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There is an urgent need for drugs, therapies and vaccines to be available to protect the human population against COVID-19. One of the first approaches taken in the COVID-19 global response was to consider repurposing licensed drugs. This commentary highlights an extraordinary international collaborative effort of independent researchers who have recently all come to the same conclusion—that chloroquine or hydroxchloroquine are unlikely to provide clinical benefit against COVID-19.

Abstract This article analyzes sleeve connections between circular hollow sections. This type of connection is composed of two tubes connected by bolts to an inner tube with a smaller diameter, and explores the efficiency, aesthetics and resistance of hollow sections subjected to tension and compression. In previous researches, sleeve connections with aligned and crossed bolt dispositions and under axial tension were studied. Herein, the behavior of sleeve connections with aligned bolts and under compression was analyzed. A model to represent the connection using the finite element method was developed, which allowed a numerical analysis with geometric property variations. In the numerical/parametric results, bearing failure was observed in all cases, either in the outer or inner tube. Limiting the number of bolts to 6 and considering that connections have a lower outer thickness than the inner tube, a formulation was proposed to determine the ultimate bearing capacity of sleeve connections under compression and with bearing failure.

Abstract: Introduction: Population aging, longer life expectancy and the increase in the prevalence of chronic diseases have brought new health demands, among them, palliative care (PC). Although present in the clinical routine, this topic has not yet been included in most medical schools in Brazil. Objective: To know the teaching-learning process in PC according to the perception of medical students from schools that have this subject. Method: Qualitative method through interviews with 35 medical students from 14 medical schools located in the Northeast, Southeast and South regions of the country. Results: The reports were classified into three categories: conception of PC, changes perceived after exposure to PC teaching, challenges and successful strategies identified in PC teaching. Students recognize the value of teaching in PC and have a greater understanding of PC approach and its early indication for people with complex chronic conditions. The inclusion of the topic contributed to the overcoming of fears and taboos related to death, providing greater comfort to deal with human suffering, adding emotional skills. The formal education in PC allowed understanding the person in their biopsychosocial and spiritual dimension. They stressed the importance of communication skills to communicate difficult news, symptom management, teamwork and an individualized approach to the person and their family. Although they identify little theoretical-practical integration in the teaching-learning scenario in PC, they report an interest in the topic, and indicated successive experiences as strategies throughout the training, in a humanist axis. Conclusion: PC teaching brings contributions to medical training that go beyond the learning of the subject and reinforces the development of empathy and compassion, recognized as essential in this profession, as well as the relevance of assertiveness in the management of suffering and the comprehensive care of people with advanced diseases.

Brain abscess is a very rare condition but has a significant mortality rate. The three main routes of inoculation are trauma, contiguous focus, and the hematogenous route. The odontogenic focus is infrequent and is usually a diagnosis of exclusion. This paper presents a brain abscess case proven to be of dental origin, caused by Actinomyces meyeri and Fusobacterium nucleatum. This case highlights the risk underlying untreated dental disease and why oral infectious foci removal and good oral health are essential in primary care.

Introdução: As meningites relacionadas às neurocirurgias causadas por bactérias Gram-negativas (BGN), especialmente resistentes aos carbapenêmicos, são complicações com alta letalidade. O tratamento dessas infecções é complexo devido ao aumento da resistência aos antimicrobianos, associada à limitação de drogas que atinjam concentração adequada em sistema nervoso central. Objetivo: Descrever os aspectos epidemiológicos e avaliar a segurança do uso empírico do meropenem para o tratamento das meningites pós neurocirúrgicas causadas por bactérias Gram negativas e descrever a letalidade dessas infecções. Material e métodos: Este é um estudo prospectivo, realizado entre dezembro de 2013 a agosto de 2021, em um hospital especializado em neurocirurgia, com 37 leitos para pacientes adultos. Para o diagnóstico de meningites relacionadas às neurocirurgias foram utilizados os critérios da ANVISA. Resultados: Foram detectados 25 casos de meningite por BGN. A mediana de idade dos pacientes foi de 55 anos (22-75 anos), com ligeiro predomínio do sexo feminino (14/25). A principal patologia relacionada a esta complicação foi hemorragia subaracnóidea, ocorrida em 52% dos casos (13/25). Em 15 pacientes (60,0%) a meningite foi relacionada a um dispositivo ventricular. A terapêutica empírica inicial foi meropenem associado a vancomicina em 24 casos. Em 15 pacientes (62,5%) o espectro de ação deste tratamento foi adequado e neste grupo ocorreram quatro óbitos (26,6%). Em seis casos (25%) a terapêutica inicial foi inadequada e neste grupo houve quatro óbitos (66,7%). Conclusão: A literatura recomenda para o tratamento empírico das meningites relacionadas a neurocirurgia o uso de uma cefalosporina com ação anti pseudomonas ou meropenem associados com vancomicina. No entanto a emergência da resistência aos carbapênemicos torna o tratamento destas infecções desafiador. Na nossa casuística esse esquema foi inadequado em 37,5% dos casos (6/24) e neste grupo houve quatro óbitos . É necessário o desenvolvimento de novas opções terapêuticas com boa penetração em sistema nervoso central para o tratamento de infecções por Gram negativos.

Introdução: Meningite é a principal complicação infecciosa pós procedimentos neurocirúrgicos, causando até 91% de infecções nessa topografia, sendo responsável por elevada morbimortalidade. Objetivo: Descrever a epidemiologia, a taxa de mortalidade e o perfil microbiológico das meningites cirúrgicas de um hospital especializado em neurocirurgia no qual os pacientes que apresentam estas complicações são internados no centro de terapia intensiva. Material e métodos: Este foi um estudo prospectivo, observacional, realizado no período de dezembro de 2013 a agosto 2021. Foram utilizados os critérios da Agência Nacional de Vigilância Sanitária para o diagnóstico de meningite pós neurocirurgias. Resultados: Foram detectados 64 casos de meningites relacionadas a neurocirurgia. A mediana da idade dos pacientes foi de 62 anos (21 a 80 anos). Houve um predomínio do sexo feminino com 39 casos (60,9%). Hemorragia subaracnóidea foi a causa da abordagem cirúrgica em 25 pacientes (39,1%), seguida por tumor intracraniano (37,5%). A taxa de mortalidade foi de 29,7% (19/64). Foram identificados microrganismos em 36 casos (56,2%) e entre estes casos houve um predomínio de Gram negativos, 72,2% (26/36). Klebsiella pneumoniae e Acinetobacter spp. foram as principais bactérias identificadas, com 25% e 19,4% dos casos respectivamente. Ocorreram infecções também por Pseudomonas spp. (3) e Enterobacter spp. (2) entre outros. Entre os Gram negativos, 10 eram multirresistentes (38,4%) sendo sete resistentes aos carbapenêmicos. Entre estes casos a mortalidade foi de 71,4% (5/7). Conclusão: Tem sido descrito pela literatura um predomínio de Gram negativos nas meningites relacionadas à neurocirurgias e os nossos dados estão de acordo com essa tendência. A letalidade destas meningites é elevada, principalmente em um cenário de multirresistência.

Third-generation cephalosporins are widely used due to the convenient spectrum of activity, safety, and posology. However, they are associated with the emergence of multidrug-resistant organisms, which makes them important targets for antimicrobial stewardship interventions. We aimed to assess the appropriateness of empirical prescriptions of ceftriaxone in a tertiary hospital. This cross-sectional study analysed empirical ceftriaxone prescriptions in January and June 2021. Patients under other antimicrobials 48 h before admission were excluded. The quality of ceftriaxone prescription was assessed regarding the initial appropriateness, duration of inappropriate ceftriaxone therapy, and missed opportunities for de-escalation. Of 465 prescriptions, 46.5% were inappropriate. The ceftriaxone prescription was inappropriate in 95.7% of lower respiratory tract infections (LRTI) globally and in nearly 40% of urinary tract infections (UTI) in medical and intensive care departments. Intensive care, internal medicine, and palliative care departments showed the highest number of inappropriate ceftriaxone prescriptions and longer length of inappropriate ceftriaxone prescriptions compared to the hospital’s average. Improvement of empirical ceftriaxone prescription in LRTI and urinary infections, adherence to local guidelines and de-escalation practices, and targeted interventions focusing on critical departments may significantly reduce the inappropriate empirical use of ceftriaxone.

Introduction: Tuberculosis is a prevalent infection worldwide, especially in low-income countries. Its manifestations are diverse, and although pulmonary affection is the most common presentation, aortic involvement has been described. When present, such involvement can ultimately result in aortic aneurysm. Tuberculous aortic aneurysm (TAA) is a rare clinical entity with few cases described to date. We present a case of tuberculous lymphadenitis with pseudoaneurysm of the abdominal aorta in an otherwise healthy patient. Case description: A 24-year-old male patient from Punjab, India, living in Portugal for 3 months before seeking medical attention, presented at the emergency department with a 5-day history of lower quadrant abdominal pain, that worsened two days before. On physical examination, the patient was febrile and had infra-umbilical tenderness at abdominal palpation. Blood tests revealed microcytic anemia and elevated C-reactive protein. Abdominal ultrasound detected a mass adjacent to the lateral aspect of the distal abdominal aorta, further better characterized by computed tomography (CT) angiography as a saccular dilatation of the infra-renal aorta suggestive of a mycotic pseudoaneurysm.Transthoracic echocardiogram excluded endocarditis. The patient was admitted to the ward and started empiric broad spectrum antibiotics. A full body CT-scan showed a left supraclavicular lymph node with necrotic center, that was surgically excised and whose cultures grew Mycobacterium tuberculosis, with full susceptibility to first line tuberculostatic drugs. Surgery, with infra-renal aortic excision and aorto-aortic interposition with a silver-impregnated Dacron graft, was implemented along with anti-TB treatment. There are no reported complications at 6 months follow-up. Conclusion: TAA is a rare and potentially fatal disease that should be considered in diagnosis of mycotic aneurisms particularly in patients from high incidence setting. Such diagnosis requires exhaustive investigation, and its treatment can be complex, requiring a multidisciplinary approach. The combination of both a medical and surgical approaches is paramount for the successful treatment of such cases.

This article presents the weather and power data files from renewable sources used to solve the economic dispatch problem of a microgrid that operates in the isolated and grid-connected modes. Methodology is used in the research article “Management of an island and grid-connected microgrid using hybrid economic model predictive control with weather data” (Silva et al., 2020). Automatic stations located in the Brazil's south and northeast furnished the weather data (global horizontal irradiance, temperature, and wind speed). A script generates files containing weather forecasts from one-day ahead using the geographical coordinates of the weather stations. Hybrid models, characterized by real and binary variables, use the weather forecasting data to calculate the photovoltaic and wind power forecasts. A microgrid management algorithm uses these forecasts to solve the optimal economic dispatch problem. This data-in-brief paper presents five datasets for each weather station: (i) Weather dataset downloaded from the website of the National Meteorological Institute, (ii) Weather research and forecasting (WRF) dataset derived from the raw data generated by the weather research and forecasting model, (iii) Weather dataset that joins the forecasted data with the measured data in a single file, (iv) Handled dataset that treats some gaps in the weather dataset and converts it to other formats, (v) Files containing only the temperature, global horizontal irradiance, and wind speed data, (vi) Files containing the measured and forecasted wind and solar power.

ABSTRACT Weeds are one of the ecological factors that directly affect agricultural costs. Thus, understanding the emergence and development of these species is essential for the decision-making on weed control strategies. This study aims to evaluate the effect of different sowing depths and luminous intensities under field conditions on the emergence and development of the Acanthospermum australe (Loefl.) Kuntze and Ipomoea grandifolia (Dammer) O’Donell. Each species constituted one experiment, and the completely randomized design with four repetitions was adopted. The treatments were arranged in a 6 x 4 factorial scheme, with six sowing depths (0.5; 1.0; 2.0; 4.0; 8.0; and 12.0 cm) associated with four luminous intensities (100%, 70%, 50%, and 30% sunlight) obtained using shade cloths. The emergence of seedlings was evaluated daily to obtain the emergence and the emergence speed index. Plant height(length), the period until flower induction, and the dry matter of plants during flowering were also analyzed. A. australe and I. grandifolia emerge under the luminous intensities of 100, 70, 50, and 30% of solar radiation and in sowings depths up to 12.0 cm. Nevertheless, A. australe is the only one affected by luminous intensity, sowing depth, and the interaction between both factors in all the analyzes conducted. Luminous intensity reduction leads to lower development of I. grandifolia.

Human norovirus is the first cause of foodborne disease worldwide, leading to extensive outbreaks of acute gastroenteritis, and causing around 200,000 children to die annually in developing countries. No specific vaccines or antiviral agents are currently available, with therapeutic options limited to supportive care to prevent dehydration. The infection can become severe and lead to life-threatening complications in young children, the elderly and immunocompromised individuals, leading to a clear need for antiviral agents, to be used as treatments and as prophylactic measures in case of outbreaks. Due to the key role played by the viral RNA-dependent RNA polymerase (RdRp) in the virus life cycle, this enzyme is a promising target for antiviral drug discovery. In previous studies, following in silico investigations, we identified different small-molecule inhibitors of this enzyme. In this study, we rationally modified five identified scaffolds, to further explore structure–activity relationships, and to enhance binding to the RdRp. The newly designed compounds were synthesized according to multiple-step synthetic routes and evaluated for their inhibition of the enzyme in vitro. New inhibitors with low micromolar inhibitory activity of the RdRp were identified, which provide a promising basis for further hit-to-lead optimization.

The aim of this study was to verify the pattern and the spatial and temporal behavior of the corn earworm and corn-silk fly in the corn crop. Hybrid corn was planted without chemical insect control in one hectare, this area was divided into 100 plots of 100 m². For the occurrence of Euxesta spp. all parts of the plants were visually analyzed, whereas for Helicoverpa zea (Boddie) 10 ears were removed at random from each plot, totaling 1,000 ears per sample. Population fluctuation was related to the phenological stages of corn. For spatial behavior, the dispersion indices, frequency distribution models and geostatistics (Krigagem) were analyzed. The corn earworm (small and large) and corn-silk fly showed aggregate pattern and spatial behavior. The reach of caterpillars 1 cm, with spatial dependence being considered moderate. The corn-silk fly had a maximum area of influence of 1.33 ha with moderate and weak spatial dependence. The maps demonstrated that these insects occur dispersed throughout the corn area, but with aggregations influenced by the adjacent areas and edges of the crop. The largest occurrence of corn earworms was at the R3 stage. It was also found that the corn-silk fly followed the occurrence of the corn earworm. It is concluded that the studied pests have an aggregate spatial tendency in the corn crop and with the influence of adjacent areas, in addition to presenting related population peaks in the reproductive period of the corn crop.

Este trabalho tem por objetivo analisar a implementação do “Projeto A Hora é Agora” que desenvolveu, em 2015, diferentes estratégias para ampliar a testagem e tratamento do HIV para os homens que fazem sexo com homens residentes em Curitiba/PR. A análise partiu da perspectiva dos atores-chave envolvidos, utilizando uma abordagem qualitativa de investigação. A metodologia baseou-se em revisão documental, observações diretas, entrevistas semiestruturais e discussão em grupos focais. Os resultados centraram-se em quatro subcategorias de acesso: cobertura; adequação; qualidade e aceitabilidade. A melhoria da cobertura foi vista no aumento de pontos de testagem, na ampliação dos dias e horários da testagem e retirada de antirretrovirais. Na adequação, os preceitos dos direitos humanos foram refletidos no respeito à privacidade e na agilidade na marcação de consultas/exames. A qualidade indicou as barreiras enfrentadas, como estigma e discriminação por parte de alguns profissionais de saúde. Por fim, a aceitabilidade revelou como cada estratégia foi aceita pelos usuários. Conclui-se que o projeto foi uma intervenção bem-sucedida, ampliando a testagem e auxiliando os usuários a iniciarem o tratamento de HIV, incorporando novas tecnologias e abordagens no cuidado aos Homens que fazem Sexo com Homens.

Esse ensaio tem por objetivo principal refletir sobre a cultura midiática e o desenho animado “Bob Esponja” na infância contemporânea. De modo específico, analisar alguns episódios de Bob Esponja Calça Quadrada e as produções de sentido sobre a infância e suas representações e relações sociais. A proposta de estudo está relacionada ao Projeto de Pesquisa – “Semiformação e Educação no contexto da Sociedade Danificada: para além do território demarcado” da Universidade Estadual de Londrina. A metodologia é de cunho bibliográfico à luz dos fundamentos da Teoria Crítica e de autores que dialogam com essa base teórica. Nesse sentido, pela autorreflexão nos limiares de Adorno e Horkheimer, é possível analisar os efeitos da cultura midiática e do respectivo desenho no processo formativo e representativo da infância no cenário atual, bem como elevar o olhar para a possibilidade do uso do desenho animado em prol de uma cultura da infância mais crítica, diversificada, participativa e emancipatória.

O trabalho examinou a situação das diferenças de expectativas de auditoria após a revisão das normas internacionais, que culminaram na aplicação do formato atualizado do Relatório dos Auditores no Brasil, no ano de 2017. Questionários aplicados resultaram em 185 respostas válidas para análises. O nível de exigência dos usuários da contabilidade em relação aos deveres dos auditores, captado pela proxy Índice de Expectativa (IE), foi calculado com base na metodologia desenvolvida por Porter (1993) e adaptado por Litjens, Buuren & Vergoossen (2015), que abrange: i) gap de razoabilidade, (ii) gap de desempenho dos auditores e (iii) gap de padrões. O teste de Mann-Whitney revelou a perpetuação de evidências empíricas acerca das diferenças de expectativas documentadas nas últimas décadas. Assim, demonstrou-se que, mesmo analisando a percepção de auditores e usuários após a alteração da norma, que trouxe melhorias significativas ao relatório, diferenças de expectativas ainda podem ser detectadas. Testes adicionais indicaram que não foram encontradas diferenças significativas do índice de expectativas entre gêneros e diferentes níveis de utilização do relatório de auditoria.

O Estado de Roraima (RR) vem recebendo recursos do governo federal, mediante transferências para o Fundo Penitenciário, a fim de aprimorar sua política de segurança pública, todavia, a mesma vem sendo alvo constante de críticas, devido ao aumento de homicídios, às constantes fugas de presos e aos indícios de desvio de dinheiro público do Fundo Penitenciário. Objetivos: Este artigo tem, portanto, tem como objetivo geral demonstrar como o controle social e o gerenciamento de riscos podem otimizar a política de segurança pública do Estado de Roraima. Buscando alcançar esse objetivo, foram elaborados os seguintes objetivos específicos: identificar o papel do controle social nas políticas públicas e explanar sobre gerenciamento de riscos. Metodologia: este artigo foi realizado por meio da técnica de pesquisa bibliográfica sobre o tema controle social e gerenciamento de riscos. Também foi realizada pesquisa documental a partir da análise dos dados constantes do Relatório de Avaliação da Execução dos Programas de Governo: Programa Nacional de Apoio ao Sistema Prisional (PNASP), resultado de auditorias realizadas pela Controladoria-Geral da União (CGU), nos anos de 2013 a 2016. Com os dados do Relatório da CGU, aplicou-se a metodologia de gerenciamento de riscos, de acordo com a ABNT NBR ISO 31000:2009. Resultados: o controle social e a metodologia de gerenciamento de riscos da ISO 31000, a partir dos dados apresentados no Relatório de Avaliação do PNASP/DEPEN, elaborado pela CGU, poderia ter minimizado a probabilidade de ocorrência da Operação Gárgulas, que apura possíveis desvio de dinheiro público do Fundo Penitenciário. Estágio da Pesquisa: concluída.

Background: Soluble transferrin receptor (sTfR) is a biomarker of erythropoiesis, which is often impaired in dialysis patients. The aim of our study was to evaluate sTfR levels in chronically dialyzed patients and assess potential determinants of its levels. Methods: We performed a cross-sectional study by evaluating 246 end-stage renal disease patients undergoing dialysis and 32 healthy controls. Circulating levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, hepcidin, sTfR, growth differentiation factor 15 (GDF15), and traditional iron metabolism markers were measured, as well as hemogram parameters. Clinical data was obtained from all patients. Results: Compared to controls, patients presented similar values of sTfR, reticulocytes and reticulocyte production index (RPI), and significantly higher levels of IL-6, CRP, ferritin, hepcidin, TNF-α, and GDF15. Iron, transferrin, hemoglobin levels, erythrocyte count, mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) values were significantly lower in dialysis group. Within patients, sTfR values were higher in diabetic patients and were positively and significantly correlated with reticulocytes and erythrocytes, RPI, and therapeutic doses of erythropoiesis stimulating agents (ESA) and intravenous iron; and inversely and significantly correlated with circulating iron, ferritin, transferrin saturation, hepcidin, MCH, and MCHC. In multiple linear regression analysis, ESA dose, RPI, serum iron, diabetes, and hepcidin levels were independently associated with sTfR levels in dialysis patients and, thus, with erythropoiesis. Conclusion: Our data suggest that, besides RPI and ESA dose, diabetes and hepcidin are closely related to erythropoiesis in dialysis patients. The influence of diabetes on sTfR levels deserves further investigation.

The industrial processing of fruits in the Amazon region, such as tucuma, generates a large amount of coproducts with great nutritional potential. In this work, phenolic compounds from tucuma coproduct almonds were extracted and microencapsulated by spray drying using maltodextrin as the encapsulating agent and verified its antioxidant activity. Phenolic compounds were determined by UV spectroscopy and identified by Ultraefficiency Liquid Chromatography. Antioxidant activity was measured by ABTS and DPPH assay. Thermogravimetric techniques, infrared spectroscopy, scanning electron microscopy, moisture content and water activity were applied to characterize the microparticle. The crude extract and microparticle had total polyphenols of 135.1 mg/g ± 0.078 and 130.5 mg/g ± 0.024, respectively. Caffeic and gallic acids were identified. The crude extract and the microparticle showed good antioxidant activity by ABTS and DPPH assay, justified by the presence of the phenolic compounds found. The microparticle showed spherical and heterogeneous structures and good encapsulation efficiency from the spray drying process using maltodextrin. The results show that the extract of the tucuma almond coproduct can be used as a phenolic compound-rich source and microencapsulated with possible application for functional food production.

RESUMO: A adubação verde pode promover mudança na população de plantas espontâneas, principalmente por efeitos alelopáticos e por competição. O objetivo desse trabalho foi avaliar a influência do girassol semeado em diferentes espaçamentos, na ocorrência de plantas infestantes em área de preservação permanente. O experimento foi realizado em blocos casualizados, com três repetições para cada tratamento. Os tratamentos foram os diferentes espaçamentos entre linhas de plantio do girassol, sendo 0,75 m; 0,55 m e 0,30 m e 0,25 m, e testemunha. Foram realizadas três avaliações de identificação e coleta das planas infestantes, utilizando um quadro vazado de 0,5 m x 0,5 m e calculados os valores fitossociológicos de frequência, densidade e dominância relativa e índice de valor de importância. Na última avaliação foi determinada a massa seca e altura do girassol. A principal espécie infestante encontrada foi a Urochloa decumbens, apresentando os maiores valores para todos os parâmetros fitossociológicos avaliados. Houve redução na densidade de plantas infestantes com o aumento da densidade de girassol, podendo ser recomendado para recuperação de áreas degradadas. PALAVRAS-CHAVE: Adubação Verde, Fitossociologia, Helianthus annuus, Recuperação de áreas degradadas.

Background: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19. Methods: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole. Primary outcome was the cumulative score of the clinical status until day 15 based on the 7-point ordinal scale of the World Health Organization. In parallel, itraconazole was evaluated in a newly established hamster model of acute SARS-CoV-2 infection and transmission, as soon as the model was validated. Findings: In the hamster acute infection model, itraconazole did not reduce viral load in lungs, stools or ileum, despite adequate plasma and lung drug concentrations. In the transmission model, itraconazole failed to prevent viral transmission. The clinical trial was prematurely discontinued after evaluation of the preclinical studies and because an interim analysis showed no signal for a more favorable outcome with itraconazole: mean cumulative score of the clinical status 49 vs 47, ratio of geometric means 1.01 (95% CI 0.85 to 1.19) for itraconazole vs standard of care. Interpretation: Despite in vitro activity, itraconazole was not effective in a preclinical COVID-19 hamster model. This prompted the premature termination of the proof-of-concept clinical study.Funding: KU Leuven, Research Foundation - Flanders (FWO), Horizon 2020, Bill and Melinda Gates Foundation

Aim: This study aimed to evaluate how meta-analyses are conducted and reported in dentistry. Methods: We conducted a search to identify dentistry-related Systematic Reviews (SRs) indexed in PubMed in 2017 (from January 01 until December 31) and published in the English language. We included only SRs reporting at least one meta-analysis. The study selection followed the 4-phase flow set forth in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), and it was independently conducted by two researchers. Data extraction was performed by one of three reviewers, and data related to conducting and reporting of the meta-analysis were collected. Descriptive data analysis was performed summarizing frequencies for categorical items or median and interquartile range for continuous data. Results: We included 214 SRs with meta-analyses. Most of the studies reported in the title that a meta-analysis was conducted. We identified three critical flaws in the included studies: Ninety (90) meta-analyses (43.1%) did not specify the primary outcome; most of the meta-analyses reported that a measure of statistical heterogeneity was used to justify the use of a fixed-effect or random-effects meta-analysis model (n=114, 58.5%); and a great part did not assess publication bias (n=106, 49.5%). Conclusion: We identified deficiencies in the reporting and conduct of meta-analysis in dentistry, suggesting that there is room for improvement. Educational approaches are necessary to improve the quality of such analyses and to avoid biased and imprecise results.

Com a cultura e a prática dos Direitos Humanos no campo educacional, pretende-se abrir espaços para o diálogo, a crítica, a tolerância, a compreensão e o respeito ao outro, contribuindo para a democratização e alteridade na escola. Busca-se ainda oportunizar a formação de sujeitos autônomos, conscientes dos seus direitos e deveres, preparados para o pleno exercício da cidadania. Nesse sentido, a questão de fundo que orienta a presente pesquisa é: como os estudantes do ensino médio representam os Direitos Humanos e como estão assimilando seus direitos e deveres, na vida e na escola? A presente investigação encontra-se referenciada no método de análise das representações sociais, sistematizado por Moscovici (2003), Jodelet (2001) e colaboradores, que se baseia na análise das práticas discursivas dos participantes, estudantes do ensino médio, de uma escola pública. As entrevistas foram gravadas, transcritas e sistematizadas por meio do procedimento de análise de conteúdo (BARDIN, 1979), obtendo-se assim, 10 categorias temáticas que foram analisadas e discutidas. Em conclusão tem-se que há uma problemática relacionada ao ensino de Direitos Humanos na Escola, que vem como um desafio para educadores e pesquisadores, que tem a missão de elaborar estratégias e métodos capazes de gerar conscientização e mudança de realidade.

Este artigo discute e desdobra questões centrais do curso de Gilbert Simondon sobre a comunicação, ministrado entre os anos de 1970 e 1971 e publicado apenas em 2010. Entende-se que o filósofo francês, que tem recebido crescente aclamação póstuma, propõe uma teoria da comunicação original, ainda por ser assimilada em nossa área. Como parte de um esforço de reconstruir essa teoria, este texto apresenta os principais argumentos de Simondon no curso de 1970-71 e, a partir de uma confrontação com a teoria da informação, defende a significação como conceito-chave para uma comunicação orientada no sentido de uma ciência das transformações.

This paper discusses and unfolds the main topics of Gilbert Simondon’s course on communication, lectured between 1970 and 1971 but published only in 2010. We believe that the French philosopher, who has been receiving a growing posthumous acclaim, brings forth an original theory of communication, still to be assimilated by our field. As a step towards rebuilding such theory, this text presents the main arguments from Simondon’s course and, confronting them with information theory, defends signification as a key concept for understanding communication as a science of transformations.

Objetivo: analisar a relação entre as intervenções realizadas durante o trabalho de parto e a duração da fase ativa em parturientes internadas. Método: estudo documental, tipo levantamento de dados, com abordagem quantitativa, realizado em uma maternidade no Pará, Brasil. A análise dos dados ocorreu por meio de estatística descritiva. Resultados: identificadas as intervenções: amniotomia (6,1%), ocitocina (64,2%) e episiotomia (16,7%). A relação das intervenções com a duração da fase ativa do trabalho de parto ocorreu com maior frequência em mulheres com menos de 5 horas na fase ativa. Conclusão: as intervenções realizadas em partos de risco habitual e no período de fase ativa menor que 5 horas não encontraram sustentação teórica e remeteram ao modelo biomédico.Descritores: Enfermagem Obstétrica. Parto Normal. Trabalho de Parto. Obstetrícia.

Ceftazidime/avibactam combines ceftazidime with a new beta-lactam that successfully that inhibits Amber Class A and D carbapenemases.We report a clinical case of a 61 year-old man with a carbapenemase-producing Klebsiella pneumoniae intra-abdominal infection after an elective abdominal hernia repair. The infection was successfully managed with multiple abdominal surgeries, drainage and combined antibiotic therapy with ceftazidime/avibactam plus tigecycline.

Khat (Catha edulis) is a recreational, chewed herbal drug that has been used as a psychostimulant for centuries in East Africa and the Arabian Peninsula, namely in Somalia, Ethiopia, and Yemen. However, the growing worldwide availability of khat has produced widespread concern. The plant comprises a large number of active substances, among which cathinone, cathine, and norephedrine are the main constituents, which can be included in the group of sympathomimetics of natural origin. In fact, these compounds are amphetamine analogues, and, as such, they have amphetamine-like nervous system stimulant effects. Chewing the leaves gives people a sensation of well-being and increases energy, alertness, and self-confidence. The chronic use of khat is, however, associated with severe cardiac, neurological, psychological, and gastrointestinal complications. The psychological dependence and withdrawal symptoms of khat are the reasons for its prolonged use. The aim of this paper is to review current knowledge on the khat plant with toxicokinetic and toxicodynamic perspectives. Namely, this review paper addresses in vitro, in vivo, and human studies. The models used, as well as the concentrations and doses with the respective biological effects, are discussed. Additionally, the main drug interactions involved with khat are described.

Neste trabalho estudou-se o corante da polpa de pitaya em pó e seu comportamento higroscópico. A pitaya é um fruto nutritivo com baixo valor calórico e alto poder antioxidante devido à presença de betalaínas, pigmentos nitrogenados e hidrossolúveis semelhantes ao grupo das antocianinas e flavonóides, com estruturas químicas diferentes. Os experimentos foram realizados adicionando maltodextrina no corante de pitaya nas proporções de 10, 20, 30, 40, 50 e 100%, visando aumentar a quantidade de sólidos no corante e analisando-se também o corante em pó puro. Em todas as amostras foi realizado o processo de branqueamento e, em seguida, a liofilização por 48 horas, aumentando, assim, a estabilidade por meio da redução da atividade de água, de modo a minimizar reações químicas enzimáticas que ocorrem durante a armazenagem do material, contribuindo para o acréscimo da vida útil do produto. Portanto, por meio da construção de isotermas de adsorção e dessorção de umidade a 25 °C em diferentes concentrações de maltodextrina analisou-se a higroscopicidade do corante de pitaya, assim como, a aplicabilidade de modelos matemáticos na predição das isotermas do produto. As isotermas obtidas foram sigmoidais, classificadas como do tipo II e o modelo de GAB mostrou-se mais adequado para ser utilizado na predição das isotermas de sorção do corante.

O objetivo do artigo foi descrever a técnica de confecção de uma moldeira individual para moldagem de preparo total para coroa, também conhecida como casquete de moldagem, além de discutir fatores e princípios envolvidos no tema. Na presente técnica, é obtido um modelo de gesso da região do preparo e um alívio em cera é realizado em suas paredes axiais. Após a aplicação de um isolante, o casquete é confeccionado utilizando pó e líquido de resina acrílica ativada quimicamente indicada para confecção de restaurações provisórias. A resina acrílica é aplicada na região cervical utilizando um pincel, e em seguida, o restante do preparo é preenchido. Após finalizado o corpo do casquete, a área de retenção é criada (chapéu do casquete), a face vestibular é demarcada, e realizado acabamento e polimento.

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The purpose of this in vitro study was to evaluate the external marginal gap variation with a 3D quantitative method and the residual fracture resistance after cyclic fatigue in endodontically treated molars restored with overlays of different materials, with and without fiber posts-supported buildups. Forty-eight human maxillary molars were selected, endodontically treated, prepared with standardized MOD cavities and randomly allocated into 6 study groups considering the “core strategy” (build-up with composite resin; build-up with composite resin supported by a fiber post); and the “restorative material” of the indirect adhesive overlay (GrandioBlocks, Voco; Cerasmart, GC; CeltraDuo, Dentsply). All procedures were executed according with manufacturers guidelines. Micro-CT analysis prior and after cyclic fatigue were executed, followed by scanning electron microscope analysis and fracture resistance test. The Two-Way ANOVA analysis showed that interfacial gap progression was significantly influenced by the “core strategy” (p < 0.01) but not of “restorative material” (p = 0.59). Concerning fracture resistance, “restorative material” was statistically significant (p < 0.01), while “core strategy” (p = 0.63) and the interaction (p = 0.84) were not. In conclusion, the fiber post presence within the build-up promoted a lower interfacial gap opening after fatigue, evaluated through micro-CT scans. In terms of fracture resistance, teeth restored with Cerasmart and Celtra Duo were statistically similar, but superior to GrandioBlocks.

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting annually in ~219,000 deaths and a societal cost of ~USD 60 billion, and no antivirals or vaccines are available. Here, we assess the anti-norovirus activity of new peptidomimetic aldehydes related to the protease inhibitor rupintrivir. The early hit compound 4 inhibited the replication of murine norovirus (MNV) and the HuNoV GI.1 replicon in vitro (EC50 ~1 µM) and swiftly cleared the HuNoV GI.1 replicon from the cells. Compound 4 still inhibits the proteolytic activity. We selected a resistant GI.1 replicon, with a mutation (I109V) in a highly conserved region of the viral protease, conferring a low yield of resistance against compound 4 and rupintrivir. After testing new derivatives, compound 10d was the most potent (EC50 nanomolar range). Molecular docking indicated that the aldehyde group of compounds 4 and 10d bind with Cys139 in the HuNoV 3CL protease by a covalent linkage. Finally, compound 10d inhibited the replication of HuNoV GII.4 in infected zebrafish larvae, and PK studies in mice showed an adequate profile.

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting in ~219,000 deaths annually and a societal cost of ~USD60 billion. There are no antivirals or vaccines available to treat and/or prevent HuNoV. In this study, we performed a large-scale phenotypical antiviral screening using the mouse norovirus (MNV), which included ~1000 drug-like small molecules from the Drug Design and Synthesis Centre (Sapienza University, Rome). Compound 3-((3,5-dimethylphenyl)sulfonyl)-5-chloroindole-N-(phenylmethanol-4-yl)-2.carboxamide (compound 1) was identified as an inhibitor of MNV replication with an EC50 of 0.5 ± 0.1 µM. A series of 10 analogs were synthesized of which compound 6 showed an improved potency/selectivity (EC50 0.2 ± 0.1 µM) against MNV; good activity was also observed against the HuNoV GI replicon (EC50 1.2 ± 0.6 µM). Time-of-drug-addition studies revealed that analog 6 acts at a time point that coincides with the onset of viral RNA replication. After six months of selective pressure, two compound 6res variants were independently selected, both harboring one mutation in VPg and three mutations in the RdRp. After reverse engineering S131T and Y154F as single mutations into the MNV backbone, we did not find a markedly compound 6res phenotype. In this study, we present a class of novel norovirus inhibitors with a high barrier to resistance and in vitro antiviral activity.

Human norovirus is the leading cause of acute gastroenteritis worldwide, affecting every year 685 million people. Norovirus outbreaks are associated with very significant economic losses, with an estimated societal cost of 60 billion USD per year. Despite this, no therapeutic options or vaccines are currently available to treat or prevent this infection. An antiviral therapy that can be used as treatment and as a prophylactic measure in the case of outbreaks is urgently needed. We previously described the computer-aided design and synthesis of novel small-molecule agents able to inhibit the replication of human norovirus in cell-based systems. These compounds are non-nucleoside inhibitors of the viral polymerase and are characterized by a terminal para-substituted phenyl group connected to a central phenyl ring by an amide-thioamide linker, and a terminal thiophene ring. Here we describe new modifications of these scaffolds focused on exploring the role of the substituent at the para position of the terminal phenyl ring and on removing the thioamide portion of the amide-thioamide linker, to further explore structure-activity relationships (SARs) and improve antiviral properties. According to three to four-step synthetic routes, we prepared thirty novel compounds, which were then evaluated against the replication of both murine (MNV) and human (HuNoV) norovirus in cells. Derivatives in which the terminal phenyl group has been replaced by an unsubstituted benzoxazole or indole, and the thioamide component of the amide-thioamide linker has been removed, showed promising results in inhibiting HuNoV replication at low micromolar concentrations. Particularly, compound 28 was found to have an EC50 against HuNoV of 0.9 µM. Although the most active novel derivatives were also associated with an increased cytotoxicity in the human cell line, these compounds represent a very promising starting point for the development of new analogues with reduced cytotoxicity and improved selectivity indexes. In addition, the experimental biological data have been used to create an initial 3D quantitative structure-activity relationship model, which could be used to guide the future design of novel potential anti-norovirus agents.

Acute gastroenteritis caused by virus has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The main culprits are rotaviruses, noroviruses, sapoviruses, astroviruses, and enteric adenoviruses. Currently, there are no antiviral drugs available for the prevention or treatment of viral gastroenteritis. Here, we describe the antivirals that were identified as having in vitro and/or in vivo activity against these viruses, originating from in silico design or library screening, natural sources or being repurposed drugs. We also highlight recent advances in model systems available for this (hard to cultivate) group of viruses, such as organoid technologies, and that will facilitate antiviral studies as well as fill some of current knowledge gaps that hamper the development of highly efficient therapies against gastroenteric viruses.

O presente estudo trata-se de uma revisão integrativa que objetivou buscar na literatura o que se tem em pesquisas realizadas sobre as boas práticas no trabalho de parto e parto.O levantamento de dados foi realizado nas bases LILACS e BDENF utilizando-se os descritores dor, parto, método e alivio, foram selecionados 10 artigos que evidenciaram como principais práticas a serem incentivadas, banho quente, escolha de posições verticalizadas, a presença de um acompanhante de escolha da mulher e a episiotomia e amniotomia de rotina com o práticas a serem desencorajadas. Concluiu-seque as boas práticas no trabalho de parto e parto são eficazes e garantem a satisfação da mulher e a humanização na assistência.

Human noroviruses (HuNoVs) are the most common cause of foodborne illness, with a societal cost of $60 billion and 219,000 deaths/year. The lack of robust small animal models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; replication peaks at day 2 post infection and is detectable for at least 6 days. The virus (HuNoV GII.4) could be passaged from larva to larva two consecutive times. HuNoV is detected in cells of the hematopoietic lineage and the intestine, supporting the notion of a dual tropism. Antiviral treatment reduces HuNoV replication by >2 log10, showing that this model is suited for antiviral studies. Zebrafish larvae constitute a simple and robust replication model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.

A liberação de diversos tipos de nanopartículas no ambiente aquático pode resultar na exposição direta ou indireta do homem e de organismos aquáticos, ou impactos no comportamento de metais. A ausência de legislação ambiental específica para o descarte de rejeitos oriundos de atividades que utilizam nanopartículas, como centros de pesquisa, serviços de medicina nuclear e a indústria, tem contribuído para a liberação descontrolada desses materiais no meio ambiente tornando-os relevantes dentro do contexto ecotoxicológico. Neste estudo, nanopartículas (nanohidroxiapatita e ácido D, L-láctico-co-glicólico - PLGA) com uso promissor pela medicina nuclear foram avaliadas por ensaios em microcosmos, reproduzindo-se as condições do Canal do Cunha (RJ), sistema aquático costeiro, impactado por rejeitos industriais, domésticos e hospitalar, com elevados teores em metais e materiais orgânicos, já reportados na literatura. Os resultados deste estudo não identificaram impactos dos diferentes nanomateriais no comportamento de metais dissolvidos (Cu, Mn e Zn), na concentração testada, provavelmente devido ao desenvolvimento de uma emulsão bacteriana nos microcosmos, que promoviam flutuações atípicas na concentração dos metais dissolvidos, principalmente Cu e Zn. Estudos similares com nanomateriais em concentrações superiores às testadas são indicados para corpos d´água em nível avançado de degradação qualitativa.

Objetivo: identificar e avaliar a adesão ao Procedimento Operacional Padrão referente à identificação dos pacientes vigente na Instituição. Método: pesquisa quantitativa, descritiva, composta de 45 pacientes selecionados intencionalmente. A coleta de dados ocorreu por método observacional, por meio de formulário estruturado, com dados referentes à utilização das pulseiras de identificação nas clínicas médicas de um hospital universitário. Para análise, foi utilizada estatística descritiva com frequências absolutas e relativas. Resultados: 82% dos pacientes encontravam-se com a pulseira corretamente e 18% dos pacientes estavam sem a pulseira. Quanto à conservação, 40% estavam em bom estado 22% em regular estado e 38% em péssimo estado. Conclusão: o estudo mostrou inconformidades no processo de identificação do paciente e contribuiu ao identificar elementos no uso de pulseiras que podem ser aprimorados para o seguro processo de identificação. Descritores: Sistemas de identificação de pacientes; Segurança do paciente; Enfermagem. ABSTRACT Objective: to identify and evaluate the adherence to the Standard Operating Procedure regarding the identification of patients in the Institution. Method: quantitative, descriptive research, consisting of 45 patients intentionally selected. The data collection was performed by observational method, using a structured form, with data referring to the use of identification wristbands in the medical clinics of a university hospital. For analysis, descriptive statistics were used with absolute and relative frequency. Results: 82% of the patients found the bracelet correctly and 18% of the patients were without the bracelet. As for conservation, 40% were in good condition 22% in regular state and 38% in poor condition. Conclusion: the study showed nonconformities in the patient identification process and contributed by identifying elements in the use of bracelets that can be improved for the safe identification process. Descriptors: Patient identification systems; Patient safety; Nursing.

Objetivo: Caracterizar as intoxicações agudas humanas registradas em hospitais de São Luís/MA, no ano de 2011. Método: Trata-se de um estudo retrospectivo, transversal, observacional e descritivo, realizado através da análise de prontuários. As variáveis analisadas foram: agente tóxico, sexo, idade, circunstância e evolução do caso. Resultados: Foram registrados 468 casos de intoxicações agudas em São Luís/MA no ano de 2011. A idade média dos indivíduos foi 24,7 ± 17,3 anos. Os agentes tóxicos mais envolvidos foram as drogas de abuso (30,13%; n=141), os medicamentos (22,65%; n=106) e os alimentos (8,33%; n=39). O sexo feminino foi o mais acometido (51,49%; n=241). As circunstâncias mais comumente associadas foram o abuso de drogas (29,27%; n=137), a circunstância ignorada (17,52%; n=82) e os acidentes com animais peçonhentos (12,39%; n=58). A maioria dos casos evoluiu para cura/alta do paciente (93,30%; n=434) e quatro casos (0,78%) resultaram em óbito. Conclusão: A cidade de São Luís/MA apresenta um perfil próprio e divergente dos perfis nacional e regional em relação às variáveis investigadas. O sistema de registro das intoxicações em São Luís/MA mostrou-se deficiente, especialmente em relação à descrição de informações acerca do histórico dos casos, o que contribui para registros incompletos e prejuízo para o conhecimento do real perfil das intoxicações no Estado do Maranhão.