Efeitos antiangiogênicos in vivo convalidam a atividade antineoplásica potencial do metiljasmonato

Molecular plant components have long been aimed at the angiogenesis and anti-angiogenesis pathways, and have been tested as sources for antineoplasic drugs with promising success. The present work deals with the anti-angiogenic effects of Methyl Jasmonate. Jasmonate derivatives were demonstrated to selectively damage the mitochondria of cancer cells. In vitro, 1-10 mM Methyl Jasmonate induced the cell death of the human umbilical vein endothelial cells (HUVEC) and the Murine melanoma cells (B16F10), while micromolar concentrations were ineffective. In vivo, comparable concentrations were toxic and reduced the vessel density of the Chorioallantoic Membrane of the Chicken Embryo (CAM). However, 1-10 µM concentrations produced a complex effect. There was increased capillary budding, but the new vessels were leakier and less organised than corresponding controls. It is suggested that not only direct toxicity, but also the drug effects upon angiogenesis are relevant to the antineoplasic effects of Methyl Jasmonate.Moléculas de origem vegetal são, há muito, conhecidas como substâncias ativas sobre as vias de angiogênese e antiangiogênese e foram testadas como fonte de drogas antineoplásicas com sucesso promissor. Este trabalho trata dos efeitos antiangiogênicos do Metiljasmonato, um protótipo da família dos derivados do ácido jasmônico, que danificam seletivamente a mitocôndria de células neoplásicas. In vitro, metiljasmonato 1-10 mM promoveu a morte celular de células endoteliais humanas de cordão umbilical (HUVEC) e de melanoma murino (B16F10); concentrações micromolares foram inócuas. In vivo, concentrações equivalentes foram tóxicas e reduziram a densidade de vasos em membranas corioalantoicas de embrião de galinha (CAM). Entretanto, concentrações entre 1-10 µM produziram um efeito complexo. Ocorreu aumento no brotamento capilar, mas os novos vasos apresentaram-se frágeis e menos organizados que os controles correspondentes. Sugere-se que, além da toxicidade direta contra as células tumorais, a ação do metiljasmonato sobre a angiogênese seja relevante para seu efeito antineoplásico

The holy grail:Environmental management, competitive advantage and business performance in the Spanish hotel industry

© Emerald Group Publishing Limited G959-6119. Purpose - This paper aims to analyse the influence of environmental proactivity on cost and differentiation competitive advantages, and to explore the double relationship between environmental proactivity and business performance. Design/methodology/approach - The population consists of all three- to five-star hotels in Spain. A sample of 350 hotels was classified according to environmental proactivity and performance levels, employing a two-step cluster analysis. Significant differences between groups were examined. Findings - The results show two types of environmental behaviour (reactive and proactive), with proactive hotels developing significantly better on both cost and differentiation competitive advantage and achieving significantly higher performance levels. Hotels which achieve above average business performance levels are significantly more environmentally proactive. Research limitations/implications - The present paper demonstrates that environmental management is related to competitive advantages and business performance. Environmental management systems are more developed in higher category, chain-affiliated and larger hotels. This could be due to having more resources to develop their environmental capability. The environmental proactivity scale employed in this study is presented as a reference measure for hotel managers to benchmark their current practices and implement environmental improvements. Originality/value - First, measuring environmental proactivity using four managerial systems (operative, information, strategic and technical) is innovative and provides a more detailed approach to measuring environmental proactivity. Second, demonstrating a double association between environmental proactivity and performance provides fresh insights into the relationship between these variables

A note on the use of the generalized odds ratio in meta-analysis of association studies involving bi- and tri-allelic polymorphisms

<p>Abstract</p> <p>Background</p> <p>The generalized odds ratio (GOR) was recently suggested as a genetic model-free measure for association studies. However, its properties were not extensively investigated. We used Monte Carlo simulations to investigate type-I error rates, power and bias in both effect size and between-study variance estimates of meta-analyses using the GOR as a summary effect, and compared these results to those obtained by usual approaches of model specification. We further applied the GOR in a real meta-analysis of three genome-wide association studies in Alzheimer's disease.</p> <p>Findings</p> <p>For bi-allelic polymorphisms, the GOR performs virtually identical to a standard multiplicative model of analysis (e.g. per-allele odds ratio) for variants acting multiplicatively, but augments slightly the power to detect variants with a dominant mode of action, while reducing the probability to detect recessive variants. Although there were differences among the GOR and usual approaches in terms of bias and type-I error rates, both simulation- and real data-based results provided little indication that these differences will be substantial in practice for meta-analyses involving bi-allelic polymorphisms. However, the use of the GOR may be slightly more powerful for the synthesis of data from tri-allelic variants, particularly when susceptibility alleles are less common in the populations (≤10%). This gain in power may depend on knowledge of the direction of the effects.</p> <p>Conclusions</p> <p>For the synthesis of data from bi-allelic variants, the GOR may be regarded as a multiplicative-like model of analysis. The use of the GOR may be slightly more powerful in the tri-allelic case, particularly when susceptibility alleles are less common in the populations.</p

Magnetic resonance spectroscopy as a non-invasive method to quantify muscle carnosine in humans: a comprehensive validity assessment

Carnosine is a dipeptide abundantly found in human skeletal muscle, cardiac muscle and neuronal cells having numerous properties that confers performance enhancing effects, as well as a wide-range of potential therapeutic applications. A reliable and valid method for tissue carnosine quantification is crucial for advancing the knowledge on biological processes involved with carnosine metabolism. In this regard, proton magnetic resonance spectroscopy (1H-MRS) has been used as a non-invasive alternative to quantify carnosine in human skeletal muscle. However, carnosine quantification by 1H-MRS has some potential limitations that warrant a thorough experimental examination of its validity. The present investigation examined the reliability, accuracy and sensitivity for the determination of muscle carnosine in humans using in vitro and in vivo experiments and comparing it to reference method for carnosine quantification (high-performance liquid chromatography – HPLC). We used in vitro 1H-MRS to verify signal linearity and possible noise sources. Carnosine was determined in the m. gastrocnemius by 1H-MRS and HPLC to compare signal quality and convergent validity. 1H-MRS showed adequate discriminant validity, but limited reliability and poor agreement with a reference method. Low signal amplitude, low signal-to-noise ratio, and voxel repositioning are major sources of error

Ultra-processed food consumption and obesity in the Australian adult population

Background: Rapid simultaneous increases in ultra-processed food sales and obesity prevalence have been observed worldwide, including in Australia. Consumption of ultra-processed foods by the Australian population was previously shown to be systematically associated with increased risk of intakes of nutrients outside levels recommended for the prevention of obesity. This study aims to explore the association between ultra-processed food consumption and obesity among the Australian adult population and stratifying by age group, sex and physical activity level. Methods: A cross-sectional analysis of anthropometric and dietary data from 7411 Australians aged &ge;20 years from the National Nutrition and Physical Activity Survey 2011&ndash;2012 was performed. Food consumption was evaluated through 24-h recall. The NOVA system was used to identify ultra-processed foods, i.e. industrial formulations manufactured from substances derived from foods and typically added of flavours, colours and other cosmetic additives, such as soft drinks, confectionery, sweet or savoury packaged snacks, microwaveable frozen meals and fast food dishes. Measured weight, height and waist circumference (WC) data were used to calculate the body mass index (BMI) and diagnosis of obesity and abdominal obesity. Regression models were used to evaluate the association of dietary share of ultra-processed foods (quintiles) and obesity indicators, adjusting for socio-demographic variables, physical activity and smoking. Results: Significant (P-trend &le;&thinsp;0.001) direct dose&ndash;response associations between the dietary share of ultra-processed foods and indicators of obesity were found after adjustment. In the multivariable regression analysis, those in the highest quintile of ultra-processed food consumption had significantly higher BMI (0.97&thinsp;kg/m2; 95% CI 0.42, 1.51) and WC (1.92&thinsp;cm; 95% CI 0.57, 3.27) and higher odds of having obesity (OR&thinsp;=&thinsp;1.61; 95% CI 1.27, 2.04) and abdominal obesity (OR&thinsp;=&thinsp;1.38; 95% CI 1.10, 1.72) compared with those in the lowest quintile of consumption. Subgroup analyses showed that the trend towards positive associations for all obesity indicators remained in all age groups, sex and physical activity level. Conclusion: The findings add to the growing evidence that ultra-processed food consumption is associated with obesity and support the potential role of ultra-processed foods in contributing to obesity in Australia

Efectos de los ejercicios pliométricos en pacientes postoperatorio de rotura del tendón calcáneo

It is known about the rupture of the Achilleus tendon since ancient Greece, which has been increasing in recent years, therefore, it seeks to implement better tools for its treatment, one of them being plyometric exercises. Meta-analysis type studies, randomized and experimental controlled trials observed that the application of plyometric exercises in most of the participants improved the quality of the tendon, increasing elasticity and decreasing its stiffness (p &lt;0.01) in 14 studies and in the remaining 3 studies. , did not improve the structure of the tendon, however, it did improve its symptoms and functionality in late studies (p &lt;0.01). The application of plyometric exercises is an additional tool to treat subjects undergoing an operation to rupture the Achilles tendon, which must be applied in the final stages of rehabilitation, improving tissue stiffness, increasing functionality and reducing chronic pain.De la ruptura del tendón Aquileo se tiene conocimiento desde la antigua Grecia, la cual ha ido en aumento en los últimos años, por ende, se busca implementar mejores herramientas para el tratamiento de la misma, siendo una de ellas los ejercicios pliométricos. Estudios tipo meta-análisis, ensayos controlados aleatorizados y experimentales observaron que la aplicación de ejercicios pliométricos en la mayoría de los participantes mejoraba la calidad del tendón, aumentando elasticidad y disminuyendo su rigidez&nbsp; (p&lt;0.01) en 14 estudios y en los 3 estudios restantes, no mejoraba la estructura del tendón, sin embargo, mejoraba la sintomatología y funcionalidad del mismo en estudios tardíos (p&lt;0.01). La aplicación de ejercicios pliométricos es una herramienta adicional para tratar a los sujetos sometidos a una operación de ruptura de tendón Aquileo, el cual debe ser aplicado en estadios finales en rehabilitación, mejorando la rigidez del tejido, aumentando la funcionalidad y disminuyendo el dolor crónico

Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

Origin and diversity of an underutilized fruit tree crop, cempedak (Artocarpus integer, Moraceae)

PREMISE OF THE STUDY: Underutilized crops and their wild relatives are important resources for crop improvement and food security. Cempedak [Artocarpus integer (Thunb). Merr.] is a significant crop in Malaysia but underutilized elsewhere. Here we performed molecular characterization of cempedak and its putative wild relative bangkong (Artocarpus integer (Thunb). Merr. var. silvestris Corner) to address questions regarding the origin and diversity of cempedak. METHODS: Using data from 12 microsatellite loci, we assessed the genetic diversity and genetic/geographic structure for 353 cempedak and 175 bangkong accessions from Malaysia and neighboring countries and employed clonal analysis to characterize cempedak cultivars. We conducted haplotype network analyses on the trnH-psbA region in a subset of these samples. We also analyzed key vegetative characters that reportedly differentiate cempedak and bangkong. KEY RESULTS: We show that cempedak and bangkong are sister taxa and distinct genetically and morphologically, but the directionality of domestication origin is unclear. Genetic diversity was generally higher in bangkong than in cempedak. We found a distinct genetic cluster for cempedak from Borneo as compared to cempedak from Peninsular Malaysia. Finally, cempedak cultivars with the same names did not always share the same genetic fingerprint. CONCLUSIONS: Cempedak origins are complex, with likely admixture and hybridization with bangkong, warranting further investigation. We provide a baseline of genetic diversity of cempedak and bangkong in Malaysia and found that germplasm collections in Malaysia represent diverse coverage of the four cempedak genetic clusters detected