In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells

INTRODUCTION: Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells. METHODS: Human MCF-7 breast cancer cells were treated with up to 100 μM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation. RESULTS: Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 μM and 20 μM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis. CONCLUSION: These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma

Long-Term Climate Forcing in Loggerhead Sea Turtle Nesting

The long-term variability of marine turtle populations remains poorly understood, limiting science and management. Here we use basin-scale climate indices and regional surface temperatures to estimate loggerhead sea turtle (Caretta caretta) nesting at a variety of spatial and temporal scales. Borrowing from fisheries research, our models investigate how oceanographic processes influence juvenile recruitment and regulate population dynamics. This novel approach finds local populations in the North Pacific and Northwest Atlantic are regionally synchronized and strongly correlated to ocean conditions—such that climate models alone explain up to 88% of the observed changes over the past several decades. In addition to its performance, climate-based modeling also provides mechanistic forecasts of historical and future population changes. Hindcasts in both regions indicate climatic conditions may have been a factor in recent declines, but future forecasts are mixed. Available climatic data suggests the Pacific population will be significantly reduced by 2040, but indicates the Atlantic population may increase substantially. These results do not exonerate anthropogenic impacts, but highlight the significance of bottom-up oceanographic processes to marine organisms. Future studies should consider environmental baselines in assessments of marine turtle population variability and persistence

Complementary intestinal mucosa and microbiota responses to caloric restriction

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR

Asma induzida pelo exercício: aspectos atuais e recomendações Asma inducido por el ejercicio: aspectos actuales y recomendaciones Exercise-induced asthma: current aspects and recommendations

OBJETIVO: Descrever os mecanismos da asma induzida pelo exercício (AIE), bem como os efeitos de diferentes tipos de treinamento físico na função pulmonar e nas capacidades aeróbia e anaeróbia. Destaca-se a importância de um diagnóstico correto mediante o teste de exercício e, no manejo, o uso de drogas beta-adrenérgicas e anticolinérgicas. FONTE DOS DADOS: Os artigos foram criteriosamente escolhidos utilizando as bases de dados PubMed e Scielo pelo ano de publicação e dando preferência a ensaios clínicos randomizados, com critérios de seleção da amostra bem definidos. SÍNTESE DOS DADOS: Os mecanismos para explicar a AIE permanecem sem conclusão, mas parece haver uma interação fisiológica entre as hipóteses aqui apresentadas. O uso de medicamentos e as freqüentes crises durante o exercício aparecem como fatores limitantes para a prática de exercícios físicos, conduzindo para um estilo de vida sedentário. CONCLUSÃO: Deve-se incentivar a prática de exercícios devidamente prescritos e minimizar as restrições aos sujeitos com AIE.<br>OBJETIVO: Describir los mecanismos del asma inducido por el ejercicio (AIE), así como los efectos de diferentes tipos de entrenamiento físico sobre la función pulmonar y las capacidades aeróbica y anaeróbica. Se destaca la importancia de un diagnóstico correcto mediante el test de ejercicio y el manejo o uso de drogas beta-adrenérgicas y anticolinérgicas. FUENTES: Los artículos fueron cuidadosamente escogidos utilizando las bases de dados de PubMed y Scielo por el año de publicación, dando preferencia a ensayos clínicos randomizados, con criterios de selección de muestra bien definidos. SÍNTESES DE DATOS: Los mecanismos para explicar la AIE permanecen sin conclusión, pero parece haber una interacción fisiológica entre las hipótesis aquí presentadas. El uso de medicamentos y las frecuentes crisis durante el ejercicio aparecen como factores limitantes para la práctica de ejercicios físicos, conduciendo esto a un estilo de vida sedentario. CONCLUSIÓN: Se debe incentivar la práctica de ejercicios debidamente prescritos y minimizar las restricciones a los individuos con AIE.<br>OBJECTIVE: To describe the mechanisms of Exercise-Induced Asthma (EIA) as well as the effect of different kinds of physical training on pulmonary function, anaerobic fitness, and aerobic fitness. We highlighted the importance of a correct diagnostic through exercise testing and, concerning treatment, the utilization of drugs such as beta-adrenergics and anticholinergics. DATA SOURCE: The articles were chosen using the PubMed and Scielo databases, considering the year of publication and giving preference to clinical randomized trials with well-defined inclusion criteria. SUMMARY OF THE FINDINGS: The medication used and the frequent symptoms during and after exercise appear as a limiting factor to the practice of exercises among subjects with EIA. This may result in a sedentary lifestyle. CONCLUSION: Subjects with EIA should be allowed to do exercise if well prescribed

A systematic review of faculty development activities in family medicine

Background: Faculty development (FD) has been defined as a planned programme to prepare institutions and faculty members for their roles in the areas of teaching, research, administration and career management. However, there are few generalisable evaluations of FD activities available to help family medicine FD planners to choose the most effective training strategies. Aim: To assess the evidence for the effectiveness of family medicine FD activities. Method: Six electronic databases were searched from 1980 to 2010 and included all articles on FD interventions in family medicine. Hand searching was also undertaken. Results: A total of 4520 articles were identified, 46 fulfilled the search criteria and were reviewed across three domains: (a) Context, i.e. setting, participation and funding. (b)Content/Process, i.e. theoretical framework, focus of intervention/learning outcomes, types of FD intervention and instructional methods. (c) Evaluation using Freeth et al's adaptation of Kirkpatrick's outcome levels. Conclusion: FD activities appear highly valued by the participants, leading to changes in learning and behaviour. Changes in organisational practice and student learning were not frequently reported. The continued success of family medicine FD will depend on the contextual approach/collegial support, adaptability of the programmes, robust evaluation and adequate funding in terms of resources and time