Petrosamine isolated from marine sponge Petrosia sp. demonstrates protection against neurotoxicity in vitro and in vivo.

According to The World Alzheimer Report 2023 by Alzheimer's Disease International (ADI) estimates that 33 to 38.5 million people worldwide suffer from Alzheimer's Disease (AD). A crucial hallmark associated with this disease is associated with the deficiency of the brain neurotransmitter acetylcholine, due to an affected acetylcholinesterase (AChE) activity. Marine organisms synthesize several classes of compounds, some of which exhibit significant AChE inhibition, such as petrosamine, a coloured pyridoacridine alkaloid. The aim of this work was to characterize the activity of petrosamine isolated for the first time from a Brazilian marine sponge, using two neurotoxicity models with aluminium chloride, as exposure to aluminium is associated with the development of neurodegenerative diseases. The in vitro model was based in a neuroblastoma cell line and the in vivo model exploited the potential of zebrafish (Danio rerio) embryos in mimicking hallmarks of AD. To our knowledge, this is the first report on petrosamine's activity over these parameters, either in vitro or in vivo, in order to characterize its full potential for tackling neurotoxicity.

Lyotropic liquid crystalline 2D and 3D mesophases: Advanced materials for multifunctional anticancer nanosystems.

Cancer remains a leading cause of mortality. Despite significant breakthroughs in conventional therapies, treatment is still far from ideal due to high toxicity in normal tissues and therapeutic inefficiency caused by short drug lifetime in the body and resistance mechanisms. Current research moves towards the development of multifunctional nanosystems for delivery of chemotherapeutic drugs, bioactives and/or radionuclides that can be combined with other therapeutic modalities, like gene therapy, or imaging to use in therapeutic screening and diagnosis. The preparation and characterization of Lyotropic Liquid Crystalline (LLC) mesophases self-assembled as 2D and 3D structures are addressed, with an emphasis on the unique properties of these nanoassemblies. A comprehensive review of LLC nanoassemblies is also presented, highlighting the most recent advances and their outstanding advantages as drug delivery systems, including tailoring strategies that can be used to overcome cancer challenges. Therapeutic agents loaded in LLC nanoassemblies offer qualitative and quantitative enhancements that are superior to conventional chemotherapy, particularly in terms of preferential accumulation at tumor sites and promoting enhanced cancer cell uptake, lowering tumor volume and weight, improving survival rates, and increasing the cytotoxicity of their loaded therapeutic agents. In terms of quantitative anticancer efficacy, loaded LLC nanoassemblies reduced the IC50 values from 1.4-fold against lung cancer cells to 125-fold against ovarian cancer cells.

Antimicrobial and anti-biofilm activity of silver nanoparticles biosynthesized with Cystoseira algae extracts.

Antimicrobial resistance is an ever-growing global concern to public health with no clear or immediate solution. Silver nanoparticles (AgNPs) have long been proposed as efficient agents to fight the growing number of antibiotic-resistant strains. However, the synthesis of these particles is often linked to high costs and the use of toxic, hazardous chemicals, with environmental and health impact. In this study, we successfully produced AgNPs by green synthesis with the aid of the extract of two brown algae-Cystoseira baccata (CB) and Cystoseira tamariscifolia (CT)-and characterized their physico-chemical properties. The NPs produced in both cases (Ag@CB and Ag@CT) present similar sizes, with mean diameters of around 22 nm. The antioxidant activity of the extracts and the NPs was evaluated, with the extracts showing important antioxidant activity. The bacteriostatic and bactericidal properties of both Ag@CB and Ag@CT were tested and compared with gold NPs produced in the same algae extracts as previously reported. AgNPs demonstrated the strongest bacteriostatic and bactericidal properties, at concentrations as low as 2.16 µg/mL against Pseudomonas aeruginosa and Escherichia coli. Finally, the capacity of these samples to prevent the formation of biofilms characteristic of infections with a poorer outcome was assessed, obtaining similar results. This work points towards an alternative for the treatment of bacterial infections, even biofilm-inducing, with the possibility of minimizing the risk of drug resistance, albeit the necessary caution implied using metallic NPs.

Impact of umbilical cord mesenchymal stromal/stem cell secretome and cord blood serum in prostate cancer progression.

Prostate cancer (PCa) is the second most common malignancy in men, and the fifth leading cause of death worldwide. Mesenchymal stromal/stem cells (MSC) have been identified in PCa, although contradictory effects in malignant transformation and tumor progression have been described. Since umbilical cord (UC) MSC and cord blood serum (CBS) are rich in numerous growth and anti-inflammatory factors, UC-MSC secretome and CBS are able to modulate tumor cell proliferation and survival as well as immunity and angiogenesis. In the present study, we address this relationship and investigate the influence of UC-MSC secretome and CBS on two human PCa cell lines (PC3 and LNCaP) and a normal epithelial prostate cell line (HPEpiC). Our results disclosed that upon exposure to UC-MSC-conditioned medium or CBS, both PC3 and LNCaP cells exhibited reduced viability, proliferation, and motility while non-malignant epithelial prostate cells were unaffected. These findings were corroborated by expression analysis of AKT/PI3K signaling pathway, p53 and interleukin genes. UC-MSC and CBS factors decreased the expression of growth-stimulating AKT and PI3K effectors and simultaneously up-regulated the expression of tumor-suppressor p53. Moreover, a more anti-inflammatory expression profile was found in both malignant PCa cell lines. Altogether, these results shed light into possible mechanisms by which UC-MSC and CBS reduce PCa progression, further reinforcing their potential use as novel therapeutic agents in PCa.

Oficina de formação bioética para a Estratégia Saúde da Família: perspectivas e olhares dos diferentes atores acerca dos cenários, montagem e espetáculo / Bioethics Training Workshop for Family Health Strategy: perspectives of the different players about scenarios, setup and show / Taller de formación en bioética para la estrategia salud de la familia: perspectivas y miradas de los diferentes actores sobre los escenarios, montaje y espectáculo

A formação dos profissionais de saúde segue em discussão há tempos ­ no Brasil e no mundo ­, assim como as mudanças dos paradigmas sanitários e dos modelos de cuidado em saúde. Com a criação do Sistema Único de Saúde e a implantação da Estratégia de Saúde da Família (ESF) como reorganizadores da atenção em saúde, brotam, neste cenário, questões e problemas bioéticos não vividos anteriormente no âmbito da prática de saúde hospitalar. Este artigo apresenta os resultados da realização de uma oficina de formação em bioética com a participação de 130 pessoas (128 profissionais da ESF no município de Viçosa, Minas Gerais, e dois convidados), promovida pela integração da universidade com o serviço de saúde local. Os referenciais utilizados incluíram o pluralismo metodológico, o trabalho em pequenos grupos, a aprendizagem significativa e o uso da arte para a construção das competências em bioética. Os resultados verificados foram otimistas quanto à efetividade da ação, tanto na ótica dos profissionais da ESF quanto dos participantes (facilitadores e docentes envolvidos), promovendo-se uma construção coletiva de saberes para a práxis.

The training of health professionals has been a point of discussion for a long time in Brazil and around the world, as well as changes in health paradigms and health care models. With the merger of the National Health System and the implementation of the Family Health Strategy (FHS) as organizer of health care, issues and problems emerged, which were not previously thought about in the context of health and hospital practice, mainly reflections on ethical and bioethical aspects. This paper presents the results of conducting a training workshop on bioethics with the participation of 130 people (128 FHS professionals in Viçosa, Minas Gerais and two guests), sponsored by the university's integration with the local health service, based on the use of methodological pluralism, small group work, learning and meaningful use of art for the construction of expertise in bioethics. Actual outcomes were optimistic about the effectiveness of the action, from the viewpoint of both the FHS professionals and participants (facilitators and professors involved), promoting a collective construction of knowledge for practice.

La formación de los profesionales de la salud es objeto de debate desde hace mucho tiempo - en Brasil y en el mundo -, así como los cambios de paradigmas y modelos de salud para el cuidado de la salud. Con la creación del Sistema Único de Salud (SUS) y de la aplicación de la Estrategia Salud de la Familia (ESF) como de reorganizadores cuidado de la salud, surgen, en este escenario, los problemas y las cuestiones de bioética que no se vivieron dentro de la práctica de la salud del hospital. Este artículo presenta los resultados de la realización de una capacitación sobre la bioética con la participación de 130 personas (128 profesionales de la ESF en Viçosa, Minas Gerais y dos invitados), promovido por la integración de la universidad con el servicio de salud local. Los puntos de referencia utilizados incluyen el pluralismo metodológico, el trabajo en pequeños grupos, el aprendizaje significativo y el uso del arte para la construcción de capacidades en bioética. Los resultados observados se mostraron optimistas acerca de la efectividad de la acción, tanto desde el punto de vista de los profesionales de la ESF, y los participantes (facilitadores y profesores involucrados), la promoción de una construcción colectiva de conocimiento a la práctica.

Mortalidade fetal em gestantes com COVID-19 e outros desfechos materno-fetais: uma revisão integrativa da literatura / Fetal mortality in pregnant women with COVID-19 and other maternal-fetal outcomes: an integrative literature review

Objetivo: Analisar os resultados apresentados sobre a relação entre COVID-19 e gravidez, com foco no desfecho fetal. Fontes dos dados: Foi realizada a busca de artigos publicados entre 1 de janeiro de 2020 e 1 de junho de 2021 nas bases de dados PubMed, Embase e Cochrane, utilizando os seguintes descritores: "coronavirus infections", "coronavirus disease 2019", "COVID-19", "fetal mortality" e "fetus mortality". Seleção dos estudos: Foram encontrados 99 artigos, sendo selecionados 28 artigos para leitura completa por meio dos critérios de inclusão e exclusão. Ao final, 14 artigos foram escolhidos para serem incluídos na presente revisão. Coleta de dados: Para a extração dos dados dos artigos selecionados, utilizou-se o instrumento validado por Ursi (2005), modificado para se adequar à demanda do tema em questão. Síntese dos dados: Encontrou-se que a infecção por COVID-19 aumentou a morbimortalidade das gestantes, principalmente aquelas que já possuíam algum fator de risco para a doença grave. Além disso, a maioria dos estudos mostrou uma taxa aumentada de nascimentos prematuros entre os filhos de mães infectadas. Não foram demonstrados resultados consistentes de aumento nas taxas de aborto, mortalidade fetal ou transmissão vertical. Conclusão: Ações de saúde devem priorizar o cuidado materno-fetal com o objetivo de prevenir a doença nas gestantes e acompanhar de forma mais cuidadosa aquelas infectadas pelo vírus, de forma a prevenir a morbimortalidade materna e a prematuridade, que são importantes marcadores de saúde pública.(AU)

Objective: To analyze the results presented on the relationship between COVID-19 and pregnancy, focusing on fetal outcome. Data sources: We searched for articles published between January 1, 2020 and June 1, 2021 in PubMed, Embase and Cochrane databases, using the following descriptors: "coronavirus infections", "coronavirus disease 2019", "COVID-19", "fetal mortality" and "fetus mortality". Selection of studies: 99 articles were found, and 28 articles were selected for full reading through inclusion and exclusion criteria. In the end, 14 articles were chosen to be included in this review. Data collection: To extract data from selected articles, the instrument validated by Ursi (2005) was used, modified to suit the demand of the topic in question. Data synthesis: It was found that COVID-19 infection increased the morbidity and mortality of pregnant women, especially those who already had some risk factor for severe disease. In addition, most studies have shown an increased rate of preterm births among children of infected mothers. No consistent results of increased rates of miscarriage, fetal mortality or mother-to-child transmission have been demonstrated. Conclusion: Health actions should prioritize maternal- fetal care in order to prevent the disease in pregnant women and more carefully monitor those infected with the virus, in order to prevent maternal morbidity and mortality and prematurity, which are important public health markers.(AU)

Bioética na odontologia: o que pensam os coordenadores dos cursos / Bioethics teaching in dentistry as seen by course coordinators / Bioética en odontología: qué piensan los coordinadores de las carreras

Resumo Este artigo analisa a importância que coordenadores dos cursos de odontologia brasileiros atribuem ao ensino da bioética e sua opinião sobre o perfil desejável para egressos desse curso. Trata-se de estudo exploratório, descritivo e transversal realizado com 130 coordenadores de cursos de odontologia brasileiros no qual foram realizadas análises descritivas e análise de conteúdo de Bardin. A grande maioria dos participantes atribui importância à bioética em diferentes situações e 23,8% deles consideram um perfil adequado o profissional com postura ética e humanizada, reflexivo e com competência técnica. A bioética está sendo inserida na matriz curricular dos cursos de odontologia, e a maioria dos coordenadores a considera importante em diferentes situações, mas nem todos os gestores entendem o que ela contempla.

Abstract This article analyzes the importance dentistry course coordinators attribute to bioethics teaching and their opinion on the expected graduate profile. An exploratory, descriptive cross-sectional study was conducted with 130 coordinators of Brazilian dentistry courses. Data underwent descriptive analysis and Bardin's content analysis. Most participants attribute importance to bioethics teaching in different situations and 23.8% considered a professional with an ethical and humanized attitude, who is reflective and technically competent as a suitable profile. Dentistry courses are increasingly including bioethics in their curricula, and although most coordinators consider it important, not all understand its principles.

Resumen Este artículo analiza la importancia que los coordinadores de las carreras de Odontología en Brasil atribuyen a la enseñanza de la bioética y su opinión sobre el perfil deseable para los graduados de esta carrera. Se trata de un estudio exploratorio, descriptivo y transversal, realizado con 130 coordinadores de las carreras de Odontología de Brasil en el que se llevaron a cabo análisis descriptivos y análisis de contenido de Bardin. La mayoría de los participantes considera que la bioética es importante en diferentes situaciones, y el 23,8% de ellos estiman que un profesional con actitud ética y humanizada, reflexivo y técnicamente competente es un perfil adecuado. La bioética se está incluyendo en el plan de estudios de las carreras de Odontología, y la mayoría de los coordinadores la consideran importante en diferentes situaciones, pero no todos los directores entienden su alcance.

Bioética como ferramenta nas decisões de cuidado paliativo em neonatologia / Bioethics as a decision-making tool in neonatal palliative care / Bioética como herramienta en las decisiones sobre cuidados paliativos en neonatología

Resumo Os avanços tecnológicos da medicina perinatal contribuem para o cuidado e a manutenção da vida dos neonatos, entretanto a utilização demasiada da tecnologia está associada ao aumento de morbidades e sofrimento. Tendo em vista a bioética, esta revisão sistemática da literatura objetivou esclarecer como estão sendo ofertados os cuidados paliativos em neonatologia. Os resultados foram divididos em quatro categorias: 1) fragilidade curricular das especializações em neonatologia referente a cuidados paliativos e bioética; 2) inabilidade dos profissionais na comunicação com familiares; 3) exclusão dos familiares na tomada de decisão; e 4) necessidade de aprofundamento dos estudos e discussões acerca de cuidados paliativos perinatais, domiciliares e doação de órgãos neonatais. Concluiu-se que os cuidados paliativos contribuem para a qualidade de vida e de morte dos indivíduos, embora ainda seja um tabu no caso de neonatos.

Abstract Technological advancements in neonatology contribute to the care and maintenance of newborns' lives; however, its overuse is associated with increased morbidities and suffering. Having bioethics as its theoretical framework, this systematic literature review elucidates the provision of neonatal palliative care. Results analysis resulted in four categories: 1) poor inclusion of palliative care and bioethics in neonatal specialization curricula; 2) professionals' inability to communicate with family members; 3) exclusion of family members from decision-making; and 4) need for further studies and discussions regarding neonatal and home palliative care and organ donation. Palliative care contributes to people's quality of life and death, despite being taboo in the case of newborns.

Resumen Los avances tecnológicos en medicina perinatal contribuyen al cuidado y al mantenimiento de la vida de los neonatos, sin embargo, el uso excesivo de la tecnología se asocia a un incremento en la morbilidad y el sufrimiento. Desde la bioética, esta revisión sistemática de la literatura pretendió aclarar cómo se ofrecen los cuidados paliativos en neonatología. Los resultados se dividieron en cuatro categorías: 1) Deficiencias en los planes de estudios de las especialidades de neonatología respecto a los cuidados paliativos y la bioética; 2) Inhabilidad de los profesionales para comunicarse con los familiares; 3) Exclusión de los familiares en la toma de decisiones; y 4) Necesidad de más estudios y debates sobre los cuidados paliativos perinatales y domiciliarios, y la donación de órganos neonatales. Los cuidados paliativos contribuyen a la calidad de vida y de muerte de las personas, aunque siguen siendo tabú en el caso de los neonatos.

Atenção integrada às doenças prevalentes na infância no contexto da atenção primária: uma revisão de escopo / Integrated care for prevalent childhoods in the context of primary care: a scoping review / Atención integrada a la infancia prevalente en el contexto de la atención primaria: a scoping review

Objetivo: Mapear e examinar as evidências científicas sobre a aplicação da estratégia de atenção às doenças prevalentes na infância no contexto da Atenção Primária. Método: Scoping Review, baseado nos procedimentos recomendados pelo instituto Joanna Briggs. Definiu-se a pergunta norteadora: "Quais evidências científicas disponíveis acerca da aplicação da estratégia de atenção às doenças prevalentes na infância (AIDPI) no contexto da atenção básica em saúde?". Realizou-se buscas em cinco bases de dados nacionais e internacionais, sobre trabalhos publicados entre 2018 até dezembro de 2022. Dos 2227 estudos encontrados, 329 foram selecionados para leitura na íntegra, resultando em uma amostragem final de 08 estudos analisados. Resultados: Os artigos foram publicados de 2018 a 2022, com abordagem quantitativa dos dados, sendo 04 estudos (50%) com delineamento transversal exploratório. No que tange a aplicação do AIDPI, 06 (75%) apontaram que a aplicabilidade da estratégia AIDPI ainda é deficitária no atendimento e manejo das doenças prevalentes na infância no contexto do primeiro nível de atenção à saúde, devido à falta de treinamento dos profissionais, escassez de recurso e problemas estruturais. Conclusão: As evidências mostram que apesar do longínquo tempo de criação da AIDPI e os estudo apontam baixo índice de adesão e a inaplicabilidade da estratégia, sua aplicação ainda é negligenciada, o que afeta diretamente nos índices de morbimortalidade infantil por causas evitáveis, passíveis de resolução e atendimento no primeiro nível de assistência à saúde.

Objective: To map and examine the scientific evidence on the application of the strategy of care for prevalent childhood diseases in the context of Primary Care. Method: Scoping Review, based on the procedures recommended by the Joanna Briggs Institute. The guiding question was defined as: "What scientific evidence is available on the application of the strategy of care for diseases prevalent in childhood (IMCI) in the context of primary health care? A search was conducted in five national and international databases, on papers published between 2018 and December 2022. Of the 2227 studies found, 329 were selected for reading in full, resulting in a final sample of 08 studies analyzed. Results: The articles were published from 2018 to 2022, with a quantitative approach to data, being 04 studies (50%) with exploratory cross-sectional design. Regarding the application of AIDPI, 06 (75%) pointed out that the applicability of the AIDPI strategy is still deficient in the care and management of prevalent childhood diseases in the context of the first level of health care, due to lack of training of professionals, scarcity of resources, and structural problems. Conclusion: The evidence shows that despite the long time since the creation of the IMCI and the studies show low rates of adherence and inapplicability of the strategy, its application is still neglected, which directly affects the rates of infant morbidity and mortality from preventable causes, amenable to resolution and care at the first level of health care.

Objetivo: Mapear y examinar la evidencia científica sobre la aplicación de la estrategia de atención a las enfermedades prevalentes de la infancia en el contexto de la Atención Primaria. Método: Scoping Review, basada en los procedimientos recomendados por el Instituto Joanna Briggs. La pregunta guía se definió como: "¿Qué evidencia científica existe sobre la aplicación de la estrategia de atención a las enfermedades prevalentes de la infancia (AIEPI) en el contexto de la Atención Primaria de Salud?". Se realizó una búsqueda en cinco bases de datos nacionales e internacionales, sobre trabajos publicados entre 2018 y diciembre de 2022. De los 2227 estudios encontrados, se seleccionaron 329 para su lectura completa, resultando una muestra final de 08 estudios analizados. Resultados: Los artículos fueron publicados entre 2018 y 2022, con un abordaje cuantitativo de los datos, siendo 04 estudios (50%) con diseño transversal exploratorio. En cuanto a la aplicación de la AIDPI, 06 (75%) señalaron que la aplicabilidad de la estrategia AIDPI es aún deficiente en la atención y manejo de las enfermedades prevalentes de la infancia en el contexto del primer nivel de atención de salud, debido a la falta de capacitación de los profesionales, escasez de recursos y problemas estructurales. Conclusiones: La evidencia muestra que a pesar del largo tiempo transcurrido desde la creación de la AIEPI y de que los estudios muestran bajos índices de adherencia e inaplicabilidad de la estrategia, su aplicación sigue siendo descuidada, lo que incide directamente en los índices de morbimortalidad infantil por causas prevenibles, susceptibles de resolución y atención en el primer nivel de atención de salud.

Mapeando o ensino da bioética nos cursos de odontologia brasileiros / Mapping bioethics teaching in Brazilian dental schools / Mapeo de la enseñanza de la bioética en las carreras de odontología en Brasil

Resumo Por meio de estudo descritivo, exploratório e transversal, objetivou-se avaliar a inserção da disciplina bioética na matriz curricular de cursos de odontologia brasileiros. Com dados coletados entre dezembro de 2021 e janeiro de 2022 nos sites das 430 instituições que divulgavam informações sobre o curso, realizou-se análise exploratória visando obter estatísticas descritivas de variáveis categóricas e contínuas. Os resultados apontaram que a descrição introdutória de 245 cursos (57%) fazia referência à formação humanista, crítica e reflexiva, e/ou enfatizava a presença de disciplina de bioética. Além disso, 345 cursos (80,2%) disponibilizavam as matrizes curriculares e em 139 (40,3%) destas havia disciplinas com a nomenclatura "bioética", ministradas principalmente nos dois primeiros anos (69%). Conclui-se que, apesar de as Diretrizes Curriculares Nacionais do Curso de Graduação em Odontologia orientarem para uma formação com condutas pautadas nos princípios éticos/bioéticos, em menos da metade das matrizes curriculares avaliadas constava disciplina de bioética.

Abstract A descriptive, exploratory, and cross-sectional study was conducted to evaluate the inclusion of bioethics in the curricula of Brazilian dental schools. Data collected between December 2021 and January 2022 from the websites of the 430 institutions that disclosed information about the program, underwent exploratory analysis to obtain descriptive statistics of categorical and continuous variables. Results showed that the introductory description of 245 courses (57%) referred to humanistic, critical and reflective education, and/or emphasized the presence of a bioethics discipline. Of the 345 curricula (80.2%) available, 139 (40.3%) had disciplines with "bioethics" on their name, taught mainly in the first two years (69%). Thus, although the National Curriculum Guidelines for Undergraduate Dentistry postulate an education based on ethical/bioethical principles, less than half of the curriculums evaluated included a bioethics discipline.

Resumen Desde un estudio descriptivo, exploratorio y transversal, se evaluó la inclusión de la asignatura de la bioética en el plan de estudios de Odontología en Brasil. Se recopilaron los datos entre diciembre de 2021 y enero de 2022 en la página web de 430 instituciones, y se aplicó un análisis exploratorio para obtener estadísticos descriptivos de variables categóricas y continuas. Los resultados mostraron que 245 carreras (57%) describían la formación humanista, crítica y reflexiva, y/o señalaba la presencia de la asignatura de bioética. Además, 345 carreras (80,2%) ponían a disposición sus planes de estudio, y 139 (40,3%) de estas presentaban asignaturas con el nombre "bioética", que eran impartidas en los dos primeros años del curso (69%). Aunque las Directrices Curriculares Nacional de la Licenciatura en Odontología preconizan la formación basada en principios éticos/bioéticos, menos de la mitad de los planes de estudio contaba con una asignatura de bioética.

Uncovering the promiscuous activity of IL-6 proteins: A multi-dimensional analysis of phylogeny, classification and residue conservation.

The IL-6 family of cytokines, known for their pleiotropic behavior, share binding to the gp130 receptor for signal transduction with the necessity to bind other receptors. Leukemia inhibitory factor receptor is triggered by the IL-6 family proteins: leukemia inhibitory factor (LIF), oncostatin-M (OSM), cardiotrophin-1 (CT-1), ciliary neurotrophic factor (CNTF), and cardiotrophin-like cytokine factor 1 (CLCF1). Besides the conserved binding sites to the receptor, not much is known in terms of the diversity and characteristics of these proteins in different organisms. Herein, we describe the sequence analysis of LIF, OSM, and CT-1 from several organisms, and m17, a LIF ortholog found in fishes, regarding its phylogenetics, intrinsic properties, and the impact of conserved residues on structural features. Sequences were identified in seven classes of vertebrates, showing high conservation values in binding site III, but protein-dependent results on binding site II. GRAVY, isoelectric point, and molecular weight parameters were relevant to differentiate classes in each protein and to enable, for the first time and with high fidelity, the prediction of both organism class and protein type just using machine learning approaches. OSM sequences from primates showed an increased BC loop when compared to the remaining mammals, which could influence binding to OSM receptor and tune signaling pathways. Overall, this study highlights the potential of sequence diversity analysis to understand IL-6 cytokine family evolution, showing the conservation of function-related motifs and evolution of class and protein-dependent characteristics. Our results could impact future medical treatment of disorders associated with imbalances in these cytokines.

Combined Inhibition of FOSL-1 and YAP Using siRNA-Lipoplexes Reduces the Growth of Pancreatic Tumor.

Pancreatic cancer evades most of the current therapies and there is an urgent need for new treatments that could efficiently eliminate this aggressive tumor, such as the blocking of routes driving cell proliferation. In this work, we propose the use of small interfering RNA (siRNA) to inhibit the combined expression of FOSL-1 and YAP, two signaling proteins related with tumor cell proliferation and survival. To improve the efficacy of cell transfection, DODAB:MO (1:2) liposomes were used as siRNA nanocarriers, forming a complex denominated siRNA-lipoplexes. Liposomes and lipoplexes (carrying two siRNA for each targeted protein, or the combination of four siRNAs) were physico-chemically and biologically characterized. They showed very good biocompatibility and stability. The efficient targeting of FOSL-1 and YAP expression at both mRNA and protein levels was first proved in vitro using mouse pancreatic tumoral cell lines (KRASG12V and p53 knockout), followed by in vivo studies using subcutaneous allografts on mice. The peri-tumoral injection of lipoplexes lead to a significant decrease in the tumor growth in both Athymic Nude-Foxn1nu and C57BL/6 mice, mainly in those receiving the combination of four siRNAs, targeting both YAP and FOSL-1. These results open a new perspective to overcome the fast tumor progression in pancreatic cancer.

Ventilador mecânico invasivo de emergência resistente e de fácil manutenção / Robust, maintainable, emergency invasive mechanical ventilator

RESUMO Objetivo: Desenvolver um ventilador mecânico invasivo simples, resistente, seguro e eficiente que possa ser utilizado em áreas remotas do mundo ou zonas de guerra, em que a utilidade prática de equipamentos mais sofisticados é limitada por questões de manutenção, disponibilidade de peças, transporte e/ou custo. Métodos: O dispositivo implementa o modo de ventilação mandatória contínua com pressão controlada, complementado por um simples modo assisto-controlado. Pode-se também utilizar a pressão positiva contínua nas vias aéreas. Ao se evitar o fluxo contínuo de oxigênio ou ar, minimiza-se o consumo de gases comprimidos. As taxas respiratórias e as relações de tempo de inspiração e expiração são determinadas eletronicamente. Além disso, conta com um alarme de apneia/falta de energia. Resultados: Os perfis de pressão foram medidos para uma série de condições, sendo considerados ajustáveis dentro de uma margem de erro de ± 2,5cmH2O, e foram considerados bem estáveis dentro dessa variação durante um período de 41 horas. Os parâmetros de tempo do ciclo respiratório foram precisos dentro de alguns pontos percentuais durante o mesmo período. O dispositivo foi testado quanto à durabilidade por um período equivalente a 4 meses. Os testes químicos e biológicos não conseguiram identificar qualquer contaminação do gás por compostos orgânicos voláteis ou micro-organismos. Em comparação com um ventilador bem estabelecido, o teste de ventilação em um animal de grande porte mostrou que este poderia ser ventilado adequadamente durante um período de 60 minutos, sem quaisquer efeitos negativos perceptíveis durante o período subsequente de 24 horas. Conclusão: Este projeto de ventilador pode ser viável após novos testes em animais e aprovação formal pelas autoridades competentes, para aplicação clínica nas circunstâncias atípicas anteriormente mencionadas.

ABSTRACT Objective: To develop a simple, robust, safe and efficient invasive mechanical ventilator that can be used in remote areas of the world or war zones where the practical utility of more sophisticated equipment is limited by considerations of maintainability, availability of parts, transportation and/or cost. Methods: The device implements the pressure-controlled continuous mandatory ventilation mode, complemented by a simple assist-control mode. Continuous positive airway pressure is also possible. The consumption of compressed gases is minimized by avoiding a continuous flow of oxygen or air. Respiratory rates and inspiration/expiration time ratios are electronically determined, and an apnea/power loss alarm is provided. Results: The pressure profiles were measured for a range of conditions and found to be adjustable within a ± 2.5cmH2O error margin and stable well within this range over a 41-hour period. Respiratory cycle timing parameters were precise within a few percentage points over the same period. The device was tested for durability for an equivalent period of four months. Chemical and biological tests failed to identify any contamination of the gas by volatile organic compounds or microorganisms. A ventilation test on a large animal, in comparison with a well established ventilator, showed that the animal could be adequately ventilated over a period of 60 minutes, without any noticeable negative aftereffects during the subsequent 24-hour period. Conclusion: This ventilator design may be viable, after further animal tests and formal approval by the competent authorities, for clinical application in the abovementioned atypical circumstances.

pH-sensitive nanoliposomes for passive and CXCR-4-mediated marine yessotoxin delivery for cancer therapy.

Background: Yessotoxin (YTX), a marine-derived drug, was encapsulated in PEGylated pH-sensitive nanoliposomes, covalently functionalized (strategy I) with SDF-1α and by nonspecific adsorption (strategy II), to actively target chemokine receptor CXCR-4. Methods: Cytotoxicity to normal human epithelial cells (HK-2) and prostate (PC-3) and breast (MCF-7) adenocarcinoma models, with different expression levels of CXCR-4, were tested. Results: Strategy II exerted the highest cytotoxicity toward cancer cells while protecting normal epithelia. Acid pH-induced fusion of nanoliposomes seemed to serve as a primary route of entry into MCF-7 cells but PC-3 data support an endocytic pathway for their internalization. Conclusion: This work describes an innovative hallmark in the current marine drug clinical pipeline, as the developed nanoliposomes are promising candidates in the design of groundbreaking marine flora-derived anticancer nanoagents.

[18F]FDG-PET in cardiac sarcoidosis: A single-centre study in a southern European population.

BACKGROUND: Cardiac sarcoidosis (CS) is clinically diagnosed in 5% of patients with sarcoidosis but imaging studies suggest higher prevalence. We evaluated the prevalence, clinical manifestations, and cardiovascular outcomes of CS, diagnosed through 18F-Fluorodeoxyglucose positron emission tomography ([18F]FDG-PET), in a southern European population. METHODS: Retrospective single-centre study of patients screened for sarcoidosis with [18F]FDG-PET. Subjects with histological confirmation were divided in two groups, CS or extracardiac sarcoidosis, according to Heart Rhythm Society's criteria. Primary endpoint was defined as the composite of heart failure hospitalizations, uncontrolled arrythmias, pacemaker implantation, and cardiovascular (CV) mortality. Secondary outcomes included each component and all-cause mortality. RESULTS: From 128 patients with biopsy-proven extracardiac sarcoidosis, 10.2% had probable CS, 54% without symptoms of cardiac involvement. Ten patients had suggestive [18F]FDG uptake patterns, three subjects had an indicative cardiac magnetic resonance (CMR). Patients with probable CS had significantly higher prevalence of coronary and valvular disease, heart failure, and atrial fibrillation compared with those without cardiac involvement. During a mean follow-up of 4.0 SD2.7 years, the primary outcome occurred more frequently in patients with probable CS (53.8% vs. 3.5%; HR 25.45; 95% CI 5.27-122.9; p < 0.01) as well as heart failure hospitalizations (46.2% vs. 0.9%), uncontrolled arrhythmias (23.1% vs. 1.7%) and pacemaker implantation (23.1% vs. 0.9%) (p < 0.01 for all). All-cause mortality was three-fold higher in probable CS, despite the absence of statistical significance (15% vs. 5%, p = 0.15). CONCLUSIONS: Among patients with biopsy-proven sarcoidosis, cardiac involvement detected by [18F]FDG-PET or CMR is associated with a higher risk of CV events, irrespective of symptoms.

Fluoride Concentration in Public Water Supply in a City in the Amazon Region

Abstract Objective: To analyze the fluoride concentration in the public water supply in Manaus, Brazil. Material and Methods: Water samples were collected in 50 mL polyethylene bottles, identified, and labeled. The collection was performed from September 2016 to August 2018. For the selection of collection points, all neighborhoods of the city of Manaus, divided into four health districts (North, South, East, and West), were mapped. From each district, 30 samples were collected, totaling 120 monthly samples. Water samples were analyzed using an ion analyzer, ORION 720-A, and a specific electrode, ORION 96-09. The ion analyzer and electrode were calibrated in standard solutions. The levels were classified in intervals based on technical consensus to guide the health surveillance agencies. Results: Of the 2,874 water samples, 50.3% were within the recommended range, and 49.7% were inadequate, with 31.6% considered above the parameters and 18.1% below. Among the districts, the North had the highest percentages of unsatisfactory samples, resulting in limited action to prevent tooth decay. During the 24 months of analysis, there were large oscillations in the values in all four districts of Manaus. Conclusion: Results reinforce the importance of heterocontrol for the city to guarantee the effectiveness of this public health measure.

Toxicity in vitro and in Zebrafish Embryonic Development of Gold Nanoparticles Biosynthesized Using Cystoseira Macroalgae Extracts.

INTRODUCTION: Research on gold nanoparticles (AuNPs) occupies a prominent place in the field of biomedicine nowadays, being their putative toxicity and bioactivity areas of major concern. The green synthesis of metallic nanoparticles using extracts from marine organisms allows the avoidance of hazardous production steps while maintaining features of interest, thus enabling the exploitation of their promising bioactivity. OBJECTIVE: To synthesize and characterize AuNPs using, for the first time, macroalga Cystoseira tamariscifolia aqueous extract (Au@CT). METHODS: Algal aqueous extracts were used for the synthesis of AuNPs, which were characterized using a wide panel of physicochemical techniques and biological assays. RESULTS: The characterization by UV-Vis spectroscopy, transmission electron microscopy, Z-potential and infrared spectroscopy confirmed that Au@CT were stable, spherical and polycrystalline, with a mean diameter of 7.6 ± 2.2 nm. The antioxidant capacity of the extract, prior to and after synthesis, was analyzed in vitro, showing that the high antioxidant potential was not lost during the synthesis. Subsequently, in vitro and in vivo toxicity was screened, by comparing two species of the genus Cystoseira (C. tamariscifolia and C. baccata) and the corresponding biosynthesized gold nanoparticles (Au@CT and Au@CB). Cytotoxicity was tested in mouse (L929) and human (BJ5ta) fibroblast cell lines. In both cases, only the highest (nominal) test concentration of both extracts (31.25 mg/mL) or Au@CB (12.5 mM) significantly affected cell viability, as measured by the MTT assay. These results were corroborated by a Fish Embryo Acute Toxicity (FET) test. Briefly, it was shown that, at the highest (nominal) tested concentration (31.25 mg/mL), CT extract induced significantly higher cytotoxicity and embryotoxicity than CB extract. However, it was demonstrated that Au@CT, but not Au@CB, were generally non-toxic. At sub-lethal (nominal) test concentrations (1.25 and 2.5 mM), Au@CT affected zebrafish embryonic development to a much lesser extent than Au@CB. In vitro wound healing assays also revealed that, while other experimental conditions did not impact cell migration, CT and Au@CT displayed a moderate positive effect. CONCLUSION: Au@CT and Au@CB display promising features, desirable for biomedical applications, as wound healing.

Human umbilical cord mesenchymal stem cells in type 2 diabetes mellitus: the emerging therapeutic approach.

The umbilical cord has been proved to be an easy-access, reliable, and useful source of mesenchymal stem cells (MSC) for clinical applications due to its primitive, immunomodulatory, non-immunogenic, secretory and paracrine, migratory, proliferative, and multipotent properties. This set of characteristics has recently attracted great research interest in the fields of nanotechnology and regenerative medicine and cellular therapy. Accumulating evidence supports a pronounced therapeutic potential of MSC in many different pathologies, from hematology to immunology, wound-healing, tissue regeneration, and oncology. Diabetes mellitus, branded the epidemic of the century, is considered a chronic metabolic disorder, representing a major burden for health system sustainability and an important public health challenge to modern societies. The available treatments for type 2 diabetes mellitus (T2DM) still rely mainly on combinations of oral antidiabetic agents with lifestyle and nutritional adjustments. Despite the continuous development of novel and better hypoglycemic drugs, their efficacy is limited in the installment and progression of silent T2DM complications. T2DM comorbidities and mortality rates still make it a serious, common, costly, and long-term manageable disease. Recently, experimental models, preclinical observations, and clinical studies have provided some insights and preliminary promising results using umbilical cord MSCs to treat and manage diabetes. This review focuses on the latest research and applications of human-derived umbilical cord MSC in the treatment and management of T2DM, exploring and systematizing the key effects of both umbilical cord MSC and its factor-rich secretome accordingly with the major complications associated to T2DM.

Humoral Immune Response of SARS-CoV-2-Infected Patients with Cancer: Influencing Factors and Mechanisms.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with cancer show worse outcomes compared with patients without cancer. The humoral immune response (HIR) of patients with cancer against SARS-CoV-2 is not well characterized. To better understand it, we conducted a serological study of hospitalized patients with cancer infected with SARS-CoV-2. MATERIALS AND METHODS: This was a unicentric, retrospective study enrolling adult patients with SARS-CoV-2 admitted to a central hospital from March 15 to June 17, 2020, whose serum samples were quantified for anti-SARS-CoV-2 receptor-binding domain or spike protein IgM, IgG, and IgA antibodies. The aims of the study were to assess the HIR to SARS-CoV-2; correlate it with different cancer types, stages, and treatments; clarify the interplay between the HIR and clinical outcomes of patients with cancer; and compare the HIR of SARS-CoV-2-infected patients with and without cancer. RESULTS: We included 72 SARS-CoV-2-positive subjects (19 with cancer, 53 controls). About 90% of controls revealed a robust serological response. Among patients with cancer, a strong response was verified in 57.9%, with 42.1% showing a persistently weak response. Treatment with chemotherapy within 14 days before positivity was the only factor statistically shown to be associated with persistently weak serological responses among patients with cancer. No significant differences in outcomes were observed between patients with strong and weak responses. All IgG, IgM, IgA, and total Ig antibody titers were significantly lower in patients with cancer compared with those without. CONCLUSION: A significant portion of patients with cancer develop a proper HIR. Recent chemotherapy treatment may be associated with weak serological responses among patients with cancer. Patients with cancer have a weaker SARS-CoV-2 antibody response compared with those without cancer. IMPLICATIONS FOR PRACTICE: These results place the spotlight on patients with cancer, particularly those actively treated with chemotherapy. These patients may potentially be more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, so it is important to provide oncologists further theoretical support (with concrete examples and respective mechanistic correlations) for the decision of starting, maintaining, or stopping antineoplastic treatments (particularly chemotherapy) not only on noninfected but also on infected patients with cancer in accordance with cancer type, stage and prognosis, treatment agents, treatment setting, and SARS-CoV-2 infection risks.

Aseptic hypertrophic pachymeningitis in a patient with Rheumatoid Arthritis - a case of involvement of the central nervous system by the disease?

Hypertrophic pachymeningitis (HP) is a rare clinical entity which uncommonly occurs in rheumatoid arthritis (RA) patients. We describe the case of a rheumatoid factor and anti-citrullinated protein antibody positive RA male that was diagnosed with HP and multiple mononeuropathy. Although histological evaluation was not performed, after excluding infectious and neoplastic causes, it was possible to determine a probable inflammatory etiology. He was treated with glucocorticoids and rituximab with a good clinical evolution. This case represented a challenging differential diagnosis but the need for an accurate diagnosis should not delay the introduction of an effective therapy for a potentially lethal disease.