Tumor-Infiltrating T Cells in Skin Basal Cell Carcinomas and Squamous Cell Carcinomas: Global Th1 Preponderance with Th17 Enrichment-A Cross-Sectional Study.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.

Implementation of the Fast-track Protocol for Total Hip Arthroplasty in a Public Hospital in the State of São Paulo - Brazil.

Objective Evaluate the results of the implementation of the Fast Track Protocol (FTP), a medical practice based on scientific evidence, for elective total hip arthroplasty surgery, mainly comparing the National Average Hospital Admission Rate of 7.1 days. Methods 98 patients who underwent elective total hip arthroplasty surgery via the direct anterior approach, anterolateral approach and posterior approach were included in the FTP from December 2018 to March 2020, being followed up preoperatively, intraoperatively and immediately postoperatively. Results The average length of hospital stay was 2.8 days, being 2.1 days for the direct anterior approach, 3.0 days for the anterolateral access approach and 4.1 days for the posterior access approach. The average surgery time was 90 minutes, 19 (19.39%) of the patients were referred to the ICU in the postoperative period, however, none of them underwent surgery using the direct anterior approach. We had no cases of deep vein thrombosis (DVT), pulmonary embolism (PTE) or neurological injury, 19 (19.39%) patients had postoperative bleeding requiring dressing change, 4 (4.08%) needed blood transfusion, 2 (2.04%) patients had implant instability, 1 (1.02%) patient had a fracture during surgery and 1 (1.02%) patient died of cardiac complications. Conclusion FTP may be a viable alternative to reduce the length of stay and immediate postoperative complications for elective total hip arthroplasty surgery decreasing the length of stay of patients by 2 to 3 times when compared to the national average of 7.1 days.

Smoking induces increased apoptosis in osteoblasts: changes in bone matrix organic components.

Clinical studies demonstrate the impact of smoking on bone tissue fragility and higher incidence of fractures. However, it is not totally understood which physiological mechanisms could be involved in these events. Previously, we showed important changes in bone tissue components in experimental model of cigarette smoke (CS) exposure. CS exposure induces worsening in bone mineralization and a decrease in collagen type I deposition, leading to bone fragility. Considering that the majority of clinical studies described bone structural changes by radiographic images, in this study we performed analyses "in situ" using tissue samples from smokers, former smokers and non-smokers to better understand how the increase in inflammatory mediators induced by smoking exposure could interfere in bone cells activity leading bone structural changes. We observed increased levels of IL-1ß, IL-6 and TNF-α in bone tissue homogenates with a concomitant increase in osteoblast apoptosis in smokers and former smokers compared with non-smokers. Histological changes in both smokers and former smokers were characterized by reduction in collagen type I. Only in smokers, it was observed decrease in trabecular area, suggesting increased bone resorption and increase in collagen type V. These results showed that osteoblasts apoptosis in association with increased bone resorption leads bone structural changes in smokers.

Inactivation Mechanism of the Fatty Acid Amide Hydrolase Inhibitor BIA 10-2474.

BIA 10-2474 is a time-dependent inhibitor of fatty acid amide hydrolase (FAAH) that was under clinical development for the treatment of neurological conditions when the program was terminated after one subject died and four were hospitalized with neurological symptoms during a first-in-human clinical study. The present work describes the mechanism of FAAH inhibition by BIA 10-2474 as a target-specific covalent inhibition, supported by quantum mechanics and molecular modelling studies. The inhibitor incorporates a weakly reactive electrophile which, upon specific binding to the enzyme's active site, is positioned to react readily with the catalytic residues. The reactivity is enhanced on-site by the increased molarity at the reaction site and by specific inductive interactions with FAAH. In the second stage, the inhibitor reacts with the enzyme's catalytic nucleophile to form a covalent enzyme-inhibitor adduct. The hydrolysis of this adduct is shown to be unlikely under physiological conditions, therefore leading to irreversible inactivation of FAAH. The results also reveal the important role played by FAAH Thr236 in the reaction with BIA 10-2474, which is specific to FAAH and is not present in other serine hydrolases. It forms a hydrogen bond with the imidazole nitrogen of the inhibitor and helps lowering the activation free energy of the first step of the reaction, by pre-orienting and stabilizing the inhibitor in a near-reactive configuration. In the second step, Thr236 can also serve as a mechanistic alternative to protonate the leaving group.

Cancer surveillance in Mato Grosso, Brazil: methodological and operational aspects of a university extension/research project.

OBJECTIVE: To describe the methodological and operational aspects of the "Project for surveillance of cancer and its associated factors: population-based and hospital-based registry" (VIGICAN), in the state of Mato Grosso (MT), Brazil. METHODS: VIGICAN was divided into two projects: a university extension one, which updated the data from the Population-based Cancer Registry (PBCR) of MT in the 2008-2016 period; and a research project, which collected primary data, through individual interviews and analysis of medical records of people with a diagnosis of cancer, aged 18 years or older, treated at reference hospitals for oncology. To analyze the factors associated with cancer, the following variables were collected: socioeconomic and demographic, social support, health status and behavior, and environmental exposure. RESULTS: In the 2008-2016 period, approximately one hundred thousand cases of cancer (incident and prevalent) were reported in the PBCR Cuiabá and PBCR Interior. After validation procedures, 50 thousand incident cases were elected. The survey interviewed 1,012 patients, 38.2% living in the municipalities of Cuiabá and Várzea Grande, 60.4% in small cities of the state, and 1.4% in other states. Preliminary data showed that the majority were women (55.0%) and younger than 60 years of age (54.3%). Among the interviewees, 7.2% reported smoking tobacco, 15.5% consumed alcoholic beverages (15.5%), and 32.7% lived nearby crops. CONCLUSION: The development of these projects allowed the integration of education with health services and will enable the recognition of specificities and different exposure scenarios and factors associated with cancer in the Mato Grosso territory.

Cancer mortality in the State of Mato Grosso from 2000 to 2015: temporal trend and regional differences.

OBJECTIVE: To analyze the trend of standardized cancer mortality rate in the state of Mato Grosso according to health regions, from 2000 to 2015. METHODS: Ecological time series study with data on deaths by cancer from the Mortality Information System. The rates were standardized using direct method and calculated by year and health regions. The annual percentage changes (APC) and respective confidence interval (95%CI) were obtained through simple linear regression. Thematic maps were built to show the spatial distribution of rates. RESULTS: There were 28,525 deaths by cancer registered in Mato Grosso, with the main types being lung, prostate, stomach, breast and liver cancer. The highest mortality rates were found in regions Médio Norte, Baixada Cuiabana and Sul Mato-Grossense. From 2000 to 2015, an upward trend was seen in the mortality rate by cancer in Mato Grosso (APC=0.81%; 95%CI 0.38-1.26), and in four health regions, Garças Araguaia (APC=2.27%; 95%CI 1.46-3.08), Sul Mato-Grossense (APC=1.12%; 95%CI 0.28-1.97), Teles Pires (APC=1.93%; 95%CI 0,11-3,74) and Vale dos Arinos (APC=2.61%; 95%CI 1.10-4.70), while the other regions remained stable. CONCLUSION: In the state of Mato Grosso and in the four health regions, cancer mortality rate showed a growing trend. The results point to the need to consider regional differences when thinking about actions for cancer prevention, control and assistance.

Incidence, mortality and survival of prostate cancer in two municipalities with a high human development index in Mato Grosso, Brazil.

OBJECTIVE: To analyze the incidence, mortality and survival of prostate cancer in Cuiabá and Várzea Grande, Brazil from 2000 to 2016. METHODS: Data from the Population-based Cancer Registry and the Mortality Information System were used. Mortality and incidence trends were analyzed using joinpoint regression models by age group. Survival analyses were performed using the Kaplan-Meier method, and hazard ratio was estimated by age group. RESULTS: From 2000 to 2016, 3,671 new cases and 892 deaths for prostate cancer were recorded. The average incidence and mortality rates were 87.96 and 20.22 per 100,000, respectively. Decreasing incidence trend was noted for all age groups from 2006 to 2016 (APC=-3.2%) and for men with 80+ years of age from 2000 to 2016 (APC=-3.0%), and increasing mortality trend for men 60-69 years of age from 2000 to 2009 (APC=3.2%). The specific five-year survival rate for prostate cancer was 79.6% (95%CI 77.2-81.9), and the rate decreased with advanced age (HR=2.43, 95%CI 1.5-3.9, for those 70 to 79 years old and HR=7.20, 95%CI 4.5-11.5, for those 80 or older). CONCLUSION: The incidence rate of prostate cancer showed a decreasing trend from 2006 for all age groups; the mortality rate was stable in that period, and worse prognosis was observed in men 70 years or older.

Cancer surveillance in Mato Grosso: methodological and operational aspects of a extension/research projects / Vigilância do câncer em Mato Grosso: aspectos metodológicos e operacionais de um projeto de extensão/pesquisa

Objective: To describe the methodological and operational aspects of the Cancer Surveillance Project and its associated factors: population-based and hospital-based registry (VIGICAN), in Mato Grosso (MT). Methods: VIGICAN was divided into two projects: an extension one, which updated the data from the Population-Based Cancer Registry (RCBP) of MT in the period 2008 to 2016; and one of research, which collected primary data, through individual interviews and analysis of medical records of people with a diagnosis of cancer, aged 18 years or over, treated at reference hospitals for oncology. To analyze the factors associated with cancer, the following variables were collected: socioeconomic and demographic, social support, status and health behavior, and environmental exposure. Results: In the períod from 2008 to 2016, approximately one hundred thousand cases of cancer (incident and prevalent) were reported in the RCBP Cuiabá and Interior. After validation procedures, fifty thousand incident cases were chosen. The survey interviewed 1,012 patients, 38.2% living in the municipalities of Cuiabá and Várzea Grande, 60.4% in the interior of the state and 1.4% in other states. Preliminary data revealed that the majority were female (55.0%) and younger than 60 years (54.3%). Among those interviewed, 7.2% reported smoking tobacco, 15.5% consumed alcoholic beverages (15.5%) and 32.7% lived close to crops. Conclusion: The development of these projects allowed the integration of education with health services and will enable the recognition of specificities and different exposure scenarios and factors associated with cancer in the Mato Grosso territory.

Objetivo: Descrever os aspectos metodológicos e operacionais do Projeto Vigilância do Câncer e seus fatores associados: registro de base populacional e hospitalar (VIGICAN), em Mato Grosso (MT). Métodos: O VIGICAN se desdobrou em dois projetos: um de extensão, que atualizou os dados dos Registros de Câncer de Base Populacional (RCBP) de MT no período de 2008 a 2016; e um de pesquisa, que coletou dados primários, por meio de entrevistas individuais e análise de prontuários de pessoas com diagnóstico de câncer, com 18 anos ou mais, atendidas em hospitais de referência para oncologia. Para analisar os fatores associados ao câncer, foram coletadas as seguintes variáveis: socioeconômicas e demográficas, suporte social, situação e comportamentos de saúde e exposição ambiental. Resultados: No período de 2008 a 2016, foram notificados nos RCBP Cuiabá e Interior, aproximadamente, 100 mil casos de câncer (incidentes e prevalentes). Após procedimentos de validação, foram eleitos 50 mil casos incidentes. A pesquisa entrevistou 1.012 pacientes, sendo 38,2% residentes nos municípios de Cuiabá e Várzea Grande, 60,4% no interior do estado e 1,4% em outros estados. Os dados preliminares revelaram que a maioria era do sexo feminino (55,0%) e tinha menos de 60 anos (54,3%). Entre os entrevistados, 7,2% relataram fumar tabaco, 15,5% consumiam bebidas alcoólicas (15,5%) e 32,7% moravam próximos a lavouras. Conclusão: O desenvolvimento desses projetos permitiu a integração do ensino com os serviços de saúde e possibilitará o reconhecimento das especificidades e diferentes cenários de exposição e fatores associados ao câncer do território mato-grossense.

Incidence, mortality and survival of prostate cancer in two municipalities with a high human development index in Mato Grosso / Incidência, mortalidade e sobrevida do câncer de próstata em dois municípios com alto Índice de Desenvolvimento Humano de Mato Grosso

Objective: To analyze the incidence, mortality and prostate cancer survival in Cuiabá and Várzea Grande, from 2000 to 2016. Methods: Data from the Population-Based Cancer Registry and the Mortality Information System were used. Mortality and incidence trends analyses were performed using joinpoint regression models by age group. Survival analyses were performed using Kaplan-Meier method and hazard ratio was estimated by age group. Results: From 2000 to 2016, 3,671 new cases and 892 deaths for prostate cancer were recorded. The average incidence and mortality rates were 87.96 and 20.22 per 100,000, respectively. Decreasing incidence trend was noted for all age groups from 2006 to 2016 (APC = -3.2%) and for men with 80+ years of age from 2000 to 2016 (APC = -3.0%), and increasing mortality trend for men 60-69 years of age from 2000 to 2009 (APC = 3.2%). Prostate cancer specific five-year survival rate was 79.6% (CI95%: 77.2; 81.9), and the rate decreased with the advanced age (HR = 2.43, CI95%: 1,5;3,9 for those with 70 to 79 years old and HR = 7.20; CI95%: 4.5;11.5 for those with 80 years old or more). Conclusion: The incidence rate of prostate cancer presented a decreasing trend from 2006, for all age groups, the mortality rate was stable in the period, and worse prognosis was observed in men with 70 years old or more.

Objetivo: analisar a incidência, a mortalidade e a sobrevida por câncer de próstata em Cuiabá e Várzea Grande, no período de 2000 a 2016. Métodos: Foram utilizados os dados do Registro de Câncer de Base Populacional e do Sistema de Informação sobre Mortalidade. Para a análise de tendência da incidência e mortalidade foi utilizada a regressão por Joinpoint segundo faixa etária. Para estimar a probabilidade de sobrevivência foi utilizado o método de Kaplan-Meier e para avaliar a associação com a faixa etária foi estimado hazard ratio. Resultados: De 2000 a 2016, foram registrados 3.671 casos novos e 892 óbitos por câncer de próstata. A média das taxas no período (100.000 habitantes) foi de 87,96 para incidência e 20,22 para mortalidade. Verificou-se tendência decrescente da taxa de incidência para todas as idades de 2006 a 2016 (APC=-3,2%) e para homens com 80 anos ou mais de 2000 a 2016 (APC=-3,0%), e tendência crescente da taxa de mortalidade nos homens de 60-69 anos de 2000 a 2009 (APC=3,2%). A probabilidade de sobrevida específica em cinco anos foi de 79,6% (IC95%: 77,2; 81,9), e diminuiu com o aumento da faixa etária (HR=2,43; IC95%: 1,5; 3,9 para aqueles de 70 a 79 anos e HR= 7,20; IC95%: 4,5;11,5 de 80 anos ou mais). Conclusão: A taxa de incidência de câncer de próstata apresentou tendência de decréscimo a partir de 2006 para todas as idades, a taxa de mortalidade foi estável no período, e pior prognóstico foi observado em homens com 70 anos ou mais.

Cancer mortality in the state of Mato Grosso from 2000 to 2015: temporal trend and regional differences / Mortalidade por câncer no Estado de Mato Grosso no período de 2000 a 2015: tendência temporal e diferenças regionais

Objective: To analyze the trend of standardized rate due to mortality by cancer in the state of Mato Grosso, according to health regions, from 2000 to 2015. Methods: Ecological study of time series with data on deaths by cancer from the Mortality Information System. The rates were standardized using direct method and calculated by year and health regions. The annual percentage change (APC) and its respective confidence interval (CI 95%) were obtained through simple linear regression. Thematic maps were built to describe the rates spatial distribution. Results: There were 28,525 deaths by cancer registered in Mato Grosso and the five main causes were lung, prostate, stomach, breast and liver cancer. The highest mortality rates were found in the Médio Norte, Baixada Cuiabana and Sul Matogrossense regions. From 2000 to 2015 a growing trend was observed in the mortality rate by cancer in Mato Grosso (APC=0.81%; CI95%: 0.38; 1.26), and in four health regions, Garças Araguaia (APC=2.27%; CI95%: 1.46; 3.08), Sul Matogrossense (APC=1.12%; CI95%: 0.28; 1.97), Teles Pires (APC=1.93%; IC95%: 0,11; 3,74) and Vale dos Arinos (APC=2.61%; CI95%: 1.10; 4.70), the oter regions presented stability. Conclusion: In the state of Mato Grosso and in the four health regions there was verified a growing trend of mortality due to cancer. The results indicate the need to consider the regional differences regarding actions for cancer prevention, control and assistance.

Objetivo: Analisar a tendência da taxa padronizada de mortalidade por câncer no Estado de Mato Grosso, conforme regiões de saúde, no período de 2000 a 2015. Métodos: Estudo ecológico de séries temporais com dados de óbitos por neoplasias do Sistema de Informações de Mortalidade. As taxas foram padronizadas pelo método direto e calculadas por ano e por regiões de saúde. A variação anual percentual (annual percent change ­ APC) e seu respectivo intervalo de 95% de confiança (IC 95%) foram obtidos por meio da regressão linear simples. Foram construídos mapas temáticos para descrever a distribuição espacial das taxas. Resultados: Foram registrados 28.525 óbitos por câncer em Mato Grosso e os cinco principais tipos de câncer foram de pulmão, próstata, estomago, mama e fígado. As maiores taxas de mortalidade foram encontradas nas regiões Médio Norte, Baixada Cuiabana e Sul Matogrossense. No período de 2000 a 2015 foi observada tendência crescente na taxa de mortalidade por câncer em Mato Grosso (APC=0,81%; IC95%: 0,38; 1,26), e em quatro regiões de saúde, Garças Araguaia (APC=2,27%; IC95%: 1,46; 3,08), Sul Matogrossense (APC=1,12%; IC95%: 0,28; 1,97), Teles Pires (APC=1,93%; IC95%: 0,11; 3,74) e Vale dos Arinos (APC=2,61%; IC95%: 1,10; 4,70), as demais regiões apresentaram estabilidade. Conclusão: No Estado de Mato Grosso e em quatro regiões de saúde foi verificada tendência crescente de mortalidade por câncer. Os resultados indicam a necessidade de se considerar as diferenças regionais para as ações de prevenção, controle e assistência ao câncer.

Incidence, mortality and survival of prostate cancer in two municipalities with a high human development index in Mato Grosso, Brazil / Incidência, mortalidade e sobrevida do câncer de próstata em dois municípios com alto índice de desenvolvimento humano de Mato Grosso, Brasil

ABSTRACT: Objective: To analyze the incidence, mortality and survival of prostate cancer in Cuiabá and Várzea Grande, Brazil from 2000 to 2016. Methods: Data from the Population-based Cancer Registry and the Mortality Information System were used. Mortality and incidence trends were analyzed using joinpoint regression models by age group. Survival analyses were performed using the Kaplan-Meier method, and hazard ratio was estimated by age group. Results: From 2000 to 2016, 3,671 new cases and 892 deaths for prostate cancer were recorded. The average incidence and mortality rates were 87.96 and 20.22 per 100,000, respectively. Decreasing incidence trend was noted for all age groups from 2006 to 2016 (APC=-3.2%) and for men with 80+ years of age from 2000 to 2016 (APC=-3.0%), and increasing mortality trend for men 60-69 years of age from 2000 to 2009 (APC=3.2%). The specific five-year survival rate for prostate cancer was 79.6% (95%CI 77.2-81.9), and the rate decreased with advanced age (HR=2.43, 95%CI 1.5-3.9, for those 70 to 79 years old and HR=7.20, 95%CI 4.5-11.5, for those 80 or older). Conclusion: The incidence rate of prostate cancer showed a decreasing trend from 2006 for all age groups; the mortality rate was stable in that period, and worse prognosis was observed in men 70 years or older.

RESUMO: Objetivo: Analisar a incidência, a mortalidade e a sobrevida por câncer de próstata em Cuiabá e Várzea Grande, no período de 2000 a 2016. Métodos: Foram utilizados os dados do Registro de Câncer de Base Populacional e do Sistema de Informações sobre Mortalidade. Para a análise de tendência da incidência e mortalidade, foi utilizada a regressão por Joinpoint segundo faixa etária. Para estimar a probabilidade de sobrevivência foi utilizado o método de Kaplan-Meier e, para avaliar a associação com a faixa etária, foi estimado o hazard ratio (HR). Resultados: De 2000 a 2016, registraram-se 3.671 casos novos e 892 óbitos por câncer de próstata. A média das taxas no período (100.000 habitantes) foi de 87,96 para incidência e 20,22 para mortalidade. Verificou-se tendência decrescente da taxa de incidência para todas as idades de 2006 a 2016 (variação percentual anual — APC=-3,2%) e para homens com 80 anos ou mais de 2000 a 2016 (APC=-3,0%), bem como tendência crescente da taxa de mortalidade nos homens de 60-69 anos de 2000 a 2009 (APC=3,2%). A probabilidade de sobrevida específica em cinco anos foi de 79,6% (intervalo de confiança — IC95%: 77,2; 81,9) e diminuiu com o aumento da faixa etária (HR=2,43; IC95%: 1,5; 3,9 para aqueles de 70 a 79 anos e HR= 7,20; IC95%: 4,5;11,5 para aqueles de 80 anos ou mais). Conclusão: A taxa de incidência de câncer de próstata apresentou tendência de decréscimo a partir de 2006 para todas as idades, a taxa de mortalidade foi estável no período e o pior prognóstico foi observado em homens com 70 anos ou mais.

Cancer surveillance in Mato Grosso, Brazil: methodological and operational aspects of a university extension/research project / Vigilância do câncer em Mato Grosso, Brasil: aspectos metodológicos e operacionais de um projeto de extensão/pesquisa

ABSTRACT: Objective: To describe the methodological and operational aspects of the "Project for surveillance of cancer and its associated factors: population-based and hospital-based registry" (VIGICAN), in the state of Mato Grosso (MT), Brazil. Methods: VIGICAN was divided into two projects: a university extension one, which updated the data from the Population-based Cancer Registry (PBCR) of MT in the 2008-2016 period; and a research project, which collected primary data, through individual interviews and analysis of medical records of people with a diagnosis of cancer, aged 18 years or older, treated at reference hospitals for oncology. To analyze the factors associated with cancer, the following variables were collected: socioeconomic and demographic, social support, health status and behavior, and environmental exposure. Results: In the 2008-2016 period, approximately one hundred thousand cases of cancer (incident and prevalent) were reported in the PBCR Cuiabá and PBCR Interior. After validation procedures, 50 thousand incident cases were elected. The survey interviewed 1,012 patients, 38.2% living in the municipalities of Cuiabá and Várzea Grande, 60.4% in small cities of the state, and 1.4% in other states. Preliminary data showed that the majority were women (55.0%) and younger than 60 years of age (54.3%). Among the interviewees, 7.2% reported smoking tobacco, 15.5% consumed alcoholic beverages (15.5%), and 32.7% lived nearby crops. Conclusion: The development of these projects allowed the integration of education with health services and will enable the recognition of specificities and different exposure scenarios and factors associated with cancer in the Mato Grosso territory.

RESUMO: Objetivo: Descrever os aspectos metodológicos e operacionais do projeto "Vigilância do câncer e seus fatores associados: registro de base populacional e hospitalar" (VIGICAN), em Mato Grosso (MT). Métodos: O VIGICAN desdobrou-se em dois projetos: um de extensão, que atualizou os dados dos Registros de Câncer de Base Populacional (RCBP) de Mato Grosso no período de 2008 a 2016; e um de pesquisa, que coletou dados primários por meio de entrevistas individuais e análise de prontuários de pessoas com diagnóstico de câncer, com 18 anos ou mais, atendidas em hospitais de referência para oncologia. Para analisar os fatores associados ao câncer, foram coletadas as seguintes variáveis: socioeconômicas e demográficas, suporte social, situação e comportamentos de saúde e exposição ambiental. Resultados: No período de 2008 a 2016, foram notificados nos RCBP Cuiabá e Interior, aproximadamente, 100 mil casos de câncer (incidentes e prevalentes). Após os procedimentos de validação, foram eleitos 50 mil casos incidentes. A pesquisa entrevistou 1.012 pacientes, sendo 38,2% residentes nos municípios de Cuiabá e Várzea Grande, 60,4% no interior do Estado e 1,4% em outros Estados. Os dados preliminares revelaram que a maioria era do sexo feminino (55,0%) e tinha menos de 60 anos (54,3%). Entre os entrevistados, 7,2% relataram fumar tabaco, 15,5% consumiam bebidas alcoólicas (15,5%) e 32,7% moravam próximo a lavouras. Conclusão: O desenvolvimento desses projetos permitiu a integração do ensino com os serviços de saúde e possibilitará o reconhecimento das especificidades e dos diferentes cenários de exposição ao câncer, bem como fatores associados a ele, no território mato-grossense.

Cancer mortality in the State of Mato Grosso from 2000 to 2015: temporal trend and regional differences / Mortalidade por câncer no estado de Mato Grosso, Brasil, no período de 2000 a 2015: tendência temporal e diferenças regionais

ABSTRACT: Objective: To analyze the trend of standardized cancer mortality rate in the state of Mato Grosso according to health regions, from 2000 to 2015. Methods: Ecological time series study with data on deaths by cancer from the Mortality Information System. The rates were standardized using direct method and calculated by year and health regions. The annual percentage changes (APC) and respective confidence interval (95%CI) were obtained through simple linear regression. Thematic maps were built to show the spatial distribution of rates. Results: There were 28,525 deaths by cancer registered in Mato Grosso, with the main types being lung, prostate, stomach, breast and liver cancer. The highest mortality rates were found in regions Médio Norte, Baixada Cuiabana and Sul Mato-Grossense. From 2000 to 2015, an upward trend was seen in the mortality rate by cancer in Mato Grosso (APC=0.81%; 95%CI 0.38-1.26), and in four health regions, Garças Araguaia (APC=2.27%; 95%CI 1.46-3.08), Sul Mato-Grossense (APC=1.12%; 95%CI 0.28-1.97), Teles Pires (APC=1.93%; 95%CI 0,11-3,74) and Vale dos Arinos (APC=2.61%; 95%CI 1.10-4.70), while the other regions remained stable. Conclusion: In the state of Mato Grosso and in the four health regions, cancer mortality rate showed a growing trend. The results point to the need to consider regional differences when thinking about actions for cancer prevention, control and assistance.

RESUMO: Objetivo: Analisar a tendência da taxa padronizada de mortalidade por câncer no estado de Mato Grosso, Brasil, conforme regiões de saúde, no período de 2000 a 2015. Métodos: Estudo ecológico de séries temporais com dados de óbitos por neoplasias do Sistema de Informação sobre Mortalidade. As taxas foram padronizadas pelo método direto e calculadas por ano e por regiões de saúde. A variação anual percentual (annual percent change — APC) e seu respectivo intervalo de 95% de confiança (IC95%) foram obtidos por meio da regressão linear simples. Construíram-se mapas temáticos para descrever a distribuição espacial das taxas. Resultados: Foram registrados 28.525 óbitos por câncer em Mato Grosso, e os cinco principais tipos de câncer foram de pulmão, próstata, estômago, mama e fígado. As maiores taxas de mortalidade foram encontradas nas regiões Médio Norte, Baixada Cuiabana e Sul-Mato-Grossense. No período de 2000 a 2015 foi observada tendência crescente na taxa de mortalidade por câncer em Mato Grosso (APC=0,81%; IC95% 0,38-1,26), e em quatro regiões de saúde, Garças Araguaia (APC=2,27%; IC95% 1,46-3,08), Sul-Mato-Grossense (APC=1,12%; IC95% 0,28-1,97), Teles Pires (APC=1,93%; IC95% 0,11-3,74) e Vale dos Arinos (APC=2,61%; IC95% 1,10-4,70). As demais regiões apresentaram estabilidade. Conclusão: No estado de Mato Grosso e em quatro regiões de saúde foi verificada tendência crescente de mortalidade por câncer. Os resultados indicam a necessidade de se considerar as diferenças regionais para as ações de prevenção e assistência ao câncer e de controle.

Lead-DBS: an additional tool for stereotactic surgery.

OBJECTIVE: Use Lead-DBS software to analyze stereotactical surgical outcome of an operated population and demonstrate that small target deviations do not compromise the stimulation of desired structures, even with small amperages. METHODS: Image exams of patients submitted to deep brain stimulation for movement disorders treatment were processed in Lead-DBS software. Electrode stereotactic coordinates were subtracted from the planned target and those deviations, compared among different anatomical targets and sides operated firstly and secondly. We also quantified the frequency of relation between the activated tissue volume and the planned target through computer simulations. RESULTS: None of the 16 electrodes were exactly implanted at the planned coordinates. A stimulation of 3 mA reached 62.5% of the times the planned coordinates, rising to 68.75% with a 3,5 mA. No statistical significance was demonstrated in any comparison of laterality and anatomical sites. CONCLUSIONS: The simulation of small amperage fields could reach the intended target even when electrode placement is suboptimal. Furthermore, such a goal can be achieved without overlapping the volume of activated tissue with undesired structures. Software Lead-DBS proved to be a valuable complementary asset for surgical stereotactical result assessment.

Study of the effects of kinesthetic motor imagery in patients with heart failure.

OBJECTIVE: The aim was to investigate the acute effect of kinesthetic motor imagery of the 2-minute walk test on hemodynamic and cardiopulmonary variables in patients with heart failure. METHODS: Twenty participants were recruited for the analysis of these variables before and after the execution and imagination of the 2-minute walk test, with the number of laps executed and imagined being recorded. RESULTS: The main results observed showed that (1) there was no difference in the number of laps executed and imagined (p=0.41), indicating that the participants actually imagined the test and (2) the motor imagery of the 2-minute walk test immediately increased (p<0.001) the heart and respiratory rates. CONCLUSION: The motor imagery seems to have acute effects on the cardiopulmonary anticipatory responses of a patient with heart failure.

EDU (5-Ethynyl-2'-Deoxyuridine)-Coupled Fluorescence-Intensity Analysis: Determining Absolute Parameters of the Cell Cycle.

The principles and practice of a methodology of cell cycle analysis that allows the estimation of the absolute length (in units of time) of all cell cycle stages (G1, S, and G2) are detailed herein. This methodology utilizes flow cytometry to take full advantage of the excellent stoichiometric properties of click chemistry. This allows detection, via azide-fluorochrome coupling, of the modified deoxynucleoside 5-ethynyl-2'-deoxyuridine (EDU) incorporated into replicated DNA through incremental pulsing times. This methodology, which we designated as EdU-Coupled Fluorescence Intensity (E-CFI) analysis, can be applied to cell types with very distinct cell cycle features, and has shown excellent agreement with established techniques of cell cycle analysis. Useful modifications to the original protocol (Pereira et al., Oncotarget, 8:40514-40,532, 2017) have been introduced to increase flexibility in data collection and facilitate data analysis.

Lead-DBS: an additional tool for stereotactic surgery

SUMMARY OBJECTIVE: Use Lead-DBS software to analyze stereotactical surgical outcome of an operated population and demonstrate that small target deviations do not compromise the stimulation of desired structures, even with small amperages. METHODS: Image exams of patients submitted to deep brain stimulation for movement disorders treatment were processed in Lead-DBS software. Electrode stereotactic coordinates were subtracted from the planned target and those deviations, compared among different anatomical targets and sides operated firstly and secondly. We also quantified the frequency of relation between the activated tissue volume and the planned target through computer simulations. RESULTS: None of the 16 electrodes were exactly implanted at the planned coordinates. A stimulation of 3 mA reached 62.5% of the times the planned coordinates, rising to 68.75% with a 3,5 mA. No statistical significance was demonstrated in any comparison of laterality and anatomical sites. CONCLUSIONS: The simulation of small amperage fields could reach the intended target even when electrode placement is suboptimal. Furthermore, such a goal can be achieved without overlapping the volume of activated tissue with undesired structures. Software Lead-DBS proved to be a valuable complementary asset for surgical stereotactical result assessment.

A new microtubule-stabilizing agent shows potent antiviral effects against African swine fever virus with no cytotoxicity.

African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity. The most promising antiviral compound (6b) reduced ASFV replication in a dose-dependent manner (IC50 = 19.5 µM) with no cellular (CC50 > 500 µM) and animal toxicity (up to 100 mg/kg). Results also revealed that compound 6b interfered with ASFV attachment, internalization and egress, with time-of-addition assays, showing that compound 6b has higher antiviral effects when added within 2-8 h post-infection. This compound significantly inhibited viral DNA replication and disrupted viral protein synthesis. Experiments with ASFV-infected porcine macrophages disclosed that antiviral effects of the compound 6b were similar to its effects in Vero cells. Tubulin polymerization assay and confocal microscopy demonstrated that compound 6b promoted tubulin polymerization, acting as a microtubule-stabilizing, rather than a destabilizing agent in cells. In conclusion, this work emphasizes the idea that microtubules can be targets for drug development against ASFV.

Lower-limb muscle strength, static and dynamic postural stabilities, risk of falling and fear of falling in polio survivors and healthy subjects.

INTRODUCTION: This study investigated the association between preserved lower-limb muscle strength, dynamic and static postural stability, risk of falling, and fear of falling in polio survivors. We also investigated whether these clinical features differ between polio survivors and healthy controls. Methods: This quasi-experimental study enrolled 16 polio survivors (13 underwent a complete-case analysis) and 12 age- and sex-matched healthy controls. Participants were assessed by the manual muscle test, Berg Balance Scale, force platform posturography, and Falls Efficacy Scale. Between-group mean differences with confidence intervals (MD, CI 95%) and Spearman's ρ are reported. Results: Compared to healthy controls, polio survivors presented reduced muscle strength (MD = -13, CI 95% -16 to -9 points), lower dynamic postural stability (MD = -14, CI 95% -19 to -8 points), and increased fear of falling (MD = 14, CI 95% 10-18 points) (all P < 0.001). In polio survivors, lower-limb muscle strength was correlated with dynamic (ρ = 0.760) and static postural stability (ρ = 0.738-0.351), risk of falling (ρ = -0.746), and fear of falling (ρ = -0.432). Dynamic postural stability was correlated with risk of falling (ρ = -0.841), fear of falling (ρ = -0.277), and static postural stability (ρ = -0.869 to -0.435; ρ = -0.361 to -0.200, respectively). Risk and fear of falling were also correlated (ρ = 0.464). Discussion: Polio survivors exhibited impaired dynamic postural stability but preserved static stability and increased risk of falling and fear of falling. Preserved lower-limb muscle strength, postural stability, fear of falling, and risk of falling are associated clinical features in this population.