Increasing FDA-accelerated approval of single-arm trials in oncology (1992 to 2020).

OBJECTIVES: We aimed to map the characteristics of single-arm trials (SAT), report the Food and Drug Administration (FDA) transparency in presenting historical control, and to assess the confirmatory randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: This metaresearch included a review of all oncology indication approved using SAT by FDA-AA (FDA-Accelerated Approval) from 1992 to 2020. Two independent reviewers identified SAT, extracted data from FDA full medical reviews for historical controls reported and MEDLINE for searching for confirmatory RCT published. RESULTS: Of 254 FDA-AA approvals, 119 (47%) were approved for oncologic indications using SAT. Fifty-four drugs for 72 oncology indications were for leukemia, lymphoma, lung cancer, urothelial cancer, multiple myeloma, and thyroid cancer. Overall, 37 (52%) treatments were converted into regular approval. Of these, 17 (46%) were based on confirmatory RCTs using overall survival (OS) as an outcome. Five indications were withdrawn from the market. Most trials outcomes were blindly assessed by independent research committees. Median trial sample size was 105 patients (min:8 to max:532). The FDA did not fully specify historical control selection in 75% of cases. CONCLUSION: The granting of FDA-AAs based on SAT in oncology is increasing with more target drugs approved over time. Transparency in historical control reporting is necessary.

Age-Associated Upregulation of Glutamate Transporters and Glutamine Synthetase in Senescent Astrocytes In Vitro and in the Mouse and Human Hippocampus.

Aging is marked by complex and progressive physiological changes, including in the glutamatergic system, that lead to a decline of brain function. Increased content of senescent cells in the brain, such as glial cells, has been reported to impact cognition both in animal models and human tissue during normal aging and in the context of neurodegenerative disease. Changes in the glutamatergic synaptic activity rely on the glutamate-glutamine cycle, in which astrocytes handle glutamate taken up from synapses and provide glutamine for neurons, thus maintaining excitatory neurotransmission. However, the mechanisms of glutamate homeostasis in brain aging are still poorly understood. Herein, we showed that mouse senescent astrocytes in vitro undergo upregulation of GLT-1, GLAST, and glutamine synthetase (GS), along with the increased enzymatic activity of GS and [3H]-D-aspartate uptake. Furthermore, we observed higher levels of GS and increased [3H]-D-aspartate uptake in the hippocampus of aged mice, although the activity of GS was similar between young and old mice. Analysis of a previously available RNAseq dataset of mice at different ages revealed upregulation of GLAST and GS mRNA levels in hippocampal astrocytes during aging. Corroborating these rodent data, we showed an increased number of GS + cells, and GS and GLT-1 levels/intensity in the hippocampus of elderly humans. Our data suggest that aged astrocytes undergo molecular and functional changes that control glutamate-glutamine homeostasis upon brain aging.

Bioactivity of essential oils from Croton grewioides and its major compounds: toxicity to soybean looper Chrysodeixis includens and selectivity to the predatory stink bug Podisus nigrispinus.

Natural biological control is a key factor that ensures the regulation of insect pest populations in agroecosystems. However, the indiscriminate use of pesticides has compromised this environmental service. Thus, the search for environmentally safe pesticides is an increasing requirement for sustainable food production. In this study, we analyzed the toxicity of essential oils from two accessions (CGR112 and CGR126) of Croton grewioides and its major compounds, methyl eugenol and eugenol, on the soybean pest Chrysodeixis includens. In addition, we investigated the sublethal effects of these compounds on the predatory bug Podisus nigrispinus, analyzing its developmental, reproduction and life table parameters. Essential oils and their major compounds were toxic to C. includens and P. nigrispinus. In general, the presence of eugenol made the essential oil more toxic to the pest and selective to the natural enemy. Eugenol was the most toxic compound for 2nd instar larvae of C. includens at LD50, followed by CGR126 essential oil from C. grewioides which was equally toxic at higher doses. The estimated lethal times for essential oils to cause mortality in 50% of the population of C. includens were less than 15 h. There was selectivity of the essential oil of CGR126 accession of C. grewioides at lethal doses above 90%. Although the treatments showed little effect on the development of P. nigrispinus, body mass and reproductive parameters were negatively affected, with the exception of the essential oil of CGR126 accession of C. grewioides. The essential oil of C. grewioides may be a promising active ingredient for the synthesis of new insecticides, which are efficient against C. includens and at the same time are safer for the natural enemy P. nigrispinus.

Stigma/Style Cell-Cycle Inhibitor 1, a Regulator of Cell Proliferation, Interacts With a Specific 14-3-3 Protein and Is Degraded During Cell Division.

The final shape and size of plant organs are determined by a network of genes that modulate cell proliferation and expansion. Among those, SCI1 (Stigma/style Cell-cycle Inhibitor 1) functions by inhibiting cell proliferation during pistil development. Alterations in SCI1 expression levels can lead to remarkable stigma/style size changes. Recently, we demonstrated that SCI1 starts to be expressed at the specification of the Nicotiana tabacum floral meristem and is expressed at all floral meristematic cells. To elucidate how SCI1 regulates cell proliferation, we screened a stigma/style cDNA library through the yeast two-hybrid (Y2H) system, using SCI1 as bait. Among the interaction partners, we identified the 14-3-3D protein of the Non-Epsilon group. The interaction between SCI1 and 14-3-3D was confirmed by pulldown and co-immunoprecipitation experiments. 14-3-3D forms homo- and heterodimers in the cytoplasm of plant cells and interacts with SCI1 in the nucleus, as demonstrated by Bimolecular Fluorescence Complementation (BiFC). Analyses of SCI1-GFP fluorescence through the cell-cycle progression revealed its presence in the nucleoli during interphase and prophase. At metaphase, SCI1-GFP fluorescence faded and was no longer detected at anaphase, reappearing at telophase. Upon treatment with the 26S proteasome inhibitor MG132, SCI1-GFP was stabilized during cell division. Site-directed mutagenesis of seven serines into alanines in the predicted 14-3-3 binding sites on the SCI1 sequence prevented its degradation during mitosis. Our results demonstrate that SCI1 degradation at the beginning of metaphase is dependent on the phosphorylation of serine residues and on the action of the 26S proteasome. We concluded that SCI1 stability/degradation is cell-cycle regulated, consistent with its role in fine-tuning cell proliferation.

Single-arm clinical trials that supported FDA accelerated approvals have modest effect sizes and were at high risk of bias.

OBJECTIVE: To describe effect sizes of single-arm clinical trials that supported AA approvals. STUDY DESIGN AND SETTING: We reviewed all the single-arm approvals granted by the FDA-AA pathway between June1992 to December2020. Two independent reviewers identified single-arm studies and extracted data from FDA Full-Medical Reviews. We performed a meta-analysis to estimate the effect sizes and compared it between studies that met post-approval FDA requirements for RCTs with those that did not. RESULTS: From the total of 254 approvals, single arm clinical trials describing effects of 54 drugs for 72 clinical indications were evaluated. The effect size estimated was OR:2.22(CI95%:1.76-2.81) [relative risk (RR) = 1.63(95CI% 1.38-1.92)]; 53% of treatments had a lower 95% CI bound crossing the null effect. Effect size did not differ between the treatments that met the FDA requirement for conducting post-approval RCTs. CONCLUSIONS AND RELEVANCE: Treatment effects observed in the FDA AA single-arm studies was modest and can be to ascribed to bias.

Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus.

The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age-related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age-associated neurodegenerative diseases, but little is known about whether this process also occurs in physiological aging, as well as its functional implication. Here, we investigated astrocyte senescence in vitro, in old mouse brains, and in post-mortem human brain tissue of elderly. We identified a significant loss of lamin-B1, a major component of the nuclear lamina, as a hallmark of senescent astrocytes. We showed a severe reduction of lamin-B1 in the dentate gyrus of aged mice, including in hippocampal astrocytes, and in the granular cell layer of the hippocampus of post-mortem human tissue from non-demented elderly. The lamin-B1 reduction was associated with nuclear deformations, represented by an increased incidence of invaginated nuclei and loss of nuclear circularity in senescent astrocytes in vitro and in the aging human hippocampus. We also found differences in lamin-B1 levels and astrocyte nuclear morphology between the granular cell layer and polymorphic layer in the elderly human hippocampus, suggesting an intra-regional-dependent aging response of human astrocytes. Moreover, we described senescence-associated impaired neuritogenic and synaptogenic capacity of mouse astrocytes. Our findings show that reduction of lamin-B1 is a conserved feature of hippocampal cells aging, including astrocytes, and shed light on significant defects in nuclear lamina structure which may contribute to astrocyte dysfunctions during aging.

Theta and gamma oscillations in the rat hippocampus support the discrimination of object displacement in a recognition memory task.

Episodic memory depends on the recollection of spatial and temporal aspects of past experiences in which the hippocampus plays a critical role. Studies on hippocampal lesions in rodents have shown that dentate gyrus (DG) and CA3 are necessary to detect object displacement in memory tasks. However, the understanding of real-time oscillatory activity underlying memory discrimination of subtle and pronounced displacements remains elusive. Here, we chronically implanted microelectrode arrays in adult male Wistar rats to record network oscillations from DG, CA3, and CA1 of the dorsal hippocampus while animals executed an object recognition task of high and low spatial displacement tests (HD: 108 cm, and LD: 54 cm, respectively). Behavioral analysis showed that the animals discriminate between stationary and displaced objects in the HD but not LD conditions. To investigate the hypothesis that theta and gamma oscillations in different areas of the hippocampus support discrimination processes in a recognition memory task, we compared epochs of object exploration between HD and LD conditions as well as displaced and stationary objects. We observed that object exploration epochs were accompanied by strong rhythmic activity in the theta frequency (6-12 Hz) band in the three hippocampal areas. Comparison between test conditions revealed higher theta band power and higher theta-gamma phase-amplitude coupling in the DG during HD than LD conditions. Similarly, direct comparison between displaced and stationary objects within the HD test showed higher theta band power in CA3 during exploration of displaced objects. Moreover, the discrimination index between displaced and stationary objects directly correlated with CA1 gamma band power in epochs of object exploration. We thus conclude that theta and gamma oscillations in the dorsal hippocampus support the successful discrimination of object displacement in a recognition memory task.

Transtornos mentais comuns em profissionais de enfermagem de serviços de emergência / Trastornos mentales comunes en profesionales de enfermería de servicios de emergencia / Common mental disorders in emergency services nursing professionals

Resumo Objetivo Analisar as variáveis sociodemográficas e de trabalho quanto ao risco de transtorno mental comum em profissionais de enfermagem que atuam em serviços de atenção às urgências e emergências. Métodos Estudo observacional, transversal com abordagem quantitativa, realizado no Pronto Socorro Adulto e nas Unidades de Terapia Intensiva Adulto e Coronariana de um hospital público de ensino e em duas Unidades de Pronto Atendimento públicos, do interior de Minas Gerais, Brasil. A coleta de dados ocorreu por meio de dois instrumentos: questionário sociodemográfico e profissional e o Self-Reporting Questionnaire. Para as análises foi realizada a estatística descritiva, Qui-quadrado de Pearson, exato de Fisher e regressão logística binomial. Resultados Participaram 302 profissionais de enfermagem. Observou-se prevalência de 20,5% para transtornos mentais comuns. Na análise bivariada, as variáveis relacionadas aos transtornos mentais comuns foram: não ter filhos (p=0,025), trabalhar nos setores da atenção terciária (p=0,008), regime de contrato estatutário (p=0,041). Na análise multivariada, os setores hospitalares (p=0,001) e o cargo de enfermeiro (p=0,017) indicaram risco elevado para transtornos mentais comuns. Conclusão As variáveis setor e cargo se comportaram como risco e apresentaram razão de chance de prevalência de 4,21 e 2,80, respectivamente, indicando que as condições de trabalho nos ambientes de urgência e emergência associadas ao cargo de enfermeiro favorecem o desenvolvimento de transtornos mentais comuns nos profissionais de enfermagem. Este estudo possibilitou conhecer a necessidade de implantação de estratégias para identificação precoce de transtornos mentais comuns e a promoção da saúde mental dos profissionais, visando a melhoria dos aspectos psicossociais nos ambientes de trabalho.

Resumen Objetivo Analizar las variables sociodemográficas y de trabajo respecto al riesgo de trastornos mentales comunes en profesionales de enfermería que actúan en servicios de atención de urgencias y emergencias. Métodos Estudio observacional, transversal, con enfoque cuantitativo, realizado en el Servicio de Urgencias Adulto y en las Unidades de Cuidados Intensivos Adulto y Coronaria de un hospital público universitario y en dos Unidades de Pronta Atención públicas del interior de Minas Gerais, Brasil. La recopilación de datos se realizó mediante dos instrumentos: cuestionario sociodemográfico y profesional y el Self-Reporting Questionnaire. Para los análisis, se utilizó la estadística descriptiva, ji cuadrado de Pearson, exacta de Fisher y regresión logística binomial. Resultados Participaron 302 profesionales de enfermería. Se observó prevalencia del 20,5 % de trastornos mentales comunes. En el análisis bivariado, las variables relacionadas con los trastornos mentales comunes fueron: no tener hijos (p=0,025), trabajar en sectores de atención terciaria (p=0,008) y el régimen de contrato estatutario (p=0,041) En el análisis multivariado, los sectores hospitalarios (p=0,001) y el cargo de enfermero (p=0,017) indicaron riesgo elevado de trastornos mentales comunes. Conclusión Las variables sector y cargo se comportan como riesgo y presentaron razón de momios de prevalencia de 4,21 y 2,80, respectivamente, lo que indica que las condiciones de trabajo en los ambientes de urgencias y emergencias asociadas al cargo de enfermero favorecen el desarrollo de trastornos mentales comunes en los profesionales de enfermería. Este estudio permitió conocer la necesidad de implementar estrategias para la identificación temprana de trastornos mentales comunes y la promoción de la salud mental de los profesionales, con el objetivo de mejorar los aspectos psicosociales en el ambiente de trabajo.

Abstract Objective To analyze sociodemographic and work variables regarding the risk for common mental disorders in nursing professionals working in urgent and emergency care services. Methods Observational, cross-sectional, quantitative study conducted in the Adult Emergency Room and Adult and Coronary Intensive Care Units of a public teaching hospital and in two public Emergency Care Units in the countryside of Minas Gerais, Brazil. Data collection was performed with use of two instruments: sociodemographic and professional questionnaire and the Self-Reporting Questionnaire. Descriptive statistics, Pearson's Chi-square, Fisher's exact and binomial logistic regression were performed in the analyzes. Results Participation of 302 nursing professionals. There was a prevalence of 20.5% for common mental disorders. In the bivariate analysis, the variables related to common mental disorders were: not having children (p=0.025), working in tertiary care departments (p=0.008), statutory contract regime (p=0.041). In the multivariate analysis, the hospital departments (p=0.001) and the nurse position (p=0.017) indicated a high risk for common mental disorders. Conclusion The variables of department and position behaved as risk and had a prevalence odds ratio of 4.21 and 2.80, respectively, indicating that the working conditions in urgent and emergency environments associated with the nurse position favor the development of common mental disorders in nursing professionals. Through this study, it was possible to understand the need to implement strategies for the early identification of common mental disorders and the promotion of mental health among professionals, aiming at improving psychosocial aspects in work environments.

Percepções de enfermeiros sobre gestão do cuidado e seus fatores intervenientes para o controle da tuberculose / Percepciones de enfermeros sobre gestión de la atención y factores intervinientes para el control de la tuberculosis / Nurses' perceptions on care management and its intervening factors for tuberculosis control

Resumo Objetivo Analisar as percepções de enfermeiros sobre gestão do cuidado e seus fatores intervenientes para o controle da tuberculose na Atenção Primária em Saúde. Método Estudo descritivo, qualitativo, realizado com 29 enfermeiros que atuavam no controle da tuberculose em 23 Unidades Básicas de Saúde de Belém, Pará. Os dados foram produzidos por entrevistas individuais, utilizando roteiro semiestruturado, e submetidos à análise de conteúdo temática, proposta por Bardin. Resultados Originaram-se duas categorias temáticas: "A gestão do cuidado de enfermeiros para o controle da tuberculose nas Unidades Básicas de Saúde" e "Fatores intervenientes na efetivação da gestão do cuidado no controle da tuberculose nas Unidades Básicas de Saúde". Conclusão e implicações para a prática O conhecimento dos enfermeiros sobre a política e a gestão do cuidado no controle da tuberculose precisa ser fortalecido, e embora eles tenham clareza sobre suas competências, não conseguem realizá-las em sua plenitude por questões referentes à pouca organização dos serviços, centralização das atividades nos enfermeiros, baixa cooperação multiprofissional, falta de insumos e de pessoal e questões socioeconômicas ligadas ao usuário com tuberculose.

Resumen Objetivo Analizar la percepción de enfermeros sobre la gestión de la atención y los factores intervinientes para el control de la tuberculosis en la Atención Primaria de la Salud. Método Estudio descriptivo cualitativo realizado con 29 enfermeros que pre en el control de la tuberculosis en 23 Unidades Básicas de Salud de Belém, Pará. Los datos fueron producidos por entrevistas individuales, utilizando un guion semiestructurado, y sometido al análisis de contenido temático propuesto por Bardin. Resultados Se originaron dos categorías temáticas: "La gestión de la atención de enfermeros para el control de la tuberculosis en las Unidades Básicas de Salud" y "Factores intervinientes en la efectividad de la gestión de la atención en el control de la tuberculosis en las Unidades Básicas de Salud". Conclusión e implicaciones para la práctica Es necesario fortalecer el conocimiento de las enfermeras sobre la política y la gestión de la atención en el control de la tuberculosis, y aunque tienen claras sus competencias, no pueden implementarlas en su totalidad debido a problemas relacionados con la mala organización de los servicios, la centralización de actividades en los enfermeros, baja cooperación multiprofesional, falta de insumos y personal y aspectos socioeconómicos relacionados con el usuario con tuberculosis.

Abstract Objective To analyze nurses' perceptions on care management and its intervening factors for tuberculosis control in Primary Health Care. Method A descriptive and qualitative study conducted with 29 nurses who worked on tuberculosis control in 23 Basic Health Units in Belém, Pará. The data were produced by individual interviews, using a semi-structured script, and submitted to thematic content analysis, as proposed by Bardin. Results Two thematic categories emerged, namely: "Care management by nurses for tuberculosis control in Basic Health Units" and "Intervening factors in the application of care management for tuberculosis control in Basic Health Units". Conclusion and implications for the practice The nurses' knowledge about the care policy and management for tuberculosis control needs to be strengthened and, although nurses are aware of their competences, they are unable to fully implement them due to issues related to poor organization services, centralization of activities on them, low multiprofessional cooperation, scarcity of supplies and personnel, and socioeconomic issues related to tuberculosis patients.

Scenario validation for clinical simulation: prenatal nursing consultation for adolescents / Validación de escenario para simulado clínico: consulta de enfermería en el prenatal para adolescente / Validação de cenário para simulação clínica: consulta de enfermagem no pré-natal para adolescente

ABSTRACT Objectives: to validate a scenario for clinical simulation: prenatal nursing consultation for adolescents. Methods: methodological study developed from January to December 2019, in five stages (overview, scenario, scenario design, progression, debriefing and assessment). The validation involved four volunteer students, a teacher as a facilitator and four judges. The judges filled out a Likert scale with four responses. Data was analyzed using Microsoft Excel® software, version 2016. Absolute and relative frequencies and the content validity index were calculated, considering a minimum acceptable value of 1.0. Results: the preparation of the scenario was based on the proposed learning objectives. The scenario was validated with a global content validity index equal to 1.0. Final Considerations: the study achieved the proposed objective. This scenario can contribute to preparing nurses to work in the care of pregnant teenagers, a representative public in Brazil that requires specific care.

RESUMEN Objetivos: validar un escenario para simulado clínico, en enseñanza de enfermería, sobre primera consulta de prenatal a gestante adolescente. Métodos: estudio metodológico desarrollado de enero a diciembre de 2019, en cinco etapas (overview, scenario, scenario design progression, debriefing y assessment). La validación involucró cuatro alumnos voluntarios, una docente como facilitadora y cuatro jueces. Los jueces rellenaron una escala Likert con cuatro respuestas. Datos fueran analizados en el software Microsoft Excel®, versión 2016. Calculadas las frecuencias absolutas y relativas y el índice de validez de contenido, considerando valor mínimo aceptable de 1,0. Resultados: la elaboración del escenario partió de los objetivos de aprendizaje propuestos. El escenario fue validado con índice de validez de contenido global igual a 1,0. Consideraciones Finales: el estudio alcanzó el objetivo propuesto. Este escenario puede contribuir para preparar enfermeros para actuación en la atención a gestantes adolescentes, un público representativo en Brasil y que requiere cuidados específicos.

RESUMO Objetivos: validar um cenário para simulação clínica, no ensino de enfermagem, sobre primeira consulta de pré-natal à gestante adolescente. Métodos: estudo metodológico desenvolvido de janeiro a dezembro de 2019, em cinco etapas (overview, scenario, scenario design progression, debriefing e assessment). A validação envolveu quatro alunos voluntários, uma docente como facilitadora e quatro juízes. Os juízes preencheram uma escala Likert com quatro respostas. Os dados foram analisados no software Microsoft Excel®, versão 2016. Calcularam-se as frequências absolutas e relativas e o índice de validade de conteúdo, considerando valor mínimo aceitável de 1,0. Resultados: a elaboração do cenário partiu dos objetivos de aprendizagem propostos. O cenário foi validado com índice de validade de conteúdo global igual a 1,0. Considerações Finais: o estudo alcançou o objetivo proposto. Este cenário pode contribuir para preparar enfermeiros para atuação na atenção às gestantes adolescentes, um público representativo no Brasil e que requer cuidados específicos.

Qualidade da informação sobre tuberculose drogarresistente nos sistemas de informação / Quality of information on drug-resistant tuberculosis in information systems

Objetivou-se analisar a qualidade da informação referente à tuberculose drogarresistente segundo os bancos oficiais que armazenam os dados epidemiológicos e operacionais sobre a doença. Pesquisa epidemiológica, descritiva, realizada com dados do Sistema de Informação de Agravos de Notificação (SINAN), Sistema Gerenciador de Ambiente Laboratorial (GAL) e Sistema de Informação de Tratamento Especiais da Tuberculose (SITE-TB), obtidos na Secretaria de Estado de Saúde Pública do Pará, referentes ao período de 2016-2020. A análise foi realizada por meio de estatística descritiva, utilizando o programa Rx64 4.0.0, através do RStudio Desktop. Foram analisados 889 registros distribuídos nas três bases de dados, com predominância de casos no GAL (433), seguido do SITE-TB (350) e do SINAN (220). Predominaram registros na faixa etária de 25 a 44 anos e no sexo masculino. O maior número de registros de cultura para tipificação do Mycobacterium tuberculosis foi identificado no GAL. Identificou-se, casos em duplicidade, sendo 121 no GAL, 45 no SITE-TB e 4 no SINAN. Dentre os 433 casos registrados no GAL, cinco constavam também no SINAN e seis foram identificados no SINAN e no SITE-TB. Dos 350 casos registrados no SITE-TB, 242 não constavam nas demais bases e 97 figuravam no SINAN. Em relação aos 220 casos do SINAN, 154 só figuravam nele e seis casos constavam nos três sistemas, simultaneamente. Em relação a distribuição dos registros nas Regiões de Saúde do Pará, identificou-se maior proporção no GAL, na região do Xingú (98,5%) e na Metropolitana I (26%), sendo que as demais regiões exibiram registros abaixo de 10 casos. Em relação aos dados constantes apenas no SINAN, a Região Metropolitana I apresentou 93 casos (18,8%) e nas demais regiões os registros foram inferiores a 10. No SITE TB a Região Metropolitana I concentrou maior frequência, com 174 casos (35,1%), seguida da Metropolitana II, com 15 (71,4%). Quanto a concomitância de dados em dois sistemas, a região Metropolitana I foi a única que apresentou registros (0.8%) no GAL e SITE-TB. E se destaca no SINAN e SITE TB, com maior frequência (18,3%), as demais apresentaram número de casos inferiores a 10 ou não apresentaram registros. Foram identificados seis registros concomitantes nas três bases de dados (SINAN, SITE TB e GAL) sendo cinco na Região Metropolitana I e um registro no Baixo Amazonas. Constatou-se a ocorrência frequente de inconformidade nos dados dos três principais Sistemas de registros de casos de tuberculose com destaque para a subnotificação que se configura como um desafio para a qualidade da informação no Brasil, em especial no Pará

The objective was to analyze the quality of information regarding drug-resistant tuber- culosis according to the official banks that store epidemiological and operational data on the disease. This is an epidemiological, descriptive research carried out with data from the Notifiable Diseases Information System (SINAN), the Laboratory Environment Management System (GAL) and the Tuberculosis Special Treatment Information Sys- tem (SITE-TB), obtained from the Pará State Department of Public Health, for the pe- riod 2016-2020. The analysis was performed using descriptive statistics, using the Rx64 4.0.0 program, through RStudio Desktop. A total of 889 records distributed in the three databases were analyzed, with a predominance of cases in the GAL (433), fol- lowed by the SITE-TB (350) and the SI-NAN (220). There was a predominance of rec- ords in the age group from 25 to 44 years and in males. The largest number of culture records for Myco-bacterium tuberculosis typing was identified in the GAL. Duplicate cases were identified, 121 in the GAL, 45 in the SITE-TB and 4 in the SINAN. Among the 433 cases registered in the GAL, five were also included in the SINAN and six were identified in the SINAN and SITE-TB. Of the 350 cases registered in SITE-TB, 242 were not included in the other databases and 97 were in SINAN. Regarding the 220 cases in SINAN, 154 were only included in it and six cases were in the three systems simultaneously. Regarding the distribution of records in the Health Regions of Pará, a higher proportion was identified in the GAL, in the Xingu region (98.5%) and in Metro- politana I (26%), with the other regions showing records below 10 cases. Regarding the data contained only in SINAN, Metropolitan I had 93 (18.8%) cases and in the other regions the records were less than 10. In SITE TB, Metropolitan I concentrated the highest frequency, with 174 (35.1%) cases, followed by the Metropolitan Region II, with 15 (71.4%). As for the concurrence of data in two systems, the Metropolitan region I was the only one that presented records (0.8%) in the GAL and SITE-TB. And it stands out in SINAN and SITE TB, with a higher frequency (18.3%), the other regions had a number of cases less than 10 or had no records. Six concurrent records were identified in the three databases (SINAN, SI-TE TB and GAL), five in Metropolitana I and one in Baixo Amazonas. The existence of underreporting in the systems is a challenge, as it raises questions about the quality of the data and, consequently, of the tuberculosis control actions

Scenario validation for clinical simulation: prenatal nursing consultation for adolescents.

OBJECTIVES: to validate a scenario for clinical simulation: prenatal nursing consultation for adolescents. METHODS: methodological study developed from January to December 2019, in five stages (overview, scenario, scenario design, progression, debriefing and assessment). The validation involved four volunteer students, a teacher as a facilitator and four judges. The judges filled out a Likert scale with four responses. Data was analyzed using Microsoft Excel® software, version 2016. Absolute and relative frequencies and the content validity index were calculated, considering a minimum acceptable value of 1.0. RESULTS: the preparation of the scenario was based on the proposed learning objectives. The scenario was validated with a global content validity index equal to 1.0. FINAL CONSIDERATIONS: the study achieved the proposed objective. This scenario can contribute to preparing nurses to work in the care of pregnant teenagers, a representative public in Brazil that requires specific care.

Saberes de adolescentes sobre saúde: implicações para o agir educativo / Adolescents knowledge about health: implications for educational action

Objetivo: Identificar os conteúdos que integram os saberes sobre saúde entre adolescentes do ensino médio. Método: Estudo descritivo, qualitativo, desenvolvido com 30 estudantes de ambos os sexos, na faixa etária de 14 a 19 anos, de uma escola pública no município de Benevides, Pará. Os dados foram produzidos utilizando-se a técnica de Grupo Focal e submetidos à análise de conteúdo temática. Resultados: A partir da análise, formaram-se duas linhas de organização dos temas que serviram de base para as categorias empíricas: 1º linha organizadora: "Dimensão saúde-família-comunidade" e 2º linha organizadora: "Assistência à Saúde". Assim, originaram-se três categorias temáticas: "O que pensam os adolescentes sobre a saúde", "A influência da família na saúde do adolescente" e "O adolescente e a busca pelo serviço de saúde". Conclusão: Os saberes sobre saúde estão imbricados no cuidado de si, importância do convívio familiar, concepções biomédicas da saúde e possibilidades de acesso ao serviço. Os jovens reconhecem a família como centro do cuidado e base para ter boa saúde, a partir do fortalecimento das relações de afeto e acolhimento. (AU)

Objective: To identify the contents that integrate health knowledge among High School adolescents. Method: Descriptive, qualitative study, developed with 30 students of both sexes, aged 14 to 19 years old, from a public school in the municipality of Benevides, Pará. Data were produced using the focus group technique and submitted by thematic content analysis. Results: From the analysis, two lines of organization of themes were formed, which served as a basis for the empirical categories: 1st organizing line: "Health-family-community dimension" and 2nd organizing line: "Health Care". Thus, three thematic categories emerged: "What do adolescents think about health", "The family's influence on adolescent health" and "Adolescent and the search for health service". Conclusion: Health knowledge is intertwined with self-care, the importance of family life, biomedical concepts of health and possibilities of access to the service. Young people recognize the family as the center of care and the basis for good health based on the strengthening of relationships of affection and welcome. (AU)

Objetivo: Identificar los contenidos que integran el conocimiento de la salud entre los adolescentes de enseñanza media. Método: Estudio descriptivo, cualitativo, desarrollado con 30 estudiantes de ambos sexos, de 14 a 19 años de edad, de una escuela pública en el municipio de Benevides, Pará. Los datos se produjeron utilizando la técnica de grupos focales y se presentaron Análisis de contenido temático. Resultados: A partir del análisis, se formaron dos líneas de organización de los temas, que sirvieron de base para las categorías empíricas: primera línea organizativa: "Dimensión salud-familia-comunidad" y segunda línea organizativa: "Atención sanitaria". Así, surgieron tres categorías temáticas: "¿Qué piensan los adolescentes sobre la salud?", "La influencia de la familia en la salud de los adolescentes" y "Adolescentes y la búsqueda de servicios de salud". Conclusión: El conocimiento de la salud se entrelaza con el autocuidado, la importancia de la vida familiar, los conceptos biomédicos de salud y las posibilidades de acceso al servicio. Los jóvenes reconocen a la familia como el centro de atención y la base de una buena salud basada en el fortalecimiento de las relaciones de afecto y acogida. (AU)

A Risk Assessment Framework Proposal Based on Bow-Tie Analysis for Medical Image Diagnosis Sharing within Telemedicine.

The purpose of this paper is to propose a framework for cybersecurity risk management in telemedicine. The framework, which uses a bow-tie approach for medical image diagnosis sharing, allows the identification, analysis, and assessment of risks, considering the ISO/TS 13131:2014 recommendations. The bow-tie method combines fault tree analysis (FTA) and event tree analysis (ETA). The literature review supported the identification of the main causes and forms of control associated with cybersecurity risks in telemedicine. The main finding of this paper is that it is possible, through a structured model, to manage risks and avoid losses for everyone involved in the process of exchanging medical image information through telemedicine services. Through the framework, those responsible for the telemedicine services can identify potential risks in cybersecurity and act preventively, recognizing the causes even as, in a mitigating way, identifying viable controls and prioritizing investments. Despite the existence of many studies on cybersecurity, the paper provides theoretical contributions to studies on cybersecurity risks and features a new methodological approach, which incorporates both causes and consequences of the incident scenario.

Ethanol Gestational Exposure Impairs Vascular Development and Endothelial Potential to Control BBB-Associated Astrocyte Function in the Developing Cerebral Cortex.

Ethanol consumption during pregnancy or lactation period can induce permanent damage to the development of the central nervous system (CNS), resulting in fetal alcohol spectrum disorders (FASD). CNS development depends on proper neural cells and blood vessel (BV) development and blood-brain barrier (BBB) establishment; however, little is known about how ethanol affects these events. Here, we investigated the impact of ethanol exposure to endothelial cells (ECs) function and to ECs interaction with astrocytes in the context of BBB establishment. Cerebral cortex of newborn mice exposed in utero to ethanol (FASD model) presented a hypervascularized phenotype, revealed by augmented vessel density, length, and branch points. Further, aberrant distribution of the tight junction ZO-1 protein along BVs and increased rates of perivascular astrocytic endfeet around BVs were observed. In vitro exposure of human brain microcapillary ECs (HBMEC) to ethanol significantly disrupted ZO-1 distribution, decreased Claudin-5 and GLUT-1 expression and impaired glucose uptake, and increased nitric oxide secretion. These events were accompanied by upregulation of angiogenesis-related secreted proteins by ECs in response to ethanol exposure. Treatment of cortical astrocytes with conditioned medium (CM) from ethanol exposed ECs, upregulated astrocyte's expression of GFAP, Cx43, and Lipocalin-2 genes, as well as the pro-inflammatory genes, IL-1beta, IL-6, and TNF-alpha, which was accompanied by NF-kappa B protein nuclear accumulation. Our findings suggest that ethanol triggers a dysfunctional phenotype in brain ECs, leading to impairment of cortical vascular network formation, and promotes ECs-induced astrocyte dysfunction, which could dramatically affect BBB establishment in the developing brain.

Rats recognize spatial and temporal attributes in a new object recognition memory task with multiple trials.

BACKGROUND: Episodic-like memory tasks based on the spontaneous exploration of objects are commonly applied in one-trial protocols. However, multiple-trial designs are known to reduce animal numbers and data variance, providing faster accumulation of data. NEW METHOD: In this study, we devised a new object recognition memory task for rats that carry out multiple trials per session. We developed three types of continual trial tasks: a longer protocol, a shorter protocol, and a protocol in which the experimental session was divided into two days. RESULTS: In our design, rats expressed temporal and spatial memory, but not what-where-when content integration. We found that shorter protocols were more efficient to evaluate memory capabilities. COMPARISON WITH EXISTING METHODS: To the best of our knowledge, it is the first object recognition task with multiple trials that simultaneously assess the temporal and spatial aspects of episodic-like memory. CONCLUSIONS: We suggest that our task is suitable for the simultaneous measurements of brain functions related to spatial and temporal attributes in rats.

Potential source of ecofriendly insecticides: Essential oil induces avoidance and cause lower impairment on the activity of a stingless bee than organosynthetic insecticides, in laboratory.

The negative effect of insecticides on bees has been reported as one of the factors associated with the decline in population of these pollinators. Thus, the aim of this study was to evaluate the response of the stingless bee Nannotrigona aff. testaceicornis (Lepeletier, 1836) to a promising source of new insecticide molecules obtained from Lippia sidoides (rosemary pepper) essential oil (EO) and its major compounds (thymol, ρ-cymene, and (E)-caryophyllene), comparing them to commercial insecticides (organosynthetic: imidacloprid, deltamethrin and semisynthetic: spinetoram). For this, stingless bees were exposed by contact with these compounds to evaluate the lethal and sublethal (locomotion and flight orientation) toxicity. The L. sidoides EO and its major compounds have low lethal toxicity to forager worker bees (N. aff. testaceicornis). The organosynthetics imidacloprid (LD50 =0.00146 µgbee-1) and deltamethrin (LD50 =0.0096 µg bee-1) were about 209,589 and 31,875 times more toxic, respectively, than the least toxic natural compound, (E)-caryophyllene (LD50 =306 µgbee-1). Locomotion ability and flight orientation were little affected by spinetoram and by L. sidoides EO and its major compounds, however, were greatly reduced by the imidacloprid and deltamethrin insecticides. Besides shows low lethal and sublethal toxicity, the bioinsecticides were also avoided by the forager bees. Individuals treated with the L. sidoides EO and thymol were avoided by the untreated bees. Therefore, the natural products studied here were promising due to their recognized effectiveness against pest insects and greater safety to bees N. aff. testaceicornis.

Wide field scanning by optical fluorescence of oral squamous cell carcinoma (SCC): case report / Fotoevidenciação de campo amplo por fluorescência óptica de carcinoma de células escamosas (CEC) oral: estudo de casos

ABSTRACT Optical fluorescence detection aims to identify precursor lesions, little noticeable to the human eye, and oral cancer. Squamous cell carcinoma or spinocellular carcinoma is a malignant neoplasm that affects the mouth more. In this article, two clinical cases are analyzed, treated with the use of two types of equipment, namely: the photoevidenciation by optical fluorescence of light-emitting violet wavelength of 405nm, power of 100mW, which is luminous radiation, not Ionizing and in the adjuvant treatment, we used low-power laser therapy, power 100mW, with two wavelengths of 808nm infrared, for pain relief, and the red 660nm, for oral mucositis. In Photodynamic therapy, the Photosensitizing Chimiolux® (methylene blue) was used to control Candida albicans. From these cases, we discuss how a more assertive diagnostic hypothesis can save a life and save time, resources, and efforts for the correct diagnosis of the pathology compared to a biopsy and histopathology negative for neoplasia. We conclude that optical fluorescence has excellent social relevance due to its potential to help the professional not specialized in the establishment of early diagnosis of oral cancer. Early diagnosis improves the rates of death caused by this carcinoma, which would extend the post-diagnosis survival and decrease the financial and emotional costs for the patient and family.

RESUMO A detecção óptica por fluorescência visa identificar lesões precursoras, pouco perceptíveis ao olho humano, e do câncer oral. O carcinoma de células escamosas ou carcinoma espinocelular (CEC), é a denominação de uma neoplasia maligna que acomete mais a boca. Neste artigo, são analisados dois casos clínicos, tratados com a utilização de dois equipamentos, a saber: o de fotoevidenciação por fluorescência óptica de emissão de luz violeta de comprimento de onda de 405nm, potência de 100mW, que é radiação luminosa não ionizante; e no tratamento coadjuvante, utilizou-se a laserterapia de baixa potência, potência 100mW, com dois comprimentos de onda de infravermelho 808nm, para alívio de dor, e o vermelho 660nm, para as mucosites orais. Na terapia fotodinâmica, empregou-se o fotossensibilizador Chimiolux® (azul de metileno) para controle de Candida albicans. A partir desses casos, discutimos como uma hipótese diagnóstica mais assertiva pode salvar uma vida e poupar tempo, recursos e esforços para o correto diagnóstico da patologia se comparado a uma biópsia e histopatológico negativo para neoplasia. Por fim, concluímos que a fluorescência óptica tem grande relevância social devido a seu potencial de auxiliar o profissional não especialista no estabelecimento de um diagnóstico precoce do câncer oral, melhorando os índices de óbito causados por esse carcinoma, o que estenderia a sobrevida pós-diagnóstico e diminuiria os custos financeiros e emocionais do paciente e familiares.

Clinical characterization and cross-mapping of the nursing interventions for hypothermia in the intraoperative period / Caracterización clínica y mapeo cruzado de las intervenciones de enfermería para hipotermia en el período intraoperatório / Caracterização clínica e mapeamento cruzado das intervenções de enfermagem para hipotermia no período intraoperatório

ABSTRACT Objectives: to map the Nursing prescriptions for patients with diagnoses related to hypothermia in the intraoperative period with the activities proposed by the Nursing Interventions Classification, and to characterize the sample based on the risk factors for the development of this discomfort. Method: a descriptive, documentary and retrospective study, with a quantitative approach that followed three stages: cataloging of the interventions, documentary analysis, and cross-mapping. The following variables were analyzed: patient's age and gender; surgery duration; minimum, mean and maximum temperatures, and variation of the surgery room and patient temperatures; and whether or not the type of surgery involved opening a body cavity, in a sample of 138 medical charts evaluated from August to September 2019 by using a checklist composed of identification data and diagnosis components from the NANDA-International diagnoses: risk of perioperative hypothermia and hypothermia. Absolute and percentage frequency analyses, mean, standard deviation, and the R software were employed. Results: 419 activities incorporated in 12 interventions were verified that were related to hypothermia in the corresponding taxonomy; as well as 13 Nursing care measures prescribed and five interventions mapped. The variables which reached significance were surgery duration and cavity opening. Conclusion: by means of cross-mapping, it can be asserted that the care measures prescribed are based on the standardized language, thus contributing to unification of the Nursing practice.

RESUMEN Objetivos: mapear las prescripciones de enfermería para pacientes con diagnósticos relacionados con hipotermia en el período intraoperatorio con las actividades propuestas por la Clasificación de Intervenciones de Enfermería y caracterizar la muestra sobre la base de los factores de riesgo para el desarrollo de este malestar. Método: estudio descriptivo, documental, retrospectivo con enfoque cuantitativo, realizado en tres etapas: catálogo de intervenciones, análisis documental y mapeo cruzado. Se evaluaron las siguientes variables: edad y sexo del paciente; tiempo de cirugía; temperatura mínima, media y máxima; variación de temperatura del quirófano y del paciente; tipo de cirugía que implique o no apertura de la cavidad corporal, en una muestra de 138 historias clínicas evaluadas de agosto a septiembre de 2019 por intermedio de un checklist compuesto por datos de identificación y componentes de los diagnósticos NANDA-International: riesgo de hipotermia e hipotermia perioperatoria. Se utilizaron análisis de frecuencias absolutas y porcentuales, media, desviación estándar y software R. Resultados: se incluyeron 419 actividades en 12 intervenciones relacionadas con la hipotermia en la taxonomía correspondiente; 13 cuidados de enfermería prescritos y cinco intervenciones mapeadas. Entre las variables, el tiempo de cirugía y la apertura de la cavidad fueron significativos. Conclusión: a través del mapeo cruzado, se puede afirmar que la atención prescrita se basa en un lenguaje estandarizado, que contribuye a la unificación de la práctica de enfermería.

RESUMO Objetivos: mapear as prescrições de enfermagem para pacientes com diagnósticos relacionados à hipotermia no período intraoperatório com as atividades propostas pela Classificação das Intervenções de Enfermagem e caracterizar a amostra a partir dos fatores de risco para o desenvolvimento desse desconforto. Método: estudo descritivo, do tipo documental, retrospectivo, com abordagem quantitativa, que seguiu três etapas: catalogação das intervenções, análise documental e mapeamento cruzado. Foram avaliadas as variáveis: idade e sexo do paciente; tempo de cirurgia; temperaturas mínima, média, máxima e variação da temperatura da sala de operação e do paciente; e tipo de cirurgia envolvendo abertura de cavidade corporal ou não, em uma amostra de 138 prontuários avaliados de agosto a setembro de 2019 através da utilização de um checklist composto por dados de identificação e componentes dos diagnósticos NANDA-International: risco de hipotermia perioperatória e hipotermia. Empregou-se análises de frequências absoluta e percentual, média, desvio padrão e software R. Resultados: verificou-se 419 atividades inseridas em 12 intervenções relacionadas à hipotermia na taxonomia correspondente; 13 cuidados de enfermagem prescritos e cinco intervenções mapeadas. Das variáveis, obtiveram significância o tempo da cirurgia e abertura da cavidade. Conclusão: por meio do mapeamento cruzado, pode se afirmar que os cuidados prescritos são embasados na linguagem padronizada contribuindo para a unificação da prática da enfermagem.

Impactos do estresse na exposição ocupacional de bombeiros: revisão integrativa / Impacts of stress on occupational exposure of firefighters: an integrative review / Impactos del estrés en la exposición ocupacional de los bomberos: una revisión integradora

Objetivo: identificar os impactos na saúde mental de bombeiros relacionados ao estresse da exposição ocupacional. Método: trata-se de uma revisão integrativa da literatura nas bases de dados CINAHL (EBSCO), PsycINFO, MEDLINE®, LILACS, Web of Science, Scopus e SCIELO. Para a estratégia de busca utilizou-se os descritores: "Occupational Stress", "Firefighters", "Occupational Exposure". Como critérios de inclusão estabeleceu-se: artigos originais; entre os anos de 2009 e 2019; disponíveis completos; estudos transversais; nos idiomas português, inglês e/ou espanhol; e cuja população de estudo incluíssem bombeiros. Resultados: nessa revisão foram analisados 11 artigos. Evidenciou-se que a exposição de bombeiros impactou o desencadeamento de sintomas de depressão e transtorno de estresse pós-traumático. Conclusão: as evidências deste estudo demonstraram que a exposição ocupacional de bombeiros interfere no seu padrão de saúde mental causando estresse por meio do sofrimento psíquico. Este estudo alerta para a necessidade de intervenção e promoção à saúde do bombeiro.

Objective: to identify mental health impacts of occupational exposure-related stress among firefighters. Method: this integrative literature review searched the CINAHL (EBSCO), PsycINFO, MEDLINE®, LILACS, Web of Science, Scopus and SCIELO databases, suing the descriptors: "Occupational Stress", "Firefighters", "Occupational Exposure". The inclusion criteria were: original articles; between the years 2009 and 2019; full text available; cross-sectional studies; in Portuguese, English and/or Spanish; and whose study population included firefighters. Results: 11 articles were analyzed. Firefighters' exposure was found to impact the triggering of depressive symptoms and post-traumatic stress disorder. Conclusion: the evidence in this study demonstrated that firefighters' occupational exposure interferes with their mental health patterns, causing stress through psychological suffering. This study warns of the need for intervention and promotion of firefighters' health.

Objetivo: identificar los impactos en la salud mental del estrés relacionado con la exposición ocupacional entre los bomberos. Método: esta revisión integradora de la literatura buscó en las bases de datos CINAHL (EBSCO), PsycINFO, MEDLINE®, LILACS, Web of Science, Scopus y SCIELO, demandando los descriptores: "Estrés ocupacional", "Bomberos", "Exposición ocupacional". Los criterios de inclusión fueron: artículos originales; entre los años 2009 y 2019; Texto completo disponible; estudios transversales; en portugués, inglés y / o español; y cuya población de estudio incluyó bomberos. Resultados: se analizaron 11 artículos. Se descubrió que la exposición de los bomberos afecta la activación de síntomas depresivos y el trastorno de estrés postraumático. Conclusión: la evidencia de este estudio demostró que la exposición ocupacional de los bomberos interfiere con sus patrones de salud mental, provocando estrés a través del sufrimiento psicológico. Este estudio advierte de la necesidad de intervención y promoción de la salud de los bomberos.