Dysthanasia: nursing professionals' perception

Dysthanasia means slow and painful death without quality of life. This study aimed to know whether nurses identify dysthanasia as part of the final process of the lives of terminal patients hospitalized at an adult ICU. This is an exploratory-qualitative study. Data were collected through semi-structured interviews with ten nurses with at least one year of experience in an ICU, and interpreted through content analysis. Results indicate that nurses understand and identify dysthanasia, do not agree with it and recognize elements of orthonasia as the adequate procedure for terminal patients. We conclude that nurses interpret dysthanasia as extending life with pain and suffering, while terminal patients are submitted to futile treatments that do not benefit them. They also identify dysthanasia using elements of orthonasia to explain it.Distanasia significa muerte lenta, con sufrimiento y sin calidad de vida. En esta investigación se buscó conocer si los enfermeros identifican la distanasia como parte del proceso final de la vida de personas en estado terminal, internadas en una UTI para adultos. El estudio es de naturaleza exploratoria, con abordaje cualitativo. Los datos fueron recolectados por medio de entrevista semiestructurada con 10 enfermeros con un mínimo de un año de experiencia en UTI; los datos fueron interpretados por el análisis de contenido. Se obtuvo como resultado que los enfermeros comprenden e identifican la distanasia y se oponen a la misma, presentando elementos de ortotanasia como procedimiento adecuado para pacientes en estado terminal. Se concluye que los enfermeros interpretan la distanasia como el prolongamiento de la vida con dolor y sufrimiento, en el cual los pacientes terminales son sometidos a tratamientos fútiles que no traen beneficios. También identifican la distanasia, usando elementos de la ortotanasia para hacerla explicita.Distanásia significa morte lenta, sofrida e sem qualidade de vida. Nesta pesquisa buscou-se conhecer se os enfermeiros identificam a distanásia como parte do processo final da vida de pessoas em terminalidade, internadas em UTI adulto. O estudo é de natureza exploratória, com abordagem qualitativa. Os dados foram coletados por meio de entrevista semiestruturada com 10 enfermeiros com, no mínimo, um ano de experiência em UTI, e interpretados pela análise de conteúdo. Teve-se como resultado que os enfermeiros compreendem e identificam a distanásia e se opõem à mesma, trazendo elementos da ortotanásia como procedimento adequado para pacientes em terminalidade. Conclui-se que os enfermeiros interpretam a distanásia como o prolongamento de vida com dor e sofrimento, onde os pacientes terminais são submetidos a tratamentos fúteis que não trazem benefícios. E também identificam a distanásia, usando elementos da ortotanásia para explicitá-la

The Breast Cancer and the Environment Research Centers: Transdisciplinary Research on the Role of the Environment in Breast Cancer Etiology

ObjectivesWe introduce and describe the Breast Cancer and the Environment Research Centers (BCERC), a research network with a transdisciplinary approach to elucidating the role of environmental factors in pubertal development as a window on breast cancer etiology. We describe the organization of four national centers integrated into the BCERC network.Data sourcesInvestigators use a common conceptual framework based on multiple levels of biologic, behavioral, and social organization across the life span. The approach connects basic biologic studies with rodent models and tissue culture systems, a coordinated multicenter epidemiologic cohort study of prepubertal girls, and the integration of community members of breast cancer advocates as key members of the research team to comprise the network.Data extractionRelevant literature is reviewed that describes current knowledge across levels of organization. Individual research questions and hypotheses in BCERC are driven by gaps in our knowledge that are presented at genetic, metabolic, cellular, individual, and environmental (physical and social) levels.Data synthesisAs data collection on the cohort, animal experiments, and analyses proceed, results will be synthesized through a transdisciplinary approach.ConclusionCenter investigators are addressing a large number of specific research questions related to early pubertal onset, which is an established risk factor for breast cancer. BCERC research findings aimed at the primary prevention of breast cancer will be disseminated to the scientific community and to the public by breast cancer advocates, who have been integral members of the research process from its inception

Promotion of variant human mammary epithelial cell outgrowth by ionizing radiation: an agent-based model supported by in vitro studies

IntroductionMost human mammary epithelial cells (HMEC) cultured from histologically normal breast tissues enter a senescent state termed stasis after 5 to 20 population doublings. These senescent cells display increased size, contain senescence associated beta-galactosidase activity, and express cyclin-dependent kinase inhibitor, p16INK4A (CDKN2A; p16). However, HMEC grown in a serum-free medium, spontaneously yield, at low frequency, variant (v) HMEC that are capable of long-term growth and are susceptible to genomic instability. We investigated whether ionizing radiation, which increases breast cancer risk in women, affects the rate of vHMEC outgrowth.MethodsPre-stasis HMEC cultures were exposed to 5 to 200 cGy of sparsely (X- or gamma-rays) or densely (1 GeV/amu 56Fe) ionizing radiation. Proliferation (bromodeoxyuridine incorporation), senescence (senescence-associated beta-galactosidase activity), and p16 expression were assayed in subcultured irradiated or unirradiated populations four to six weeks following radiation exposure, when patches of vHMEC became apparent. Long-term growth potential and p16 promoter methylation in subsequent passages were also monitored. Agent-based modeling, incorporating a simple set of rules and underlying assumptions, was used to simulate vHMEC outgrowth and evaluate mechanistic hypotheses.ResultsCultures derived from irradiated cells contained significantly more vHMEC, lacking senescence associated beta-galactosidase or p16 expression, than cultures derived from unirradiated cells. As expected, post-stasis vHMEC cultures derived from both unirradiated and irradiated cells exhibited more extensive methylation of the p16 gene than pre-stasis HMEC cultures. However, the extent of methylation of individual CpG sites in vHMEC samples did not correlate with passage number or treatment. Exposure to sparsely or densely ionizing radiation elicited similar increases in the numbers of vHMEC compared to unirradiated controls. Agent-based modeling indicated that radiation-induced premature senescence of normal HMEC most likely accelerated vHMEC outgrowth through alleviation of spatial constraints. Subsequent experiments using defined co-cultures of vHMEC and senescent cells supported this mechanism.ConclusionsOur studies indicate that ionizing radiation can promote the outgrowth of epigenetically altered cells with pre-malignant potential

Collagen density promotes mammary tumor initiation and progression

<p>Abstract</p> <p>Background</p> <p>Mammographically dense breast tissue is one of the greatest risk factors for developing breast carcinoma. Despite the strong clinical correlation, breast density has not been causally linked to tumorigenesis, largely because no animal model has existed for studying breast tissue density. Importantly, regions of high breast density are associated with increased stromal collagen. Thus, the influence of the extracellular matrix on breast carcinoma development and the underlying molecular mechanisms are not understood.</p> <p>Methods</p> <p>To study the effects of collagen density on mammary tumor formation and progression, we utilized a bi-transgenic tumor model with increased stromal collagen in mouse mammary tissue. Imaging of the tumors and tumor-stromal interface in live tumor tissue was performed with multiphoton laser-scanning microscopy to generate multiphoton excitation and spectrally resolved fluorescent lifetimes of endogenous fluorophores. Second harmonic generation was utilized to image stromal collagen.</p> <p>Results</p> <p>Herein we demonstrate that increased stromal collagen in mouse mammary tissue significantly increases tumor formation approximately three-fold (<it>p </it>< 0.00001) and results in a significantly more invasive phenotype with approximately three times more lung metastasis (<it>p </it>< 0.05). Furthermore, the increased invasive phenotype of tumor cells that arose within collagen-dense mammary tissues remains after tumor explants are cultured within reconstituted three-dimensional collagen gels. To better understand this behavior we imaged live tumors using nonlinear optical imaging approaches to demonstrate that local invasion is facilitated by stromal collagen re-organization and that this behavior is significantly increased in collagen-dense tissues. In addition, using multiphoton fluorescence and spectral lifetime imaging we identify a metabolic signature for flavin adenine dinucleotide, with increased fluorescent intensity and lifetime, in invading metastatic cells.</p> <p>Conclusion</p> <p>This study provides the first data causally linking increased stromal collagen to mammary tumor formation and metastasis, and demonstrates that fundamental differences arise and persist in epithelial tumor cells that progressed within collagen-dense microenvironments. Furthermore, the imaging techniques and signature identified in this work may provide useful diagnostic tools to rapidly assess fresh tissue biopsies.</p

Impacto das mudanças climáticas sobre a leishmaniose no Brasil

Resumo Este estudo buscou verificar como as mudanças climáticas podem afetar a proliferação das leishmanioses no Brasil, em três períodos, 2010-2039, 2040-2079 e 2080-2100 e dois cenários de mudanças climáticas. Realizou-se uma estimação da relação entre temperatura, precipitação e números de internações por leishmaniose e, posteriormente, a equação estimada foi utilizada para prever o impacto da mudança climática na proliferação da doença no Brasil até o fim do século XXI. Os resultados encontrados indicam que a precipitação possui forte relação com a incidência de leishmaniose e as projeções indicam que haverá uma elevação, para o final do século, da quantidade anual de internações por essa doença, em cerca de 15%, em relação a 1992-2002 (cenário base). Em termos regionais, as projeções indicam crescimento em todas as regiões, com exceção do Centro-Oeste. No Sul do país haverá o maior crescimento relativo no número de internações anuais, ao passo que no Nordeste haverá o maior aumento absoluto. No geral, verifica-se que a leishmaniose aumentará sua incidência no país com a mudança climática