Drogas e prisões em Portugal

Circulam e consomem-se drogas nas prisões da maior parte dos países do mundo. Este é um fenómeno que se acentuou ao longo dos últimos anos do século XX, provocando alterações significativas no sistema prisional. Conhecer os contornos do fenómeno para o caso de Portugal foi o objectivo da pesquisa que está na base do presente livro.Este livro foi adjudicado pelo Instituto Português da Droga e Toxicodependência e resultou de uma deliberação conjunta de Suas Excelências, o Sr. Ministro da Ciência e Tecnologia, Professor Doutor José Mariano Gago, o Sr. Ministro da Justiça, Dr. António Costa e o Secretário de estado da Presidência do Conselho de Ministros, Dr. Vitalino Canas, do XIV Governo Constitucional

Fatores associados a sintomas osteomusculares em profissionais que trabalham sentados

OBJETIVOS: Estimar a prevalência de sintomas osteomusculares e analisar os fatores a eles associados em profissionais de setores administrativos que trabalham predominantemente na postura sentada. MÉTODOS: Trata-se de estudo transversal com dados obtidos de 451 trabalhadores de instituição pública federal na região Sul do país. A variável dependente foi o número de sintomas osteomusculares nos últimos 12 meses, aferido utilizando-se o Questionário Nórdico de Sintomas Osteomusculares. Foram investigadas 19 variáveis independentes, divididas em quatro categorias: características sociodemográficas, comportamentais, ocupacionais e de saúde. Foi realizada análise univariada e, na sequência, regressão múltipla de Poisson com variância robusta. As variáveis independentes foram inseridas em blocos com critério backward stepwise, considerando o valor para estatística de Wald igual a 0,20. As medidas de efeito foram expressas em aumento relativo (AR) no valor médio, sendo os dados analisados para um nível de significância de 5%. RESULTADOS: A prevalência estimada de sintomas osteomusculares nos últimos 12 meses foi de 90% (intervalo de confiança – IC95% 87–93). No modelo final da análise de regressão, as variáveis sexo feminino (AR = 14,75%), índice de capacidade para o trabalho baixo (AR = 100,02%) e moderado (AR = 64,06%), uso de medicamentos (AR = 48,06%) e circunferência da cintura em risco (AR = 15,59%) tiveram associação significativa com o aumento da média de sintomas; já a escolaridade com ensino técnico atuou como fator de proteção, reduzindo a média em 36,46%. CONCLUSÕES: A alta prevalência de sintomas osteomusculares encontrada e os fatores associados indicam a necessidade de propor ações e cuidados específicos para essa população, como tratamento imediato dos sintomas e mudanças na organização e no ambiente laboral, a fim de alcançar equilíbrio e harmonia nas exigências do trabalho sentado prolongado e evitar o impacto dessa condição na saúde pública. DESCRITORES: Saúde do Trabalhador. Medidas de Associação, Exposição, Risco ou Desfecho. Transtornos Traumáticos Cumulativos. Postura. Estilo de Vida Sedentário.OBJECTIVE: To estimate the prevalence of musculoskeletal symptoms and analyze their associated factors in professionals from administrative sectors working predominantly in sitting position. METHODS: This is a cross-sectional study with data obtained from 451 workers from a federal public institution in Southern Brazil. The dependent variable was the number of musculoskeletal symptoms in the prior 12 months, measured using the Nordic Musculoskeletal Questionnaire. In the analyses, 19 independent variables were investigated, divided into four categories: sociodemographic, behavioral, occupational and health characteristics. Univariate analysis and multiple Poisson regression with robust variance were performed. The independent variables were inserted into blocks with stepwise backward criterion, considering the value for Wald statistics equal to 0.20. The effect measures were expressed in a relative increase (RI) in the mean value, and the data were analyzed for a 5% significance level. RESULTS: The estimated prevalence of musculoskeletal symptoms in the prior 12 months was 90% (confidence interval – 95%CI 87–93). In the final model of regression analysis, the variables female gender (RI = 14.75%), low (RI = 100.02%) and moderate (RI = 64.06%) work ability index, use of medications (RI = 48.06%) and waist circumference at risk (RI = 15.59%) had a significant association with the increase in the mean number of symptoms; schooling with technical education acted as a protective factor, reducing the mean by 36.46%. CONCLUSIONS: The high prevalence of musculoskeletal symptoms found and the associated factors indicate the need to propose specific actions and care for this population, such as immediate treatment of symptoms and changes in the organization and work environment, to achieve balance and harmony in the demands of prolonged sitting work and avoid its impact effect of this condition on public health. DESCRIPTORS: Occupational Health. Measures of Associa

CuMV VLPs Containing the RBM from SARS-CoV-2 Spike Protein Drive Dendritic Cell Activation and Th1 Polarization.

Dendritic cells (DCs) are the most specialized and proficient antigen-presenting cells. They bridge innate and adaptive immunity and display a powerful capacity to prime antigen-specific T cells. The interaction of DCs with the receptor-binding domain of the spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pivotal step to induce effective immunity against the S protein-based vaccination protocols, as well as the SARS-CoV-2 virus. Herein, we describe the cellular and molecular events triggered by virus-like particles (VLPs) containing the receptor-binding motif from the SARS-CoV-2 spike protein in human monocyte-derived dendritic cells, or, as controls, in the presence of the Toll-like receptors (TLR)3 and TLR7/8 agonists, comprehending the events of dendritic cell maturation and their crosstalk with T cells. The results demonstrated that VLPs boosted the expression of major histocompatibility complex molecules and co-stimulatory receptors of DCs, indicating their maturation. Furthermore, DCs' interaction with VLPs promoted the activation of the NF-kB pathway, a very important intracellular signalling pathway responsible for triggering the expression and secretion of proinflammatory cytokines. Additionally, co-culture of DCs with T cells triggered CD4+ (mainly CD4+Tbet+) and CD8+ T cell proliferation. Our results suggested that VLPs increase cellular immunity, involving DC maturation and T cell polarization towards a type 1 T cells profile. By providing deeper insight into the mechanisms of activation and regulation of the immune system by DCs, these findings will enable the design of effective vaccines against SARS-CoV-2

Factors associated with musculoskeletal symptoms in professionals working in sitting position

Objetivos: Estimar a prevalência de sintomas osteomusculares e analisar os fatores a eles associados em profissionais de setores administrativos que trabalham predominantemente na postura sentada.Métodos: Trata-se de estudo transversal com dados obtidos de 451 trabalhadores de instituição pública federal na região Sul do país. A variável dependente foi o número de sintomas osteomusculares nos últimos 12 meses, aferido utilizando-se o Questionário Nórdico de Sintomas Osteomusculares. Foram investigadas 19 variáveis independentes, divididas em quatro categorias: características sociodemográficas, comportamentais, ocupacionais e de saúde. Foi realizada análise univariada e, na sequência, regressão múltipla de Poisson com variância robusta. As variáveis independentes foram inseridas em blocos com critério backward stepwise, considerando o valor para estatística de Wald igual a 0,20. As medidas de efeito foram expressas em aumento relativo (AR) no valor médio, sendo os dados analisados para um nível de significância de 5%. Resultados: A prevalência estimada de sintomas osteomusculares nos últimos 12 meses foi de 90% (intervalo de confiança – IC95% 87–93). No modelo final da análise de regressão, as variáveis sexo feminino (AR = 14,75%), índice de capacidade para o trabalho baixo (AR = 100,02%) e moderado (AR = 64,06%), uso de medicamentos (AR = 48,06%) e circunferência da cintura em risco (AR = 15,59%) tiveram associação significativa com o aumento da média de sintomas; já a escolaridade com ensino técnico atuou como fator de proteção, reduzindo a média em 36,46%. Conclusões: A alta prevalência de sintomas osteomusculares encontrada e os fatores associados indicam a necessidade de propor ações e cuidados específicos para essa população, como tratamento imediato dos sintomas e mudanças na organização e no ambiente laboral, a fim de alcançar equilíbrio e harmonia nas exigências do trabalho sentado prolongado e evitar o impacto dessa condição na saúde pública.Objective: To estimate the prevalence of musculoskeletal symptoms and analyze their associated factors in professionals from administrative sectors working predominantly in sitting position. Methods: This is a cross-sectional study with data obtained from 451 workers from a federal public institution in Southern Brazil. The dependent variable was the number of musculoskeletal symptoms in the prior 12 months, measured using the Nordic Musculoskeletal Questionnaire. In the analyses, 19 independent variables were investigated, divided into four categories: sociodemographic, behavioral, occupational and health characteristics. Univariate analysis and multiple Poisson regression with robust variance were performed. The independent variables were inserted into blocks with stepwise backward criterion, considering the value for Wald statistics equal to 0.20. The effect measures were expressed in a relative increase (RI) in the mean value, and the data were analyzed for a 5% significance level. Results: The estimated prevalence of musculoskeletal symptoms in the prior 12 months was 90% (confidence interval – 95%CI 87–93). In the final model of regression analysis, the variables female gender (RI = 14.75%), low (RI = 100.02%) and moderate (RI = 64.06%) work ability index, use of medications (RI = 48.06%) and waist circumference at risk (RI = 15.59%) had a significant association with the increase in the mean number of symptoms; schooling with technical education acted as a protective factor, reducing the mean by 36.46%. Conclusions: The high prevalence of musculoskeletal symptoms found and the associated factors indicate the need to propose specific actions and care for this population, such as immediate treatment of symptoms and changes in the organization and work environment, to achieve balance and harmony in the demands of prolonged sitting work and avoid its impact effect of this condition on public health

Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma is a bone-forming tumor of mesenchymal origin that presents a clinical pattern that is consistent with the cancer stem cell model. Cells with stem-like properties (CSCs) have been identified in several tumors and hypothesized as the responsible for the relative resistance to therapy and tumor relapses. In this study, we aimed to identify and characterize CSCs populations in a human osteosarcoma cell line and to explore their role in the responsiveness to conventional therapies.</p> <p>Methods</p> <p>CSCs were isolated from the human MNNG/HOS cell line using the sphere formation assay and characterized in terms of self-renewal, mesenchymal stem cell properties, expression of pluripotency markers and ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to conventional chemotherapeutic agents and to irradiation was analyzed and related with cell cycle-induced alterations and apoptosis.</p> <p>Results</p> <p>The isolated CSCs were found to possess self-renewal and multipotential differentiation capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs were relatively more resistant to both chemotherapy and irradiation. None of the treatments have induced significant cell-cycle alterations and apoptosis in CSCs.</p> <p>Conclusions</p> <p>MNNG/HOS osteosarcoma cells contain a stem-like cell population relatively resistant to conventional chemotherapeutic agents and irradiation. This resistant phenotype appears to be related with some stem features, namely the high expression of the drug efflux transporters P-glycoprotein and BCRP and their quiescent nature, which may provide a biological basis for resistance to therapy and recurrence commonly observed in osteosarcoma.</p

Drugs and prisons in Portugal: synopsis and technical appendix of a research.

The concept of drugs circulating and being trafficked and consumed in prison just as in the outside world is in the first instance not only strange, but it also tends to go against our commonsense notions. Do we not have the image of prison establishments as being fortresses, closed institutions, impenetrable by the outside world, where surveillance is a constant factor? How can illicit business be conducted when there is permanent control over the lives of the inmates and no privacy at all? When we look closer, however, these ideas start to vanish. Just as in the free world, drug circulation in prisons is a reality in all developed countries, independently of their penal systems and legal frameworks. In fact, these fortresses are much more permeable than they appear to be. There are daily and permanent contacts established with the prison world by the suppliers of goods and services – e.g. meals, maintenance, education, training, health, medicines and other pharmaceutical and clinical products. Visitors are another source of almost daily interaction between prisons and the outside world, and so are the prison staff – e.g. administrative, health and rehabilitation technicians, surveillance and maintenance personnel. Last but not least, a specific group of inmates contacts the free world almost daily thanks to its special regime. These regular exchanges are the weak links, virtually unpreventable, by an institution that seems invulnerable and impenetrable. Other factors explain, however, this permeability to drug trafficking and consumption in the prison system. The reasons that make drugs a highly profitable business opportunity – i.e. their illicitness and the high returns of their trade – also apply in the prison environment and are even taken to a higher and more serious level. Our major research aim is to assess and understand the prevalence and characteristics of the drug issue in Portuguese prisons

Implicação do óxido nítrico na alteração da barreira hemato-retiniana de modelos animais da diabetes

Tese de doutoramento em Biologia (Biologia Celular) apresentada à Fac. de Ciências e Tecnologia de Coimbr

Effect of Temozolamide in the U-118 glioma cell line

Dissertação de Mestrado Integrado em Medicina apresentada à Faculdade de Medicina da Universidade de Coimbra.Glioblastomas (GBM) are the most lethal subtype of astrocytomas, with a survival rate of 12 months after diagnosis. The gold standard treatment of GBM, which comprises surgery followed by the combination of radiotherapy and chemotherapy with temozolomide (TMZ), increases the survival rate to 14.6 months. The success of TMZ seems to be limited by the occurrence of chemoresistance that allows glioma cells to escape from death signaling pathways. The mechanisms of TMZ action and of chemoresistance development are not completely understood. When TMZ started to be used the chemoresistance was associated to an increased activity of DNA repair enzymes, namely MGMT. However, recent studies pointed that the activity of survival signaling pathways such as PI3K/AKT, ERK 1/2 MAP kinase and autophagy also contributes to chemoresistence, but the interaction between those signaling pathways and TMZ has not been fully investigated. Therefore, our aim was to study the TMZ mechanism of action in the U-118 human glioma cell line and at the same time to investigate the possible mechanisms associated to the development of chemoresistance. For that, U-118 cells were incubated with TMZ and the activity of the survival pathways PI3K/AKT, ERK 1/2 MAP kinase and autophagy as well as the proliferation and apoptosis ability were studied. Cell proliferation was evaluated by incorporation of bromodeoxyuridine. Apoptosis was studied by flow cytometry and also by fluorescence confocal microscopy. The expression of LC3, PI3/AKT and ERK1/2 was evaluated by western blot. In U-118 cells, TMZ induced a significant reduction of the proliferation ability, but only a slight increase in the percentage of apoptotic cells. The evaluation of autophagy revealed that TMZ induced an increase in LC3 expression, the autophagyassociated protein, suggesting that U-118 cells may use autophagy to escape from cell death. In addition, TMZ induced a slight reduction in the phosphorylation status of PI3K/AKT, but did not alter the phosphorylation status of ERK1/2 MAP kinase which suggests that these signaling pathways may also contribute to chemoresistance. In order to confirm the contribution of autophagy, PI3K/AKT and ERK 1/2 MAP kinase to chemoresistance, U-118 cells were incubated with specific inhibitors of the pathways plus TMZ and the occurrence of apoptosis was evaluated by flow cytometry. The results showed that chemoresistance was partially overwhelmed when the cells were simultaneously treated with TMZ plus the inhibitors. Therefore, our results indicated that the treatment of GBM with alkylating agents such as TMZ should be accompanied by the use of inhibitors of the survival pathways.Os glioblastomas (GBM) são considerados os astrocitomas mais letais, apresentando uma taxa de sobrevivência de 12 meses após o diagnóstico. O tratamento dos GBM assenta na cirurgia seguida de radioterapia e quimioterapia com temozolamida (TMZ). A TMZ é considerada o padrão de ouro no tratamento destes tumores desde que foi demonstrado que a taxa de sobrevivência dos doentes tratados com TMZ aumentava em média para 14.6 meses, após o diagnóstico. No entanto, o sucesso da TMZ é limitado pela ocorrência de quimioresistência que permite que as células activem mecanismos de fuga às alterações induzidas pela TMZ. Os mecanismos celulares e moleculares que contribuem para a quimioresistência não são bem conhecidos. Nos estudos iniciais pensou-se que a resistência estava associada à actividade das enzimas reparadoras do DNA, nomeadamente à MGMT. No entanto, estudos mais recentes demonstraram que as vias de sinalização associadas à sobrevivência celular como a PI3K/AKT, cinase ERK 1/2 MAP e autofagia pareciam também contribuir para a quimioresistência. Os mecanismos de interação entre a TMZ e as vias de sinalização não foram ainda completamente estudados. Assim, o objectivo deste trabalho foi estudar o mecanismo de acção da TMZ na linha celular de glioma U-118 e ao mesmo tempo tentar identificar os mecanismos envolvidos na quimioresistência. Para tal, incubaram-se células U-118 com TMZ e avaliou-se a actividade das vias de sinalização PI3K/AKT, ERK 1/2 MAP cinase e autofagia bem como a taxa de proliferação e de apoptose. A proliferação celular foi determinada utilizando a bromodeoxiuridina. A percentagem de células apoptóticas foi avaliada por citometria de fluxo e por microscopia confocal de fluorescência de modo a determinar a percentagem de células em sub G0/G1 e o grau de condensação de cromatina, respectivamente. A expressão de LC3, PI3/AKT e de ERK1/2 foi avaliada por "western blot". Verificou-se que nas células U-118 a TMZ induziu uma redução significativa da proliferação mas que apenas induziu um ligeiro aumento na percentagem de células apoptóticas. Verificou-se também que a TMZ induziu um aumento significativo na expressão de LC3, o que parece indicar que a TMZ induz autofagia e consequentemente pode contribuir para que as células U-118 sejam resistentes ao tratamento com TMZ. Os resultados obtidos demonstraram também que a TMZ induz uma ligeira redução na fosforilação da PI3K/AKT mas que não altera o estado de fosforilação da cinase ERK1/2 MAP. A manutenção da actividade destas vias de sinalização pode também contribuir para a quimioresistência. Para confirmar que a autofagia, a PI3K/AKT e a cinase ERK 1/2 MAP podem contribuir para quimioresistência, células U-118 foram incubadas com inibidores específicos destas vias de sinalização e a percentagem de células apoptóticas foi determinada por citometria de fluxo. Os resultados demonstraram que na presença destes inibidores a percentagem de células apoptóticas aumentava quando comparada com a percentagem de células apoptóticas obtida apenas na presença de TMZ. Assim, os resultados obtidos neste trabalho parecem indicar que o tratamento de células de glioma deve ser um tratamento combinado envolvendo não só agentes alquilantes como a TMZ mas também inibidores específicos das vias de sinalização envolvidas na sobrevivência e morte celular