Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels? A device-based cohort study

Objectives This study aims to examine the associations of daily step count with all- cause mortality and incident cardiovascular disease (CVD) by sedentary time levels and to determine if the minimal and optimal number of daily steps is modified by high sedentary time. Methods Using data from the UK Biobank, this was a prospective dose–response analysis of total daily steps across low (<10.5 hours/day) and high (≥10.5 hours/day) sedentary time (as defined by the inflection point of the adjusted absolute risk of sedentary time with the two outcomes). Mortality and incident CVD was ascertained through 31 October 2021. Results Among 72 174 participants (age=61.1±7.8 years), 1633 deaths and 6190 CVD events occurred over 6.9 (±0.8) years of follow- up. Compared with the referent 2200 steps/day (5th percentile), the optimal dose (nadir of the curve) for all- cause mortality ranged between 9000 and 10 500 steps/day for high (HR (95% CI)=0.61 (0.51 to 0.73)) and low (0.69 (0.52 to 0.92)) sedentary time. For incident CVD, there was a subtle gradient of association by sedentary time level with the lowest risk observed at approximately 9700 steps/day for high (0.79 (0.72 to 0.86)) and low (0.71 (0.61 to 0.83)) sedentary time. The minimal dose (steps/day associated with 50% of the optimal dose) of daily steps was between 4000 and 4500 steps/day across sedentary time groups for all- cause mortality and incident CVD. Conclusions Any amount of daily steps above the referent 2200 steps/day was associated with lower mortality and incident CVD risk, for low and high sedentary time. Accruing 9000–10 500 steps/day was associated with the lowest mortality risk independent of sedentary time. For a roughly equivalent number of steps/ day, the risk of incident CVD was lower for low sedentary time compared with high sedentary time

Mujeres en Bioquímica

We are pleased to present in the magazine "Encounters in Biology" the series of profiles published online in the «Portrait Gallery of Women in Biochemistry» on the SEBBM website, which began in 2011, with the centenary of the Nobel Prize awarded to Marie Curie, International Year of Chemistry. During the celebration of the 22nd IUBMB - 37th FEBS Congress and XXXV Congress of the SEBBM that took place in Seville from September 4 to 9, 2012, a traveling exhibition was inaugurated with this information in panel format.Tenemos el placer de presentar en la revista "Encuentros en la Biología" la serie de perfiles publicados on-li- ne en la «Galería de retratos de Mujeres en Bioquímica» de la web de la SEBBM, que comenzó en 2011, con el centenario del premio Nobel otorgado a Marie Curie, Año Internacional de la Química. Durante la celebra- ción del 22nd IUBMB - 37th FEBS Congress y XXXV Congreso de la SEBBM que tuvo lugar en Sevilla del 4 al 9 de septiembre de 2012 se inauguró una exposición itinerante con esta información en formato de paneles

Caveolin-1 is required for TGF-β-induced transactivation of the EGF receptor pathway in hepatocytes through the activation of the metalloprotease TACE/ADAM17

Transforming growth factor-beta (TGF-β) plays a dual role in hepatocytes, inducing both pro- and anti-apoptotic responses, whose balance decides cell fate. Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-β in these cells. Caveolin-1 (Cav1) is a structural protein of caveolae linked to TGF-β receptors trafficking and signaling. Previous results have indicated that in hepatocytes, Cav1 is required for TGF-β-induced anti-apoptotic signals, but the molecular mechanism is not fully understood yet. In this work, we show that immortalized Cav1(-/-) hepatocytes were more sensitive to the pro-apoptotic effects induced by TGF-β, showing a higher activation of caspase-3, higher decrease in cell viability and prolonged increase through time of intracellular reactive oxygen species (ROS). These results were coincident with attenuation of TGF-β-induced survival signals in Cav1(-/-) hepatocytes, such as AKT and ERK1/2 phosphorylation and NFκ-B activation. Transactivation of the EGFR pathway by TGF-β was impaired in Cav1(-/-) hepatocytes, which correlated with lack of activation of TACE/ADAM17, the metalloprotease responsible for the shedding of EGFR ligands. Reconstitution of Cav1 in Cav1(-/-) hepatocytes rescued wild-type phenotype features, both in terms of EGFR transactivation and TACE/ADAM17 activation. TACE/ADAM17 was localized in detergent-resistant membrane (DRM) fractions in Cav1(+/+) cells, which was not the case in Cav1(-/-) cells. Disorganization of lipid rafts after treatment with cholesterol-binding agents caused loss of TACE/ADAM17 activation after TGF-β treatment. In conclusion, in hepatocytes, Cav1 is required for TGF-β-mediated activation of the metalloprotease TACE/ADAM17 that is responsible for shedding of EGFR ligands and activation of the EGFR pathway, which counteracts the TGF-β pro-apoptotic effects. Therefore, Cav1 contributes to the pro-tumorigenic effects of TGF-β in liver cancer cells.This work was supported by grants from: (1) the Ministry of Economy and Competitiveness (MINECO), Spain (BFU2012-35538 and ISCIII-RTICC: RD12-0036-0029 to IF; SAF2013-43713 to PM-S; BFU2012-33932 to GE; SAF2011-25047 and CSD2009-00016 to MAdP); (2) AGAUR-Generalitat de Catalunya (2009SGR-312 to IF); and (3) People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. PITN-GA-2012-316549 (IT LIVER) to IF JM-C and RM-V were recipients of pre-doctoral fellowships from the FPU program (Ministry of Education, Culture and Sport, Spain) and the FPI program (associated to SAF201125047, MINECO, Spain), respectively. We acknowledge the review and suggestions of Dr. Christoph Meyer (University of Heidelberg, Mannheim, Germany).S

4D Reconstruction and Visualization of Cultural Heritage: Analysing our Legacy Through Time

Temporal analyses and multi-temporal 3D reconstruction are fundamental for the preservation and maintenance of all forms of Cultural Heritage (CH) and are the basis for decisions related to interventions and promotion. Introducing the fourth dimension of time into three-dimensional geometric modelling of real data allows the creation of a multi-temporal representation of a site. In this way, scholars from various disciplines (surveyors, geologists, archaeologists, architects, philologists, etc.) are provided with a new set of tools and working methods to support the study of the evolution of heritage sites, both to develop hypotheses about the past and to model likely future developments. The capacity to “see” the dynamic evolution of CH assets across different spatial scales (e.g. building, site, city or territory) compressed in diachronic model, affords the possibility to better understand the present status of CH according to its history. However, there are numerous challenges in order to carry out 4D modelling and the requisite multi-data source integration. It is necessary to identify the specifications, needs and requirements of the CH community to understand the required levels of 4D model information. In this way, it is possible to determine the optimum material and technologies to be utilised at different CH scales, as well as the data management and visualization requirements. This manuscript aims to provide a comprehensive approach for CH time-varying representations, analysis and visualization across different working scales and environments: rural landscape, urban landscape and architectural scales. Within this aim, the different available metric data sources are systemized and evaluated in terms of their suitability

Effects of Açai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: A pilot study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the effect of açai fruit pulp on risk factors for metabolic disorders in overweight subjects. The açaí palm (<it>Euterpe oleracea </it>Mart.), which is native to South America, produces a small, black-purple fruit which is edible. The fruit has recently become popular as a functional food due to its antioxidant potential. Although several studies have been conducted in vitro and with animals, little is known about the potential health benefits in humans aside from an increase in plasma anti-oxidant capacity. Metabolic syndrome is a condition which is defined by a cluster of risk factors for cardiovascular disease and/or type-2 diabetes. Preliminary studies indicate that a reduction in reactive oxygen species can assist in the normalization of the metabolic pathways involved in this syndrome.</p> <p>Methods</p> <p>This was an open label pilot study conducted with 10 overweight adults (BMI ≥ 25 kg/m²and ≤ 30 kg/m²) who took 100 g açai pulp twice daily for 1 month. The study endpoints included levels of fasting plasma glucose, insulin, cholesterol, triglycerides, exhaled (breath) nitric oxide metabolites (eNO) and plasma levels of high sensitivity C-reactive protein (hs-CRP). The response of blood glucose, blood pressure and eNO to a standardized meal was determined at baseline and following the 30 day treatment.</p> <p>Results</p> <p>Compared to baseline, there were reductions in fasting glucose and insulin levels following the 30 day treatment (both p < 0.02). There was also a reduction in total cholesterol (p = 0.03), as well as borderline significant reductions in LDL-cholesterol and the ratio of total cholesterol to HDL-cholesterol (both p = 0.051). Compared to baseline, treatment with açai ameliorated the post-prandial increase in plasma glucose following the standardized meal, measured as the area under the curve (p = 0.047). There was no effect on blood pressure, hs-CRP or eNO.</p> <p>Conclusion</p> <p>In this uncontrolled pilot study, consumption of açai fruit pulp reduced levels of selected markers of metabolic disease risk in overweight adults, indicating that further studies are warranted.</p

Binaries with the eyes of CTA

The binary systems that have been detected in gamma rays have proven very useful to study high-energy processes, in particular particle acceleration, emission and radiation reprocessing, and the dynamics of the underlying magnetized flows. Binary systems, either detected or potential gamma-ray emitters, can be grouped in different subclasses depending on the nature of the binary components or the origin of the particle acceleration: the interaction of the winds of either a pulsar and a massive star or two massive stars; accretion onto a compact object and jet formation; and interaction of a relativistic outflow with the external medium. We evaluate the potentialities of an instrument like the Cherenkov telescope array (CTA) to study the non-thermal physics of gamma-ray binaries, which requires the observation of high-energy phenomena at different time and spatial scales. We analyze the capability of CTA, under different configurations, to probe the spectral, temporal and spatial behavior of gamma-ray binaries in the context of the known or expected physics of these sources. CTA will be able to probe with high spectral, temporal and spatial resolution the physical processes behind the gamma-ray emission in binaries, significantly increasing as well the number of known sources. This will allow the derivation of information on the particle acceleration and emission sites qualitatively better than what is currently available

In vivo testing of novel vaccine prototypes against Actinobacillus pleuropneumoniae

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a Gram-negative bacterium that represents the main cause of porcine pleuropneumonia in pigs, causing significant economic losses to the livestock industry worldwide. A. pleuropneumoniae, as the majority of Gram-negative bacteria, excrete vesicles from its outer membrane (OM), accordingly defined as outer membrane vesicles (OMVs). Thanks to their antigenic similarity to the OM, OMVs have emerged as a promising tool in vaccinology. In this study we describe the in vivo testing of several vaccine prototypes for the prevention of infection by all known A. pleuropneumoniae serotypes. Previously identified vaccine candidates, the recombinant proteins ApfA and VacJ, administered individually or in various combinations with the OMVs, were employed as vaccination strategies. Our data show that the addition of the OMVs in the vaccine formulations significantly increased the specific IgG titer against both ApfA and VacJ in the immunized animals, confirming the previously postulated potential of the OMVs as adjuvant. Unfortunately, the antibody response raised did not translate into an effective protection against A. pleuropneumoniae infection, as none of the immunized groups following challenge showed a significantly lower degree of lesions than the controls. Interestingly, quite the opposite was true, as the animals with the highest IgG titers were also the ones bearing the most extensive lesions in their lungs. These results shed new light on A. pleuropneumoniae pathogenicity, suggesting that antibody-mediated cytotoxicity from the host immune response may play a central role in the development of the lesions typically associated with A. pleuropneumoniae infections

MAGIC J0616+225 as delayed TeV emission of cosmic-rays diffusing from SNR IC 443

We present a theoretical model that explains the high energy phenomenology of the neighborhood of SNR IC 443, as observed with the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) telescope and the Energetic Gamma-Ray Experiment Telescope (EGRET). We interpret MAGIC J0616+225 as delayed TeV emission of cosmic-rays diffusing from IC 443 and interacting with a known cloud located at a distance of about 20 pc in the foreground of the remnant. This scenario naturally explains the displacement between EGRET and MAGIC sources, their fluxes, and their spectra. We compare this model with others recently presented, and discuss how it can be tested with observations by the Gamma-ray Large Area Telescope (GLAST).Comment: Accepted for publication in MNRAS Letter

A Methodological Approach for Implementing an Integrated Multimorbidity Care Model: Results from the Pre-Implementation Stage of Joint Action CHRODIS-PLUS

Patients with multimorbidity (defined as the co-occurrence of multiple chronic diseases) frequently experience fragmented care, which increases the risk of negative outcomes. A recently proposed Integrated Multimorbidity Care Model aims to overcome many issues related to fragmented care. In the context of Joint Action CHRODIS-PLUS, an implementation methodology was developed for the care model, which is being piloted in five sites. We aim to (1) explain the methodology used to implement the care model and (2) describe how the pilot sites have adapted and applied the proposed methodology. The model is being implemented in Spain (Andalusia and Aragon), Lithuania (Vilnius and Kaunas), and Italy (Rome). Local implementation working groups at each site adapted the model to local needs, goals, and resources using the same methodological steps: (1) Scope analysis; (2) situation analysis-"strengths, weaknesses, opportunities, threats" (SWOT) analysis; (3) development and improvement of implementation methodology; and (4) final development of an action plan. This common implementation strategy shows how care models can be adapted according to local and regional specificities. Analysis of the common key outcome indicators at the post-implementation phase will help to demonstrate the clinical effectiveness, as well as highlight any difficulties in adapting a common Integrated Multimorbidity Care Model in different countries and clinical settings