Flipped classroom and the use of role-play in the COVID-19 pandemic: challenges and learning

Aim In Brazil, COVID-19 remains one of the epicenters of the pandemic, thus, presential educational activities are suspended. The study aimed to describe the approach of flipped classroom performed to provide social distancing and to maintain teaching activities during COVID-19-pandemic. Methods Flipped Classroom was chosen to be associated with the role-play technique as a central methodology. To bring students closer to activities performed in the non-pandemic period, some actions and assessments were also role-played by Professor simulating patients in virtual meetings. Results Although the changes in the format of the lessons, our approaches stimulated the students maintained the high frequency of students in the activities (almost 100%) providing continuity activities. Conclusions This report can reinforce that meaningful learning can be taught by using a virtual/remote approach. However, the potential positive results observed cannot be used as an excuse to maintain remote teaching activities with the objective of cost-cutting by the institutions.

Current jakinibs for the treatment of rheumatoid arthritis: a systematic review.

OBJECTIVE: One-third of patients with severe rheumatoid arthritis (RA) do not achieve remission or low disease activity, or they have side effects from cDMARD and bDMARD. They will need a new treatment option such as the small molecule JAK inhibitors. In this systematic review, we evaluate the efficacy and safety data of the current jakinibs: tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib and filgotinib in patients in whom treatment with conventional or biological disease-modifying antirheumatic drugs (cDMARD and/or bDMARD) failed. METHODS: We searched for randomized controlled trials comparing efficacy and safety of jakinibs for RA treatment using the Web of Science, Scopus, PubMed, and clinicaltrials.gov databases with the terms: "rheumatoid arthritis" OR "arthritis rheumatoid" OR "RA" AND "inhibitor" OR "jak inhibitor" AND "clinical trial" OR "treatment" OR "therapy". RESULTS: All jakinibs achieved good results in ACR 20, 50, 70 and with CRP-DAS28 for LDA and remission, upadacitinib showed better results compared to the others. In ESR-DAS28 for remission, tofacitinib achieved the best result. Regarding the safety of all jakinibs, peficitinib, baricitinib and filgotinib did not register deaths in their studies unlike tofacitinib that presented 11 deaths. Despite all benefits of jakinibs, the use in patients with severe liver and kidney disease should be avoided. CONCLUSIONS: Jakinibs in monotherapy or in combination with methotrexate can be considered a viable alternative in the treatment of moderate-to-severe RA. Even after failures with combination of cDMARDS and bDMARDS, jakinibs demonstrated efficacy.

Processos de encaminhamento a serviços especializados em cardiologia e endocrinologia pela Atenção Primária à Saúde / Referral processes to services specialized in cardiology and endocrinology for Primary Health Care

RESUMO Este estudo objetivou analisar encaminhamentos de pessoas a serviços de cardiologia e endocrinologia pelos médicos da Atenção Primária à Saúde (APS) de um município do Rio Grande do Sul. Estudo transversal com questionários a 25 médicos da APS, 2 cardiologistas, 2 endocrinologistas e 1 médico regulador. A análise estatística foi realizada no SPSS, sendo as variáveis contínuas apresentadas como média ou mediana; e as variáveis categóricas, como frequência absoluta e relativa. Entre os médicos da APS, 96% conhecem, 84% utilizam protocolos de encaminhamento e 92% encaminham os pacientes principalmente para manejo de doenças complicadas que necessitam de avaliação do especialista. Entre os especialistas, 50% conhecem os protocolos, e todos apontam que o principal motivo de encaminhamentos para eles ocorre devido a condições crônicas prevalentes mal controladas na APS, sendo considerados pelos endocrinologistas como mal indicados. O médico regulador avalia que a maioria dos documentos de encaminhamento é incompleta e não permite verificar a gravidade do problema. Conclui-se que os protocolos de encaminhamento não estão sendo utilizados de forma a otimizar os fluxos dos usuários na rede de atenção à saúde, indicando a necessidade de revisão de processos de trabalho, capacitação dos profissionais e articulação entre APS, regulação e Atenção Especializada.

ABSTRACT This study aimed to analyze referrals of people to cardiology and endocrinology services by doctors in Primary Health Care (PHC) in a city in Rio Grande do Sul. Cross-sectional study with questionnaires applied to 25 PHC doctors, 2 cardiologists, 2 endocrinologists and 1 regulatory doctor. Statistical analysis was performed in SPSS, with continuous variables being presented as mean or median; and categorical variables, such as absolute and relative frequencies. Among PHC doctors, 96% know, 84% use referral protocols, and 92% refer patients mainly to manage complicated diseases that require specialist evaluation. Among the specialists, 50% know the protocols, and all point out that the main reason for referrals to them occurs due to prevalent chronic conditions poorly controlled in PHC, being considered by endocrinologists as poorly indicated. The regulatory doctor assesses that most referral documents is incomplete and does not allow to verify the seriousness of the problem. It is concluded that the referral protocols are not being used in order to optimize the flow of users in the health care network, indicating the need for review of work processes, training of professionals and articulation between PHC, regulation and Specialized Care.

High CD3+ lymphocytes, low CD66b+ neutrophils, and scarce tumor budding in the invasive front of lip squamous cell carcinomas.

OBJECTIVE: This study aimed to evaluate tumor budding (TB) and quantify the neutrophilic and lymphocytic infiltration in the invasive front of lip squamous cell carcinomas. In addition, the associations between these features and the histopathological grading in the invasive front were analyzed. DESIGN: A total of 43 lip squamous cell carcinoma surgical specimens were included and classified in accordance with a histological invasive front grading system. Immunohistochemistry was performed for CD66b and CD3 for the evaluation of neutrophils and T lymphocytes, respectively, in the invasive front of the tumors. Tumor budding was evidenced by AE1/AE3 staining. RESULTS: Thirty-six (83.7%) of the tumors were well-differentiated tumors. Eleven (25.6%) of the cases exhibited high-intensity tumor budding. There were low neutrophil and high T lymphocyte infiltrations in the invasive front, leading to a low neutrophil/T lymphocyte ratio in the same region. Moreover, we found an association between tumor budding and the pattern of invasion, and between the CD3+ cell count and the inflammatory infiltrate (p < 0.05). CONCLUSIONS: The low neutrophil and high T lymphocyte infiltration in the invasive front, and the few high-intensity tumor budding cases are in accordance with the histopathological features of well-differentiated lip tumors. If these characteristics remain in lip squamous cell carcinomas with more aggressive histopathological features, it deserves to be investigated.

NADPH-oxidase-derived ROS alters cell migration by modulating adhesions dynamics.

BACKGROUND INFORMATION: Cell migration requires the coordinated activation of structural and signalling molecules, such as the RhoGTPase Rac1. It is known that the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex assembly, which generates reactive oxygen species (ROS) at the cell membrane, also relies on Rac1 activation, indicating a possible effect of ROS during cell migration. In this study, we evaluated the effect of NADPH-oxidase-derived ROS on the migration process. RESULTS: Using time-lapse videos of CHO.K1 cells plated on fibronectin (2 µg/ml) or collagen (5 µg/cm2 ), we observed that depletion of ROS by N-acetyl-cysteine (NAC, 10 mM), an unspecific antioxidant, or diphenyliodonium (DPI, 10 µM), a NADPH-oxidase inhibitor, induced a ∼50% decrease in migration speed and severely impacted migration directionality. Then, we analysed the effects of NADPH oxidase on three migratory events: protrusion rate, adhesion process and signalling pathways related to cell migration. DPI induced an increase of ∼3 protrusion/cell, which were 2× faster but had a ∼50% retraction when compared with control. By pull-down assay, we observed no changes on Rac1 activation, indicating that ROS-mediated effects were related to downstream molecules, such as adhesion-related molecules. A reduction of the adhesion marker FAK-Y397 levels in cells treated with NAC and DPI was observed. In order to analyse adhesion dynamics, CHO.K1 cells transfected with paxillin-GFP analysed with total internal reflectance fluorescence (TIRF) indicated that DPI (5 µM) induced larger adhesions when compared with control. CONCLUSION: These results indicate that the local generation of NADPH-oxidase-derived ROS can modulate cell migration due to changes on adhesion dynamics and signalling. SIGNIFICANCE: This study highlights the physiological requirement of ROS for cell migration and the potential use of these molecules as targets to modulate the cell migration process at different diseases.

Macrophages and prognosis of oral squamous cell carcinoma: A systematic review.

Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2 profile, where M1 acts as proinflammatory and antitumor, and M2 is anti-inflammatory and shows protumor activity. Several studies have shown that macrophages are important to the prognosis of patients with different types of cancer. Our aim was to conduct a systematic review to evaluate the role of macrophages in the prognosis of OSCC patients. A search in the Pubmed, Scopus, and ISI Web of Knowledge database was performed, and it was included only studies that evaluated the importance of macrophages in the prognosis of OSCC patients. From initial 286 articles, 14 fully attended the inclusion criteria. In the majority of the articles, it was evaluated only CD68, a panmacrophage marker, or CD163, a M2 marker. Only one article evaluated the M1 marker, CD11c. Besides, 5 articles analyzed the presence of macrophages in different areas of the tumor. Higher concentrations of CD68 and CD163 were associated with worse survival. In conclusion, macrophages are important to OSCC patients' prognosis; however, it is necessary to address in which tumor region the presence of polarized macrophage is more important to the outcome.

Low Doses of Curcuma longa Modulates Cell Migration and Cell-Cell Adhesion.

Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 µM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 µM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 µM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell-cell adhesion, especially on tumor-derived spheroids. Also, in a xenograft model with patient-derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd.

Demographic and Clinical Profile of Oral Squamous Cell Carcinoma from a Service-Based Population

Abstract The aim of this study was to evaluate the demographic and clinical profile of the oral squamous cells carcinoma (OSCC) cases registered in a center of oral diagnosis in southern Brazil. Eight hundred and six individuals with OSCC from 1959 to 2012 were included in this study. The variables recorded were: sex, age, occupation according to workplace, alcohol and tobacco consumption, skin color, tumor location, histological type, clinical appearance, size, evolution time, presence of pain and lymph node metastasis. Descriptive analysis was performed and the associations between variables were assessed using the chi-square and Fisher's exact test, with a confidence level of 5%. OSSC was more common in males (76.6%) aged between 51 to 70 years (53.9%). The most frequent sites were lower lip vermilion (23.3%), tongue (20.2%) and gingiva/alveolar ridge (18.1%). There was a strong association between outdoor occupation and white skin color with lip squamous cell carcinoma (LSCC). OSCC intraoral lesions were commonly more painful, larger than 2 cm and presented lymphatic metastasis. In conclusion, most of the results confirm the data from literature about sex, age, tumor location and occupation. Moreover, the positive correlations between LSCC and occupation, between LSCC and white skin color, and between bigger lesions and presence of pain/cervical metastasis also corroborate the literature data.

Resumo O objetivo desse estudo foi avaliar o perfil clínico-demográfico dos casos de carcinoma de células escamosas oral (CCEO) oral registrados em um centro de diagnóstico bucal no Sul do Brasil. Oitocentos e seis indivíduos com CCEO de 1959 a 2012 foram incluídos no estudo. As variáveis coletadas foram: sexo, idade, ocupação de acordo com o ambiente de trabalho, consumo de álcool e tabaco, cor de pele, localização do tumor, tipo histológico, aparência clínica, tamanho, tempo de evolução, presença de dor e metástase linfonodal. Foi realizada análise descritiva e as associações entre as variáveis foram avaliadas usando qui-quadrado e teste exato de Fisher, com nível de confiança de 5%. CCE oral foi mais comum em homens (76,6%), entre 51 e 70 anos de idade (53,9%). Os sítios mais frequentes foram vermelhão de lábio inferior (23,3%), língua (20,2%) e gengiva/rebordo alveolar (18,1%). Houve uma forte associação entre ocupação em ambiente externo e cor de pele branca com CCEO em lábio. Lesões intraorais de CCEO foram comumente mais dolorosas, maiores que 2 cm e apresentaram metástase linfática. Em conclusão, a maioria dos resultados confirma os dados da literatura em relação a sexo, idade, localização do tumor e ocupação. Além disso, as correlações positivas entre CCE em lábio e ocupação, entre CCEO em lábio e cor de pele branca, e entre lesões maiores e presença de dor/metástase cervical também corroboram os dados da literatura.

Demographic and Clinical Profile of Oral Squamous Cell Carcinoma from a Service-Based Population.

The aim of this study was to evaluate the demographic and clinical profile of the oral squamous cells carcinoma (OSCC) cases registered in a center of oral diagnosis in southern Brazil. Eight hundred and six individuals with OSCC from 1959 to 2012 were included in this study. The variables recorded were: sex, age, occupation according to workplace, alcohol and tobacco consumption, skin color, tumor location, histological type, clinical appearance, size, evolution time, presence of pain and lymph node metastasis. Descriptive analysis was performed and the associations between variables were assessed using the chi-square and Fisher's exact test, with a confidence level of 5%. OSSC was more common in males (76.6%) aged between 51 to 70 years (53.9%). The most frequent sites were lower lip vermilion (23.3%), tongue (20.2%) and gingiva/alveolar ridge (18.1%). There was a strong association between outdoor occupation and white skin color with lip squamous cell carcinoma (LSCC). OSCC intraoral lesions were commonly more painful, larger than 2 cm and presented lymphatic metastasis. In conclusion, most of the results confirm the data from literature about sex, age, tumor location and occupation. Moreover, the positive correlations between LSCC and occupation, between LSCC and white skin color, and between bigger lesions and presence of pain/cervical metastasis also corroborate the literature data.

Tumor angiogenesis and lymphangiogenesis: tumor/endothelial crosstalk and cellular/microenvironmental signaling mechanisms.

Tumor angiogenesis and lymphangiogenesis are key features of tumor progression and metastasis. The role of tumor cells-derived factors in the promotion of associated angiogenesis and lymphangiogenesis is much studied and, no doubt, very important for the understanding of cancer progression. This review aims to present and discuss the work done on the pro-angiogenic and lymphangiogenic cellular interactions within the tumor microenvironment and the signaling pathways that regulate this crosstalk. Such multifactor studies are critical for the development of future therapeutic approaches for cancer because they take into account the complexities of cellular interactions within the tumor microenvironment.

Keratoacanthoma in the cutaneous area of the upper lip: a case report / Ceratoacantoma em região cutânea de lábio superior: relato de caso

PURPOSE: The aim of this paper is to briefly review and discuss the literature about KA and present a case report with a 2-year follow-up of the removal of a KA lesion in the upper lip. CASE DESCRIPTION: A 53-year-old woman complained of a painless, aesthetically unpleasant brownish, hard lesion in the cutaneous area of the upper lip. The lesion had grown rapidly in the last 30 days (size: ~10×5 mm), and was associated with a hot waxing hair removal. Surgical excision was the treatment chosen in order to differentiate the lesion from squamous cell carcinoma (SCC). An oval-shaped incision was created with an in-depth wedge shape for the removal of the lesion and better approximation of the edges after synthesis. Histopathological analysis confirmed the diagnosis of KA. After 2 years, the patient was completely satisfied with the treatment, and no scar was evident. CONCLUSION: Due to the clinical difficulty in differentiating KA from SCC and the risk for formation of an aesthetically unpleasant scar upon spontaneous resolution of KA, surgical removal might be considered the treatment of choice for a solitary KA.

OBJETIVO: O objetivo deste trabalho é revisar e discutir brevemente a literatura sobre CA e apresentar o relato de um caso da remoção de CA em lábio superior com 2 anos de acompanhamento. DESCRIÇÃO DO CASO: Mulher com 53 anos queixava-se de lesão indolor, esteticamente desagradável, dura e de coloração marrom na área cutânea do lábio superior. A lesão havia crescido rapidamente nos últimos 30 dias (tamanho: ~10×5 mm), e estava associada à remoção de pêlos com cera quente. Excisão cirúrgica foi o tratamento escolhido para diferenciar a lesão de carcinoma espinocelular (CEC). Uma incisão em forma oval aprofundada em forma de cunha foi realizada para remoção da lesão e melhor aproximação das bordas após a síntese. A análise histopatológica confirmou o diagnóstico de CA. Após 2 anos, a paciente estava completamente satisfeita com o tratamento, e nenhuma cicatriz era evidente. CONCLUSÃO: Devido à dificuldade na diferenciação clínica entre CA e CEC, e o risco de formação de cicatriz esteticamente desagradável quando da resolução espontânea do CA, a remoção cirúrgica pode ser considerada o tratamento de escolha para CA solitário.