Abstract In Argentina, few cost studies evaluate the impacts of irrigation on wine-growing productivity, quality and profitability. Even less relating volume, price and costs of the winegrower. This article analyzes the Cost-Volume-Profit ratio in the production of Torrontés Riojano grapes under controlled deficit irrigation (IDC) at 50% from veraison to harvest. In the Antinaco Valley - Los Colorados, La Rioja, Argentina we evaluate variations in the volume of production and quality of the grapes. Then, we determine the break-even point, margin of safety, operating leverage and perform a sensitivity study on sale prices. The results show that the IDC per hectare reduced the kilos of grapes harvested and the total costs. But, unit costs grew, negatively affecting break-even levels, security and operating leverage. The oenological quality of the grape improved, but the market maintained fixed prices. It is concluded that the IDC contributes to water savings, improves grape quality, but not profitability per hectare. This opens the discussion on profitability as an incentive to expand the cultivated area, saving water, without harming the quality of the grapes in the provincial wine sector. JEL: M41.

Resumen En Argentina, pocos estudios de costos evalúan los impactos del riego en la productividad, calidad y rentabilidad vitícola. Menos aún relacionando volumen, precio y costos del viticultor. Este artículo analiza la relación costo-volumen-utilidad en la producción de uva Torrontés Riojano bajo riego deficitario controlado (RDC) al 50% desde enero hasta la cosecha. En el Valle de Antinaco - Los Colorados, La Rioja, Argentina evaluamos variaciones del volumen de producción y calidad de las uvas. Luego, determinamos el punto de equilibrio, margen de seguridad, apalancamiento operativo y realizamos un estudio de sensibilidad sobre precios de venta. Los resultados muestran que el RDC por hectárea redujo los kilos de uva cosechados y los costos totales. Pero, los costos unitarios crecieron, afectando negativamente los niveles de equilibrio, seguridad y el apalancamiento operativo. La calidad enológica de la uva mejoró, pero el mercado mantuvo los precios fijos. Se concluye que el RDC contribuye al ahorro de agua, mejora la calidad de la uva, pero no la rentabilidad por hectárea. Así se abre la discusión sobre la rentabilidad como incentivo para expandir la superficie cultivada, economizando agua, sin perjudicar la calidad de las uvas en el sector vitícola provincial. JEL: M41.

Résumé En Argentine, peu d’études sur les coûts évaluent les impacts de l’irrigation sur la productivité, la qualité et la rentabilité du vin. Encore moins en ce qui concerne le volume, le prix et les coûts du vigneron. Cet article analyse le rapport Coût-Volume-Utilité dans la production de raisins Torrontés Riojano sous irrigation déficitaire contrôlée (IDC) à 50% de la véraison à la récolte. Dans la vallée d’Antinaco - Los Colorados, La Rioja, Argentine, nous avons évalué les variations du volume de production et de la qualité des raisins. Ensuite, nous déterminons le pont mort, la marge de sécurité, le levier d’exploitation et réalisons une étude de sensibilité sur les prix de vente. Les résultats montrent que le IDC par hectare a réduit les kilos de raisins récoltés et les coûts totaux. Toutefois, les coûts unitaires ont augmenté, ce qui a eu un impact négatif sur le niveaux d’équilibre, la sécurité et le levier d’exploitation. La qualité œnologique des raisins s’est améliorée, mais le marché a maintenu les prix fixes. On en conclut que le IDC contribue aux économies d’eau, améliore la qualité des raisins, mais pas la rentabilité à l’hectare. Cela ouvre la discussion sur la rentabilité en tant qu’incitation à étendre la surface cultivée, en économisant l’eau, sans nuire à la qualité des raisins dans le secteur viticole provincial. JEL: M41.

Resumo Na Argentina, poucos estudos de custo avaliam os impactos da irrigação na produtividade, qualidade e rentabilidade do vinho. Menos ainda quando se trata do volume, preço e custos do viticultor. Este artigo analisa a relação Custo-Volume-Utilidade na produção de uvas Torrontés Riojano irrigadas por déficit controlado (RDC) a 50% do período de colheita até a colheita. No Vale Antinaco - Los Colorados, La Rioja, Argentina, avaliamos variações no volume de produção e qualidade das uvas. Em seguida, determinamos o ponto de equilíbrio, margem de segurança, alavancagem operacional e realizamos um estudo de sensibilidade sobre os preços de venda. Os resultados mostram que a RDC por hectare reduziu os quilos de uvas colhidas e os custos totais. Mas, os custos unitários cresceram, afetando negativamente os níveis de equilíbrio, a segurança e a alavancagem operacional. A qualidade enológica das uvas melhorou, mas o mercado manteve os preços fixos. Conclui-se que a RDC contribui para a economia de água, melhora a qualidade da uva, mas não a rentabilidade por hectare. Isso abre a discussão sobre a rentabilidade como incentivo à expansão da área cultivada, economizando água, sem prejudicar a qualidade das uvas no setor vitivinícola provincial. JEL: M41.

ABSTRACT Introduction: Medical Residency (MR) is considered, both academically and professionally, the gold standard method in teaching university graduates. The Integrated Residency Program in Family and Community Medicine (PIRMFC) in Fortaleza-CE brings together the programs of Universidade Federal do Ceará, the School of Public Health of Ceará and the City Hall of Fortaleza and is the first of its kind on a large scale, with about 70 residents in the first edition, implemented in a capital city, concomitantly with the process of implementation of the Family Health Strategy (ESF) service network by the City Hall. Objective: To evaluate an Integrated Residency Program in Family and Community Medicine, from the perspective of resident doctors. Method: This is an exploratory study, with a qualitative approach, using the Kirkpatrick model in its first level, reaction and satisfaction of residents. Data collection was carried out with the participation of 18 residents (R2) in five Focus Groups, in the second half of 2020. Questionnaires with closed questions were also applied to characterize the sample, followed by multiple-choice questions graded on a Likert scale. The qualitative data were analyzed by the Thematic Analysis technique and quantitative data through simple frequency and percentage. Results: The following main categories were identified: Teaching-learning strategies, Evaluation of the teaching-learning process, Production of autonomy, Transfer of training into practice, Weaknesses and Potentialities of the residency. Residents understand the responsibility they have in daily medical care, even if they are apprentices. They felt insecure as training subjects, feeling more comfortable when they are placed in the passive role. On the other hand, the program students recognize the active teaching-learning methodology as adequate for teaching adults but need strategies to be used to solve common problems in their professional practice. Conclusion: The Program was not able to establish the basis for the engagement of residents in some simulated active teaching-learning strategies, such as Tutorial Groups. It is necessary to value the experiences and competences heterogeneously acquired by the residents to constitute moments of equalization of learning, seeking the student’s protagonism instead of the imposition of knowledge. Introduction MR (MR considered professionally graduates PIRMFC (PIRMFC FortalezaCE CE scale 7 edition city ESF (ESF Objective doctors Method study approach level 1 R2 R (R2 Groups 2020 sample multiplechoice multiple choice percentage Results identified Teachinglearning Teaching learning teachinglearning autonomy practice residency care apprentices subjects role hand Conclusion student s knowledge (R 202 20 2

RESUMO Introdução: A residência médica (RM) é considerada acadêmica e profissionalmente o método padrão ouro no ensino de médicos egressos da universidade. O Programa Integrado de Residência em Medicina de Família e Comunidade (PIRMFC) de Fortaleza, no Ceará, reúne os programas da Universidade Federal do Ceará, da Escola de Saúde Pública do Ceará e da prefeitura, e é o primeiro do gênero em larga escala, contando com cerca de 70 residentes na primeira edição, implantado em uma capital, paralelamente ao processo de implantação da rede de serviços da Estratégia Saúde da Família (ESF) pela prefeitura. Objetivo: Este estudo teve como objetivo avaliar um PIRMFC a partir da ótica dos residentes. Método: Trata-se de uma pesquisa exploratória, com abordagem qualitativa, utilizando o modelo de Kirkpatrick no seu primeiro nível: reação e satisfação dos residentes. A coleta de dados foi realizada com a participação de 18 residentes (R2) em cinco grupos focais, no segundo semestre de 2020. Aplicaram-se também questionários com perguntas fechadas para caracterização da amostra, seguidas de questões de múltipla escolha graduadas em escala Likert. Os dados qualitativos foram examinados pela técnica de análise temática, e os quantitativos, por meio de frequências simples e percentuais. Resultado: Identificaram-se as seguintes categorias principais: estratégias de ensino-aprendizagem, avaliação do processo ensino-aprendizagem, produção de autonomia, transferência da formação para a prática, fragilidades e potencialidades da residência. Os residentes compreendem a responsabilidade que têm no atendimento médico diário, ainda que como aprendizes. Eles demonstram insegurança como sujeitos da formação, sentindo-se mais confortáveis quando são colocados no papel passivo. Contudo, os discentes do programa reconhecem a metodologia ativa de ensino-aprendizagem como adequada para o ensino de adultos, mas precisam que as estratégias estejam voltadas para a resolução de problemas comuns à prática profissional deles. Conclusão: O programa não conseguiu firmar bases para o engajamento dos residentes em algumas estratégias ativas simuladas de ensino-aprendizagem, como grupos tutoriais. É preciso valorizar as experiências e competências adquiridas heterogeneamente pelos residentes para compor momentos de equalização do aprendizado, buscando o protagonismo do aluno em vez da imposição de conhecimentos. Introdução RM (RM universidade (PIRMFC Fortaleza prefeitura 7 edição capital ESF (ESF Objetivo Método Tratase Trata se exploratória qualitativa nível 1 R2 R (R2 focais 2020 Aplicaramse Aplicaram amostra Likert temática quantitativos percentuais Resultado Identificaramse Identificaram principais ensinoaprendizagem, ensinoaprendizagem aprendizagem, aprendizagem autonomia diário aprendizes sentindose sentindo passivo Contudo adultos deles Conclusão tutoriais aprendizado conhecimentos (R 202 20 2

ABSTRACT The use of Stizolobium aterrimum (velvet bean) as green manure has been encouraged in agriculture as a source of nitrogen-rich phytomass for incorporation into the soil to enhance subsequent crop yield. The nitrogen-fixing capacity of this legume can be optimized through symbiosis with selected strains of rhizobia. The aim of this study was to evaluate the effectiveness of new strains of Bradyrhizobium in promoting the growth of velvet bean plants, both in potted soil and in the field. The study involved three experiments (two in pots and one in the field) with four replications of each in an Oxisol. An additional experiment was carried out to estimate the native rhizobial community in the experimental soil. The efficiency of the strains was estimated by compared plant growth with them to plant growth in two non-inoculated controls (one without mineral N and the other with mineral N) and plant growth with the strain BR2811, which is approved as an inoculant for velvet bean plants. Evaluations of velvet bean were performed at 60 and 100 days after emergence in non-sterile soil pots, and at 170 days after sowing (at flowering) in the field. Native rhizobia are efficient in symbiosis with velvet bean, as they were similar to BR2811 and to the control with mineral N, but they had lower biological nitrogen fixation efficiency than the new strains tested–UFLA05-18 and UFLA05-20. The new strains increased velvet bean yield and accumulation of N in velvet bean phytomass and, therefore, have potential for being used as inoculants for this species. nitrogenrich rich nitrogenfixing fixing plants field Oxisol noninoculated non inoculated BR 6 10 nonsterile sterile 17 flowering BR281 tested–UFLA0518 testedUFLA0518 testedUFLA tested–UFLA05 18 tested UFLA05 UFLA tested–UFLA05-1 UFLA0520. UFLA0520 20. 20 UFLA05-20 therefore species 1 BR28 UFLA0518 tested–UFLA051 testedUFLA051 testedUFLA05 tested–UFLA0 UFLA0 tested–UFLA05- UFLA052 2 UFLA05-2 BR2 UFLA051 testedUFLA0 tested–UFLA UFLA05-

Resumo As lagoas costeiras da bacia do Rio Tramandaí são ecossistemas dinâmicos que apresentam uma alta biodiversidade e fornecem importantes serviços ecossistêmicos como água para consumo humano, para indústrias, agricultura, criação animal, áreas para lazer, turismo e pesca. Com o constante aumento populacional e o uso e ocupação do solo ao entorno das lagoas, crescem as demandas por seus recursos, pressionando e comprometendo cada vez mais esses ecossistemas. Desta forma, faz-se necessário compreender como as populações biológicas respondem a essas pressões antropogênicas. Esse estudo tem por objetivo avaliar se diferenças no grau de urbanização ao entorno das lagoas afetam a biomassa e comprimento de uma espécie de Characidae (Diapoma alburnum) presente em 23 lagoas da bacia do rio Tramandaí. Exemplares foram coletados entre os anos de 2009 e 2012, utilizando redes de arrasto. Para a coleta e análise de dados foi medido o comprimento padrão dos indivíduos, e para biomassa foi feita a pesagem de todos os peixes, dividido pelo número de indivíduos coletados por lagoa. Para mensurar a urbanização ao entorno das lagoas, utilizou-se imagem de satélite representando luz noturna como proxy de urbanização e extraiu-se a intensidade de luz noturna em buffers de 1 km, 3 km e 5 km ao redor de cada lagoa. O índice de urbanização variou entre 6% e 44% para o buffer de 5 km, de 3% a 55% para o buffer de 3 km e 1% a 65% para o buffer de 1 km ao redor dessas lagoas. Os resultados de análises de regressões mostraram que D. alburnum apresentou relação significativa positiva para biomassa nos buffers de 3 km e 5 km, e uma relação significativa positiva no comprimento médio para o buffer de 3 km, conforme aumenta a urbanização ao entorno das lagoas costeiras. Evidenciamos neste estudo, que apesar da urbanização ao entorno das lagoas ainda não está totalmente consolidada, é possível ver impactos em tamanho e biomassa em populações de D. alburnum, e por ser mais tolerante a fatores de pressão antrópica, a espécie pode ser usada como bioindicador. humano indústrias agricultura animal lazer pesca recursos forma fazse faz antropogênicas Diapoma 2 200 2012 arrasto peixes lagoa utilizouse utilizou extraiuse extraiu 6 44 55 65 D consolidada antrópica bioindicador 20 201 4

Abstract The coastal lagoons of the Tramandaí River basin are dynamic ecosystems characterized by high biodiversity. They provide important ecosystem services, such as water supply for human consumption, industry, agriculture, animal husbandry, leisure activities, tourism and fishing. Constant increases in the human population and the use and occupation of the land around the lagoons has brought growing demands for their resources, resulting in increased pressure that compromises these ecosystems. Understanding how biological populations respond to these anthropogenic pressures is essential. This study examined whether the degree of urbanization around 23 lagoons in the Tramandaí River basin influences the size and biomass of the characid fish species Diapoma alburnum. Specimens were collected between 2009 and 2012 using standardized drag nets. All specimens were measured for standard length to determine average length (size) per lagoon, while all fish collected per lagoon were weighed together to determine average biomass per lagoon by dividing by the number of specimens. Urbanization around the lagoons was measured using satellite images representing artificial nocturnal light as a proxy for urbanization. Nocturnal light intensity was measured within 1 km, 3 km, and 5 km buffers around each lagoon. The resulting urbanization index ranged 6 – 44% for the 5 km buffer, from 3 – 55% for the 3 km buffer and 1 – 65% for the 1 km buffer. Regression analyses showed a significant positive relationship with increasing urbanization around lagoons for D. alburnum average biomass in the 3 km and 5 km buffers and for D. alburnum average length in the 3 km buffer. Although urbanization around the lagoons is not fully established, the results indicate its impact on the size and biomass of D. alburnum. biodiversity services consumption industry agriculture husbandry activities fishing resources essential 2 200 201 nets (size 44 55 65 D established 20 4

Abstract The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy. EZH (ACC . (PA) 1 metastasis recurrence invasion areas malignancy (PA

RESUMO As aves silvestres têm grande destaque na transmissão de doenças ao homem, principalmente pela facilidade de acesso à população humana, levantando preocupações sobre o potencial impacto dessa proximidade no contexto da saúde pública. O presente estudo relata a ocorrência de ARV e PBV em aves silvestres de uma área de proteção ambiental no bioma Amazônico. Obtivemos 155 espécimes fecais de 47 espécies de aves silvestres, que foram submetidos a extração de RNA, detecção de ARV e PBV por técnicas moleculares, sequenciamento nucleotídico e análise filogenética. A prevalência de infecção por ARV foi 0,6% (1/155), sendo positivo em um indivíduo de Myrmotherula longipennis, e a prevalência de PBV foi 1,29% (2/155), afetando dois insdivíduos de Guira guira. A análise filogenética agrupou as cepas de PBV no genogrupo I, mostrando intensa relação filogenética com cepas isoladas de outras regiões geográficas. A cepa de ARV esteve mais relacionada filogeneticamente a cepas previamente circulantes na mesma região. Este é o primeiro estudo sobre detecção de ARV em aves silvestres no Brasil e o primeiro relato sobre a ocorrência de PBV em Guira guira. A circulação de ARV e PBV nesse ambiente demonstra que os ciclos desses agentes estão ocorrendo de forma natural no ecossistema silvestre, o que pode desencadear possíveis eventos de transmissão entre as espécies aviárias e humanos. Estudos adicionais são necessários para determinar a epidemiologia, origem, evolução e surgimento de novos vírus potencialmente patogênicos na Amazônia. homem humana pública Amazônico 15 4 RNA moleculares 06 0 6 0,6 1/155, 1155 1/155 , 1 (1/155) longipennis 129 29 1,29 2/155, 2155 2/155 2 (2/155) guira I geográficas região silvestre humanos epidemiologia origem Amazônia 0, 115 1/15 (1/155 12 1,2 215 2/15 (2/155 11 1/1 (1/15 1, 21 2/1 (2/15 1/ (1/1 2/ (2/1 (1/ (2/ (1 (2 (

ABSTRACT Wild birds have great prominence in the transmission of diseases to humans, mainly due to their ease of access to human populations, raising concerns about the potential impact of that proximity on public health. The present study reports ARV and PBV occurrence in wild birds from an environmental protection area in the Amazon biome, in Pará state, Brazil. We obtained 155 fecal specimens from 47 species of wild birds for RNA extraction, ARV and PBV detection utilizing molecular methods, nucleotide sequencing, and phylogenetic analysis. ARV prevalence was 0.6% (1/155), being positive in an individual of Myrmotherula longipennis, and PBV prevalence was 1.29% (2/155), affecting two individuals of Guira guira. The PBV strains were assigned to genogroup I based on phylogenetic analysis, and they shared a strong phylogenetic link with strains isolated from different geographic locations. The ARV strain was more closely related to strains that had previously circulated in the same region. The presence of ARV and PBV in this habitat suggests that infection cycles of these agents occur naturally in the wild ecosystem, potentially triggering transmission events between bird species and humans. This is the first study on ARV detection in wild birds in Brazil and the first report on the occurrence of PBV in wild Guira guira. Additional studies are required to determine the epidemiology, origin, evolution, and emergence of new potentially pathogenic viruses in the Amazon. humans populations health biome state 15 4 extraction methods sequencing analysis 06 0 6 0.6 1/155, 1155 1/155 , 1 (1/155) longipennis 129 29 1.29 2/155, 2155 2/155 2 (2/155) guira locations region ecosystem epidemiology origin evolution 0. 115 1/15 (1/155 12 1.2 215 2/15 (2/155 11 1/1 (1/15 1. 21 2/1 (2/15 1/ (1/1 2/ (2/1 (1/ (2/ (1 (2 (

ABSTRACT Species of the Amaranthus genus are very versatile and have potential for the application in the development of commercial products. The near infrared spectroscopy (NIR) is an efficient tool that can help in the quality control of products, quickly and non-destructive to the sample. The goal of this study was to carry out the distinction of seed and oils of different Amaranthus species using the near infrared spectroscopy. Three species were used: A. viridis L., A. hybridus L. e Amaranthus sp. (commercial). The spectra acquired from the sample using the near infrared spectroscopy were submitted to the partial least squares discriminant analysis (PLS-DA) and to the principal component analysis (PCA). Through PCA, it was possible to differentiate the Amaranthus species both for seeds and oils. Through PLS-DA, it was possible to predict the classes of the species with high degree of correct classification, with 96.67% of correct classifications for seeds and 98.89% for oil. Thus, with the use of the near infrared spectroscopy associated with the multivariate statistical analysis, it is possible to classify the different Amaranthus species, especially when using the oil. products NIR (NIR nondestructive non destructive used A L sp commercial. . (commercial) PLSDA PLS DA (PLS-DA PCA. PCA (PCA) PLSDA, DA, PLS-DA classification 9667 96 67 96.67 9889 98 89 98.89 oil Thus (commercial (PCA 966 9 6 96.6 988 8 98.8 96. 98.

RESUMO O objetivo do estudo é oferecer um resgate histórico do conjunto de ações em governança do solo implementados no estado do Paraná, desde a década de 1970, que vão dos trabalhos desenvolvidos pelos institutos de pesquisa, aos programas governamentais. São ações que possibilitaram o desenvolvimento de tecnologias e a ampla adoção de práticas conservacionistas pelos produtores. Além de indicar os fatores que deram base para a retomada das discussões, em período recente, sobre conservação do solo e da água. Como fontes de informações foram utilizados relatórios de pesquisa e dos programas desenvolvidos no Paraná, empregando o método de revisão histórico-bibliográfica. Verificou-se que foi executado um amplo trabalho de planificação de uso, manejo e conservação dos recursos naturais no Paraná, denotando a construção de uma governança forte em solo e água. Destacam-se no Paraná as ações realizadas em microbacias hidrográficas, pelo pioneirismo do seu enfoque, duração e dimensões, e o desenvolvimento do Sistema Plantio Direto. Contudo, nem tudo foi sempre linear nessa evolução, uma vez que com o passar do tempo foi se constituindo a falsa percepção – principalmente entre os produtores – de que o problema da erosão já estava solucionado. Em consequência disso, muitos agricultores passaram a negligenciar práticas de conservação do solo com uso de terraços, o abandono das operações agrícolas em nível, bem como a rotação de culturas. Tais condutas reavivaram problemas conhecidos e graves de degradação, acentuando os processos de perdas de solo e água pela erosão, e seus prejuízos associados. Neste contexto, descreve-se os instrumentos que estão sendo utilizados em uma nova estratégia paranaense para a retomada de uma efetiva governança do solo, por meio de políticas públicas e de parcerias público-privadas na promoção da conservação de solos e água. 1970 governamentais discussões recente históricobibliográfica. históricobibliográfica bibliográfica. bibliográfica histórico-bibliográfica Verificouse Verificou Destacamse Destacam hidrográficas enfoque dimensões Direto Contudo evolução solucionado disso terraços nível culturas degradação associados contexto descrevese descreve públicoprivadas público privadas 197 19 1

ABSTRACT This study is a historical overview of land governance initiatives implemented in Parana state, Brazil, since the 1970s, ranging from the work carried out by research institutes to government-sponsored programs. These initiatives encouraged the development of technologies and farmers’ widespread adoption of conservation practices. Furthermore, they highlight the factors that brought soil and water conservation to the forefront in discussions on agriculture. This bibliographic review was based on information in research papers and programs developed in Parana. We show that extensive work on management planning and natural resource conservation was undertaken in Parana to strengthen soil governance. The initiatives implemented in watersheds and the development of the no-tillage system represent considerable achievements. However, it was not always that straightforward. As time progressed, the false perception – mainly among farmers – that the erosion problem had been solved led many farmers to neglect soil conservation practices, and in some cases, to abandon agricultural terracing, contour farming, and crop rotation. This resulted in a resurgence of problems related to environmental degradation, aggravating erosion and causing losses of soil and water, with the concomitant environmental damage. In this regard, we describe the means deployed in a new strategy to stimulate a resurgence of effective soil governance based on public policies and public-private partnerships to promote soil and water conservation. state Brazil 1970s s governmentsponsored government sponsored practices Furthermore agriculture notillage no tillage achievements However straightforward progressed cases terracing farming rotation degradation damage regard publicprivate private

Abstract Scientific evidence about genetic and molecular changes in oral squamous cell carcinoma (OSCC) among smokers and non-smokers is inconclusive. This systematic review and meta-analysis assessed the effects of tobacco on the DNA of individuals with OSCC based on protein mutations. Electronic searches were conducted on PubMed, Ovid, Web of Science, and Scopus to identify observational studies published up to January/2022. The Joanna Briggs Institute tool was used for the critical appraisal of studies. The certainty of the evidence was evaluated. Twenty-three studies assessing 4,060 individuals (2,967 smokers vs. 1,093 non-smokers) were included in this review. Fifteen groups of proteins/genes were investigated. Analysis of the quality of articles revealed low risk of bias in most studies. The certainty of the evidence was very low. The meta-analysis confirmed no significant difference between smokers and non-smokers with respect to damage to GSTM1 (OR: 0.60; 95%CI: 0.30–1.18), GSTT1 (OR: 1.18; 95%CI:0.49–2.83), hydrolase proteins (Ku70 and Ku80) (OR: 0.74; 95%CI: 0.18–3.05), and transferase proteins (GSTM1, GSTT1, GSTM3) (OR: 0.74; 95%CI: 0.47–1.18). Most of the studies included showed that smokers are more likely to exhibit genetic instability. However, the meta-analysis revealed that smokers do not necessarily have more genetic alterations in the DNA than non-smokers. (OSCC nonsmokers non inconclusive metaanalysis meta analysis mutations PubMed Ovid Science January2022 January 2022 January/2022 evaluated Twentythree Twenty three 4060 4 060 4,06 2,967 2967 2 967 (2,96 vs 1093 1 093 1,09 proteinsgenes genes investigated GSTM OR (OR 0.60 0 60 95%CI 95CI CI 95 0.30–1.18, 030118 0.30–1.18 , 30 18 0.30–1.18) GSTT 1.18 118 95%CI0.49–2.83, 95CI049283 0.49–2.83 49 83 95%CI:0.49–2.83) Ku70 Ku (Ku7 Ku80 0.74 074 74 0.18–3.05, 018305 0.18–3.05 3 05 0.18–3.05) GSTM1, (GSTM1 GSTM3 0.47–1.18. 047118 0.47–1.18 . 47 0.47–1.18) instability However nonsmokers. smokers. January202 202 January/202 406 06 4,0 2,96 296 96 (2,9 109 09 1,0 0.6 6 9 03011 0.30–1.1 1.1 11 CI0 95%CI0.49–2.83 95CI04928 049283 0.49–2.8 8 95%CI:0.49–2.83 Ku7 (Ku Ku8 0.7 07 7 01830 0.18–3.0 (GSTM 04711 0.47–1.1 January20 20 January/20 40 4, 2,9 29 (2, 10 1, 0. 0301 0.30–1. 1. 95%CI0.49–2.8 95CI0492 04928 0.49–2. 95%CI:0.49–2.8 0183 0.18–3. 0471 0.47–1. January2 January/2 2, (2 030 0.30–1 95%CI0.49–2. 95CI049 0492 0.49–2 95%CI:0.49–2. 018 0.18–3 047 0.47–1 January/ ( 03 0.30– 95%CI0.49–2 95CI04 049 0.49– 95%CI:0.49–2 01 0.18– 04 0.47– 0.30 95%CI0.49– 95CI0 0.49 95%CI:0.49– 0.18 0.47 0.3 95%CI0.49 0.4 95%CI:0.49 0.1 95%CI0.4 95%CI:0.4 95%CI0. 95%CI:0. 95%CI0 95%CI:0

Resumo O objetivo deste estudo foi analisar os fatores relacionados à saúde mental dos agentes comunitários de saúde (ACS) no contexto da COVID-19. Participaram 1.935 ACS de quatro capitais nordestinas e de quatro cidades do interior do Ceará. Foram coletados dados sociodemográficos e profissiográficos; SRQ-20; WHOQOL-Bref; exposição à violência; Escala de Autoeficácia Geral (EAEG); Escala Multidimensional de Suporte Social Percebido (MSPSS); informações relacionadas à COVID-19 e Escala de Ansiedade para Coronavírus (EAC). 40,5% exibiram SRQ > 7, sinalizando altos níveis de transtornos mentais comuns (TMC)/problemas de saúde mental. Utilizou-se a regressão linear múltiplas (backward). Observou-se que o aumento de risco de TCM foi influenciado pelos seguintes fatores: exposição à violência; EAC; não saber se teve COVID-19; desconhecer as variáveis que diminuíam o risco; os domínios físico e psicológico do WHOQOL-Bref; não ter aumento da jornada de trabalho; e não ter tido COVID-19. Os dados revelam a dinâmica multidimensional da saúde mental e ajudam a compreender a relação entre violência comunitária, COVID-19, qualidade de vida, idade e tempo de atuação na ESF com a saúde mental dos ACS. (ACS COVID19. COVID19 COVID 19. 19 1935 1 935 1.93 Ceará profissiográficos SRQ20 20 SRQ-20 WHOQOLBref WHOQOL Bref WHOQOL-Bref EAEG (EAEG) MSPSS (MSPSS) COVID-1 EAC. EAC . (EAC) 405 40 5 40,5 7 TMC/problemas TMCproblemas TMC /problemas problemas Utilizouse Utilizou backward. backward (backward) Observouse Observou trabalho comunitária COVID19, 19, vida COVID1 193 93 1.9 SRQ2 2 SRQ-2 (EAEG (MSPSS COVID- (EAC 4 40, (backward 9 1. SRQ-

Abstract This study aimed to analyze the factors related to the mental health of Community Health Workers (ACS) in the COVID-19 context. A total of 1,935 ACS from four Northeastern capitals and four cities in the inland region of Ceará participated. The following data were collected: sociodemographic; professional; SRQ-20; WHOQOL-Bref, exposure to violence, General Self-Efficacy Scale (EAEG), Multidimensional Scale of Perceived Social Support (MSPSS), COVID-19-related information, and the coronavirus anxiety scale (EAC). Approximately 40.5% had SRQ > 7, signaling high levels of Common Mental Disorders (CMD)/mental health issues. We adopted the Multiple linear (backward) regression. We observed that the increased risk of CMD was influenced by exposure to violence, EAC, not knowing they had COVID-19, not knowing the variables that reduced the risk, the physical and psychological domains of the WHOQOL-Bref, not having increased working hours, and not having had COVID-19. The data reveal the multidimensional dynamics of mental health and help understand the relationship between community violence, COVID-19, quality of life, age, and ESF working time with the mental health of ACS. (ACS COVID19 COVID 19 COVID-1 context 1935 1 935 1,93 participated collected sociodemographic professional SRQ20 20 SRQ-20 WHOQOLBref, WHOQOLBref WHOQOL Bref, Bref WHOQOL-Bref violence SelfEfficacy Self Efficacy EAEG, EAEG , (EAEG) MSPSS, MSPSS (MSPSS) COVID19related COVIDrelated information EAC. EAC . (EAC) 405 40 5 40.5 7 CMD/mental CMDmental /mental issues backward (backward regression COVID19, 19, hours COVID19. 19. life age COVID1 COVID- 193 93 1,9 SRQ2 2 SRQ-2 (EAEG (MSPSS (EAC 4 40. 9 1, SRQ-

Abstract Introduction Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. Objective To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. Method Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann–Whit-ney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). Results 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) (‘p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. Conclusions ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development. (RA extraarticular extra articular (ExtRA time cohort Crosssectional Cross sectional study multicentric multi centric 1 1987 (198 201 ACREULAR. ACREULAR ACR EULAR . ACR-EULAR) 082015, 082015 08 2015, 2015 08-2015 record Mann–Whitney MannWhitney Mann–Whit ney Mann Whit Utest, Utest U U-test Fishers Fisher s chisquare chi square appropriate 5 p 0.05. 005 0.05 0 05 0.05) 111 included 89 women mean SD 582 58 2 58. 115 11. years 145 14 14. 122 12 12. RF, (RF 1108 77 77% anticyclic anti cyclic ACPA, ACPA (ACPA 477 78 78% 33 26 234 23 4 23.4 NonExtRA Non 0.001, 0001 0.001 , 001 0.018, 0018 0.018 018 0.018) CDAI (CDAI DAS HAQ (HAQ group 0.002, 0002 0.002 002 0.002) 0.049 0049 049 GC (GC ‘p nonsteroidal non steroidal antiinflammatory NSAIDs (NSAIDs underestimated longterm long term development 198 (19 20 ACR-EULAR 08201 08-201 Whitney MannWhit 00 0.0 8 110 7 47 3 23. 000 0.00 0.01 01 0.04 004 04 19 (1 0820 08-20 0. ( 082 08-2 08-

Abstract Background Management delays imply worse outcomes in rheumatoid arthritis (RA) and, therefore, should be minimized. We evaluated changes in diagnostic and treatment delays regarding RA in the last decades in Brazil. Methods Adults fulfilling the ACR/EULAR (2010) criteria for RA were assessed. Delays in diagnosis and treatment, and the frequencies of early management initiation within thresholds (windows of opportunity) of 3, 6, and 12 months from symptoms onset were evaluated. The Mann–Kendall trend test, chi-squared tests with Cramer’s V effect sizes and analysis of variance were conducted. Results We included 1116 patients: 89.4% female, 56.8% white, mean (SD) age 57.1 (11.5) years. A downward trend was found in diagnostic (tau = - 0.677, p < 0.001) and treatment (tau = - 0.695, p < 0.001) delays from 1990 to 2015. The frequency of early management increased throughout the period, with ascending effect sizes across the 3-, 6-, and 12-month windows (V = 0.120, 0.200 and 0.261, respectively). Despite all improvements, even in recent years (2011–2015) the diagnostic and treatment delays still remained unacceptably high [median (IQR): 8 (4–12) and 11 (5–17) months, respectively], with only 17.2% of the patients treated within the shortest, 3-month window. Conclusion The delays in diagnosis and treatment of RA decreased during the last decades in Brazil. Improvements (effect sizes) were greater at eliminating extreme delays (≥ 12 months) than in attaining really short management windows (≤ 3 months). Very early treatment was still an unrealistic goal for most patients with RA. (RA therefore minimized Brazil ACREULAR ACR EULAR 2010 (2010 assessed opportunity 6 1 MannKendall Mann Kendall test chisquared chi squared Cramers Cramer s conducted 111 894 89 4 89.4 female 568 56 56.8 white SD (SD 571 57 57. 11.5 115 5 (11.5 tau 0677 0 677 0.677 0.001 0001 001 0695 695 0.695 199 2015 period , 3- 6- 12month month 0120 120 0.120 0200 200 0.20 0261 261 0.261 respectively. respectively . respectively) improvements 2011–2015 20112015 2011 (2011–2015 median IQR (IQR) 4–12 412 (4–12 5–17 517 17 (5–17 respectively, respectively] 172 2 17.2 shortest 3month window ≥ ( ≤ months. 201 (201 89. 56. 11. (11. 067 67 0.67 0.00 000 00 069 69 0.69 19 012 0.12 020 20 0.2 026 26 0.26 2011–201 2011201 (2011–201 (IQR 4–1 41 (4–1 5–1 51 (5–1 17. (20 (11 06 0.6 0.0 01 0.1 02 0. 2011–20 201120 (2011–20 4– (4– 5– (5– (2 (1 2011–2 20112 (2011–2 (4 (5 2011– (2011– (2011

Abstract Background Early rheumatoid arthritis (RA) offers an opportunity for better treatment outcomes. In real-life settings, grasping this opportunity might depend on access to specialized care. We evaluated the effects of early versus late assessment by the rheumatologist on the diagnosis, treatment initiation and long-term outcomes of RA under real-life conditions. Methods Adults meeting the ACR/EULAR (2010) or ARA (1987) criteria for RA were included. Structured interviews were conducted. The specialized assessment was deemed “early” when the rheumatologist was the first or second physician consulted after symptoms onset, and “late” when performed afterwards. Delays in RA diagnosis and treatment were inquired. Disease activity (DAS28-CRP) and physical function (HAQ-DI) were evaluated. Student's t, Mann-Whitney U, chi-squared and correlation tests, and multiple linear regression were performed. For sensitivity analysis, a propensity score-matched subsample of early- vs. late-assessed participants was derived based on logistic regression. The study received ethical approval; all participants signed informed consent. Results We included 1057 participants (89.4% female, 56.5% white); mean (SD) age: 56.9 (11.5) years; disease duration: 173.1 (114.5) months. Median (IQR) delays from symptoms onset to both RA diagnosis and initial treatment coincided: 12 (6–36) months, with no significant delay between diagnosis and treatment. Most participants (64.6%) first sought a general practitioner. Notwithstanding, 80.7% had the diagnosis established only by the rheumatologist. Only a minority (28.7%) attained early RA treatment (≤ 6 months of symptoms). Diagnostic and treatment delays were strongly correlated (rho 0.816; p < 0.001). The chances of missing early treatment more than doubled when the assessment by the rheumatologist was belated (OR 2.77; 95% CI: 1.93, 3.97). After long disease duration, late-assessed participants still presented lower chances of remission/low disease activity (OR 0.74; 95% CI: 0.55, 0.99), while the early-assessed ones showed better DAS28-CRP and HAQ-DI scores (difference in means [95% CI]: −0.25 [−0.46, −0.04] and − 0.196 [−0.306, −0.087] respectively). The results in the propensity-score matched subsample confirmed those observed in the original (whole) sample. Conclusions Early diagnosis and treatment initiation in patients with RA was critically dependent on early access to the rheumatologist; late specialized assessment was associated with worse long-term clinical outcomes. (RA reallife real life settings care longterm term conditions ACREULAR ACR EULAR 2010 (2010 1987 (1987 conducted “early “late afterwards inquired DAS28CRP DASCRP DAS28 CRP DAS (DAS28-CRP HAQDI HAQ DI (HAQ-DI Students Student s t MannWhitney Mann Whitney U chisquared chi squared tests analysis scorematched score vs lateassessed assessed approval consent 105 89.4% 894 89 4 (89.4 female 565 56 5 56.5 white white) SD (SD age 569 9 56. 11.5 115 11 (11.5 years duration 1731 173 1 173. 114.5 1145 114 (114.5 IQR (IQR coincided 6–36 636 36 (6–36 64.6% 646 64 (64.6% practitioner Notwithstanding 807 80 7 80.7 28.7% 287 28 (28.7% ≤ ( symptoms. . symptoms) rho 0.816 0816 0 816 0.001. 0001 0.001 001 0.001) OR 2.77 277 2 77 95 CI 193 93 1.93 3.97. 397 3.97 3 97 3.97) remissionlow remission low 0.74 074 74 055 55 0.55 0.99, 099 0.99 , 99 0.99) earlyassessed difference [95 CI] 025 25 −0.2 −0.46, 046 46 [−0.46 −0.04 004 04 0196 196 0.19 −0.306, 0306 306 [−0.306 −0.087 0087 087 respectively. respectively respectively) propensityscore whole (whole sample 201 (201 198 (198 DAS2 10 89.4 8 (89. 11. (11. 17 114. (114. 6–3 63 (6–3 64.6 (64.6 80. 28.7 (28.7 0.81 081 81 000 0.00 00 2.7 27 19 1.9 39 3.9 0.7 07 05 0.5 09 0.9 [9 02 −0. −0.46 [−0.4 −0.0 019 0.1 −0.306 030 30 [−0.30 −0.08 008 08 20 (20 (19 89. (89 (11 (114 6– (6– 64. (64. 28. (28. 0.8 0.0 2. 1. 3. 0. [ −0 −0.4 [−0. 01 −0.30 03 [−0.3 (2 (1 (8 (6 (64 (28 [−0 −0.3 [−