence d'un groupe de 10 professeurs retenant un plus grand nombre de directions: 74 % des directeurs, 82,28 % des auteurs et 100 % du peloton de tête des directeurs de thèse étaient des chercheurs du sexe féminin. Ces indicateurs identifient certaines des racines historiques du champ scientifique de la littératie au Brésil et apportent de la lumière à sa comprehension.

Resumen Con el propósito de identificar la constitución del campo científico del letramiento en Brasil, se analizaron 237 tesis defendidas entre 1997 y 2016 disponibles en la Biblioteca Digital Brasileira de Teses e Dissertações, lo que permitió que se realizara un mapeo bibliométrico con enfoque en las siguientes variables: a) evolución temporal; b) distribución geográfica e institucional; y c) orientación y género. Se observó un crecimiento de investigaciones de doctorado sobre el tema, con un 88,6% defendido entre 2007 y 2016. Se percibió una discrepancia geográfica, con 51,48% de tesis desarrolladas en el Sureste y ningún trabajo realizado en el Norte del país. El equipo de tutores señaló un grupo de 10 docentes con más orientaciones. Se verificó que el 74% de las orientaciones, un 82,28% de la autoría y un 100% del equipo de tutores son formados por investigadores del género femenino. Los indicadores lanzan luz sobre la comprensión del campo científico sobre alfabetización en Brasil, en función de la identificación de algunas de sus raíces históricas.

Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design, release profile and cytotoxicity in human Colon adenocarcinoma cell line.

The aim of this work is development of a nontoxic, long-term stable solid lipid nanoparticles (SLN) formulation for the loading of Nimesulide (NiM) by a 22 factorial design. The optimized formulation was composed of 10 wt% of glyceryl behenate and 2.5 wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1 ± 0.114 nm, with a polydispersity index (PI) of 0.171 ± 0051 and zeta potential nearly neutral (-3.10 ± 0.166 mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25 °C for a period of 15 days, whereas at 4 °C particles kept size within similar range. Long-term stability was monitored using TurbiscanLab®, showing a high stability of the nanoparticles with variations in the backscattering profiles below 10%. The release profile of NiM-SLN followed a sustained pattern with ca. 30% of drug released up to 24 h. Empty-SLN and NiM-SLN were nontoxic after exposing Caco-2 cells to the highest concentration (100 µg/mL) up to 48 hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1 ± 36.63 nm (PI 0.491 ± 0.027) with 5% trehalose. Solid character of NiM-SLN was confirmed by DSC, recording a recrystallization index of 83% for NiM-SLN and of 74% for lyophilized SLN.