Triagem de fármacos em efluente hospitalar mediante o uso de UHPLC-QTOF MS

A contaminação dos sistemas aquáticos é motivo de preocupação devido à presença de contaminantes emergentes possivelmente perigosos ao meio ambiente e à saúde humana. Dentre os contaminantes emergentes, os fármacos têm destaque devido à grande presença destes no meio ambiente, que se dá pelo seu uso abundante e, consequentemente, constante introdução destes em efluentes domésticos, industriais e hospitalares. Os efluentes hospitalares possuem elementos de caráter nocivo em sua composição e, comumente, são coletados pela mesma rede de esgotos e conduzidos para as mesmas estações de tratamento que os efluentes domésticos. No entanto, os processos convencionalmente empregados nas estações de tratamento de esgotos (ETEs) não são capazes de promover a total remoção destes compostos e, dessa forma, essa representa uma das principais fontes pelas quais os fármacos adentram o meio ambiente. Com o avanço tecnológico das instrumentações analíticas foi possível monitorar esses contaminantes, uma vez que estes estão presentes no meio aquático em concentrações traço/ultratraço. Dessa forma, este trabalho avaliou a ocorrência de fármacos em efluente hospitalar mediante uso de uma metodologia de triagem baseada em cromatografia a líquido acoplada a espectrometria de massa de alta resolução com analisador de massa quadrupolo/tempo de voo (do inglês, UHPLC-QTOF MS). Seis amostragens de águas residuais hospitalares foram realizadas, mensalmente, no período de agosto de 2017 a janeiro de 2018. As amostras foram previamente filtradas e pré-concentradas/extraídas empregando a técnica de extração em fase sólida (do inglês, SPE). O método de identificação dos fármacos fundamentou-se no uso de uma base de dados personalizada contendo 974 fármacos no modo de ionização positivo e outra base de dados, no modo de ionização negativo, contendo 158 fármacos. Foram identificados em média 30 fármacos nas amostras de efluente hospitalar sendo a maioria classificada como de alta toxicidade oral (regras de Cramer) e persistentes no meio ambiente (biodegradabilidade START).The contamination of aquatic systems is a matter of concern due to the presence of emerging contaminants possibly dangerous to the environment and to human health. Among the emerging contaminants, the pharmaceuticals are prominent due to their high presence in the environment, which is due to their abundant use and, consequently, constant introduction into domestic, industrial and hospital effluents. Hospital effluents have harmful elements in their composition and are commonly collected by the same sewage network and conducted to the same treatment plants as domestic effluents. However, the processes conventionally employed in sewage treatment plants are not capable of promoting the complete removal of these compounds and thus this represents one of the main sources by which the drugs enter the environment. With the technological advance of the analytical instrumentations it was possible to monitor these contaminants, since these are present in the aquatic environment in trace/ultratrace concentrations. Thus, this work evaluates the occurrence of pharmaceuticals in hospital wastewater using a screening methodology based on liquid chromatography coupled to high resolution mass spectrometry with a quadrupole-time of flight mass analyser (UHPLC-QTOF MS). Six hospital wastewater samples were collected monthly from august 2017 to january 2018. The samples were pre-filtered and pre-concentrated/extracted using the solid phase extraction technique (SPE). The pharmaceuticals identification method was based on the use of a personalized database containing 974 drugs in the positive ionization mode and another database in the negative ionization mode containing 158 pharmaceuticals. An average of 30 pharmaceuticals were identified in hospital wastewater samples, most of which were classified as high oral toxicity (Cramer rules) and persistent in the environment (START biodegradability)

Triagem de fármacos e metabólitos em efluente hospitalar associada à sobreclassificação pelo risco ambiental e à saúde humana utilizando Método Electre

A presença de fármacos e metabólitos em efluentes tornou-se um grave problema ambiental, podendo, também, impactar prejudicialmente a saúde humana. Assim sendo, é essencial o monitoramento desses microcontaminantes, bem como a avaliação dos potenciais riscos ambientais e à saúde humana que tais compostos podem apresentar. Neste sentido, neste estudo foi realizada uma análise de triagem de 2030 fármacos e metabólitos em efluente hospitalar, avaliando diferentes técnicas de preparo de amostras. Adicionalmente, uma associação pioneira do uso de ferramentas in silico baseadas na abordagem (quantitativa) estrutura-atividade ((Q)SAR), para a predição de oito parâmetros de risco, com a técnica de análise de decisão multicritério ELECTRE possibilitou a sobreclassificação dos analitos de acordo com seu risco ambiental e à saúde humana. A técnica de preparo de amostra que se mostrou mais vantajosa consistiu na limpeza (100 mg de sílica/alumina) associada à Microextração Líquido-Líquido Dispersiva (DLLME) (7,5 de matriz, 600 μL de clorofórmio como solvente extrator e 1000 μL de acetonitrila como solvente dispersor), resultando na identificação de 77 analitos. A análise de triagem identificou um total de 105 microcontaminantes, sendo 28 deles “compostos confirmados” e 77 sendo “compostos suspeitos”. Desses compostos, 89% eram fármacos e 11% metabólitos. Os compostos identificados foram posteriormente avaliados por predições in silico, usando diferentes programas de livre acesso, considerando oito parâmetros: mobilidade, persistência, ligação ao receptor de estrogênio, remoção total em estação de tratamento de efluentes, biodegradabilidade, PBT (persistência, bioacumulação e toxicidade), mutagenicidade e carcinogenicidade. Os resultados quantificados das predições realizadas por ferramentas in silico baseadas na abordagem (Q)SAR foram usados como dados de entrada para o método de sobreclassificação ELECTRE. A categorização dos compostos através do ELECTRE resultou no kernel (compostos prioritários) e mais 19 grupos. A avaliação da sensibilidade do ELECTRE indicou que, para todos os casos, o kernel e os dois grupos seguintes coincidiram. Assim, o método ELECTRE constitui uma ferramenta de decisão altamente intuitiva, que pode auxiliar na seleção de compostos para inclusão em programas de monitoramento ambiental.The presence of pharmaceuticals and metabolites in effluents has become a serious environmental problem and can also have a harmful impact on human health. Therefore, it is essential to monitor these microcontaminants, as well as to assess the potential environmental and human health risks that such compounds may present. In this sense, in this study, a screening analysis of 2030 pharmaceuticals and metabolites in hospital effluent was performed, evaluating different sample preparation techniques. Additionally, a pioneer association of the use of in silico tools to assess the (quantitative) structure-activity relationship ((Q)SAR), for the prediction of eight risk parameters, with the ELECTRE multicriteria decision analysis technique, it was possible to overclassify the analytes according to their environmental and human health risk. The sample preparation technique that proved to be the most advantageous consisted of cleaning (100 mg of silica/alumina) associated with Dispersive Liquid-Liquid Microextraction (DLLME) (7.5 matrix, 600 μL of chloroform as extracting solvent and 1000 μL of acetonitrile as dispersing solvent), resulting in the identification of 77 analytes. The screening analysis identified a total of 105 microcontaminants, with 28 of them being “confirmed compounds” and 77 being “suspect compounds”. Of these compounds, 89% were pharmaceuticals and 11% were metabolites. The identified compounds were further evaluated by in silico predictions, using different open access programs, considering eight endpoints: mobility, persistence, estrogen receptor binding, total removal in wastewater treatment plant, biodegradability, PBT (persistence, bioaccumulation and toxicity), mutagenicity and carcinogenicity. The quantified results of predictions made by in silico tools based on the (Q)SAR approach were used as input data for the ELECTRE overclassification method. The categorization of compounds through ELECTRE resulted in the kernel (priority compounds) and 19 more groups. The ELECTRE sensitivity assessment indicated that, for all cases, the kernel and the following two groups coincided. Thus, the ELECTRE method constitutes a highly intuitive decision tool, which can assist in the selection of compounds for inclusion in environmental monitoring programs

Oportunidades de aprendizagem com apoio da Comunicação Aumentativa e Alternativa em tempos de COVID-19

This study analyzes the content of posts involving Augmentative and Alternative Communication (AAC) on Instagram by ComunicaTEA_pais page to identify what materials are being created and made available to support the learning of students with complex communication needs (CCN) during the closing of schools due to the pandemic caused by the new coronavirus. Based on the Content Analysis technique, this exploratory qualitative research analyzed 94 posts. Five categories stood out, namely: guidelines on Covid-19; formal educational activities; non-formal educational activities; guidance on the use of AAC and technological resources. The contents of the posts reveal the contribution of the page in providing information to mitigate inequalities by promoting access to resources to support communication. There is a dynamic process of educational and psychosocial support for the community of people with CCN and their support network in face of changes in the school routine of students with disabilities and CCN.Este estudio analiza el contenido de las publicaciones que involucran la Comunicación Aumentativa y Alternativa (CAA) en la página ComunicaTEA_pais en Instagram para identificar qué materiales se están creando y poniendo a disposición para apoyar el aprendizaje de los estudiantes con necesidades de complejas de comunicación (NCC) durante el cierre de las escuelas debido a la pandemia causada por el nuevo coronavirus. Basado en la técnica de Análisis de Contenido, esta investigación exploratoria cualitativa analizó 94 publicaciones. Se destacaron cinco categorías, a saber: directrices sobre Covid-19; actividades educativas formales; actividades educativas no formales; orientación sobre el uso de CAA y recursos tecnológicos. El contenido de las publicaciones revela la contribución de la página para difundir información y mitigar las desigualdades al promover el acceso a recursos para apoyar la comunicación. Se percibe un proceso dinámico de apoyo educativo y psicosocial para la comunidad de personas con NCC y su red de apoyo ante los cambios en la rutina escolar de los estudiantes con discapacidades y NCC.Este estudo analisa os conteúdos de postagens envolvendo Comunicação Aumentativa e Alternativa (CAA) na página ComunicaTEA_pais no Instagram, para identificar que materiais estão sendo criados e disponibilizados para apoiar a aprendizagem de estudantes com necessidades complexas de comunicação (NCC) durante o fechamento das escolas devido à pandemia pelo novo coronavírus. A partir da técnica de Análise de Conteúdo, esta pesquisa qualitativa exploratória analisou 94 postagens. Cinco categorias se destacaram, a saber: orientações sobre a Covid-19; atividades educativas formais; atividade educativas não formais; orientações sobre o uso de CAA e recursos tecnológicos. Os conteúdos das postagens revelam a contribuição da página para difundir informações e atenuar desigualdades ao promover acesso a recursos de apoio à comunicação. Constata-se um processo dinâmico de apoio educacional e psicossocial para a comunidade de pessoas com NCC e sua rede de apoio frente às mudanças na rotina escolar de alunos com deficiência e NCC

El lagarto que nunca duerme: actividad del gecko del pampa Homonota uruguayensis

It is generally assumed that lizards are active whenever climatic conditions are favorable. Homonota uruguayensis (Vaz-Ferreira & Sierra de Soriano, 1961) is the only native gecko – and nocturnal lizard – living in the northern Pampa biome, and its ecology is poorly known. This study aimed at describing this species’ pattern of daily and annual activity and its relation with environmental temperatures. The study was conducted in the extreme south of Brazil (Rosário do Sul, State of Rio Grande do Sul), between May 2010 and January 2011 at a rocky outcrop located in the Pampa biome. The study was carried out in a total of four seasonal field trips, totalizing 1185 hours of field work. The data were collected, both during the day and the night in 6-hour shifts (duration of the sampling period). The area was randomly covered at each shift to record activity and microhabitat use by the lizards. In total 1541 specimens were recorded throughout the study. Homonota uruguayensis showed diurnal and nocturnal activity in the four seasons, with periods of daily activity varying significantly between all seasons in a cyclic and multimodal pattern, with no significant relation with environmental temperatures. There was no difference in activity related to sex and age classes. Most active lizards were found when air temperatures ranged from 14 °C to 32.9 °C (82% of active lizards) and substrate temperatures ranged from 10 °C to 32.9 °C (87% of active lizards).La suposición general ha sido que los lagartos son activos cuando las condiciones climáticas son favorables. Homonota uruguayensis (Vaz-Ferreira & Sierra de Soriano, 1961) es la única lagartija nativa – y la lagartija nocturna – que vive en el norte de bioma Pampa. La ecología de esta especie es poco conocida y este estudio tuvo como objetivo describir su patrón de actividad diaria y anual y su relación con las temperaturas ambientales. El estudio se llevó a cabo en el extremo sur de Brasil (Rosário do Sul, Rio Grande do Sul), a partir de mayo 2010 - enero 2011, en un afloramiento rocoso situado en el bioma Pampa. El estudio totalizó cuatro excursiones de campo estacionales y 1185 horas. Los datos fueron recogidos a lo largo de los turnos de 6 horas durante el día y la noche. El área fue recorrida aleatoriamente en cada turno siempre registrandose la actividad y el microhabitat utilizado por los lagartos. A lo largo del estudio, 1541 especímenes se registraron. Homonota uruguayensis presentó hábito diurno y nocturno en las cuatro estaciones, con períodos de actividad diaria variando significativamente entre todas las estaciones en forma cíclica y multimodal, no se observó relación significativa con las temperaturas ambientales. No fue constatada diferencia entre los sexos con relación a la actividad y las clases de edad. La mayoría de los lagartos activos fue encontrada a temperaturas del aire que variaron de 14 °C a 32,9 °C (82% de lagartos activos) y a temperaturas del sustrato entre 10 °C y 32,9 °C (87% de lagartos activos)

Cambios en la Ley de Inmigración Brasileña

Migrar es un derecho forjado por necesidades. El migrante se encuentra en una situación de vulnerabilidad delante del Estado “destino” y de los habitantes del mismo. El paradigma fraternal está previsto en la Constitución federal y orienta normas internacionales relacionadas a la situación del migrante, como la Convención Nº 143 de la Organización Internacional del Trabajo. La implementación de estas normas hace posible una comunidad fraternal en el deber de la justicia social.Abstract: Migrating is a right forged by needs. The migrant finds himself in a situation of vulnerability in the presence of the "destination" State and its inhabitants. The fraternal paradigm is foreseen in the Federal Constitution and it guides international norms related to the situation of the migrant as Convention No. 143 of the International Labor Organization. The implementation of these norms makes possible a fraternal community in the duty of social justice.

Different concentrations of fetal bovine serum affect cytokine modulation in Lipopolysaccharide-activated apical papilla cells in vitro

Fetal bovine serum (FBS) is the most used supplement in culture media; however, it may interfere with in vitro assays via effects on cell proliferation and cytokine production. The ideal FBS concentration for assays using apical papilla cells (APCs) remains unknown. Therefore, this study aimed to evaluate the effects of FBS on APC activation, cell viability/proliferation, and cytokine production. Methodology: Human APCs were cultured, plated, and maintained in media containing increasing concentrations of FBS for 24 h, 48 h, 72 h, 7 days, and 14 days in the presence of Lipopolysaccharide (LPS - 1 µg/mL). At each time point, the cells were subjected to the MTT assay. The cytokines transforming growth factor (TGF)-β1, osteoprotegerin (OPG), and interleukin (IL)-6, along with the chemokine CCL2, were quantified using the enzyme-linked immunosorbent assay at the 24-h time-point. Statistical analysis was performed using two-way analysis of variance (ANOVA) followed by Tukey's post-hoc test (p<0.05). Results: In general, APCs exhibited increasing metabolic activity in an FBS concentration-dependent fashion, regardless of the presence of LPS. In contrast, FBS interfered with the production of all the cytokines evaluated in this study, affecting the response induced by the presence of LPS. Conclusion: FBS increased APC metabolism in a concentration-dependent manner and differentially affected the production of TGF-β1, OPG, IL-6, and CCL2 by APCs in vitro

Pancreatic cancer associated- cachexia: Role of the Modified Glasgow Prognostic Score in outcome prediction

Cancer-associated-cachexia (CAC) is a ubiquitous characteristic of pancreatic cancer (PC) and 1/3 of patients die from its complications. Systemic inflammation is key in CAC and the modified Glasgow Prognostic Score (mGPS) is a reliable inflammation-based prognostic tool. We aimed to evaluate the prognostic value of consensus-based cachexia classification and mGPS, their agreement and to analyze relevant clinical predictors of cachexia. This unicentric, retrospective, cohort study included patients with advanced PC treated over a 5-year period. Cachexia was classified according to weight loss, body mass index and mGPS. Fisher’s test was used to test correlation between classifications and logistic regression models were performed to test their association with other variables. Survival was analyzed with cox regression and Kaplan-Meier curves. 88 eligible patients (mean age 72, 56% female) were reviewed. At baseline, cachectic patients (CP) (77%), when compared with pre-CP, had worse performance status (p=0.016), more NLR>3,5 (p3.5 was a significant predictor of both cachexia (p<0.001) and positive mGPS (p<0.01). Median overall survival (OS) for pre-CP was 19.1 months vs. 4.9 months in the CP (HR 1.94 95% CI 1.10-3.43 p=0.02). A positive mGPS at baseline was an independent predictor of worst OS (HR 2.73, 95% CI 1.12- 6.66, p=0.027). CAC leads to worst survival and a better understanding of this syndrome in PC may improve outcomes for these patients. Our study suggests a baseline predominant fat-only loss phenotype, that patients with positive mGPS are at higher risk of worst outcomes and that NLR is a potential predictor of CAC. A prompt identification of prognostic markers may lead to a better standardized management of CAC

Perfil sorológico dos anticorpos colostrais para Neospora caninum em bezerros livres da infecção

Neospora caninum is considered the main cause of bovine abortion worldwide. The correct laboratorial diagnose is very important to identify the infected animals and to apply control measure. The objetive of this study was to show the persistence period of colostral antibodies in calves. Eight newborn Holstein Friesan calves, males, were selected from N. caninum soronegative dams. Pre-colostral blood samples were collected of these calves and all of them were seronegative to N. caninum. They were fed with two liters of pooled colostrum from seropositive cows within two hours after birth. Blood samples were collected and tested weekly until the animals turned negative. Serum samples were tested for antibodies to N. caninum using indirect fluorescence antibody test at 1:50; 1: 100 and 1:200 dilutions. Antibodies were not detected from three out of eight calves and they were excluded from the study. The remaining 5 calves seroconverted in all dilutions at the fifth day after colostrums ingestion. At 1:50 dilution, one calf remained positive for 21 weeks, two for 20 weeks and one for 13 weeks. At 1:100, one calf was positive for 15 weeks and the remaining 4 calves for 13 weeks. At 1:200, each calf was positive for 1, 7, 12, 12 and 13 weeks, respectively. These results demonstrate that the colostral antibody to N. caninum may persist until 21 weeks after birth in calves and it's very important to exclud the calves at the first month of age in the seroprevalence studies to avoid the false-positive results.Neospora caninum é considerado a principal causa de aborto bovino mundial. O diagnóstico laboratorial correto é muito importante para identificar os animais infectados e para aplicar medidas de controle. O objetivo deste trabalho foi mostrar o declínio de anticorpos colostral em bezerros. Este estudo empregou oito bezerros holandeses, recém-nascidos, machos, descendentes de vacas soronegativas para N caninum. Amostra de sangue pré-colostral foram colhidas destes bezerros e todos estavam soronegativos pra N. caninum. Estes bezerros foram alimentados com dois litros de um pool de colostro de vacas soropositivas dentro de duas horas após o nascimento. Amostras de sangue dos bezerros foram colhidas semanalmente até os animais soroconverterem negativo. As amostras foram testadas para anticorpos de N. caninum usando teste de imunofluorescência indireta nos títulos de 1:50; 1: 100 e 1:200. Os resultados mostraram que 3 dos 8 bezerros não soroconverteram e foram excluídos do estudo. Os restantes cinco bezerros soroconverteram em todos os títulos no quinto dia após a inoculação. No título 1:50, um bezerro permaneceu positivo por 21 semanas, dois por 20 semanas e um por 13 semanas. No título 1:100, um bezerro foi positivo por 15 semanas e o restante quatro bezerros por 13 semanas. No título 1:200, cada bezerro foi positivo por 1; 7; 12; 12 e 13 semanas, respectivamente. Estes resultados demonstram que o anticorpo colostral para N. caninum pode permanecer até 21 semanas após o nascimento nos bezerros e é muito importante excluir os bezerros até quatro meses de idade nos estudos de soroprevalência para impedir os resultados falso-positivos

Oxygen consumption and rate of perceived exertion at different rhythms in water aerobics

O objetivo do estudo foi correlacionar o consumo de oxigênio (VO2) e o percentual do VO2 máximo (%VO2máx) com o índice de esforço percebido (IEP) e comparar essas variáveis entre exercícios de hidroginástica executados no meio aquático em diferentes ritmos de execução. Seis mulheres realizaram quatro sessões de testes, uma no meio terrestre (teste de esforço máximo) e três no meio aquático, cada uma com a execução de um exercício de hidroginástica: corrida estacionária, deslize lateral e chute frontal até 45. Cada exercício aquático foi realizado em três ritmos de execução, 80, 100 e 120bpm, durante 6 min (intervalo de 30 min). Para todas as variáveis, não foram observadas diferenças significativas entre os três exercícios, todavia, as mesmas apresentaram diferenças significativas entre os ritmos, indicando que com o aumento do ritmo, o esforço para executar os exercícios foi intensificado. Correlações significativas foram observadas entre VO2 e IEP e entre %VO2máx e IEP. Logo, baseado nessas associações, sugere-se que a prescrição da intensidade dos exercícios analisados possa ser feita através do IEP durante aulas de hidroginástica.The purpose of the study was to correlate the oxygen consumption (VO2) and the percentage of maximal VO2 (%VO2max) with the rate of perceived exertion (RPE) and to compare these variable between water aerobic exercises performed in aquatic environment at different rhythms. Six women performed four test sessions, one on dry land environment (maximal effort test) and three in aquatic environment, each one with the performance of a water aerobic exercise: stationary running, jumping jacks and frontal kick up to 45. Each aquatic exercise was performed at three rhythms of execution, 80, 100 and 120 bpm, during 6 min (interval of 30 min). For all variables, no significant differences were observed between three exercises, however, significant differences were found between rhythms of execution for all of them, indicating that with the increase of the rhythm, the effort to perform the exercises was intensified. Significant correlations were observed between VO2 and RPE, and between %VO2max and RPE. Therefore, based on this association it is suggested that the prescription of intensity of the exercises analyzed can be done by RPE during water aerobic classes