Regulation of tumor growth by CHOP chemotherapy-generated debris

While CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), the current standard of care for non-Hodgkin lymphoma (NHL), kills tumor cells, the accumulation of tumor cell “debris” can stimulate inflammation and tumor growth. Thus, cytotoxic cancer therapies are a double-edged sword. Previous studies have shown that apoptotic debris stimulates tumor growth. We hypothesize that (1) CHOP-generated tumor cell debris can promote lymphoma progression via release of pro-inflammatory cytokines; (2) blocking phosphatidylserine (PS), which is presented on the surface of apoptotic cells, may inhibit debris-stimulated cancer progression. METHODS: Lymphoma EL4 debris was generated by treating tumor cells with CHOP chemotherapy. EL4 debris was isolated via Ficoll gradient and co-injected with living EL4 tumor cells into immunocompetent C57BL/6 mice. Macrophage-secreted cytokines were measured via array analysis. RESULTS: Flow cytometry confirmed CHOP chemotherapy generated apoptotic/necrotic debris. Vincristine-, mafosfamide-, and prednisolone-generated lymphoma EL4 debris stimulated tumor growth by over 100-fold in a dose-dependent manner. Debris alone did not induce tumors, even at 250 days post-injection. Doxorubicin-generated EL4 debris stimulated tumor growth at low dose (1x105), but inhibited growth at high dose (9x105). Systemic administration of doxorubicin-generated EL4 debris or blocking PS in the cell debris generated by doxorubicin using annexin V or an anti-PS neutralizing antibody inhibited doxorubicin-generated debris-stimulated tumor growth. Therapy-generated debris stimulated macrophage pro-inflammatory cytokine production. CONCLUSIONS: CHOP chemotherapy-generated debris regulates tumor growth via cytokine production. Thus, harnessing the anti-tumor activity of inhibitory debris or neutralizing PS on stimulatory debris may be a novel anti-cancer approach.2018-07-11T00:00:00

Host-Pathogen Interactions at the Intestinal Epithelial Barrier

This thesis reports investigations of the interactions between the intestinal epithelial barrier and the intracellular apicomplexan Eimeria spp., both in vivo and in vitro. Initially, conventional in vivo studies using genetically modified animals were used to investigate the contribution of innate lymphoid cells (ILCs) to immune protection of the intestinal barrier. Additionally, to understand complex epithelial host-pathogen interactions a novel in vitro model of small intestine organoids was developed. Data suggest that immunoprotection against Eimeria vermiformis infections is mediated by T cells. Furthermore, there is an indication that ILCs have a detrimental effect in Eimeria vermiformis-infected immunocompromised animals. However, the role for ILCs in the regulation of the immune response remains unclear. The life cycles of Eimeria vermiformis and Eimeria falciformis are highly complex, comprising multiple schizogonies followed by a gametogony. In vitro life cycle completion has not been achieved to date due to the limitations of monolayer cell line models. It is likely that for a successful parasite development the interaction of the different epithelial cell types present in intestinal organoids is required. The development of intestinal organoids by Sato and colleagues gave rise to a breakthrough in cellular studies, providing the tools to study complex interactions between host tissues and invading pathogens in vitro. I showed that small intestine-derived organoids grow exponentially after passage and that each organoid contains distinct specialised epithelial cell types, such as Paneth, Goblet or enteroendocrine cells, suggesting that the organoid model closely resembles the native intestinal epithelium and that Eimeria spp. benefit from the three-dimensional structure and physiological characteristics of the organoid model. Intestinal organoids were infected with E. vermiformis or E. falciformis sporozoites. These completed several rounds of asexual replication but did not proceed to the final gametogony. Despite the need for the development of sensitive techniques applicable to three-dimensional cell culture models, these results indicate that intestine-derived organoids are a promising model to study host-parasite interactions at the intestinal epithelial barrier at the cellular and molecular levels.BEC (Babraham Executive Committee

Self-reported work-related musculoskeletal disorders among health professionals at a hospital in Portugal

Background: Work-related musculoskeletal disorders (WMSDs) are responsible for morbidity among many health professionals. Objective: To establish the prevalence of self-reported WMSDs among health professionals. Methods: Descriptive and exploratory study with health professionals at a hospital in northern Portugal. Data were collected in December 2017 by means of an electronic questionnaire applied to the total target population (n=435). We applied instruments for sociodemographic characterization, perception of knowledge on ergonomics and manual mobilization of loads, the Patient Handling Burden Scale (PHBS) and the Nordic Musculoskeletal Questionnaire (NMQ) for self-reporting musculoskeletal symptoms. Results: The sample comprised 105 professionals, mainly nurses and nursing assistants, who exhibited high frequency of symptoms in several body areas, mainly the spine. Conclusions: WMSDs involving health professionals should be considered a problem for health institutions which do not implement interventions beyond traditional training programs, especially multifactorial programs of systemic nature.info:eu-repo/semantics/publishedVersio

More Than Meets The Eye : Has the Eye Care Policy in Scotland Had Wider Health Benefits?

Publisher PD

Robust surface modelling of visual hull from multiple silhouettes

Reconstructing depth information from images is one of the actively researched themes in computer vision and its application involves most vision research areas from object recognition to realistic visualisation. Amongst other useful vision-based reconstruction techniques, this thesis extensively investigates the visual hull (VH) concept for volume approximation and its robust surface modelling when various views of an object are available. Assuming that multiple images are captured from a circular motion, projection matrices are generally parameterised in terms of a rotation angle from a reference position in order to facilitate the multi-camera calibration. However, this assumption is often violated in practice, i.e., a pure rotation in a planar motion with accurate rotation angle is hardly realisable. To address this problem, at first, this thesis proposes a calibration method associated with the approximate circular motion. With these modified projection matrices, a resulting VH is represented by a hierarchical tree structure of voxels from which surfaces are extracted by the Marching cubes (MC) algorithm. However, the surfaces may have unexpected artefacts caused by a coarser volume reconstruction, the topological ambiguity of the MC algorithm, and imperfect image processing or calibration result. To avoid this sensitivity, this thesis proposes a robust surface construction algorithm which initially classifies local convex regions from imperfect MC vertices and then aggregates local surfaces constructed by the 3D convex hull algorithm. Furthermore, this thesis also explores the use of wide baseline images to refine a coarse VH using an affine invariant region descriptor. This improves the quality of VH when a small number of initial views is given. In conclusion, the proposed methods achieve a 3D model with enhanced accuracy. Also, robust surface modelling is retained when silhouette images are degraded by practical noise

Riesgos psicosociales de los enfermeros que prestan asistencia al paciente crítico

Background: Psychosocial risks are a growing public health problem which, within the context of the care delivery to critically-ill patients, can affect the quality of care provided by health professionals. Objective: To identify the psychosocial risks of Portuguese nurses who provide care to critically ill patients. Methodology: Quantitative and cross-sectional study, with a non-probabilistic sample of nurses (n = 61) who work in pre-hospital emergency care (n = 6), emergency rooms (n = 20), and intensive care units (n = 35), in northern Portugal. The COPSOQ II questionnaire was applied between July and December 2018. A descriptive and exploratory analysis of the data was carried out, using the SPSS® software. Results: There was a moderate to high risk in 20 of the 29 dimensions evaluated by the questionnaire, and significant differences among the nurses of the emergency rooms and intensive care stand out, particularly in leadership quality, job satisfaction, and offensive behavior. Conclusion: The dimensions related to the area of management emerged as the main focus of psychosocial risks.Enquadramento: Os riscos psicossociais são um problema crescente de saúde pública que, nos contextos de prestação de cuidados ao doente crítico, podem afetar a qualidade dos cuidados prestados pelos profissionais. Objetivo: Identificar os riscos psicossociais a que estão sujeitos os enfermeiros portugueses que prestam assistência ao doente crítico. Metodologia: Estudo quantitativo e transversal, com uma amostragem não probabilística de enfermeiros (n = 61) que executam funções na emergência pré-hospitalar (n = 6), serviços de urgência (n = 20) e unidades de cuidados intensivos (n = 35), a norte de Portugal. Foi aplicado o questionário COPSOQ II entre julho e dezembro de 2018. Realizou-se uma análise descritiva e exploratória dos dados, com recurso ao SPSS®. Resultados: Verificou-se um risco moderado a elevado em 20 das 29 dimensões avaliadas pelo questionário, realçando-se diferenças significativas entre os enfermeiros da urgência e dos cuidados intensivos, nomeadamente na qualidade da liderança, satisfação no trabalho e comportamentos ofensivos. Conclusão: As dimensões relacionadas com os domínios da gestão, emergiram como principal foco de risco psicossocial.Marco contextual: Los riesgos psicosociales son un problema de salud pública cada vez mayor que, en entornos de prestación de cuidados al paciente crítico, pueden afectar a la calidad de la atención prestada por profesionales. Objetivo: Identificar los riesgos psicosociales a los que están sujetos los enfermeros portugueses que prestan asistencia al paciente crítico. Metodología: Estudio cuantitativo y transversal, com una muestra no probabilística de enfermeros (n = 61) que ejercen sus funciones en la sala de urgencias prehospitalaria (n = 6), servicios de urgencias (n = 20) y unidades de cuidados intensivos (n = 35), en el norte de Portugal. El cuestionario COPSOQ II se aplicó entre julio y diciembre de 2018. Se realizó un análisis de datos descriptivo y exploratorio mediante el SPSS®. Resultados: Se encontró un riesgo de moderado a alto en 20 de las 29 dimensiones evaluadas por el cuestionario, lo que resalta las diferencias significativas entre los enfermeros de urgencias y de cuidados intensivos, principalmente en la calidad del liderazgo, la satisfacción en el trabajo y las conductas ofensivas. Conclusión: Las dimensiones relacionadas con los domínios de gestión aparecieron como el foco principal del riesgo psicosocial.info:eu-repo/semantics/publishedVersio

Redescobrindo-se cidadão por meio da inclusão tecnológica e digital

Trabalho de Conclusão de Curso (especialização)—Universidade de Brasília, Universidade Aberta do Brasil, Faculdade de Educação, III Curso de Especialização em Educação na Diversidade e Cidadania, com Ênfase em EJA, 2015.A proposta desse projeto surgiu diante de diversas discussões das experiências dos educandos no primeiro segmento da EJAT nas atividades da Casa Paulo Freire. Diante de um diagnóstico realizado pôde-se contextualizar e perceber que muitos deles não tinham acesso direto ou indireto às ferramentas tecnológicas. Esse público, que já é excluído decorrente de variáveis sócio - cognitivas, tem revelado suas dificuldades em entender e lidar com situações simples no uso de eletrodomésticos como TV digital, computador, celular, caixas eletrônicos de instituições financeiras, o que aumenta a exclusão. Por isso, é de suma importância possibilitar a inclusão tecnológica e digital. As questões decorrentes da globalização e da tecnologia alteram, principalmente na EJA, as relações tradicionais de ensino, pois precisamos prepará-los para o trabalho daí a necessidade de diversificação de estratégias pedagógicas e de aprendizagem como forma de trabalhar além de palavras e sentidos, a utilização de recursos tecnológicos. A qualificação para o trabalho e o acesso às informações como instrumento de motivação para a adaptação não só da autoaprendizagem, mas também, visando o atendimento às oportunidades em diversas áreas como empregos, cursos, lazer e cultura, ou seja, incluir tecnológica e digitalmente, por conseguinte, socialmente. Sentir-se incluídos em todas as situações cotidianas para ampliação dos direitos sociais, pode-se dizer, significa a reconstrução da identidade cidadã.The purpose of this project appeared before several discussions of the experiences of students in the first segment of EJA and in which one can contextualize and realize that many of them had no direct or indirect access to technological tools. This audience is already excluded due to socio cognitive variables, have revealed their difficulties in understanding and dealing with simple situations in the use of appliances such as digital TV, computer, mobile, ATMs of financial institutions, which increases the exclusion, so It is of paramount importance to enable digital inclusion. Issues arising from globalization and technological change mainly in EJAT the traditional relations of teaching, because we need to prepare them for work hence the need for diversification of teaching strategies and learning as a way to work beyond words and senses, use of technological resources. Qualification for work and access to information as a motivation tool to adapt not only self-learning, but also in order to care opportunities in areas such as jobs, courses, leisure and culture, ie include digitally therefore socially. Feeling included in all everyday situations for expansion of social rights, it can be said reconstruction of citizen identity