A web-based multidomain lifestyle intervention with connected devices for older adults: research protocol of the eMIND pilot randomized controlled trial.

BACKGROUND: Multidomain interventions composed of nutritional counseling, exercise and cognitive trainings have shown encouraging results as effective preventive strategies delaying age-related declines. However, these interventions are time- and resource-consuming. The use of Information and Communication Technologies (ICT) might facilitate the translation from research into real-world practice and reach a massive number of people. AIM: This article describes the protocol of the eMIND study, a randomized controlled trial (RCT) using a web-based multidomain intervention for older adults. METHODS: One hundred and twenty older adults (≥ 65 years), with a spontaneous memory complaint, will be randomly assigned to a six-month web-based multidomain (nutritional counseling, physical and cognitive trainings) intervention group with a connected accelerometer (number of steps, energy expenditure), or to a control group with access to general information on healthy aging plus the accelerometer, but no access to the multidomain intervention. The main outcome is the feasibility/acceptability of the web-based intervention. Secondary clinical outcomes include: cognitive functions, physical performance, nutritional status and cost-effectiveness. RESULTS: We expect a high amount of adherers (ie, > 75% compliance to the protocol) to reflect the feasibility. Acceptability, assessed through interviews, should allow us to understand motivators and barriers to this ICT intervention. We also expect to provide data on its effects on various clinical outcomes and efficiency. CONCLUSION AND DISCUSSION: The eMIND study will provide crucial information to help developing a future and larger web-based multidomain lifestyle RCT, which should facilitate the translation of this ICT intervention from the research world into real-life clinical practice for the healthcare of older adults.

Effects of two distamycin-ellipticine hybrid molecules on topoisomerase I and II mediated DNA cleavage: relation to cytotoxicity.

Two distamycin-ellipticine conjugates were examined for their ability to modulate topoisomerase I and topoisomerase II-DNA cleavable complex formation in vitro. Hybrid molecules Distel (1+) and Distel (2+) both contain a DNA-intercalating chromophore and a tris-pyrrole element capable of binding within the minor groove of DNA. The two drugs differ only in the nature of the side chain attached to the distamycin moiety. The monocationic hybrid Distel (1+) is a dual topoisomerase I and II inhibitor with characteristics differing from those of the parent compounds distamycin and ellipticine. By contrast, the biscationic hybrid Distel (2+) exerts no significant effects on either topoisomerase I or II. The cytotoxic properties of the two drugs towards P388 leukaemic cells sensitive and resistant to camptothecin correlate with topoisomerase inhibitory properties but not with DNA-binding properties.

Sequential modifications of topoisomerase I activity in a camptothecin-resistant cell line established by progressive adaptation.

The DNA-topoisomerase I (Topo I) inhibitor, camptothecin (CPT), is a plant alkaloid with an important antitumor activity. In order to investigate the cellular mechanism leading to the development of the resistance to this agent, we have established by progressive adaptation a P388 subline resistant to CPT. After 5 months of continuous drug exposure, the resistance index reached a value of 20 and the resistant cell line, P388CPT0.3, was maintained in the presence of CPT. CPT-induced single strand breaks measured by alkaline elution were found drastically reduced in the resistant cell line. Topo I activity and CPT-induced DNA cleavage were measured on cells at different steps of resistance. We first observed that the Topo I activity was strongly decreased. In addition, the resistant cells recovered the ATP-independent relaxation activity after 3 months of exposure to CPT, but still kept a reduced CPT-induced DNA cleavage. Further evaluations at the final stage of the resistance induction have indicated that cells presented a CPT-resistant form of Topo I. Rearranged Topo I gene on one allele and a reduced Topo I transcription were also observed in resistant cells. The putative role of the rearrangement was discussed. These data show that the resistance mechanism has evolved from a decreased Topo I activity to an altered form of the enzyme, and suggest that multiple mechanisms of Topo I modifications could contribute to CPT resistance.

Estimation of genetic parameters for test-day milk yield in first calving buffaloes / Estimación de parámetros genéticos para producción de leche en el día de control en búfalas de primer parto / Estimação de parâmetros genéticos para produção do leite no dia do controle em búfalas de primeiro parto

Background: the milk yield records measured along lactation provide an example of repeated measures; the random regression models are an appealing approach to model repeated measures and to estimate genetic parameters. Objective: to estimate the genetic parameters by modeling the additive genetic and the residual variance for test-day milk yield in first calving buffaloes. Methods: 3,986 test-day data from 1,246 first lactations of crossbred buffalo daughters of 23 sires and 391 dams between 1997 and 2008 from five farms were used. The model included the genetic and permanent environment additive as the random effect and the contemporary group (year, month of test-day) and age at calving as covariable (linear) fixed effects. The fixed (third order) and random (third to ninth order) regressions were obtained by Legendre polynomials. The residual variances were modeled with a homogeneous structure and various heterogeneous classes. The variance components were estimated using the WOMBAT statistical program (Meyer, 2006). Results: according to the likelihood ratio test, the best model included four variance classes, considering Legendre polynomials of the fourth order for permanent environment and additive genetic effects. The heritabilities estimates were low, varying from 0.0 to 0.14. The estimates of genetic correlations were high and positive among PDC1 and PDC8, except for PCD9, which was negative. This indicates that for any of the selection criteria adopted, the indirect genetic gain is expected for all lactation curves, except for PCD9. Conclusion: heterogeneity of residual variances should be considered in models whose goal is to examine the alterations of variances according to day of lactation.

Antecedentes: los registros de producción de leche medidos a lo largo de la lactancia son un ejemplo de medidas repetidas, los modelos de regresión aleatoria presentan un enfoque atractivo para modelar medidas repetidas y para estimar parámetros genéticos. Objetivo: estimar parámetros genéticos a través de la modelación de la varianza genética y residual para producción de leche en el día de control en búfalas de primer parto. Métodos: fueron analizados 3986 controles de producción de leche en la primera lactancia de 1246 búfalas, hijas de 391 hembras y 23 toros, durante los años 1997 hasta 2008 en 5 fincas. El modelo incluyó como efectos aleatorios genético aditivo y de ambiente permanente, como efectos fijos grupo contemporáneo compuesto por mes, año de control y la covariable de la edad de la búfala al parto (lineal). Las regresiones fijas (3er orden) y aleatorias (3er a 9no orden) fueron obtenidas mediante polinomios de Legendre. Las varianzas residuales fueron modeladas con una estructura homogénea y varias clases heterogéneas. Los componentes de varianza fueron estimados utilizando el programa WOMBAT. Resultados: de acuerdo con la prueba de la razón de verosimilitud, el mejor modelo fue con 4 clases de varianzas residuales, siendo considerado un polinomio de Legendre de cuarto orden para el efecto de ambiente permanente y genético aditivo. Las heredabilidades fueron bajas, variando desde 0,00 hasta 0,14. Las correlaciones genéticas fueron altas y positivas entre los PDC1 a PDC8, excepto en el PDC9 que fue negativo con respecto a los demás controles. Conclusiones: es necesario considerar la heterogeneidad de varianzas residuales en los modelos estudiados, con el fin de modelar los cambios en las variaciones respecto a los días en lactancia.

Antecedentes: os registros da produção do leite medidos ao longo da lactação, apresentam um exemplo de medidas repetidas. Os modelos de regressão aleatória apresentam abordagem atraente para modelar medidas repetidas e estimar parâmetros genéticos. Objetivo: estimar parámetros genéticos mediante a modelação das variâncias genéticas e residual da produção do leite no dia do controle em búfalas de primeiro parto. Métodos: foram analisados 3986 controles de produção de leite em primeiras lactações de 1246 búfalas, filhas de 391 fêmeas e 23 touros, entre 1997 e 2008 em 5 fazendas. No modelo foram incluídos como efeitos aleatórios o genético aditivo e ambiente permanente, e como fixos o grupo contemporâneo (mês e ano de controle) e a covariável a idade da búfala ao parto (Lineal). As regressões fixas (3° ordem) e aleatórias (3° a 9° ordem) foram obtidas mediante polinômios ortogonais de Legendre. As variâncias residuais foram modeladas mediante estruturas homogêneas e diferentes classes heterogêneas. Os componentes de variância foram estimadas mediante o software WOMBAT. Resultados: de acordo com a prova da máxima verossimilhança, o melhor modelo foi com 4 classes de variâncias residuais, sendo considerado polinômios de Legendre de quarto ordem para o efeito de ambiente permanente e genético aditivo. As herdabilidades foram baixas, variando desde 0,00 até 0,14. As correlações genéticas foram altas e positivas entre o PDC1 e PDC8, a exceção do PDC9 que apresentou valores negativos com respeito aos outros controles. Conclusões:é necessário considerar heterogeneidade de variâncias nos modelos estudados, tentando modelar as mudanças nas variações respeito aos dias em lactação.

Effects of Taxotere on murine and human tumor cell lines.

Taxotere (RP 56976, NSC 628503), an analog of taxol, is an inhibitor of depolymerisation of microtubules and is currently in Phase I clinical trials. Comparisons of the cytotoxicities of Taxotere and taxol have been studied on several murine (P388, SVras) and human cell lines (Calc18, HCT116, T24, N417, KB). Taxotere was found more potent than taxol (1.3-12 fold), a result which could be explained by its higher affinity than taxol for microtubules. In agreement with its postulated mechanism of action, Taxotere is more cytotoxic on proliferating than on non proliferating N417 cells and does not inhibit cellular DNA, RNA and protein synthesis. Taxotere gives partial cross resistance on P-glycoprotein resistant P388/DOX cell line, in contrast to taxol which gives a complete cross resistance. On the other hand, no cross resistances were observed on Calc18/AM and P388/CPT5 cell lines, bearing modified activities of topoisomerase II and topoisomerase I, respectively. These results underline the higher cytotoxic activity of Taxotere compared to taxol, and the lack of cross resistance of that class of agent with the topoisomerase I and II-related multidrug resistance phenotypes.

Modelos matemáticos para curvas delactancia en ganado lechero / Mathematical models for lactation curves of dairy cattle

La curva de lactancia es un proceso biológico que puede ser explicado por medio de una funciónmatemática y la cual es útil en el pronóstico de la producción total a partir de muestras parciales,planificación del hato con la ayuda de la predicción confiable de la producción y la selección a partir delconocimiento de las relaciones entre las diferentes partes de la curva. Pero es importante encontrar en cadamedio de producción, la función matemática que mejor describa la curva de lactancia de los animales.Para describir la producción de leche a través de la lactancia en animales domésticos, se han propuestodiversos modelos matemáticos, entre los cuales se encuentran los modelos de Papajcsik y Bordero 1988,Sikka 1950, Brody 1923, 1924, Wood 1967. En investigaciones recientes se ha sugerido la modelaciónde datos experimentales desde la metodología de modelos mixtos, la cual ha brindado la posibilidad deanalizar datos con estructuras de dependencia, no balanceados y en ocasiones con falta de normalidad;esta metodología es una herramienta importante para la evaluación de la curva de lactancia. Dependiendodel método de estimación de curvas de lactancia por medio de modelos matemáticos, se da la validez delos resultados obtenidos en extensiones de lactancia. Además, permiten predecir la producción total deleche a partir de producciones parciales, característica de gran importancia para la evaluación genéticaen bovinos lecheros. El objetivo es presentar una revisión sobre las diferentes expresiones matemáticasempleadas en el área de las ciencias pecuarias, con el fin de interpretar los cambios que ocurren en laproducción de leche de una hembra a lo largo de la lactancia.

A lactation curve can be explained by a mathematical function of a biological process, that can be usefulfor prognosis of the total production starting from partial samples, planning of the herd with the help of areliable prediction of production, and selection based in a previous knowledge of the relationships betweenthe different parts of the curve, among others. Of key relevance is to find the mathematical function that better describes the curve of lactation of the animals in a particular environment of production. In orderto describe the production of milk throughout lactation in dairy, diverse mathematical models have beenproposed, among which are the models of Papajcsik and Bordero in 1988, Sikka in 1950, Brody in 1923,Brody in 1924, and Wood in 1967. In recent reports the modeling of experimental data has been suggestedby using of mixed models, which has offered the possibility to analyze data with dependence structures,not balanced data and data with lack of normality, a methodology that is an important tool for evaluatinglactation curve. According to the method of estimation of lactation curves by means of mathematicalmodels, will be the validity of the results on lactation extension. In addition, they permit the prediction oftotal milk production from partial productions, a characteristic of great importance for genetic evaluationin dairy cattle. The objective of this paper is to review the mathematical models commonly used in livestockfor interpretation of changes that occurs in cow milk production throughout lactation.