Soluble isoforms of the DC-SIGN receptor can increase the dengue virus infection in immature dendritic cells.

Dengue is a disease with a high-impact on public health worldwide. Many researches have focused on the cell receptors involved in its pathogenesis. The role of soluble isoforms of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin) receptor in the process of Dengue Virus (DENV) infection is not well understood. This work proposes to evaluate changes in the infection process of Immature Dendritic Cells (iDCs) by DENV in the presence of DC-SIGN recombinant soluble isoforms 8, 10, and 12. The recombinant isoforms were built by heterologous expression, the DENV-2 was multiplied in the Aedes albopictus C6/36 cells and quantified in BHK-21 cells, and the iDCs were produced from the THP-1 strain. Infection assays were performed in the presence of iDCs, DENV-2, and isoforms 8, 10, and 12 separately at 25, 50 and 100 ng/mL. The final viral load was estimated by qPCR and statistical analysis was performed by Kruskal-Wallis and ANOVA tests. The iDC profile was confirmed by increasing expression of CD11c, CD86, and CD209 surface markers and maintaining CD14 expression. Infection assays demonstrated a 23-fold increase in DENV viral load in the presence of isoforms 8 and 10 at 100 ng/mL compared to the viral control (p < 0.05), while isoform 12 did not alter the viral load. It was possible to conclude that at 100 ng/mL isoforms (8 and 10) can interact with DENV, increasing viral infection, and potentially acting as opsonins.

Development of a cationic bacterial cellulose film loaded with anionic liposomes for prolonged release of oxacillin in wound dressing applications.

Dressings should protect wounds, promote healing, absorb fluids, and maintain moisture. Bacterial cellulose is a biopolymer that stands out in biomaterials due to its high biocompatibility in several applications. In the area of dressings, it is already marketed as an alternative to traditional dressings. However, it lacks any intrinsic activity; among these, the need for antimicrobial activity in infected wounds stands out. We developed a cationic cellulose film by modifying cellulose with 1-(5-carboxypentyl)pyridin-1-ium bromide, enhancing its wettability (contact angle: 26.6°) and water retention capacity (2714.37 %). This modified film effectively retained oxacillin compared to the unmodified control. Liposomal encapsulation further prolonged oxacillin release up to 11 days. Both oxacillin-loaded films and liposomal formulations demonstrated antimicrobial activity against Staphylococcus aureus. Our findings demonstrate the potential of chemically modified cellulose as a platform for controlled anionic antibiotics and/or their formulations delivery in wound care.

Metabolic imprinting in beef calves supplemented with creep feeding on performance, reproductive efficiency and metabolome profile.

This experiment evaluated the influence of creep feeding supplementation on productive and reproductive performance and on serum metabolome profile in Nelore (Bos indicus) heifers. Female calves were assigned to treatments: Creep (n = 190), with ad libitum access to a nutritional supplement from 70 to 220 days after birth, or Control (n = 140), without supplementation. After weaning (Day 220), both groups followed the same pasture and nutritional management. Body weight (BW) and backfat thickness (BFAT) were measured over time. Blood samples were collected at 220 and 360 days for LC-MS/MS targeted metabolomics. On day 408, during the synchronization timed artificial insemination (TAI) protocol, reproductive status (RS: diameter of uterine horn and largest follicle, and presence of CL) was assessed. Creep feeding increased BW and BFAT at weaning, but no differences in BW, BFAT, or RS after weaning were observed. Nonetheless, the pregnancy per AI (P/AI) for 1st service was 28.9% higher in the Creep group. On day 220, 11 significant metabolites influenced five metabolic pathways: Glucose-alanine cycle, alanine, glutathione, phenylalanine and tyrosine metabolism, and urea cycle. On day 360, 14 significant metabolites influenced eight metabolic pathways: Malate-aspartate shuttle, arginine and proline metabolism, urea cycle, aspartate, beta-alanine, glutamate metabolism, ammonia recycling and citric acid cycle. In conclusion, creep feeding supplementation improved calf performance and induced metabolic changes at weaning and 360 days of age. Although heifers had similar productive performance and reproductive status, when submitted to TAI, those supplemented with creep feeding had greater P/AI.

Social representations of tuberculosis by people with the disease.

OBJECTIVE: To understand the social representations of people with tuberculosis about the disease and its implications for following treatment. METHOD: A descriptive, qualitative study based on the Theory of Social Representations. It was conducted in a municipal health unit in the city of Belém. The participants were people diagnosed with tuberculosis and undergoing directly observed treatment, with the sample size defined by the data saturation technique. Data collection was done through semi-structured interviews. For data analysis it was used thematic content analysis. RESULTS: The records converged into three categories: Representations of tuberculosis and its impacts on the diagnosis; The faces of treatment: challenges facing follow-up and hope; and Constructions of living with the disease in family and society. FINAL CONSIDERATIONS: Living with the disease transforms everyday life and relationships. Discrimination and prejudice denote the need to reconfigure such representations for patients to be embraced.

Activity of extracts and terpenoids from Tontelea micrantha (Mart. ex Schult.) A.C.Sm. (Celastraceae) against pathogenic bacteria.

The pharmacological properties of plant extracts and phytochemicals, such as flavonoids and terpenoids, remain of great interest. In this work, the effect of extracts, friedelan-3,21-dione, and 3ß-O-D-glucosyl-sitosterol isolated from Tontelea micrantha roots was evaluated against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli. The antibacterial activity was evaluated by the minimum inhibitory and bactericidal concentrations (MIC and MBC, respectively), and the synergistic effect was assessed by the Checkerboard assay. Furthermore, the cytotoxicity of the plant-derived compounds against Vero cells was measured by the 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide (MTT) method. The biological effects of the isolated compounds were predicted using the PASS online software. The chloroform and hexane extracts of T. micrantha roots showed promising antibacterial effect, with MIC in the range of 4.8-78.0 µg/mL. Further analyses showed that these compounds do not affect the integrity of the membrane. The combination with streptomycin strongly reduced the MIC of this antibiotic and extracts. The extracts were highly toxic to Vero cells, and no cytotoxicity was detected for the two terpenoids isolated from them (i.e. friedelan-3,21-dione and 3ß-O-D-glucosyl-sitosterol; CC50 > 1000 µg/mL). Therefore, extracts obtained from T. micrantha roots significantly inhibited bacterial growth and are considered promising agents against pathogenic bacteria. The cytotoxicity results were very relevant and can be tested in bioassays.

Binary decisions of artificial intelligence to classify third molar development around the legal age thresholds of 14, 16 and 18 years.

Third molar development is used for dental age estimation when all the other teeth are fully mature. In most medicolegal facilities, dental age estimation is an operator-dependent procedure. During the examination of unaccompanied and undocumented minors, this procedure may lead to binary decisions around age thresholds of legal interest, namely the ages of 14, 16 and 18 years. This study aimed to test the performance of artificial intelligence to classify individuals below and above the legal age thresholds of 14, 16 and 18 years using third molar development. The sample consisted of 11,640 panoramic radiographs (9680 used for training and 1960 used for validation) of males (n = 5400) and females (n = 6240) between 6 and 22.9 years. Computer-based image annotation was performed with V7 software (V7labs, London, UK). The region of interest was the mandibular left third molar (T38) outlined with a semi-automated contour. DenseNet121 was the Convolutional Neural Network (CNN) of choice and was used with Transfer Learning. After Receiver-operating characteristic curves, the area under the curve (AUC) was 0.87 and 0.86 to classify males and females below and above the age of 14, respectively. For the age threshold of 16, the AUC values were 0.88 (males) and 0.83 (females), while for the age of 18, AUC were 0.94 (males) and 0.83 (females). Specificity rates were always between 0.80 and 0.92. Artificial intelligence was able to classify male and females below and above the legal age thresholds of 14, 16 and 18 years with high accuracy.

Representações sociais do cuidador familiar sobre cuidados paliativos em paciente terminal / Social representations of the family caregiver about palliative care in terminal patient / Representaciones sociales del cuidador familiar sobre cuidados paliativos en pacientes terminales

Objetivo: analisar as representações sociais dos cuidadores familiares sobre os cuidados paliativos em paciente terminal. Método: estudo descritivo com abordagem qualitativa. Para a interpretação dos resultados foi empregado como aporte teórico a Teoria das Representações Sociais. A pesquisa foi realizada com 30 cuidadores familiares de pacientes com câncer em estágio final. Resultado: observou-se a dimensão do cuidador familiar e o meio inserido das representações sociais. O cuidador não é um mero familiar, mas sim alguém que sofre junto com o doente, principalmente, os que estão com câncer em fase terminal, e por isso também precisa de orientações para seus cuidados físico e emocional. Discussão: A teoria das representações sociais, vinculada a área da saúde do cuidador familiar. Considerações finais: As representações sociais do cuidador familiar possibilitaram identificar a verdadeira extensão das questões diárias no cotidiano profissional

Objective: to analyze the social representations of family caregivers about palliative care in terminally ill patients. Method: descriptive study with a qualitative approach. For the interpretation of the results, the Theory of Social Representations was used as a theoretical contribution. The research was conducted with 30 family caregivers of end-stage cancer patients. Result: the dimension of the family caregiver and the inserted environment of the social representations were observed. The caregiver is not a mere family member, but someone who suffers together with the patient, especially those with terminal cancer, and therefore also needs guidance for their physical and emotional care. Discussion: the theory of social representations, linked to the area of family caregiver health. Final considerations:The social representations of the family caregiver made it possible to identify the true extent of daily issues in the professional routine

Objetivos: analizar las representaciones sociales de los cuidadores familiares sobre los cuidados paliativos en pacientes terminales. Método: estudio descriptivo con enfoque cualitativo. Para la interpretación de los resultados se utilizó como aporte teórico la Teoría de las Representaciones Sociales. La investigación se llevó a cabo con 30 cuidadores familiares de pacientes con cáncer en etapa terminal. Resultado: se observó la dimensión del cuidador familiar y el ambiente inserto de las representaciones sociales. El cuidador no es un simple miembro de la familia, sino alguien que sufre junto con el paciente, especialmente aquellos con cáncer terminal, y por lo tanto también necesita orientación para su cuidado físico y emocional. Discusión: La teoría de las representaciones sociales, vinculada al área de la salud del cuidador familiar. Consideraciones finales: las representaciones sociales del cuidador familiar permitieron identificar la verdadera extensión de las cuestiones cotidianas en el cotidiano profesional

Social representations of tuberculosis by people with the disease / Representaciones sociales de tuberculosis por personas con la enfermedad / Representações sociais da tuberculose por pessoas com a doença

ABSTRACT Objective: To understand the social representations of people with tuberculosis about the disease and its implications for following treatment. Method: A descriptive, qualitative study based on the Theory of Social Representations. It was conducted in a municipal health unit in the city of Belém. The participants were people diagnosed with tuberculosis and undergoing directly observed treatment, with the sample size defined by the data saturation technique. Data collection was done through semi-structured interviews. For data analysis it was used thematic content analysis. Results: The records converged into three categories: Representations of tuberculosis and its impacts on the diagnosis; The faces of treatment: challenges facing follow-up and hope; and Constructions of living with the disease in family and society. Final considerations: Living with the disease transforms everyday life and relationships. Discrimination and prejudice denote the need to reconfigure such representations for patients to be embraced.

RESUMEN Objetivo: Comprender las representaciones sociales de personas con tuberculosis sobre la enfermedad y sus implicaciones para el seguimiento del tratamiento. Método: Estudio descriptivo, con abordaje cualitativo, basado en la Teoría de las Representaciones Sociales. Se llevó a cabo en una unidad de salud municipal de la ciudad de Belém. Los participantes fueron personas con diagnóstico de tuberculosis y en tratamiento bajo observación directa, cuyo cuantitativo fue definido por la técnica de saturación de datos. La recolección de datos se realizó a través de una entrevista semiestructurada. Para analizar dos datos, utilice un análisis de contenido temático. Resultados: Los registros convergieron en tres categorías: Representaciones de la tuberculosis y sus impactos en el diagnóstico; Como enfrenta el tratamiento: desafíos que enfrenta el seguimiento y la esperanza; y Construcciones de convivencia con la enfermedad en familia y sociedad. Consideraciones finales: O vivir con una enfermedad transforma la vida cotidiana y las relaciones. La discriminación y el prejuicio denotan la necesidad de reconfigurar estas representaciones, para que el docente sea aceptado.

RESUMO Objetivo: Compreender as representações sociais de pessoas com tuberculose sobre a doença e implicações no tratamento. Método: Estudo descritivo, de abordagem qualitativa, com base na Teoria das Representações Sociais. Realizado em uma unidade municipal de saúde no município de Belém. Os participantes foram pessoas com diagnóstico de tuberculose e em tratamento diretamente observado, cujo quantitativo foi definido pela técnica da saturação de dados. A coleta de dados foi realizada por meio de entrevista semiestruturada. Para análise dos dados utilizou-se a análise temática de conteúdo. Resultados: Os registros convergiram em três categorias: Representações da tuberculose e seus impactos frente ao diagnóstico; as faces do tratamento: desafios frente ao seguimento e esperança; e Construções do conviver com a doença em família e sociedade. Considerações finais: O conviver com a doença transforma o cotidiano e as relações. A discriminação e preconceito denotam a necessidade de reconfigurar tais representações, para o doente ser acolhido.

Psiconeurodontologia, (bio)decodificação dental e os mil e um nomes para o charlatanismo odontológico no século XXI: uma revisão de escopo / Psychoneurodontology, dental (bio)decoding and a thousand terms for odontological charlatanism in the 21st century: a scoping review

Junto às tecnologias que surgem para aprimorar a Odontologia mundial, emergem temáticas que progressivamente prosperam no obscuro e na incerteza. Tais "áreas odontológicas" se caracterizam por uma roupagem prolixa e de alto apelo público (como por meio de inferências sobre o emocional e os mistérios do corpo humano). Em tempos de disseminação da psiconeurodontologia e (bio)decodificação dental, assim como da incerteza acerca de sua confiabilidade, faz-se imperativa a busca pela fundamentação científica que sustenta esta temática. Para isto, foi realizada uma revisão de escopo seguindo as recomendações do PRISMA-ScR e JBI. Uma ampla busca foi realizada em cinco bases de dados e em parte da literatura cinza. Não houve restrição quanto ao ano de publicação e nem quanto ao idioma. Os dados foram coletados e expostos na forma narrativa/descritiva. De maneira complementar, utilizou-se a ferramenta JBI para avaliação da qualidade metodológica. A busca resultou em 4.785 registros iniciais, dos quais somente dois foram classificados como elegíveis. Ambos os estudos foram detectados a partir da literatura cinzenta e consistiam em trabalhos peruanos de conclusão de curso em nível de graduação (Bacharelado) em Odontologia. Os trabalhos aferiam a ocorrência de lesão de cárie em quadrantes de dentes permanentes e decíduos e correlacionavam com um questionário psicoemocional. Os dois trabalhos concluíram em prol da aplicação da psiconeurodontologia e da (bio)decodificação dental como ferramentas adicionais ao armamentário diagnóstico do Cirurgião-dentista. Detectou-se alto risco de viés, em especial acerca das limitações metodológicas dos estudos elegíveis. Tendo em vista os métodos e resultados observados nos estudos elegíveis, pode-se concluir que não há fundamentação científica na psiconeurodontologia ou na (bio)decodificação dental, muito menos validade e confiabilidade para a sua aplicação na prática clínica odontológica atual

Along with the technologies that emerged to improve Dentistry worldwide, there are themes that progressively dive into darkness and uncertainty. Such "dental areas" are characterized by a verbose approach and strong public appeal (such as through inferences about the emotions and mysteries of the human body). In times of dissemination of psychoneurodontology and dental (bio)decoding, as well as uncertainty about their reliability, the search for alleged scientific foundations that support this theme is imperative. To this end, a scoping review was carried out following the recommendations of PRISMA-ScR and JBI. A broad search was carried out in five databases and part of the gray literature. There was no restriction on the year of publication or language. Data were collected and presented in narrative/descriptive form. Complementarily, the JBI tool was used to assess methodological quality. The search resulted in 4.785 initial records, of which only two were classified as eligible. Both studies were detected from the gray literature and consisted of Peruvian studies at Bachelor's degree in Dentistry. The studies measured the occurrence of caries lesions in quadrants of permanent and deciduous teeth and correlated them with a psychoemotional questionnaire. The two studies concluded in favor of the application of psychoneurodontology and dental (bio)decoding as additional tools to the dental surgeon's diagnostic armamentarium. A high risk of bias was detected, especially regarding the methodological limitations of the eligible studies. Considering the methods and results observed in the eligible studies, it can be concluded that there is no scientific basis in psychoneurodontology or dental (bio)decoding, as well as lack of validity and reliability for its application in current clinical dental practice

Virucidal antiviral activity of Maytenus quadrangulata extract against Mayaro virus: Evidence for the presence of catechins.

ETHNOPHARMACOLOGICAL RELEVANCE: Mayaro virus (MAYV) is an arbovirus endemic to the Amazon region, which comprises the states of the North and Midwest region of Brazil and encompasses the largest tropical forest in the world, the Amazon Forest. The confirmation of its potential transmission by Aedes aegypti and recent cases in Brazil, mainly in large centers in the northern region, led to the classification of Mayaro fever as an emerging disease. Traditional medicine is commonly used to treat various diseases, mainly by local riverside populations. Some species of the genus Maytenus, which have similar morphologies, are popularly used to treat infections and inflammations. In this context, our research group has studied and confirmed the antiviral activity of several plant-derived compounds. However, several species of this same genus have not been studied and therefore deserve attention. AIM OF THE STUDY: This study aimed to demonstrate the effects of ethyl acetate extracts of leaves (LAE) and branches (TAE) of Maytenus quadrangulata against MAYV. MATERIALS AND METHODS: Mammalian cells (Vero cells) were used to evaluate the cytotoxicity of the extracts. After cell infection by MAYV and the treatment with the extracts, we evaluated the selectivity index (SI), the virucidal effect, viral adsorption and internalization, and the effect on viral gene expression. The antiviral action was confirmed by quantifying the viral genome using RT-qPCR and by analyzing the effect on virus yield in infected cells. The treatment was performed based on the effective concentration protective for 50% of the infected cells (EC50). RESULTS: The leaves (LAE; EC50 12.0 µg/mL) and branches (TAE; EC50 101.0 µg/mL) extracts showed significative selectivity against the virus, with SI values of 79.21 and 9.91, respectively, which were considered safe. Phytochemical analysis revealed that the antiviral action was associated with the presence of catechins, mainly in LAE. This extract was chosen for the subsequent studies since it reduced the viral cytopathic effect and virus production, even at high viral loads [MOI (multiplicity of infection) 1 and 5]. The effects of LAE resulted in a marked reduction in viral gene expression. The viral title was drastically reduced when LAE was added to the virus before infection or during replication stages, reducing virus production up to 5-log units compared to infected and untreated cells. CONCLUSION: Through kinetic replication, MAYV was not detected in Vero cells treated with LAE throughout the viral cycle. The virucidal effect of LAE inactivates the viral particle and can intercept the virus at the end of the cycle when it gains the extracellular environment. Therefore, LAE is a promising source of antiviral agents.

Representações sociais sobre o processo de saúde e doença na crença católica / Social representations about the health and disease process in catholic belief / Representaciones sociales sobre el proceso de salud y enfermedad en la creencia católica

Objetivo: estudo objetivou descrever as representações sociais de pacientes católicos e analisar as implicações do seu imaginário para o processo saúde-doença. Método: estudo descritivo, com abordagem qualitativa. Realizado em um hospital oncológico, tendo como participantes pessoas autodeclaradas católicas. Utilizou-se entrevista semiestruturada e técnica de livre associação de palavras para coleta de dados. Resultados: emergiram três unidades temáticas: A representação da doença para cristãos católicos; A religião católica como alicerce no processo de adoecimento; Representação da doença para católicos: enfermidades adquiridas por infringirmos as leis de Deus. Considerações finais: a religiosidade é parte significativa no cotidiano das pessoas e deve ser respeitada independente da crença do profissional.

Objective: the study aimed to describe the social representations of Catholic patients and analyze the implications of their imaginary for the health-disease process. Method: descriptive study, with qualitative approach. Carried out in an oncology hospital, having as participants self-declared Catholic people. Semi-structured interviews and a technique of free word association were used for data collection. Results: three thematic units emerged: The representation of the disease for Catholic christians; The Catholic religion as a foundation in the process of illness; Representation of the disease for Catholics: diseases acquired by breaking the laws of God. Final considerations: religiosity is a significant part of people's daily lives and should be respected regardless of the professional's belief.

Objetivo: el estudio tuvo como objetivo describir las representaciones sociales de los pacientes católicos y analizar las implicaciones de su imaginario para el proceso salud-enfermedad. Método: estudio descriptivo, con enfoque cualitativo. Realizado en un hospital oncológico, teniendo como participantes personas autodeclaradas católicas. Para la recolección de datos se utilizaron entrevistas semiestructuradas y una técnica de asociación libre de palabras. Resultados: surgieron tres unidades temáticas: La representación de la enfermedad para los cristianos católicos; La religión católica como fundamento en el proceso de la enfermedad; Representación de la enfermedad para los católicos: enfermedades adquiridas por la ruptura de las leyes de Dios. Consideraciones finales: la religiosidad es una parte importante de la vida cotidiana de las personas y debe ser respetada independientemente de la creencia del profesional.

Musculação como espaço generificado e sexualizado? notas etnográficas / Is body building sector gendered and sexualized? ethnographic notes / ¿Musculación como espacio generificado y sexualizado? notas etnográficas

Objetivo: Com base na micros sociologia de Erving Goffman e na teoria sociológica de Pierre Bourdieu, o presente estudo objetivou analisar até que ponto o setor da musculação pode ser considerado um espaço generificado e sexualizado. Metodologia: Durante um ano, entre 2012-2013, realizou-se uma etnografia interacionista comparativa entre duas academias inseridas em dois bairros distintos da zona oeste da cidade do Rio de Janeiro. Resultados e discussão: Os resultados indicaram como os espaços no interior dos estabelecimentos e as interações sociais entre os(as) frequentadores(as) se estabeleciam de modo eminentemente binário e sexista. Foi possível também apreender como as intersecções entre gênero e camada social revelam as formas como as academias se constituem como locais de práticas corporais (in)viáveis para determinados sujeitos. Considerações finais: Conclui-se que tais achados podem ser importantes para gestores(as), professores(as) de Educação Física e alunos(as) compreenderem alguns aspectos socioculturais que atravessam as interações entre as pessoas que circulam nesses estabelecimentos cotidianamente.

Objective: Based on Erving Goffman's microsociology and Pierre Bourdieu's sociological theory, this study aimed to analyze if the bodybuilding sector can be considered a gendered and sexualized space. Methodology: During one year, between 2012-2013, comparative interactionist ethnography was carried out between two gyms located in two different neighborhoods in the west zone of the city of Rio de Janeiro. Results and discussion: The results indicated how the spaces inside the gyms and the social interactions between the practitioners were established in an eminently binary and sexist way. It was also possible to detect how the intersections between gender and social class reveal the ways in which gyms are constituted as places of (un)feasible body practices for certain subjects. Final considerations: It is concluded that such findings may be important for managers, Physical Education teachers and practitioners to understand some sociocultural aspects about the interactions between people who circulate in the gyms on a daily basis.

Objetivo: Con base en la microsociología de Erving Goffman y enlateoría sociológica de Pierre Bourdieu, el presente estudiotuvo como objetivo analizar hasta quépuntoel sector de la musculación puede ser considerado um espacio generificado y sexualizado. Metodologia: Durante unaño, entre 2012-2013, se realizó una etnografia interaccionista comparativa entre dos academias insertadas en dos barrios distintos de la zona oeste de laciudad de Río de Janeiro. Resultados y Discusión: Los resultados indicaron cómolos espaciosenel interior de losestablecimientos y lasinteraccionessociales entre los(as) frecuentadores(as) se establecían de modo eminentemente binario y sexista. Fue posible también aprender cómo las intersecciones entre género y capa social revelan las formas como las academias se constituy en como locales de prácticas corporales (in)viables para determinados sujetos. Consideraciones finales: Se concluye que tales resultados pueden ser importantes para que gestores(as), profesores(as) de Educación Física y practicantes comprendan algunos aspectos socioculturales que atraviesan lãs interacciones entre las personas que circulan em esosestablecimientos cotidianamente.

Flavonoid-Rich Fractions of Bauhinia holophylla Leaves Inhibit Candida albicans Biofilm Formation and Hyphae Growth.

This study evaluated the effect of the extract and fractions of Bauhinia holophylla on Candida albicans planktonic growth, biofilm formation, mature biofilm, and hyphae growth. Three C. albicans strains (SC5314, ATCC 18804, and ATCC 10231) were tested. The crude extract and the fractions were obtained by exhaustive percolation and liquid-liquid partition, respectively. Phytochemical analyses of B. holophylla extract and fractions were performed using high-performance liquid chromatography coupled with a diode-array detector and mass spectrometry (HPLC-DAD-MS). A microdilution assay was used to evaluate the effect of the B. holophylla extract and fractions on C. albicans planktonic growth, and crystal violet staining was used to measure the total biomass of the biofilm. Hyphae growth was analyzed using light microscopy. Thirteen flavonoids were identified, with a predominance of the flavonol-3-O-glycoside type based on quercetin, myricetin, and kaempferol. Flavonoid-rich fractions of B. holophylla leaves displayed antifungal activity and inhibited both biofilm formation and hyphae growth in all the tested strains, but were not effective on C. albicans planktonic growth and mature biofilm. This study indicates that flavonoid-rich fractions from B. holophylla leaves interfere with the virulence of Candida species and support the use of Bauhinia spp. in folk medicine to treat infections.

Animal venoms as a source of antiviral peptides active against arboviruses: a systematic review.

Arthropod-borne viruses (arboviruses), such as Zika virus (ZIKV), chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and West Nile virus (WNV), are pathogens of global importance. Therefore, there has been an increasing need for new drugs for the treatment of these viral infections. In this context, antimicrobial peptides (AMPs) obtained from animal venoms stand out as promising compounds because they exhibit strong antiviral activity against emerging arboviral pathogens. Thus, we systematically searched and critically analyzed in vitro and in vivo studies that evaluated the anti-arbovirus effect of peptide derivatives from toxins produced by vertebrates and invertebrates. Thirteen studies that evaluated the antiviral action of 10 peptides against arboviruses were included in this review. The peptides were derived from the venom of scorpions, spiders, wasps, snakes, sea snails, and frogs and were tested against DENV, ZIKV, YFV, WNV, and CHIKV. Despite the high structural variety of the peptides included in this study, their antiviral activity appears to be associated with the presence of positive charges, an excess of basic amino acids (mainly lysine), and a high isoelectric point (above 8). These peptides use different antiviral mechanisms, the most common of which is the inhibition of viral replication, release, entry, or fusion. Moreover, peptides with virucidal and cytoprotective (pre-treatment) effects were also identified. In conclusion, animal-venom-derived peptides stand out as a promising alternative in the search and development of prototype antivirals against arboviruses.

NS2B-NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review.

Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising molecular target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 µM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1388.02 µM and the selectivity index was 3.07-1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases.

Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids.

Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 µg/mL and MFC 62.5 µg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 µg/mL), and C. tropicalis (MIC 31.2 µg/mL and MFC 125 µg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained.

Epilepsy in children with Congenital Zika Syndrome: A systematic review and meta-analysis.

OBJECTIVES: To estimate the overall frequency of epilepsy in children with congenital Zika syndrome (CZS) and describe the profile of seizures and the response rate to anti-epileptic treatment in this group of patients. METHODS: A systematic review and meta-analysis were conducted following the Cochrane Handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed/MEDLINE, Scopus, Cochrane Library, SciELO, and LILACS were searched until June 23, 2020. Observational studies that evaluated the frequency of epilepsy in children diagnosed with CZS according to international criteria were included in the study. RESULTS: Fourteen studies evaluating 903 patients diagnosed with CZS were pooled in a meta-analysis. All studies were conducted in Brazil, with reports published between 2016 and 2020, and included children diagnosed with CSZ from 0 to 40 months of age. The overall rate of epilepsy in children diagnosed with CZS was estimated at 60% (95% confidence interval [CI] 0.51-0.68). The studies included in this review show that the frequency of epilepsy in patients with CSZ varies with age, with higher rates in older children. Epileptic spasms was the primary type of seizure observed in this group, followed by focal and generalized crisis. The response rate to anti-epileptic drugs was considerably low, ranging from 20% of seizure control in the first year and 30% in the second year. SIGNIFICANCE: Children with CZS presented a high cumulative incidence of epilepsy episodes with increased severity and a low response to anti-epileptic therapy, which is associated with the extensive damage caused by the Zika virus on the cortical structures of patients.