8-Bicycloalkyl-CPFPX derivatives as potent and selective tools for in vivo imaging of the A1 adenosine receptor.

Imaging of the A1 adenosine receptor (A1R) by positron emission tomography (PET) with 8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propyl-xanthine ([18F]CPFPX) has been widely used in preclinical and clinical studies. However, this radioligand suffers from rapid peripheral metabolism and subsequent accumulation of radiometabolites in the vascular compartment. In the present work, we prepared four derivatives of CPFPX by replacement of the cyclopentyl group with norbornane moieties. These derivatives were evaluated by competition binding studies, microsomal stability assays and LC-MS analysis of microsomal metabolites. In addition, the 18F-labeled isotopologue of 8-(1-norbornyl)-3-(3-fluoropropyl)-1-propylxanthine (1-NBX) as the most promising candidate was prepared by radiofluorination of the corresponding tosylate precursor and the resulting radioligand ([18F]1-NBX) was evaluated by permeability assays with Caco-2 cells and in vitro autoradiography in rat brain slices. Our results demonstrate that 1-NBX exhibits significantly improved A1R affinity and selectivity when compared to CPFPX and that it does not give rise to lipophilic metabolites expected to cross the blood-brain-barrier in microsomal assays. Furthermore, [18F]1-NBX showed a high passive permeability (Pc = 6.9 ± 2.9 × 10-5 cm/s) and in vitro autoradiography with this radioligand resulted in a distribution pattern matching A1R expression in the brain. Moreover, a low degree of non-specific binding (5%) was observed. Taken together, these findings identify [18F]1-NBX as a promising candidate for further preclinical evaluation as potential PET tracer for A1R imaging.

Radiosynthesis and In Vitro Evaluation of [11C]tozadenant as Adenosine A2A Receptor Radioligand.

Tozadenant (4-hydroxy-N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide) is a highly selective adenosine A2A receptor (A2AR) antagonist and a promising lead structure for the development of A2AR-selective positron emission tomography (PET) probes. Although several 18F-labelled tozadenant derivatives showed favorable in vitro properties, recent in vivo PET studies observed poor brain penetration and lower specific binding than anticipated from the in vitro data. While these findings might be attributable to the structural modification associated with 18F-labelling, they could also reflect inherent properties of the parent compound. However, PET studies with radioisotopologues of tozadenant to evaluate its cerebral pharmacokinetics and brain distribution are still lacking. In the present work, we applied N-Boc-O-desmethyltozadenant as a suitable precursor for the preparation of [O-methyl-11C]tozadenant ([11C]tozadenant) by O-methylation with [11C]methyl iodide followed by acidic deprotection. This approach afforded [11C]tozadenant in radiochemical yields of 18 ± 2%, with molar activities of 50-60 GBq/µmol (1300-1600 mCi/µmol) and radiochemical purities of 95 ± 3%. In addition, in vitro autoradiography in pig and rat brain slices demonstrated the expected striatal accumulation pattern and confirmed the A2AR specificity of the radioligand, making it a promising tool for in vivo PET studies on the cerebral pharmacokinetics and brain distribution of tozadenant.

Integrity and filtration efficiency of decontaminated N95/PFF2 masks to protect health care professionals against COVID-19: A systematic literature review and meta-analysis.

BACKGROUND: To evaluate the evidence related to maintaining the integrity and filtration efficiency of N95 and/or PFF2 respirators after decontamination in health care professionals' protection against COVID-19. METHODS: Systematic review, developed based on the guidelines from Joanna Briggs Institute for syntheses focusing on effectiveness evidence. The protocol was registered on the International Prospective Register of Ongoing Systematic Reviews platform, under the number CRD42022354256. This study report was developed in accordance with the guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Publications between January 2020 and August 2022 were selected of Embase, Medline, CINAHL, Web of Science, Cochrane, SciELO and Virtual Health Library databases. Joanna Briggs critical appraisal tool for nonrandomized experimental tests was used to evaluate the evidence quality. RESULTS: Seven articles were included in the data extraction and critical evaluation, and 3 in the meta-analysis. Four studies evaluated the integrity by visual inspection and 2 by electron microscopy. There was no association between the number of cycles increase and the reduction in filtration in up to 10 cycles. None study was considered of high methodological quality. CONCLUSIONS: There is some evidence that integrity and filtration capacity were maintained after decontamination of N95/PFF2 respirators to prevent COVID-19.

A chimeric protein-based vaccine elicits a strong IgG antibody response and confers partial protection against Shiga toxin-producing Escherichia coli in mice.

Background: Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen that causes gastrointestinal infections, ranging from acute diarrhea and dysentery to life-threatening diseases such as Hemolytic Uremic Syndrome. Currently, a vaccine to prevent STEC infection is an unmet medical need. Results: We developed a chimeric protein-based vaccine targeting seven virulence factors of STEC, including the Stx2B subunit, Tir, Intimin, EspA, Cah, OmpT, and AggA proteins. Immunization of mice with this vaccine candidate elicited significant humoral and cellular immune responses against STEC. High levels of specific IgG antibodies were found in the serum and feces of immunized mice. However, specific IgA antibodies were not detected in either serum or feces. Furthermore, a significantly higher percentage of antigen-specific CD4+ T cells producing IFN-γ, IL-4, and IL-17 was observed in the spleens of immunized mice. Notably, the immunized mice showed decreased shedding of STEC O157:H7 and STEC O91:H21 strains and were protected against weight loss during experimental infection. Additionally, infection with the STEC O91:H21 strain resulted in kidney damage in control unimmunized mice; however, the extent of damage was slightly lower in immunized mice. Our findings suggest that IgG antibodies induced by this vaccine candidate may have a role in inhibiting bacterial adhesion and complement-mediated killing. Conclusion: This study provides evidence that IgG responses are involved in the host defense against STEC. However, our results do not rule out that other classes of antibodies also participate in the protection against this pathogen. Additional work is needed to improve the protection conferred by our vaccine candidate and to elucidate the relevant immune responses that lead to complete protection against this pathogen.

Avaliabilidade do Programa Descolado na prevenção do uso de drogas no contexto escolar / Evaluability of the Descolado Program in preventing drug use in the school context

RESUMO A prevenção do uso abusivo de álcool e drogas na adolescência tem se tornado um tema transversal nas políticas públicas e incentivado a construção de programas preventivos. Entretanto, ainda existe uma necessidade de avaliar o processo de implementação desses programas. O Estudo de Avaliabilidade (EA) é uma etapa de pré-avaliação e descreve de forma lógica como se dará o processo avaliativo. Este artigo tem como objetivo apresentar os resultados do EA do Programa Descolado - estratégia de prevenção do uso de álcool e outras drogas desenvolvida em escolas do município de Recife, Pernambuco. Trata-se de estudo avaliativo, de abordagem qualitativa, realizado por meio de pesquisa documental, entrevistas e reuniões com informantes-chave. Utilizou-se a técnica de consenso Delphi para análise dos modelos lógico da intervenção e teórico da avaliação. Os resultados demonstraram que o programa é avaliável, e a modelização permitiu melhor entendimento dos envolvidos sobre o programa. As equipes técnica e gestora refletiram criticamente sobre o programa, possibilitando ajustes nos objetivos, atividades e recursos desde o início do processo avaliativo. As perguntas avaliativas identificadas segundo componentes do Modelo Lógico podem nortear estudos subsequentes, tendo sinalizado a realização de uma avaliação de implantação - estudo de caso - do Programa Descolado.

ABSTRACT The abusive use of alcohol and drug prevention in adolescence has become a cross-cutting theme in policies and encouraged the construction of preventive programs. However, there is still a need to evaluate the implementation process of these programs. The Evaluability Study (EA) is a pre-assessment stage and describes the logical way in which the assessment process will take place. This article aims to present the results of the EA of Descolado Program - alcohol and other drug prevention strategy developed in schools in the city of Recife, Pernambuco. It is an evaluative study, with qualitative approach, carried out through documental research, interviews and meetings with key informants. The Delphi consensus technique was used to analyze intervention models and evaluation theory. The results showed that the program is evaluable, and the modeling allowed for better understanding about the program by those involved. The technical and management teams critically reflected on the program, enabling adjustments in objectives, activities and resources since the beginning of the evaluation process. The evaluation questions identified according to components of the Logic Model can guide subsequent studies, having signaled for an implementation evaluation - case study of the Descolado Program.

Multiple introgressions shape mitochondrial evolutionary history in Drosophila paulistorum and the Drosophila willistoni group.

Hybridization and the consequent introgression of genomic elements is an important source of genetic diversity for biological lineages. This is particularly evident in young clades in which hybrid incompatibilities are still incomplete and mixing between species is more likely to occur. Drosophila paulistorum, a representative of the Neotropical Drosophila willistoni subgroup, is a classic model of incipient speciation. The species is divided into six semispecies that show varying degrees of pre- and post-mating incompatibility with each other. In the present study, we investigate the mitochondrial evolutionary history of D. paulistorum and the willistoni subgroup. For that, we perform phylogenetic and comparative analyses of the complete mitochondrial genomes and draft nuclear assemblies of 25 Drosophila lines of the willistoni and saltans species groups. Our results show that the mitochondria of D. paulistorum are polyphyletic and form two non-sister clades that we name α and ß. Identification and analyses of nuclear mitochondrial insertions further reveal that the willistoni subgroup has an α-like mitochondrial ancestor and strongly suggest that both the α and ß mitochondria of D. paulistorum were acquired through introgression from unknown fly lineages of the willistoni subgroup. We also uncover multiple mitochondrial introgressions across D. paulistorum semispecies and generate novel insight into the evolution of the species.

Fronteiras entre morar e habitar, coletivo e individual: desafios de (con)viver em moradia universitária / Límites entre vivir y habitar, colectivo e individual: desafíos de (con) vivir en vivienda universitaria / Boundaries between living and dwelling, collective and individual: challenges of (co) living in university housing

Resumo O convívio em moradia estudantil revela desafios nas relações entre seus moradores e destes com o espaço que, então, habitam. O objetivo deste artigo foi o de apresentar os principais desafios de ser morador nesse contexto, compreendendo as sociabilidades e as relações com o lugar. Este estudo constitui-se, a partir de uma abordagem qualitativa, em uma pesquisa de intervenção participativa, com observação participante e entrevistas semiestruturadas. Os sujeitos da pesquisa apontaram a moradia como espaço que amplia a qualidade de vida e viabiliza laços de amizade, permitindo-lhes apropriar-se do lugar como lar. É na dimensão das sociabilidades que, comumente, encontram-se desafios como negociar rotinas, privacidade e organização do espaço e convivência com diferenças culturais, o que resulta situações de conflito. É relevante conhecer caminhos que contribuam para ações coletivas, formação de redes de apoio e mediações frente situações de vulnerabilidade e conflitos.

Resumen Vivir en viviendas para estudiantes revela desafíos en las relaciones entre sus residentes y entre ellos y el espacio que habitan. El objetivo de este artículo fue presentar los principales desafíos de ser residente en este contexto, comprendiendo las sociabilidades y las relaciones con el lugar. Este estudio se constituye, desde un enfoque cualitativo, en una investigación de intervención participativa, con observación participante y entrevistas semiestructuradas. Los sujetos de investigación señalaron que la vivienda como un espacio que potencia la calidad de vida y posibilita lazos de amistad, permitiéndoles apropiarse del lugar como hogar. Es en la dimensión de la sociabilidad donde comúnmente se encuentran desafíos, como las negociación de rutinas, la privacidad y la organización del espacio y la convivencia con las diferencias culturales, lo que resulta en situaciones de conflicto. Es importante conocer formas que contribuyan a acciones colectivas, formación de redes de apoyo y mediación en situaciones de vulnerabilidad y conflictos.

Abstract Living in student housing reveals challenges in the relationships between residents, as well as their interactions with the space they inhabit. The aim of this article was to present the main challenges of being a resident in this context, understanding the sociability and relationships with the place. This study is constituted, from a qualitative approach, in a participatory intervention research, with participant observation and semi-structured interviews. The research subjects indicated housing as a space that enhances the quality of life and enables bonds of friendship, allowing them to appropriate the place as a home. It is in the dimension of sociability that challenges commonly found, such as negotiating routines, privacy and organization of space and coexistence with cultural differences, which results in situations of conflict. It is important to know ways that contribute to collective actions, formation of support networks, and mediation in situations of vulnerability and conflict.

Atividades do enfermeiro de centro cirúrgico no cenário brasileiro: scoping review / Actividades de los enfermeros de quirófano en el escenario brasileño: scoping review / Perioperative nurses' activities in the brazilian scenario: a scoping review

Resumo Objetivo Mapear as principais atividades do enfermeiro de Centro Cirúrgico no cenário brasileiro, explicitadas na literatura vigente. Métodos Trata-se de uma scoping review elaborada de acordo com as diretrizes vigentes do Joanna Briggs Institute, utilizando o checklist para condução e relatório do estudo. A busca foi realizada por duas pesquisadoras independentes, no período entre agosto e dezembro de 2021, em seis bases de dados da área da saúde, utilizando os descritores: nurses, nurse role, intraoperative period, perioperative nursing, surgical centers . Fizeram parte da amostra artigos publicados entre janeiro de 2011 e outubro de 2022, nos idiomas inglês, português ou espanhol. As informações foram extraídas, classificadas, sintetizadas e apresentadas descritivamente. Resultados Foram incluídos 18 na síntese da pesquisa. A análise dos resultados possibilitou evidenciar como as atividades prevalentes na assistência a implementação de medidas de segurança cirúrgica (50%); na gestão, o gerenciamento de materiais, insumos e equipamentos (72%) e preparo das salas (39%); no ensino, educação permanente da enfermagem (50%). Não foram identificados estudos relacionados à atividade de pesquisador. Conclusão No cenário brasileiro, as atividades do enfermeiro de Centro Cirúrgico circundam-se entre gerenciais, assistenciais com menor proporção no ensino, destacando-se sua posição estratégica na mobilização das ações que promovem segurança e qualidade nos processos perioperatórios.

Resumen Objetivo Mapear las principales actividades de los enfermeros de quirófano en el escenario brasileño mencionadas en la literatura vigente. Métodos Se trata de una scoping review elaborada de acuerdo con las directrices vigentes del Joanna Briggs Institute, utilizando la lista de chequeo para la conducción e informe del estudio. La búsqueda fue realizada por dos investigadoras independientes, entre agosto y diciembre de 2021, en seis bases de datos del área de la salud, utilizando los descriptores: nurses, nurse role, intraoperative period, perioperative nursing, surgical centers . Artículos publicados entre enero de 2011 y octubre de 2022, en inglés, portugués y español formaron parte de la muestra. La información se extrajo, se clasificó, se sintetizó y se presentó descriptivamente. Resultados Se incluyeron 18 artículos en la síntesis del estudio. El análisis de los resultados permitió evidenciar las siguientes actividades predominantes: en la atención, la implementación de medidas de seguridad quirúrgica (50 %); en la gestión, la administración de material, insumos y equipos (72 %) y la preparación de las salas (39 %); en la enseñanza, la educación permanente de la enfermería (50 %). No se identificaron estudios relacionados con la actividad del investigador. Conclusión En el escenario brasileño, las actividades de los enfermeros de quirófano giran en torno de la gestión, la atención con menor proporción la enseñanza, y se destaca su posición estratégica en la movilización de las acciones que promueven seguridad y calidad en los procesos perioperatorios. Registro do protocolo na plataforma Open Science Framework: https://osf.io/8jmq6/

Abstract Objective To map perioperative nurses' main activities in the Brazilian scenario, explained in the current literature. Methods This is a scoping review prepared in accordance with current JBI guidelines, using the checklist for conducting and reporting the study. The search was carried out by two independent researchers, between August and December 2021, in six databases in the health area, using the descriptors nurses, nurse role, intraoperative period, perioperative nursing, surgical centers. Articles published between January 2011 and October 2022, in English, Portuguese or Spanish, were part of the sample. The information was extracted, classified, synthesized and presented descriptively. Results Eighteen were included in the research synthesis. The analysis of results made it possible to highlight the implementation of surgical safety measures as prevalent activities in care (50%); in management, material, input and equipment (72%) and room preparation (39%) management; in teaching, permanent nursing education (50%). No studies related to researcher activity were identified. Conclusion In the Brazilian scenario, perioperative nurses' activities range from management to assistance with a smaller proportion in teaching, highlighting their strategic position in mobilizing actions that promote safety and quality in perioperative processes. Protocol registration on the Open Science Framework platform: https://osf.io/8jmq6/

Viabilidade e custo-benefício no reúso de respiradores PFF2 durante a pandemia da COVID-19: um estudo multimétodos / Feasibility and cost-effectiveness of reusing PFF2 respirators during the COVID-19 pandemic: a multimethod study

No final do primeiro trimestre de 2020 a Organização Mundial da Saúde reconheceu a contaminação pelo novo SARS-Cov2 como uma pandemia. Diante disso, encontrar alternativas diante das dificuldades de fornecimento de EPIs, incluindo aqueles de difícil fabricação e considerados descartáveis, como os respiradores do tipo N95 e/ou PFF2, tornou-se uma das tarefas difíceis e primordiais para garantir assistência aos pacientes com a doença do coronavírus (COVID-19). Objetivo: Avaliar a segurança no uso de respiradores descontaminados do tipo PFF2, equipamentos de proteção individual (EPIs) considerados de uso único por profissional de saúde em situações de pandemia. Método: Pesquisa de abordagem de multimétodos. O estudo foi dividido em três desdobramentos metodológicos: uma revisão sistemática com metanálise, um estudo com desenho quase-experimental e um estudo de caso. O relatório da revisão sistemática com metanálise foi desenvolvido em oito bases científicas, de acordo com as orientações de Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com busca de publicações entre janeiro de 2020 e agosto de 2022. A pergunta norteadora foi: o reúso e/ou descontaminação de máscaras N95 viabiliza a manutenção da integridade e eficiência de filtração para os profissionais de saúde na prevenção da COVID-19? A meta-análise foi realizada usando meta-regressão, com variação inversa. A avaliação metodológica dos artigos foi realizada através do instrumento Joanna Briggs critical appraisal para ensaios experimentais não randomizados. O quase-experimento e o estudo de caso foram realizados na Central de Materiais e Esterilização (CME), em um hospital público, universitário e federal da região Sul do Brasil. Foi definido o cálculo do tamanho amostral mínimo de seis respiradores PFF2 para cada tipo de intervenção e tempo de uso para o desenvolvimento do quase-experimento. Este cálculo foi baseado no estudo piloto com máscaras novas com simulação de uso, com análise de potência de 90%, com dois desvios- padrão e com nível de confiança de 95%. As amostras foram coletadas de forma não aleatória, com recrutamento sequencial em duas unidades: Unidade de Terapia Intensiva (UTI não- COVID), na qual os profissionais utilizavam respiradores PFF2 por 42 horas, e a UTI-COVID, na qual as máscaras PFF2 foram utilizadas por 6 horas. O período da coleta foi de 60 dias, entre os meses de abril e junho de 2021. Os critérios de inclusão foram: respiradores do tipo PFF2 fornecidos pela instituição para uso profissional contra agentes biológicos, com laudos de certificação de eficiência bacteriológica, e usados pelos profissionais das UTIs COVID e não- COVID, conforme o protocolo. Os critérios de exclusão foram: respiradores com deformidades ou danificados, com perda de integridade aparente, com marcações que não fossem decorrentes de uso, respiradores valvulados, bem como respiradores da UTI não-COVID descartados com tempo de uso inferior ou superior às 42 horas (7 plantões de 6 horas) preconizadas. Os grupos foram divididos por tempo de uso e tipo de intervenção: Grupo Controle, composto de respiradores novos, e nove grupos experimentais adicionais. Foram consideradas como variáveis dependentes quantitativas: os resultados dos testes de resistência à respiração, à penetração do filtro e à inflamabilidade relacionada à segurança do usuário após o processo de descontaminação de respiradores PFF2. Como variáveis independentes qualitativas foram considerados os tipos de processo de descontaminação. As amostras foram analisadas em laboratório tecnológico de materiais e produtos para o controle da qualidade na cidade de São Paulo, certificado pela Rede Brasileira de Laboratórios de Ensaio (RBLE), com base na norma ABNT NBR 13698/2022, avaliando resistência à respiração com fluxo contínuo de inalação e exalação, penetração através do filtro e inflamabilidade. Os dados foram analisados por meio de estatística descritiva. Para analisar se o respirador permaneceu seguro para o uso após a descontaminação em relação ao grupo controle, foi empregado o teste t Student, para verificar a diferença da resistência à respiração (inalação e exalação) e à penetração do filtro da PFF2 entre os grupos foi utilizado o teste Anova. Foram considerados significativos os valores de p <0,05. Para o estudo de caso, foram aplicadas fontes institucionais, registros de tempo e recursos utilizados para a descontaminação de respirador PFF2. Baseado no modelo de IOWA, foi elaborado o fluxo do processo com a identificação das etapas para viabilizar a descontaminação dos respiradores. Posteriormente, foi elaborada uma planilha para coleta dos dados e comparação dos custos diretos no período pré e durante a pandemia. Quanto aos preceitos bioéticos, esta pesquisa foi orientada pela legislação, aprovada pelo comitê de ética da instituição, CAAE 702207717.4.0000.5327, parecer de aprovação n.2.183.123. Resultados: Como resultados da revisão sistemática, sete artigos foram incluídos na extração dos dados e avaliação crítica, e três na meta-análise. Quatro estudos avaliaram a integridade por inspeção visual e dois por microscopia eletrônica. Não se constatou associação entre o aumento do número de ciclos e a redução da filtração em até 10 ciclos. Nenhum estudo foi considerado de alta qualidade metodológica. Quanto aos resultados do quase-experimento, a resistência à respiração da PFF2 se manteve dentro dos limites preconizados pela norma para os diferentes fluxos de pressão (p<=0,001) na comparação entre as máscaras novas e usadas, independente do tempo de uso. Em relação à manutenção da filtração da PFF2, verifica-se que todos os grupos se mantiveram dentro do limite preconizado de penetração (<6%) utilizando cloreto de sódio em um fluxo contínuo de 95l/min. No entanto, constata-se diferença significativa (p=0,002) entre as máscaras descontaminadas e as novas, independentemente do tipo de tratamento no requisito de penetração. Ao avaliar o tempo de uso, as máscaras descontaminadas e utilizadas por 42h apresentaram, quando comparadas às máscaras novas, diferença significativa na penetração (p=0,012). Em relação ao estudo de caso, afirma-se que, no cenário analisado, o custo do processo de descontaminação de respiradores do tipo PFF2 de uso único durante a pandemia da COVID-19 não é justificável em períodos em que não há escassez de recursos. Conclusão: A partir da revisão sistemática, há evidências da manutenção da integridade e filtração após reúso de respiradores N95/PFF2 para prevenir a COVID-19. O quase-experimento ratificou alguns achados da revisão sistemática, mostrando que a descontaminação de máscara PFF2 é viável nos tipos de descontaminações propostos neste estudo, em situações de pandemia, quando avaliados os requisitos de resistência e manutenção da filtragem em acordo com a norma preconizada. Resíduos de suor e/ou maquiagem não se configuraram como fatores impeditivos para manutenção da filtragem dos respiradores PFF2, além de não terem influenciado no risco de maior ou menor inflamabilidade da máscara. Quanto ao custo do processo de descontaminação desses respiradores, a única justificativa viável para a prática da descontaminação seria a indisponibilidade e o desabastecimento deste EPI.

At the end of the first quarter of 2020, the World Health Organization recognized the contamination by the new SARS-Cov2 as a pandemic. Finding alternatives for the difficulties in providing PPE, including those that are difficult to manufacture and are considered disposable, such as N95 and/or PFF2 respirators, became one of the hardest and fundamental tasks to ensure assistance to patients with coronavirus disease (COVID-19). Objective: To evaluate the safety in the use of PFF2 respirators decontaminated type, personal protective equipment (PPE) considered for one-time use by a health professional in pandemic situations. Method: Research was based on a multimethod approach. This study was developed in three methodological unfoldings: a systematic-metanalysis review, a study with a quasi-experimental design and a case-study. The systematic-metanalysis review report was developed based on the orientations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) on eight scientific basis, looking for publications between January of 2020 and August of 2022. The guiding question was: does the reuse and/or decontamination of N95 masks enable to maintain the integrity and efficiency of filtration for health professionals in the COVID-19 prevention? The metanalysis was carried out using meta-regression with inverse variance. The articles methodological evaluation was performed through the tool Joanna Briggs critical appraisal for not randomized experimental tests. The quasis-experiment and the case study were carried out at the Materials and Sterilization Center, in a public, federal and university hospital in the southern region of Brazil. It was established the sample size calculation minimum of six PFF2 respirators for each type of intervention and time of use for the development of the quasis-experiment. The calculation was based on the pilot study with new masks with simulated use, with power analysis of 90%, with two standard deviations and confidence level of 95%. The samples were collected non-randomly, with sequential recruitment in two units: Intensive Care Unit (non-COVID ICU), in which professionals used PFF2 respirators for 42 hours, and the ICU-COVID, in which PFF2 masks were used for 6 hours. The collection period was of 60 days between the months of April and June of 2021. As inclusion criteria, were used PFF2 respirators for professional use against biological agents provided by the institution, with bacteriological efficiency certification reports, and used by professionals of COVID and non-COVID ICUs, according to the protocol. Exclusion criteria were respirators with deformities or damaged, with apparent loss of integrity, with marks that were not due to use, valved respirators, as well as non-COVID ICU respirators discarded with time of use less than or greater than 42 hours (7 shifts of 6 hours) recommended. The groups were divided by time of use and type of intervention: Control Group, composed of new respirators, and nine additional experimental groups. The following quantitative dependent variables were considered: results of breath resistance tests, of filter penetration and of flammability related to user safety after the decontamination process of PFF2 respirators. As qualitative independent variables, the types of decontamination process were considered. The samples were analyzed in a materials and products technological laboratory for quality control in the city of São Paulo, certified by the Rede Brasileira de Laboratórios de Ensaio (RBLE), based on the ABNT NBR 13698/2022 norm, evaluating the resistance of breathing with a continuous flow of inhalation and exhalation, penetration through the filter and flammability. Data were analyzed using descriptive statistics. To analyze if the respirator remained safe for use after decontamination compared to the control group T Student test was used to verify the difference of breathing resistance (inhalation and exhalation) and to the penetration of the PFF2 filter was used the ANOVA test. Values of p<0.05 were considered significant. For the case study, institutional sources, time registrations and resources used for the decontamination of PFF2 respirator were applied. Based on the IOWA model, the process flow was elaborated with the identification stages to enable respirators decontamination. Afterwards, a spreadsheet was made to collect data and to compare direct costs in the periods of before and during the pandemic. As for the bioethical precepts, this research was guided by the legislation, approved by the institution's ethics committee, CAAE 702207717.4.0000.5327, approval opinion n.2.183.123. Results: As systematic review results, seven articles were included in the data extraction and critical evaluation, and three articles in the metanalysis. Four studies evaluated the integrity by visual inspection and two studies by electronic microscopy. There was not observed any association between the increase in the number of cycles and the filtration reduction in up to ten cycles. Any study was considered of high methodological quality. As for the quasi-experiment results, the PFF2 breathing resistance remained within the limits recommended by the norm for the different pressure flows (p<=0.001) in the comparison between new and used masks, regardless of the time of use. Regarding the PFF2 filtration maintenance, it is verified that all groups remained within the recommended penetration limit (<6%) using sodium chloride in a continuous flow of 95l/min. However, there is a significant difference (p=0.002) between decontaminated and new masks, regardless of the type of treatment in the penetration requirement. When evaluating the time of use, the masks decontaminated and used for 42 hours presented, when compared to new masks, a significant difference in penetration (p=0.012). Regarding the case study, it is stated that, in the scenario analyzed, the costs of PFF2 respirators decontamination process of single use during the COVID-19 pandemic is not justifiable in periods where there is no resource shortage. Conclusion: From the systematic review, there is integrity and filtration maintenance evidence after the reuse of N95/PFF2 respirators to prevent COVID-19. The quasi-experiment ratified findings of systematic review, showing that PFF2 mask decontamination is practicable in the types of decontamination proposed in this study, in pandemic situations, when the resistance and filtering maintenance requirements were evaluated in accordance with the recommended norm. Sweat and/or makeup residues were not configured as deterrent factors for the filtering of PFF2 respirators maintenance, as well as not influencing the risk of greater or lesser flammability of the mask. In terms of decontamination process cost of single-use PFF2 respirators, the only viable justification for the practice of PFF2 masks decontamination would be the unavailability and shortage of this PPE.

Aspectos existenciais e bioéticos nos cuidados paliativos oncológicos / Existential and bioethical aspects of palliative care in cancer / Aspectos existenciales y bioéticos en cuidados paliativos oncológicos

Resumo O adoecimento grave lança o sujeito à facticidade da morte, que faz parte da experiência do viver. Realizaram-se 12 entrevistas com adultos em cuidados paliativos oncológicos, as quais foram analisadas sob a perspectiva fenomenológica, com descrição dos eixos de significado produzidos nas narrativas. Verificaram-se três dimensões do modo como as pessoas (re)organizam seus projetos de ser a partir do adoecimento e da finitude: espiritualidade/religiosidade; ser em família; relação com a morte. O significado atribuído às trajetórias existenciais e à relação estabelecida com projeto de ser são fundamentais para o paciente aderir ao tratamento e enfrentamento da morte. Além disso, ressignificar vida, doença e morte oferece alívio ao sofrimento e auxilia o paciente a dar sentido ao tempo que ainda lhe resta. Tais questões são importantes para refletir sobre a dimensão bioética nos cuidados paliativos e auxiliam no planejamento desta modalidade de atenção.

Abstract Severe illness places individuals in direct confrontation with death, an element of the experience of living. A total of 12 interviews were conducted with adults undergoing palliative care in cancer, and investigated by phenomenological analysis, describing the axes of meaning produced in the narratives. Analysis of the ways individuals (re)organize their life projects based on illness and finitude identified three dimensions: spirituality/religiosity; life in the family; relationship with death. The meaning patients attribute to existential trajectories and the relationship established with their life project are essential for treatment adherence and coping with death. Resignifying life, illness and death can relieve suffering and help patients give meaning to the time left. Such questions help us reflect on the bioethical dimension of palliative care and enable planning in this modality of care.

Resumen La enfermedad grave lleva al sujeto a la factibilidad de la muerte, una experiencia del vivir. Se realizaron 12 entrevistas con adultos en cuidados paliativos oncológicos; y para el análisis se aplicó la perspectiva fenomenológica, con una descripción de los ejes de sentido producidos en los relatos. Se encontraron tres dimensiones de cómo las personas (re)organizan sus proyectos de ser a partir de la enfermedad y la finitud: Espiritualidad/religiosidad; ser en familia; relación con la muerte. El sentido de las trayectorias existenciales y la relación con el proyecto de ser son fundamentales para la adherencia al tratamiento y el enfrentamiento de la muerte. Resignificar la vida, la enfermedad y la muerte alivia el sufrimiento del paciente y le ayuda a dar sentido al tiempo que aún le queda. Estos interrogantes permiten reflexionar sobre la dimensión bioética en los cuidados paliativos y auxilian en la planificación de ese tipo de asistencia.

Elos Program's Efficacy Evaluation in School Management of Child Behavior: A Non-Randomized Controlled Trial / Avaliação da Eficácia do Programa Elos no Manejo Escolar do Comportamento Infantil: Um Ensaio Controlado Não Randomizado

Abstract The Elos Program resulted from a Brazilian cultural adaptation of the Good Behavior Game, a preventive strategy for classroom management to reduce aggressive and disruptive behaviors. The goal is to discuss the Elos Program's efficacy during its implementation in 16 elementary Brazilian public schools in two cities in 2016. The design was a non-randomized controlled trial with 80 classes in each group, experimental and control, involving 1,731 students. The study used the Generalized Estimating Equation model to verify the program's effect. Elos seemed to be effective in reducing aggressiveness and disruptive behavior in boys. These results are aligned with others GBG international studies and suggest that, after a randomized trial, the program would be ready to be disseminated in Brazil.

Resumo O Programa Elos é resultante da adaptação cultural brasileira do Good Behavior Game (GBG), uma estratégia preventiva para a gestão de sala de aula, visando diminuir comportamentos agressivos e disruptivos. O objetivo foi discutir a eficácia do Elos em sua implementação, em 16 escolas públicas de ensino fundamental, em duas cidades brasileiras, em 2016. Delineado como ensaio clínico controlado não randomizado, com 1.731 estudantes, em 80 turmas divididas entre experimental e controle, utilizou-se Generalized Estimating Equation para verificar o efeito do programa. Houve indicações da eficácia do Elos na redução da agressividade em meninos. Esses resultados estão alinhados com outros estudos internacionais do GBG e sugerem que, após um estudo randomizado, o programa estaria pronto para sua disseminação no Brasil.

As contribuições do pensamento sistêmico nos estudos sobre paternidade / The contributions of systemic thinking in studies on paternity

Há um crescente interesse pela relação pai-filho, visto que na sociedade contemporânea, a figura paterna está, gradativamente, conquistando espaços significativos no contexto familiar. No âmbito científico, entre as vertentes teórico-epistemológicas que fundamentam as pesquisas nacionais e internacionais, sobre o tema da paternidade, vem ganhando destaque no campo epistemológico o pensamento sistêmico. Desse modo, o presente artigo tem como objetivo realizar considerações sobre as pesquisas, cujo objeto é a paternidade, pautadas no pensamento sistêmico. O ponto de partida é o entendimento de que o pai é um ser inter-relacional, o que permite diferentes modos de produzir conhecimento sobre a paternidade com base nos pressupostos sistêmicos da complexidade, instabilidade e intersubjetividade.

Interest in the father-son relationship is growing since, in contemporary society, the father figure is conquering significant spaces in the family context. In the scientific field, among the theoretical-epistemological aspects that underlie national and international research on paternity, systemic thinking has gained prominence in the epistemological field. Thus, this article aims to consider research, whose object is paternity, based on systemic thinking. The starting point is the understanding that the father is an interrelational being, which allows different ways to produce knowledge about fatherhood from the systemic assumptions of complexity, instability, and intersubjectivity.

Caracterização de atores e práticas de Redução de Danos na região Sul do país / Characterization of actors and practices of Harm Reduction in the South region of Brazil

Resumo O uso de conceitos e práticas de Redução de Danos (RD) na atenção às pessoas que usam drogas foi iniciado no Brasil nos anos 1990, como resposta preventiva à propagação do HIV/aids. Ao longo dos anos, ganhou espaço em outros campos de ação, como a saúde mental e a proteção social. Em 2019, com as mudanças no governo federal, esta prática foi retirada da definição da política sobre drogas. Com foco nos reflexos dessas mudanças, este estudo visou caracterizar quem atua e quais ações são desenvolvidas junto às pessoas que usam drogas, sob a perspectiva da RD, em municípios da região Sul do Brasil (RS, SC e PR). Trata-se de um estudo exploratório descritivo e transversal, que usou um questionário virtual composto por questões abertas, fechadas e métodos mistos de análise de dados. Os participantes foram recrutados por meio do método Snowball Sampling, de forma virtual, alcançando 72 questionários validados. Foi desenvolvida uma análise exploratória dos dados quantitativos. Para as respostas qualitativas foi usada a Análise Textual Discursiva e o software NVivo (versão 12). Os resultados demonstraram o perfil dos profissionais; mudanças ao longo dos anos e a necessidade de ampliar investimentos em pesquisas sobre RD.

Abstract Harm Reduction (HR) concepts and practices in the care of people who use drugs stared being used in Brazil in the 1990s, as a preventive response to the spread of HIV/AIDS. Over the years, it gained space in other fields, such as mental health and social protection. In 2019, with changes in the federal government, this practice was removed from the definitions of the drug policy. Focusing on the consequences of these changes, this study aimed to characterize who works and what actions are developed with the people who use drugs, in the HR perspective, in the southern region of Brazil. This is a descriptive and cross-sectional exploratory study, which used an online questionnaire with open and closed questions, and mixed methods of data analysis. Participants were recruited using the Snowball Sampling method, by virtual means, reaching 72 validated questionnaires. An exploratory analysis of the quantitative data was developed. For the qualitative data, the Discursive Textual Analysis and NVivo software (version 12) were used. The results showed the profile of professionals; the changes over the years; and the need to expand investments in HR research.

Central Sterile Services Department: psychosocial risks related to the prescribed organization of nursing work.

OBJECTIVE: The aim of this study is to investigate the characteristics of work-flow organization of the Central Sterile Services Department and analyze whether nursing workers are subject to psychosocial risks. METHOD: Mixed study, carried out between November 2017 and July 2019 with nursing workers of the Department of Central Sterile Services of a university hospital. Sampling for the quantitative stage of this study consisted of 36 professionals who have filled the Prescribed Work Organization Scale form, followed by statistical analysis. Qualitative sampling was obtained through collective interview with 19 members of the nursing team. RESULTS: Of the 36 nursing workers, 68.3% were female, 69.4% were over 45 years of age and 75% of the professionals assessed reported as being exposed to a medium psychosocial risk with the emergence of two categories. The aspects related to pleasure at work were highlighted as being the importance of the unit, indirect patient care, professional recognition, and teamwork. The main reported suffering triggers were the lack of human resources, supplies, maintenance, communication, and the devaluation of the unit. CONCLUSION: The prevalence of medium psychosocial risks indicated the need for actions aiming at improving work processes.

Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis.

Tsetse flies (Glossina spp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host's metabolic, reproductive, and immune physiologies. One of these endosymbionts, Spiroplasma, was recently discovered to reside within multiple tissues of field captured and laboratory colonized tsetse flies grouped in the Palpalis subgenera. In various arthropods, Spiroplasma induces reproductive abnormalities and pathogen protective phenotypes. In tsetse, Spiroplasma infections also induce a protective phenotype by enhancing the fly's resistance to infection with trypanosomes. However, the potential impact of Spiroplasma on tsetse's viviparous reproductive physiology remains unknown. Herein we employed high-throughput RNA sequencing and laboratory-based functional assays to better characterize the association between Spiroplasma and the metabolic and reproductive physiologies of G. fuscipes fuscipes (Gff), a prominent vector of human disease. Using field-captured Gff, we discovered that Spiroplasma infection induces changes of sex-biased gene expression in reproductive tissues that may be critical for tsetse's reproductive fitness. Using a Gff lab line composed of individuals heterogeneously infected with Spiroplasma, we observed that the bacterium and tsetse host compete for finite nutrients, which negatively impact female fecundity by increasing the length of intrauterine larval development. Additionally, we found that when males are infected with Spiroplasma, the motility of their sperm is compromised following transfer to the female spermatheca. As such, Spiroplasma infections appear to adversely impact male reproductive fitness by decreasing the competitiveness of their sperm. Finally, we determined that the bacterium is maternally transmitted to intrauterine larva at a high frequency, while paternal transmission was also noted in a small number of matings. Taken together, our findings indicate that Spiroplasma exerts a negative impact on tsetse fecundity, an outcome that could be exploited for reducing tsetse population size and thus disease transmission.

Multiplexed Workplace Measurements in Biogas Plants Reveal Compositional Changes in Aerosol Properties.

Anaerobic digestion is an emerging technology producing energy from renewable resources or food waste. Exposure screenings, comprising hazardous substances and biological agents, at different workplaces are necessary for a comprehensive overview of potential hazards in order to assess the risk of employees in biogas plants. In order to analyse these parameters, workplace measurements were conducted in seven full-scale anaerobic digesters. Personal and stationary sampling was performed for inhalable and respirable particles, volatile organic compounds, ammonia, hydrogen sulphide, carbon monoxide, and carbon dioxide. Furthermore, concentrations of the total cell count, endotoxins, and fungi-down to species level-were determined in comparison to windward air. Sequencing of the 16S rRNA genes was utilized for the determination of the bacterial composition inside the biogas plants. Measurements of hazardous substances show hardly values reaching the specific occupational exposure limit value, except ammonia. An approximate 5-fold increase in the median of the total cell count, 15-fold in endotoxins, and 4-fold in fungi was monitored in the biogas plants compared with windward air. Specifying the comparison to selected workplaces showed the highest concentrations of these parameters for workplaces related to delivery and cleaning. Strikingly, the fungal composition drastically changed between windward air and burdened workplaces with an increase of Aspergillus species up to 250-fold and Penicillium species up to 400-fold. Sequence analyses of 16S rRNA genes revealed that many workplaces are dominated by the order of Bacillales or Lactobacillales, but many sequences were not assignable to known bacteria. Although significant changes inside the biogas plant compared with windward air were identified, that increase does not suggest stricter occupational safety measures at least when applying German policies. However, exposure to biological agents revealed wide ranges and specific workplace measurements should be conducted for risk assessment.

Territorialidades e Contexto Urbano nos Estudos sobre a Relação Pessoa-Ambiente: Revisão Integrativa de Literatura / Territorialities and Urban Context in Studies on the Person-Environment Relationship: Integrative Literature Review / Territorialidades y Contexto Urbano en Estudios sobre la Relación Persona-Medio Ambiente: Revisión de la Literatura Integrativa

Grande parte da população mundial vive atualmente nas cidades, sendo a territorialidade um modo de compreensão contemporâneo da constituição desses espaços de vida. Esse estudo teve como objetivo compreender de que modo o conceito de territorialidade tem se relacionado com os estudos sobre a relação pessoa-ambiente no contexto urbano. A pesquisa propõe uma revisão integrativa utilizando bases nacionais como Scielo e Pepsic, e internacionais, como Web of Science, Sage Journal e Science Direct. As buscas resultaram em 219 artigos e, após seleção conforme os critérios de elegibilidade, obtiveram-se 21 artigos completos para análise. Os resultados indicaram um aumento da produção nos últimos anos, com temas relacionados a aspectos psicossociais, planejamento urbano, criminalidade e segurança, aspectos culturais e religiosos, saúde, educação. Destacou-se o entendimento da territorialidade atrelado aos contextos urbanos a partir de aspectos físicos e simbólicos do uso, ocupação e transformação dos espaços. A territorialidade, tomada como um conceito interdisciplinar, permite dialogar com a psicologia ambiental e com a psicologia existencialista, sustentando a importância dos territórios na dimensão social da existência. (AU)

Much of the world population currently lives in cities, with territoriality being a contemporary way of understanding the constitution of these living spaces. This study aimed to understand how the concept of territoriality has been related to studies on the person-environment relationship in the urban context. The research proposes an integrative review using national bases such as Scielo and Pepsic, and international ones, such as Web of Science, Sage Journal and Science Direct. The searches resulted in 219 articles and, after selection according to the eligibility criteria, 21 complete articles were obtained for analysis. The results indicated a greater production in recent years, with themes related to psychosocial aspects, urban planning, crime and security, cultural and religious aspects, health, education. The studies pointed to the understanding of the concept of territorialities linked to urban contexts from physical and symbolic aspects of the use, occupation and transformation of spaces. Territoriality, taken in an interdisciplinary concept, allows the dialogue with environmental psychology and existentialist psychology and to understand the importance of territories in the social dimension of existence. (AU)

Gran parte de la población mundial vive actualmente en ciudades, así que la territorialidad es una forma contemporánea de entender la constitución de estos espacios de vida. Este estudio tuvo como objetivo comprender cómo el concepto de territorialidad se ha relacionado con estudios sobre la relación persona-entorno en el contexto urbano.La investigación propone una revisión integradora utilizando bases nacionales como Scielo y Pepsic, e internacionales, como Web of Science, Sage Journal y Science Direct. Las búsquedas dieron como resultado 219 artículos y, tras la selección de acuerdo con los criterios de elegibilidad, se obtuvieron 21 artículos completos para su análisis. Los resultados indicaron una mayor producción en los últimos años, con temas relacionados con aspectos psicosociales, planificación urbana, crimen y seguridad, aspectos culturales y religiosos, salud, educación. Los estudios apuntaron a la comprensión del concepto de territorialidades vinculadas a los contextos urbanos desde aspectos físicos y simbólicos del uso, ocupación y transformación de los espacios. La territorialidad, presentada de manera interdisciplinar, permite dialogar con la psicología ambiental y la psicología existencialista y comprender la importancia de los territorios en la dimensión social de la existencia. (AU)

Vulnerabilidade, família e o uso de drogas: uma revisão integrativa de literatura / Vulnerability, family and drug use: an integrating literature review / Vulnerabilidad, familia y el uso de drogas: una revisión integral de literatura

Os problemas relacionados ao uso de álcool e outras drogas é uma realidade na sociedade atual e revela a existência de diferentes fatores relacionados. Entre eles, destaca-se a condição de vulnerabilidade como importante elemento contribuinte para o uso abusivo, bem como a família, sendo entendida como fator de risco e/ou proteção e como sistema diretamente afetado pelo problema. Diante disso, este estudo teve como objetivo realizar uma revisão integrativa de literatura sobre a relação entre vulnerabilidade, drogas e contexto familiar. Para tanto, foi realizada uma busca por artigos nas bases de dados Scielo e BVS utilizando os descritores "vulnerabilidade AND drogas AND família" que rastreou um total de 105 artigos. Após a aplicação dos critérios de inclusão, restaram 22 artigos. Desses, sete envolveram adolescentes escolares, cinco pessoas em situação de rua e cinco familiares de usuários, quatro foram realizados com os próprios usuários de drogas e um com profissionais da saúde. Os resultados das análises dos estudos sugerem que a relação entre uso de drogas, família e condição de vulnerabilidade é intrínseca, sendo difícil analisá-los isoladamente. A compreensão do problema das drogas requer uma visão ampliada e sistêmica de todos os fatores envolvidos neste complexo processo para ser possível o planejamento e a qualificação das políticas públicas.

The problems related to the use of alcohol and other drugs are a reality in today's society and reveal the existence of different related factors. Among them, the condition of vulnerability stands out as an important contributing element to abusive use, as well as family context, being understood as a risk and/or protective factor and as a system directly affected by the problem. Therefore, this study aimed to carry out an integrative literature review on the relationship between vulnerability, drugs and family. For this, a search for articles in the Scielo and VHL databases was carried out combining the descriptors "AND drugs AND family vulnerability", which tracked a total of 105 articles. After using the inclusion criteria, there were 22 articles remaining to be analyzed. From the 22 studies, seven involved school adolescents, five with street people, five with family members, four with drug users and one with health professionals. Results have shown that the relationship between drug use, family and vulnerability is intrinsic, making it difficult to analyze them in isolation. Understanding the drug problem requires an expanded and systemic view of all factors involved in this complex process in order to plan and qualify public policies.

Los problemas relacionados con el uso de alcohol y otras drogas es una realidad en la sociedad actual y revela la existencia de diferentes factores constitutivos y activos para determinar el fenómeno. Entre éstos, la condición de vulnerabilidad se destaca como un contribuyente importante al uso abusivo, así como a la familia, que se entiende como un factor de riesgo y / o protección y como un sistema directamente afectado por el problema. Por lo tanto, este estudio tuvo como objetivo realizar una revisión bibliográfica integradora sobre la relación entre vulnerabilidad, drogas y contexto familiar. Para este fin, se realizó una búsqueda de artículos en las bases de datos Scielo y BVS apoyada en la combinación de los descriptores "vulnerabilidad Y drogas Y familia" que rastrearon un total de 105 artículos. Después de aplicar los criterios de inclusión, quedaron 22 artículos, que fueron analizados en su totalidad. De éstos, siete se llevaron a cabo con adolescentes escolares, cinco con personas sin hogar, cinco con familiares de usuarios, cuatro con consumidores de drogas y uno con profesionales de la salud. Los resultados del análisis de los estudios sugieren que la relación entre el consumo de drogas, la familia y la condición de vulnerabilidad es intrínseca, lo que dificulta su análisis de forma aislada. Comprender el problema de las drogas requiere una visión ampliada y sistémica de todos los factores involucrados en este complejo proceso, para que sea posible planificar y calificar las políticas públicas.

Species Differences in Microsomal Metabolism of Xanthine-Derived A1 Adenosine Receptor Ligands.

Tracer development for positron emission tomography (PET) requires thorough evaluation of pharmacokinetics, metabolism, and dosimetry of candidate radioligands in preclinical animal studies. Since variations in pharmacokinetics and metabolism of a compound occur in different species, careful selection of a suitable model species is mandatory to obtain valid data. This study focuses on species differences in the in vitro metabolism of three xanthine-derived ligands for the A1 adenosine receptor (A1AR), which, in their 18F-labeled form, can be used to image A1AR via PET. In vitro intrinsic clearance and metabolite profiles of 8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX), an established A1AR-ligand, and two novel analogs, 8-cyclobutyl-3-(3-fluoropropyl)-1-propylxanthine (CBX) and 3-(3-fluoropropyl)-8-(1-methylcyclobutyl)-1-propylxanthine (MCBX), were determined in liver microsomes from humans and preclinical animal species. Molecular mechanisms leading to significant differences between human and animal metabolite profiles were also examined. The results revealed significant species differences regarding qualitative and quantitative aspects of microsomal metabolism. None of the tested animal species fully matched human microsomal metabolism of the three A1AR ligands. In conclusion, preclinical evaluation of xanthine-derived A1AR ligands should employ at least two animal species, preferably rodent and dog, to predict in vivo behavior in humans. Surprisingly, rhesus macaques appear unsuitable due to large differences in metabolic activity towards the test compounds.

Leadership development of nursing students in a material and sterilization center.

OBJECTIVE: To analyze the experiences of Nursing students during the mandatory hospital internship at a Material and Sterilization Center with a focus on leadership development. METHOD: This is an experience report of a mandatory hospital curricular internship anchored in the national curricular guidelines for Nursing, of a descriptive-reflective nature, and carried out in a general university hospital in southern Brazil, from March to June 2019. RESULTS: Activities were developed in order to develop leadership aspects such as people, orthotics and prosthetics management, surgical planning, conflict management, and assertive communication. FINAL CONSIDERATIONS: The mandatory hospital curricular internship at the Material and Sterilization Center favored the students in the leadership process, management, decision-making, and development of autonomy for leading nurses.