Strenuous exercise worse than sedentarism?

Schnohr et al. (1) reported a U-shaped association between all-cause mortality and exercise dose in a Danish cohort. Jogging 1 to 2.4 h/week was associated with the lowest mortality, whereas jogging >3 times/week was no better than being inactive and was worse than light jogging (adjusted hazard ratio [HR]: 9.08; 95% confidence interval [CI]: 1.87 to 44.01). Furthermore, older (61.3 16.2 years) sedentary nonjoggers with cardiovascular disease (CVD) risk factors...

The Era of Smartphones: Back to Our Biological Makeup?

Physical inactivity is a major modifiable cardiovascular risk factor that has become a growing health problem in the 21st century: 83% of adolescents aged 13-15 years and approximately 1/3 of adults worldwide are inactive, that is, not meeting the minimum international physical activity (PA) recommendations (=150 minutes/week of moderate to vigorous PA) [1, 2]. Thus, the PA levels of the general population, especially of individuals at cardiovascular risk, should be routinely assessed by health care professionals, as it has been recently recommended by the American Heart Association [3]. To this end, accelerometers (usually attached to an elastic belt around the waist) allow objective quantification of PA by providing continuous recordings. At least 3 to 5 days of accelerometer monitoring (including weekend days) are required to determine habitual PA, and it is generally accepted that the device should be worn for =10 hours/day [4]. For this reason, the simple and inexpensive method of PA questionnaires is more widely used and generally better accepted. Unfortunately, the validity of self-reported PA is questionable..

Regular physical activity: A little is good, but is it good enough?

Ekelund et al. (1) nicely showed that physical inactivity causes an approximate twofold increase in the numbers of deaths compared with those attributable to obesity [BMI (in kg/m2) .30] in a Euro- pean cohort (n 1/4 334,161) that was followed up to 12.4 y on average. Physical activity (PA) levels were estimated by using a standardized questionnaire or in-person interviews and were found to be inversely associated with all-cause mortality at all levels of BMI and waist circumference. Another important finding from their study is that substantial survival benefits may be achieved by fairly small amounts of moderate-intensity PA: that is, ;20 min/d of brisk walking, which is below the current PA recommendations of !30 min/d on most, if not all, days of the week (or !150 min/wk). These important findings in Caucasians are in line with those recently reported in an Asiatic cohort, in whom 15 min/d or 90 min/wk of moderate-intensity PA was associated with lower all-cause mor- tality, even for persons at risk of cardiovascular diseas

Methylation panel is a diagnostic biomarker for Barrett’s oesophagus in endoscopic biopsies and non-endoscopic cytology specimens

Objective Barrett’s Oesophagus is a premalignant condition that occurs in the context of gastro-oesophageal reflux. However, most Barrett’s cases are undiagnosed because of reliance on endoscopy. We have developed a non-endoscopic tool; the Cytosponge™ which when combined with TFF3 immunohistochemistry can diagnose Barrett’s. We investigated whether a quantitative methylation test that is not reliant on histopathological analysis could be used to diagnose Barrett’s oesophagus. Design Differentially methylated genes between Barrett’s and normal squamous oesophageal biopsies were identified from whole methylome data and confirmed using MethyLight PCR in biopsy samples of squamous oesophagus, gastric cardia and Barrett’s oesophagus. Selected genes were then tested on Cytosponge™ BEST2 trial samples comprising a pilot cohort (n=20 cases, n=10 controls) and a validation cohort (n=149 cases, n=129 controls). Results Eighteen genes were differentially methylated in patients with Barrett’s compared to squamous controls. Hypermethylation of TFPI2, TWIST1, ZNF345 and ZNF569 was confirmed in Barrett’s biopsies compared with biopsies from squamous oesophagus and gastric cardia (p<0.05). When tested in Cytosponge™ samples these four genes were hypermethylated in patients with Barrett’s oesophagus compared to patients with reflux symptoms (p<0.001). The optimum biomarker to diagnose Barrett’s was TFPI2 with a sensitivity and specificity of 82.2% and 95.7 % respectively. Conclusion TFPI2, ZNF345 and ZNF569 CpG methylation has promise as a diagnostic biomarker panel for Barrett’s when used in combination with a simple and cost effective non-endoscopic cell collection device.The BEST2 study was funded by Cancer Research UK (C14478/ A12088). RCF receives core funding from the Medical Research Council. The study received infrastructure support from the Cambridge Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and the Experimental Cancer Medicine Centre

Galectin-3, osteopontin and successful aging

Background: Individuals who reach exceptional longevity (100+ years of age) free of common chronic age diseases (i.e. ''dodgers'') arguably represent the paradigm of successful aging in humans. As such, identification of potential biomarkers associated with this phenomenon is of medical interest. Methods: We measured serum levels of galectin-3 and osteopontin, both of which have been shown to be linked with major chronic or aging-related disorders in younger populations, in centenarian ''dodgers'' (n=81; 40 men; 100-104 years) and healthy controls (n=41; 24 men, 70-80 years). Results: Both biomarkers showed significantly lower values (p<0.001) in the former (galectin-3: 2.4±1.7 vs. 4.8±2.8 ng/mL; osteopontin: 38.1±27.7 vs. 72.6±33.1 µg/mL). Logistic regression analysis identified the combination of these two biomarkers as a significant predictor variable associated with successful aging regardless of sex (p<0.001). The area under the curve (AUC) classified the ability of galectin-3 and osteopontin to predict the likelihood of successful aging as ''fair'' (AUC=0.75) and ''good'' (AUC=0.80), respectively. Particularly, the combination of the two biomarkers showed good discriminatory power for successful aging (AUC=0.86), with sensitivity=83% and specificity=74%. Conclusions: Lower levels of both galectin-3 and osteopontin are associated with successful aging, representing potential biomarkers of this condition. Our cross-sectional data must be however approached with caution. Further research is necessary to replicate the present preliminary results in other cohorts and to identify the potential use of galectin-3 and osteopontin as potential targets (or at least predictors) in future personalized anti-aging therapies

Estimation of Relevant Variables on High-Dimensional Biological Patterns Using Iterated Weighted Kernel Functions

BACKGROUND The analysis of complex proteomic and genomic profiles involves the identification of significant markers within a set of hundreds or even thousands of variables that represent a high-dimensional problem space. The occurrence of noise, redundancy or combinatorial interactions in the profile makes the selection of relevant variables harder. METHODOLOGY/PRINCIPAL FINDINGS Here we propose a method to select variables based on estimated relevance to hidden patterns. Our method combines a weighted-kernel discriminant with an iterative stochastic probability estimation algorithm to discover the relevance distribution over the set of variables. We verified the ability of our method to select predefined relevant variables in synthetic proteome-like data and then assessed its performance on biological high-dimensional problems. Experiments were run on serum proteomic datasets of infectious diseases. The resulting variable subsets achieved classification accuracies of 99% on Human African Trypanosomiasis, 91% on Tuberculosis, and 91% on Malaria serum proteomic profiles with fewer than 20% of variables selected. Our method scaled-up to dimensionalities of much higher orders of magnitude as shown with gene expression microarray datasets in which we obtained classification accuracies close to 90% with fewer than 1% of the total number of variables. CONCLUSIONS Our method consistently found relevant variables attaining high classification accuracies across synthetic and biological datasets. Notably, it yielded very compact subsets compared to the original number of variables, which should simplify downstream biological experimentation

Resistindo ao desenvolvimento neocolonial: a luta do povo de Andalgalá contra projetos megamineiros

A América Latina vem experimentando uma nova era de declarada fé dos governos no mito do desenvolvimento, em articulação com a expansão de políticas extrativistas exportadoras em um contexto de renovada dependência. A face mais dramática do extrativismo na região tem sido a crescente presença de corporações mineiras transnacionais apoiadas por governos nacionais e regionais e por instituições internacionais financeiras e de apoio ao desenvolvimento, e intensamente resistidas por movimentos sociais populares. Neste artigo apresentamos o caso de Andalgalá (uma pequena cidade na Província de Catamarca, na Argentina) e as lutas do povo contra corporações mineiras transnacionais e seus aliados. Na tradição da Filosofia da Libertação e do método ana-dialético de Dussel, nos engajamos com o que tem sido denominado "comunidades argentinas do NÃO", expressando sua oposição a formas neocoloniais de desenvolvimento e gestão. Neste artigo estamos especificamente interessados em compreender como dois dispositivos gerencialistas usados pelas corporações mineiras, responsabilidade social corporativa (RSC) e pactos de governança, impactam a luta do povo. Acima de tudo, este artigo oferece instantâneos de batalhas na linha de frente do extrativismo. Esperamos ter dado voz àquelas pessoas que normalmente não são ouvidas, criando um espaço para suas visões sobre um tipo diferente de desenvolvimento.</jats:p