Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans.

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.

Putative mechanism of a multivitamin treatment against insulin resistance.

Insulin resistance is caused by the abnormal secretion of proinflammatory cytokines in adipose tissue, which is induced by an increase in lipid accumulation in adipocytes, hepatocytes, and myocytes. The inflammatory pathway involves multiple targets such as nuclear factor kappa B, inhibitor of nuclear factor κ-B kinase, and mitogen-activated protein kinase. Vitamins are micronutrients with anti-inflammatory activities that have unclear mechanisms. The present study aimed to describe the putative mechanisms of vitamins involved in the inflammatory pathway of insulin resistance. The strategy to achieve this goal was to integrate data mining and analysis, target prediction, and molecular docking simulation calculations to support our hypotheses. Our results suggest that the multitarget activity of vitamins A, B1, B2, B3, B5, B6, B7, B12, C, D3, and E inhibits nuclear factor kappa B and mitogen-activated protein kinase, in addition to vitamins A and B12 against inhibitor of nuclear factor κ-B kinase. The findings of this study highlight the pharmacological potential of using an anti-inflammatory and multitarget treatment based on vitamins and open new perspectives to evaluate the inhibitory activity of vitamins against nuclear factor kappa B, mitogen-activated protein kinase, and inhibitor of nuclear factor κ-B kinase in an insulin-resistant context.

Indeterminate pulmonary nodules and prior malignancy: survival and recurrence after surgery in newly diagnosed stage I non-small cell lung cancer.

Background: Surgical excision biopsy remains the only reliable option in most cases of indeterminate pulmonary nodules, particularly in cancer survivors for whom surgery provides local control of pulmonary metastasis and the best chance of cure for early-stage lung cancer. Nevertheless, unnecessary surgeries remain a concern and the prognosis of newly diagnosed lung cancer might be influenced by the history of previous malignancy. We aimed to analyze the outcomes of resected indeterminate pulmonary nodules in patients with and without previous malignancy, and the impact of prior cancer history on survival and recurrence in stage I non-small cell lung cancer (NSCLC) patients. Methods: We retrospectively studied 176 resected indeterminate pulmonary nodules from 169 patients (58% with and 42% without previous cancer). Recurrence and overall survival (OS) were analyzed in newly diagnosed stage I NSCLC using the Kaplan-Meier method and Cox proportional hazard models. Results: The rate of benign lesions was 15.3% (9.6% in the previous cancer group and 23.6% in the no previous cancer group). In stage I NSCLC patients (n=86), previous malignancy was associated with recurrence (P<0.001) but not OS (P=0.23). Chronic obstructive pulmonary disease and visceral pleural invasion were associated with impaired OS and recurrence. Mediastinal lymph node removal was associated with better OS. Conclusions: The rate of benign resections among indeterminate pulmonary nodules in the no-previous cancer group more than doubled that of the previous cancer group and, in newly diagnosed stage I NSCLC patients, recurrence was independently associated with prior cancer. Therefore, in this setting, a history of previous malignancy should be taken into consideration when identifying patients at risk of tumor recurrence.

Early Intraprosthetic Dislocation of Total Hip Arthroplasty with Double Mobility Implant: Case Report.

Total hip arthroplasty (THA) is a successful surgery in the treatment of hip pain, but there are potential complications, of which dislocation is one of the most common. Dislocation management is a challenging problem that requires a multimodal approach, and the use of dual mobility implants is an option. We present a patient with a history of femoral neck fracture who underwent THA with a double mobility implant. On the 18 th postoperative day, after a fall to the ground, she developed prosthesis dislocation and had a complication after closed reduction, a subsequent intraprosthetic dislocation. After a radiographic diagnosis, the patient presented mechanical signs of hip flexion caused by a disassociated double mobility implant. The revision surgery was indicated, but the patient chose not to perform the necessary surgical procedure. A careful postoperative study of the radiographs revealed an eccentric femoral head and evidence of disassociated implantation in the surrounding soft tissues. Radiographs after closed reduction of intraprosthetic dislocations should be examined thoroughly.

Toward structure-multiple activity relationships (SMARts) using computational approaches: A polypharmacological perspective.

In the current era of biological big data, which are rapidly populating the biological chemical space, in silico polypharmacology drug design approaches help to decode structure-multiple activity relationships (SMARts). Current computational methods can predict or categorize multiple properties simultaneously, which aids the generation, identification, curation, prioritization, optimization, and repurposing of molecules. Computational methods have generated opportunities and challenges in medicinal chemistry, pharmacology, food chemistry, toxicology, bioinformatics, and chemoinformatics. It is anticipated that computer-guided SMARts could contribute to the full automatization of drug design and drug repurposing campaigns, facilitating the prediction of new biological targets, side and off-target effects, and drug-drug interactions.

Consensus Pharmacophore Strategy For Identifying Novel SARS-Cov-2 Mpro Inhibitors from Large Chemical Libraries.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome and is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development, and multiple Mpro crystals complexed with competitive inhibitors have been reported. In this study, we aimed to develop an Mpro consensus pharmacophore as a tool to expand the search for inhibitors. We generated a consensus model by aligning and summarizing pharmacophoric points from 152 bioactive conformers of SARS-CoV-2 Mpro inhibitors. Validation against a library of conformers from a subset of ligands showed that our model retrieved poses that reproduced the crystal-binding mode in 77% of the cases. Using models derived from a consensus pharmacophore, we screened >340 million compounds. Pharmacophore-matching and chemoinformatics analyses identified new potential Mpro inhibitors. The candidate compounds were chemically dissimilar to the reference set, and among them, demonstrating the relevance of our model. We evaluated the effect of 16 candidates on Mpro enzymatic activity finding that seven have inhibitory activity. Three compounds (1, 4, and 5) had IC50 values in the midmicromolar range. The Mpro consensus pharmacophore reported herein can be used to identify compounds with improved activity and novel chemical scaffolds against Mpro. The method developed for its generation is provided as an open-access code (https://github.com/AngelRuizMoreno/ConcensusPharmacophore) and can be applied to other pharmacological targets.

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning.

SARS-CoV-2 Main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome, which is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development. Herein, we performed a large-scale virtual screening by comparing multiple structural descriptors of reference molecules with reported anti-coronavirus activity against a library with >17 million compounds. Further filtering, performed by applying two machine learning algorithms, identified eighteen computational hits as anti-SARS-CoV-2 compounds with high structural diversity and drug-like properties. The activities of twelve compounds on Mpro's enzymatic activity were evaluated by fluorescence resonance energy transfer (FRET) assays. Compound 13 (ZINC13878776) significantly inhibited SARS-CoV-2 Mpro activity and was employed as a reference for an experimentally hit expansion. The structural analogues 13a (ZINC4248385), 13b (ZNC13523222), and 13c (ZINC4248365) were tested as Mpro inhibitors, reducing the enzymatic activity of recombinant Mpro with potency as follows: 13c > 13 > 13b > 13a. Then, their anti-SARS-CoV-2 activities were evaluated in plaque reduction assays using Vero CCL81 cells. Subtoxic concentrations of compounds 13a, 13c, and 13b displayed in vitro antiviral activity with IC50 in the mid micromolar range. Compounds 13a-c could become lead compounds for the development of new Mpro inhibitors with improved activity against anti-SARS-CoV-2.

Cocaine regulates antiretroviral therapy CNS access through pregnane-x receptor-mediated drug transporter and metabolizing enzyme modulation at the blood brain barrier.

BACKGROUND: Appropriate interactions between antiretroviral therapies (ART) and drug transporters and metabolizing enzymes at the blood brain barrier (BBB) are critical to ensure adequate dosing of the brain to achieve HIV suppression. These proteins are modulated by demographic and lifestyle factors, including substance use. While understudied, illicit substances share drug transport and metabolism pathways with ART, increasing the potential for adverse drug:drug interactions. This is particularly important when considering the brain as it is relatively undertreated compared to peripheral organs and is vulnerable to substance use-mediated damage. METHODS: We used an in vitro model of the human BBB to determine the extravasation of three first-line ART drugs, emtricitabine (FTC), tenofovir (TFV), and dolutegravir (DTG), in the presence and absence of cocaine, which served as our illicit substance model. The impact of cocaine on BBB integrity and permeability, drug transporters, metabolizing enzymes, and their master transcriptional regulators were evaluated to determine the mechanisms by which substance use impacted ART central nervous system (CNS) availability. RESULTS: We determined that cocaine had a selective impact on ART extravasation, where it increased FTC's ability to cross the BBB while decreasing TFV. DTG concentrations that passed the BBB were below quantifiable limits. Interestingly, the potent neuroinflammatory modulator, lipopolysaccharide, had no effect on ART transport, suggesting a specificity for cocaine. Unexpectedly, cocaine did not breach the BBB, as permeability to albumin and 4 kDa FITC-dextran, as well as tight junction proteins and adhesion molecules remained unchanged. Rather, cocaine selectively decreased the pregnane-x receptor (PXR), but not constitutive androstane receptor (CAR). Consequently, drug transporter expression and activity decreased in endothelial cells of the BBB, including p-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 4 (MRP4). Further, cytochrome P450 3A4 (CYP3A4) enzymatic activity increased following cocaine treatment that coincided with decreased expression. Finally, cocaine modulated adenylate kinases that are required to facilitate biotransformation of ART prodrugs to their phosphorylated, pharmacologically active counterparts. CONCLUSION: Our findings indicate that additional considerations are needed in CNS HIV treatment strategies for people who use cocaine, as it may limit ART efficacy through regulation of drug transport and metabolizing pathways at the BBB.

Knockdown of calpain1 in lumbar motoneurons reduces spasticity after spinal cord injury in adult rats.

Spasticity, affecting ∼75% of patients with spinal cord injury (SCI), leads to hyperreflexia, muscle spasms, and cocontractions of antagonist muscles, greatly affecting their quality of life. Spasticity primarily stems from the hyperexcitability of motoneurons below the lesion, driven by an upregulation of the persistent sodium current and a downregulation of chloride extrusion. This imbalance results from the post-SCI activation of calpain1, which cleaves Nav1.6 channels and KCC2 cotransporters. Our study was focused on mitigating spasticity by specifically targeting calpain1 in spinal motoneurons. We successfully transduced lumbar motoneurons in adult rats with SCI using intrathecal administration of adeno-associated virus vector serotype 6, carrying a shRNA sequence against calpain1. This approach significantly reduced calpain1 expression in transduced motoneurons, leading to a noticeable decrease in spasticity symptoms, including hyperreflexia, muscle spasms, and cocontractions in hindlimb muscles, which are particularly evident in the second month post-SCI. In addition, this decrease, which prevented the escalation of spasticity to a severe grade, paralleled the restoration of KCC2 levels in transduced motoneurons, suggesting a reduced proteolytic activity of calpain1. These findings demonstrate that inhibiting calpain1 in motoneurons is a promising strategy for alleviating spasticity in SCI patients.

A criação da Fundação Brasileira para a Conservação da Natureza / The creation of the Fundação Brasileira para a Conservação da Natureza

Abstract This study within the field of environmental history explores the scenario amid which the Fundação Brasileira para a Conservação da Natureza (Brazilian Foundation for Nature Conservation) was founded between 1958 and 1966; this important Brazilian non-governmental organization headquartered in Rio de Janeiro worked at the local, national, and international levels. Primary documentary sources were utilized, along with research of the related literature. The conclusions demonstrate the importance of non-governmental organizations predating this foundation, and the influence of conservationists on its establishment and current work.

Resumo Este estudo se insere no campo da história ambiental e tem o objetivo de compreender o cenário de criação, entre 1958 e 1966, da Fundação Brasileira para a Conservação da Natureza, importante organização não governamental ambientalista brasileira, com sede no Rio de Janeiro e atuação local, nacional e internacional. Para isso, utiliza fontes documentais primárias e pesquisa bibliográfica relacionada. As conclusões demonstraram a importância da existência de organizações não governamentais mais antigas que a fundação e a influência de conservacionistas sobre sua criação e sua atuação inicial.

Development and Implementation of an Enhanced Recovery Protocol for Bariatric Patients in a Third World Environment.

Introduction: An applicable and reproducible enhanced recovery protocol was developed and implemented to improve our outcomes in a third-world environment. Methods: We compared the results obtained prospectively. The group treated before the application of the enhanced recovery protocol was called usual care (UC) and included all bariatric surgeries operated on between 2014 and 2017. The new protocol was applied between 2017 and 2019 including all operated patients, and this group was called Fast Track (FT). The variables analyzed were the length of stay, readmissions, and complications recorded during the first 30 days. We also analyzed the milligrams of morphine used by each patient, and a cost analysis was performed. Results: During the study period, 816 patients were studied. Of these, 385 (47.2%) belonged to the UC group and 431 (52.8%) to the FT group. The mean hospital stay was 58.5 hours (UC) versus 40.3 hours (FT) (P = .0001). When comparing the global morbidity of both groups, we did not find significant differences (P = .47). There was also no statistically significant difference when comparing major complications (P = .79). No mortality was recorded. Morphine indication reported a statistically significant difference that favored FT. Costs were significantly higher in UC than in FT (P < .0001). Conclusions: We believe that the implementation of an enhanced recovery protocol in bariatric surgery is a reliable measure and can be implemented even in an underdevelopment environment enlarging the benefit for patients.

Toward α-1,3/4 fucosyltransferases targeted drug discovery: In silico uncovering of promising natural inhibitors of fucosyltransferase 6.

Sialyl Lewis X (sLex ) antigen is a fucosylated cell-surface glycan that is normally involved in cell-cell interactions. The enhanced expression of sLex on cell surface glycans, which is attributed to the upregulation of fucosyltransferase 6 (FUT6), has been implicated in facilitating metastasis in human colorectal, lung, prostate, and oral cancers. The role that the upregulated FUT6 plays in the progression of tumor to malignancy, with reduced survival rates, makes it a potential target for anticancer drugs. Unfortunately, the lack of experimental structures for FUT6 has hampered the design and development of its inhibitors. In this study, we used in silico techniques to identify potential FUT6 inhibitors. We first modeled the three-dimensional structure of human FUT6 using AlphaFold. Then, we screened the natural compound libraries from the COCONUT database to sort out potential natural products (NPs) with best affinity toward the FUT6 model. As a result of these simulations, we identified three NPs for which we predicted binding affinities and interaction patterns quite similar to those we calculated for two experimentally tested FUT6 inhibitors, that is, fucose mimetic-1 and a GDP-triazole derived compound. We also performed molecular dynamics (MD) simulations for the FUT6 complexes with identified NPs, to investigate their stability. Analysis of the MD simulations showed that the identified NPs establish stable contacts with FUT6 under dynamics conditions. On these grounds, the three screened compounds appear as promising natural alternatives to experimentally tested FUT6 synthetic inhibitors, with expected comparable binding affinity. This envisages good prospects for future experimental validation toward FUT6 inhibition.

Oleogels and reverse emulsions stabilized by acetylated Kraft lignins.

Acetylated Kraft lignins were evaluated for their ability of structuring vegetable oils into oleogels. Microwave-assisted acetylation was used to adjust lignin's degree of substitution according to reaction temperature (130 to 160 °C), and its effect in improving the viscoelasticity of the oleogels, which was related to the hydroxyl group content. The results were compared with those obtained by Kraft lignins acetylated using conventional methods at room temperature. A higher microwave temperature resulted in gel-like oil dispersions with improved viscoelastic properties, and stronger shear-thinning character, along with enhanced long-term stability. Lignin nanoparticles structured castor oil by enhancing hydrogen bonding between the hydroxyl groups of the oil and the nanoparticles. The oil structuring capacity of the modified lignins enhanced the stability of water-in-oil Pickering emulsions that resulted from low-energy mixing.

Knowledge about COVID-19 and perception of health safety among mexican dental students / Conocimiento sobre COVID-19 y percepción de seguridad en la salud de estudiantes mexicanos de odontología

This study aimed: 1) to investigate sources of information used by students to learn about COVID-19, 2) to investigate levels of knowledge about COVID-19 and about conditions for the treatment of patients during the COVID-19 lockdown, and 3) to evaluate students' perceptions of safety regarding their return to in-person activities at the School of Dentistry. Dental students answered a questionnaire (29 items; n=371) that explored the aims of the study, based on a Likert scale (Cronbach's alpha, 0.778). Data were tested with the Mann-Whitney U test and Kendall's Tau-c. Dental students received information about COVID-19 from the Mexican Health Ministry as their first source (45.28%). Students had good knowledge about the main characteristics of COVID-19, and 59.3% of students had excellent knowledge about the factors relevant to dental treatment of patients. Half of the students said they felt safe regarding a possible return to in-person activities at the dental school, while the other half did not. Statistically significant differences were noted between the students' scholar year and their level of knowledge (P<0.001) and between their perception of safety (very unsafe, unsafe, safe, and very safe) and scholar year (P=0.000). Dental students had good knowledge about COVID-19 and about the dental care for patients during the lockdown. Half of the dental students felt unsafe about a possible return to in-person school activities.

Los objetivos del estudio fueron 1) investigar que fuentes de información usaron los participantes para conocer sobre la COVID-19, 2) evaluar cuál es el nivel de conocimiento que tienen sobre COVID-19 y la atención a pacientes durante la contingencia, y 3) evaluar la percepción de seguridad sobre el regreso a actividades presenciales en la facultad. Estudio transversal. Se aplicó un cuestionario en línea (29 ítems; n=371) que exploró cada objetivo e incluyó una escala de Likert (Alfa de Cronbach de 0.778). Los datos fueron analizados con las pruebas de U de Mann Whitney y con Tau-c de Kendall. La mayoría de los participantes obtuvieron información sobre la COVID-19 a través de la Secretaría de Salud (45.28%), tuvieron un conocimiento bueno sobre las generalidades de la COVID-19 y el 59.3% tuvo un conocimiento excelente sobre la atención a pacientes. La mitad de los encuestados tuvo una percepción de inseguridad en un posible regreso a actividades en la facultad. Hubo diferencia estadística significativa para la asociación entre año escolar y grado de conocimiento (p<0.001) y entre la percepción en la seguridad en el regreso a actividades (muy inseguro, inseguro, seguro y muy seguro) y el grado escolar (P=0.000). Los participantes tuvieron buen conocimiento sobre las generalidades de la COVID-19 y sobre la atención a pacientes en situación de contingencia. La mitad de los EO sienten inseguridad sobre un posible regreso a actividades.

Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.

BACKGROUND: Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. METHODS: We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. RESULTS: Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. CONCLUSIONS: We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.

Towards Decoding Hepatotoxicity of Approved Drugs through Navigation of Multiverse and Consensus Chemical Spaces.

Drug-induced liver injury (DILI) is the principal reason for failure in developing drug candidates. It is the most common reason to withdraw from the market after a drug has been approved for clinical use. In this context, data from animal models, liver function tests, and chemical properties could complement each other to understand DILI events better and prevent them. Since the chemical space concept improves decision-making drug design related to the prediction of structure-property relationships, side effects, and polypharmacology drug activity (uniquely mentioning the most recent advances), it is an attractive approach to combining different phenomena influencing DILI events (e.g., individual "chemical spaces") and exploring all events simultaneously in an integrated analysis of the DILI-relevant chemical space. However, currently, no systematic methods allow the fusion of a collection of different chemical spaces to collect different types of data on a unique chemical space representation, namely "consensus chemical space." This study is the first report that implements data fusion to consider different criteria simultaneously to facilitate the analysis of DILI-related events. In particular, the study highlights the importance of analyzing together in vitro and chemical data (e.g., topology, bond order, atom types, presence of rings, ring sizes, and aromaticity of compounds encoded on RDKit fingerprints). These properties could be aimed at improving the understanding of DILI events.

Consensus Virtual Screening Protocol Towards the Identification of Small Molecules Interacting with the Colchicine Binding Site of the Tubulin-microtubule System.

Modification of the tubulin-microtubule (Tub-Mts) system has generated effective strategies for developing different treatments for cancer. A huge amount of clinical data about inhibitors of the tubulin-microtubule system have supported and validated the studies on this pharmacological target. However, many tubulin-microtubule inhibitors have been developed from representative and common scaffolds that cover a small region of the chemical space with limited structural innovation. The main goal of this study is to develop the first consensus virtual screening protocol for natural products (ligand- and structure-based drug design methods) tuned for the identification of new potential inhibitors of the Tub-Mts system. A combined strategy that involves molecular similarity, molecular docking, pharmacophore modeling, and in silico ADMET prediction has been employed to prioritize the selections of potential inhibitors of the Tub-Mts system. Five compounds were selected and further studied using molecular dynamics and binding energy predictions to characterize their possible binding mechanisms. Their structures correspond to 5-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2,3-dimethoxyphenol (1), 9,10-dihydro-3,4-dimethoxy-2,7-phenanthrenediol (2), 2-(3,4-dimethoxyphenyl)-5,7-dihydroxy-6-methoxy-4H-1-benzopyran-4-one (3), 13,14-epoxyparvifoline-4',5',6'-trimethoxybenzoate (4), and phenylmethyl 6-hydroxy-2,3-dimethoxybenzoate (5). Compounds 1-3 have been associated with literature reports that confirm their activity against several cancer cell lines, thus supporting the utility of this protocol.

Hearing health educational interventions for school students / Intervenções educativas em saúde auditiva para escolares

ABSTRACT Purpose: to implement and assess hearing health interventions for school students, using Dangerous Decibels® Program activities in partnership with the Young Doctor Project, approaching noise-induced hearing loss prevention. Methods: the study encompassed 41 students, aged 12 to 14 years, from two schools in inland São Paulo and a social institution for public school students. Activities were based on the Young Doctor Project and the Dangerous Decibels® Brazil Program. The students answered a questionnaire administered in three situations: before the intervention (pre), right after the intervention (post), and 4 months after the intervention. The ANOVA, Friedman (p < 0.001), and Tukey´s (p < 0.05) statistical tests were used. Results: the 41 students who participated in the program were protagonists of knowledge, spreading the content they learned to another 954 students in the three schools through cultural workshops. The analysis of program effectiveness revealed improved results right after the intervention and 4 months afterward. Conclusion: combining these two programs encouraged the protagonism of young people to increase their involvement with the community. Moreover, the students changed their attitude toward potentially dangerous sounds.

RESUMO Objetivo: implementar e avaliar intervenções em saúde auditiva para escolares, utilizando as atividades do Programa Dangerous Decibels ®, em parceria com o Projeto Jovem Doutor, abordando aspectos preventivos da perda auditiva induzida por níveis de pressão sonora elevados. Métodos: participaram do estudo 41 escolares, com idade entre 12 e 14 anos, de duas escolas no interior de São Paulo e uma Instituição Social direcionada a estudantes de escolas públicas. As atividades foram baseadas no Projeto Jovem Doutor e no programa Dangerous Decibels ® Brasil. Os escolares responderam a um questionário aplicado em três situações, antes da intervenção (pré), logo após a intervenção (pós) e quatro meses após a intervenção. Foram utilizados os testes estatísticos ANOVA, FRIEDMAN; p<0,001 e TUKEY; p<0,05. Resultados: os 41 escolares que participaram do programa atuaram como protagonistas do conhecimento, multiplicando o conteúdo aprendido através das oficinas culturais, envolvendo 954 escolares das três escolas. Ao analisar a eficácia do programa, observou-se melhora nos resultados logo após a intervenção e, também, após 4 meses. Conclusão: a união desses dois programas incentivou o protagonismo juvenil, objetivando o maior envolvimento dos estudantes junto da comunidade. Foi possível observar a mudança de atitude dos escolares frente aos sons potencialmente perigosos.

Impact of the Morphology of Electrospun Lignin/Ethylcellulose Nanostructures on Their Capacity to Thicken Castor Oil.

This study reports on a novel strategy for manufacturing thickened gel-like castor oil formulations by dispersing electrospun lignin/ethylcellulose nanostructures. These thickened formulations were rheologically and tribologically evaluated with the aim of being proposed as alternative ecofriendly lubricating greases. Low-sulfonate kraft lignin (LSL) and ethylcellulose (EC) were dissolved in a DMAc:THF mixture at different concentrations (8, 10, and 15 wt.%) and LSL:EC ratios (50:50, 70:30, and 90:10) and subjected to electrospinning. The resulting electrospun nanostructures were morphologically characterized. EC acting as the cospinning polymer improved both LSL spinnability and the oil structuring ability. Solutions with a high lignin content achieved microsized particles connected by fibrils, whereas solutions with a high EC content (50:50 ratio) and LSL/EC total concentration (10 and 15 wt.%) yielded beaded or bead-free nanofibers, due to enhanced extensional viscoelastic properties and nonNewtonian characteristics. The gel-like properties of electrospun nanostructure dispersions in castor oil were strengthened with the nanostructure concentration and the EC:LSL ratio, as a result of the formation of a more interconnected fiber network. The oleodispersions studied exhibited a satisfactory frictional response in a tribological contact, with friction coefficient values that were comparable to those achieved with traditional lithium-lubricating greases.

Potential Anticancer Activity of Pomegranate (Punica granatum L.) Fruits of Different Color: In Vitro and In Silico Evidence.

Pomegranate (PMG; Punica granatum L.) fruits possess a well-balanced nutrient/phytochemical composition, with proven adjuvant benefits in experimental cancer chemotherapy; however, such bioactivity could be affected by PMG's phenogenotype (varietal). Here, the chemical and phytochemical (UPLC-DAD-MS2) composition, antioxidant capacity and anticancer potential [in vitro (MTT assay) and in silico (foodinformatics)] of three PMG fruits of different aryl color [red (cv. Wonderful), pink (cv. Molar de Elche), and white (cv. Indian)] were evaluated. The macro/micronutrient (ascorbic acid, tocols, carotenoids), organic acid (citric/malic), and polyphenol content were changed by PMG's varietal and total antioxidant activity (ABTS, alcoholic > hexane extract) in the order of red > pink > white. However, their in vitro cytotoxicity was the same (IC50 > 200 µg.mL-1) against normal (retinal) and cancer (breast, lung, colorectal) cell lines. Sixteen major phytochemicals were tentatively identified, four of them with a high GI absorption/bioavailability score [Ellagic (pink), vanillic (red), gallic (white) acids, D-(+)-catechin (white)] and three of them with multiple molecular targets [Ellagic (52) > vanillic (32) > gallic (23)] associated with anticancer (at initiation and promotion stages) activity. The anticancer potential of the PMG fruit is phenogenotype-specific, although it could be more effective in nutraceutical formulations (concentrates).