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El propósito central de este trabajo fue diagnosticar y determinar la relación existente entre la gestión del conocimiento y la competitividad en el clúster del mezcal de Durango México. Se utilizó una metodología cuantitativa correlacional y en cuanto a su temporalidad fue transversal. Para la recopilación de la información se utilizó la técnica de la encuesta, se tomó como unidad de análisis a los miembros activos y colaboradores de la estructura del clúster. Los resultados muestran, que el diagnóstico realizado, permite identificar las áreas de oportunidad de las variables estudiadas, así mismo, se tiene evidencia estadística de que existe una relación positiva significativa entre la gestión del conocimiento y la competitividad. Se concluye que, para mejorar las áreas de oportunidad detectadas en el clúster de mezcal, es necesario diseñar e implementar un plan de acción estratégico a través de una intervención organizacional, debido a que las variables tienen una relación y el impacto positivo en una, se verá reflejado en la otra.

Motivated by the empirical evidence of the effects of unanticipated nominal interest rate increases on the evolution of household inequality in Mexico, which highlight the importance of insurance mechanisms to deal with idiosyncratic risks, the paper uses a Heterogeneous Agent New Keynesian model to analyze the relationship between monetary policy and household inequality. The model is able to capture the main features that characterise both the business cycle dynamics, as well as the distribution of income and wealth. Results indicate that heterogeneity affects the transmission of monetary policy, and that the design of monetary policy has important distributive effects.

One of the most abundant flavonoids present in cacao is (-)-epicatechin (Epi) and this flavanol has been linked to the cardiovascular health promoting actions of cocoa products. We previously demonstrated that Epi reduces infarct size in rodent models of ischemia/reperfusion and permanent coronary occlusion. Reduced infarct size was associated with decreased left ventricular (LV) oxidative stress (OS) and indicators of inflammation factors, which foster myocardial fibrosis. In this study, we examine the antifibrotic actions of Epi in an aging female rat model of pre-heart failure with preserved ejection fraction (pre-HFpEF) as well as its potential to mitigate plasma levels of OS, proinflammatory/profibrotic cytokines, and improve passive and active LV function. Epi treatment [1 mg/(kg·d)] was provided daily by gavage from 21 to 22 months of age, whereas controls received water. A Millar catheter was used to assess hemodynamic function. Subsequently, hearts were arrested in diastole, a balloon inserted into the LV and passive pressure-volume curves generated. Fixed LV sections were processed for collagen area fraction quantification using Sirius Red staining. Treatment with Epi did not lead to detectable changes in LV contractile function. However, passive LV pressure volume curves were significantly right shifted with Epi. Collagen area fraction values indicated that Epi treatment significantly reduces LV fibrosis. Epi also significantly reduced plasma OS markers and levels of profibrotic and proinflammatory cytokines. In conclusion, Epi reduces cardiac fibrosis in an aged, female rat model of pre-HFpEF, which correlates with significant reductions in OS and cytokine levels in the absence of changes in LV contractile function.

El presente trabajo intenta acreditar que la solución dada por el Tribunal del Mar en el Caso del Atún Rojo del Sur, si bien resultó ser epistémicamente superadora a aquella que hubiera supuesto atenerse a únicamente considerar el dictum de los expertos que asesoraran a cada una de las partes enfrentadas, sería, de todos modos, subóptima. Ello desde que los magistrados de tal foro, pese a las provisiones ental sentido del artículo 289 de la Convención de las Naciones Unidas sobre el Derecho del Mar, se abstendrían de consultar y debatir con los expertos la naturaleza de la cuestión sometida a su examen. Cual implicancia directa de ello, el Tribunal del Mar no podría haber contribuido a que las propias partes enfrentadas conocieran, trascendentalmente a los términos en los que estas los plantearan, los fundamentos de sus pretensiones. En consecuencia, el Tribunal del Mar se privó de realizar un aporte veraderamente consistente a la solución del conflicto, independientemente de lo que en tal sentido dictara el Tribunal Arbitral. En ese sentido, este trabajo intenta acreditar la relación de estricta causalidad existente entre dejar de considerar el dictum de la alteridad y tomar decisiones epistémicamente deficientes.

We examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

La pertenencia del investigador a una comunidad científica posee particulares beneficios mas simultáneamente también, costos de oportunidad. Entre estos últimos ha de referirse la imposibilidad de cuestionar los fundamentos que explican el corpus de premisas y tesis en virtud de las que la corporación de referencia se entiende a sí misma como acreedora de un determinado saber imparcial. El presente trabajo proveerá, en este sentido, a analizar las posibilidades sociológicas que poseen los investigadores de poder cuestionar el conjunto de estas últimas sin que ello suponga, forzosamente la génesis de un cambio abrupto de paradigmas.

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Made available in DSpace on 2021-07-14T10:37:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-05. Added 1 bitstream(s) on 2021-07-14T11:34:27Z : No. of bitstreams: 1 S2676-00292021000100139.pdf: 778329 bytes, checksum: cab29c161e19a48506643ac8173d3518 (MD5) Neste trabalho, uma análise comparativa entre as wavelets Gaussianas e Golden é apresentada. Tais wavelets são geradas pela derivada de uma função basica específica. Nesse caso, a ordem da derivada também indica o número de momentos nulos da wavelet. Embora essas wavelets tenham formas de onda muito semelhantes, elas possuem várias características distintas nos domínios do tempo e da frequência. Essas distinções são exploradas aqui no espaço de escalas. A fim de comparar os resultados das wavelets para um sinal real, essas wavelets são usadas na decomposição de um sinal inserido no contexto do sistemas de monitoramento de integridade estrutural. In this work, a comparative analysis between Gaussian and Golden wavelets is presented. These wavelets are generated by the derivative of specific base functions. In this case, the order of the derivative also indicates the number of vanishing moments of the wavelet. Although these wavelets have a similar waveform, they have several distinct characteristics in time and frequency domains. These distinctions are explored here in the scale space. In order to compare the results provided by these wavelets for a real signal, they are used in the decomposition of a signal inserted in the context of structural health monitoring. São Paulo State University, Department of Electrical Engineering Mato Grosso do Sul State University, Department of Mathematics São Paulo State University, Department of Mathematics São Paulo State University, Department of Electrical Engineering São Paulo State University, Department of Mathematics

Objective of the study: to examine the thesis according to which a criterion of synonymity can be predicated between the notion of "Islamic fundamentalism" and the universe of juridical-political predicates inherent to the practice of this creed. Conceptual foundation: it will be studied what is to be understood by such "Islamic fundamentalism", as well as the historical course on which the typification of the juridical-political manifestations stemming from within the Muslim religion as “extremist” became generalized. Methodology: a critical hermeneutic method was used, analyzing, by means of sociological and discourse analysis provisions, the content of those doctrines that preached the effective virtuality of the synonymy in question. Main results: the conclusion of this paper supports the idea according to which the criterion of identity between the so-called “Islamic fundamentalism” and the plurality of juridical-political predicates inherent to the practice of such dogma can only be predicated for very concrete historical processes which are, as such, limited in the annals of such religion. Consequently, this article contravene the validity of the referred analogy. Contributions or implications: This article vindicates the need for a heuristic exercise that contests the hegemonic representations according to which the Islamic socio-political logos is constructed as intrinsically fundamentalist, especially in those cases in which the discursive and semiotic practices that validate such readings are structured on the basis of the radical suppression of the universe of ideas, values and beliefs of the identity of the Muslim as an otherness.

Purpose Reducing fuel consumption of unmanned aerial vehicles (UAVs) during transient operation is a cornerstone to achieve environment-friendly operations. The purpose of this paper is to develop a control scheme that improves the fuel economy of a turbojet in its full operating envelope. Design/methodology/approach A novel direct-thrust linear quadratic integral (LQI) approach, comprised by an optimal observer/controller satisfying specified performance parameters, is presented. The thrust estimator, based in a Wiener model, is validated with the experimental data of a micro-turbojet. Model uncertainty is characterized by analyzing variations between the identified model and measured data. The resulting uncertainty range is used to verify closed-loop stability with the circle criterion. The proposed controller provides stable responses with the specified performance in the whole operating range, even with after considering plant nonlinearities. Finally, the direct-thrust LQI is compared with a standard thrust controller to assess fuel economy and performance. Findings The direct-thrust LQI approach reduced the fuel consumption by 2.1090% in the most realistic scenario. The controllers were also evaluated using the environmental effect parameter (EEP) and transient-thrust-specific fuel consumption (T-TSFC). These novel metrics are proposed to evaluate the environmental impact during transient-thrust operations. The direct-thrust LQI approach has a more efficient fuel consumption according to these metrics. The results also show that isolating the thrust dynamics within the feedback loop has an important impact in fuel economy. Controllers were also evaluated using the EEP and T-TSFC. These novel metrics are proposed to evaluate the environmental impact during transient-thrust operations. The direct-thrust LQI approach has a more efficient fuel consumption according to these metrics. The results also show that isolating the thrust dynamics within the feedback loop has an important impact in fuel economy. Originality/value This study shows the design of an effective direct-thrust control approach that minimizes fuel consumption, ensures stable responses for the full operation range, allows isolating the thrust dynamics when designing the controller and is compatible with classical robustness and performance metrics. Finally, the study shows that a simple controller can reduce the fuel consumption of the turbojet during transient operation in scenarios that approximate realistic operating conditions.

Skeletal muscle (SkM) is a highly dynamic tissue that responds to physiological adaptations or pathological conditions, and SkM mitochondria play a major role in bioenergetics, regulation of intracellular calcium homeostasis, pro-oxidant/antioxidant balance, and apoptosis. Flavonoids are polyphenolic compounds with the ability to modulate molecular pathways implicated in the development of mitochondrial myopathy. Therefore, it is pertinent to explore its potential application in conditions such as aging, disuse, denervation, diabetes, obesity, and cancer. To evaluate preclinical and clinical effects of flavonoids on SkM structure and function. We performed a systematic review of published studies, with no date restrictions applied, using PubMed and Scopus. The following search terms were used: "flavonoids" OR "flavanols" OR "flavones" OR "anthocyanidins" OR "flavanones" OR "flavan-3-ols" OR "catechins" OR "epicatechin" OR "(-)-epicatechin" AND "skeletal muscle." The studies included in this review were preclinical studies, clinical trials, controlled clinical trials, and randomized-controlled trials that investigated the influence of flavonoids on SkM health. Three authors, independently, assessed trials for the review. Any disagreement was resolved by consensus. The use of flavonoids could be a potential tool for the prevention of muscle loss. Their effects on metabolism and on mitochondria function suggest their use as muscle regulators.

Therapeutic approaches to decrease serum triglyceride (TG) concentrations are not successful mainly due to poor adherence or adverse effects of therapies. In consequence, the search for new low-cost and safer therapeutic alternatives is mandatory. Dark chocolate and cacao have shown promising results improving lipid profiles. Recently, using cacao by-products to reduce elevated cardiometabolic risk markers in an animal model of obesity induced by a high-fat diet and fructose, we showed that TGs, low-density lipoprotein cholesterol, and the TG/high-density lipoprotein (HDL) ratio decreased, suggesting that cacao by-products improved the metabolic function of obese animals. Based on these results, as a proof of concept, a blinded placebo-controlled study was implemented to explore the effects of cacao by-products on anthropometric and biochemical variables in a group of overweight subjects participating in a program composed of reduced-calorie-diet counseling plus a simple aerobic exercise plan. The results showed that counseling induced weight and abdominal circumference reductions in both groups. TGs did not change in the control group; however, TG decreased significantly by 54.9 mg/dL (27.9%) in the experimental group. The TG/HDL cholesterol ratio changed markedly (1.5) in the experimental group. The results reported suggest the use of cacao by-products as an alternative for the treatment of hypertriglyceridemia.

Purpose Aircraft pitch control is fundamental for the performance of micro aerial vehicles (MAVs). The purpose of this paper is to establish a simple experimental procedure to calibrate pitch instrumentation and classical control algorithms. This includes developing an efficient pitch angle observer with optimal estimation and evaluating controllers under uncertainty and external disturbances. Design/methodology/approach A wind tunnel test bench is designed to simulate fixed-wing aircraft dynamics. Key elements of the instrumentation commonly found in MAVs are characterized in a gyroscopic test bench. A data fusion algorithm is calibrated to match the gyroscopic test bench measurements and is then integrated into the autopilot platform. The elevator-angle to pitch-angle dynamic model is obtained experimentally. Two different control algorithms, based on model-free and model-based approaches, are designed. These controllers are analyzed in terms of parametric uncertainties due to wind speed variations and external perturbation because of sudden weight distribution changes. A series of experimental tests is performed in wind-tunnel facilities to highlight the main features of each control approach. Findings With regard to the instrumentation algorithms, a simple experimental methodology for the design of optimal pitch angle observer is presented and validated experimentally. In the context of the platform design and identification, the similitude among the theoretical and experimental responses shows that the platform is suitable for typical pitch control assessment. The wind tunnel experiments show that a fixed linear controller, designed using classical frequency domain concepts, is able to provide adequate responses in scenarios that approximate the operation of MAVs. Research limitations/implications The aircraft orientation observer can be used for both pitch and roll angles. However, for simultaneousyaw angle estimation the proposed design method requires further research. The model analysis considers a wind speed range of 6-18 m/s, with a nominal operation of 12 m/s. The maximum experimentally tested reference for the pitch angle controller was 20°. Further operating conditions may require more complex control approaches (e.g. scheduling, non-linear, etc.). However, this operating range is enough for typical MAV missions. Originality/value The study shows the design of an effective pitch angle observer, based on a simple experimental approach, which achieved locally optimum estimates at the test conditions. Additionally, the instrumentation and design of a test bench for typical pitch control assessment in wind tunnel facilities is presented. Finally, the study presents the development of a simple controller that provides adequate responses in scenarios that approximate the operation of MAVs, including perturbations that resemble package delivery and parametric uncertainty due to wind speed variations.

We previously reported on the development of left ventricular (LV) structural and functional changes in an aged, female rat model where the effects of ovariectomy and excess weight (stimulated by fructose in water) were also explored. Ovariectomy and/or excess weight led to a prolongation of active relaxation, loss of cardiac output, and LV fibrosis in the setting of preserved ejection fraction. In this follow-up study, we wished to characterize the possible role of LV inflammation, oxidative stress (OS), and cell death in inducing such changes. Four experimental groups were studied: young (3 months old), aged (18 months old), aged + ovariectomy (OVX), and aged + ovariectomy + 10% fructose (OVF). Using conventional histology and immunohistochemistry of myocardium as well as biochemical assays of plasma samples, we document the presence of inflammatory cell aggregates in LV myocardium which are associated to high levels of plasma inflammatory cytokines (IL-1β, TNF-α, IFN-γ, TGF-β1) and OS (carbonyl proteins) in aged, OVX, and OVF vs. young animals. In the inflammatory areas, normal cardiac tissue was substituted by replacement and interstitial fibrosis and M1 macrophages, (as per by CD68 immunostaining) as we all as by co-localization with TGF-β1. We also document increases in plasma troponin I levels, loss of capillary density, cardiomyocyte hypertrophy, and death. Select changes were further aggravated by ovariectomy and/or excess weight. In conclusion, aging in the female rat heart, when compounded with estrogen depletion and excess weight promotes the development of greater levels inflammation, OS, fibrosis, capillary rarefaction, cardiomyocyte hypertrophy, and injury/death. These factors likely play an important role in the development of LV remodeling that leads to the development of a “pre-HFpEF” phenotype. Impact statement The incidence of HFpEF continues to increase and ∼2/3 of the patient population are post-menopausal women. Unfortunately, most studies focus on the use of male animal models of remodeling. In this study, however, using female rats to set a model of pre-HFpEF, we provide insights to possible mechanisms that contribute to HFpEF development in humans that will lead us to a better understanding of the underlying pathophysiology of HFpEF.

En el decurso de las últimas tres décadas, la República Popular China ha sido sujeto de un cambio por demás radical en lo relativo a las implicancias de la estrategia geopolítica en virtud de la cual se desarrolla su participación en las misiones de paz de las Naciones Unidas. El presente trabajo, a partir del análisis para el caso de China de los principios del Derecho Internacional Público, se abocará a dar cuenta del modo en el cual los mismos también habrían de incidir en una similar estrategia por parte de Brasil y la Argentina como presupuesto para la inserción internacional.Misiones de paz – multilateralismo - Derecho Internacional Público - República Popular China, Brasil y Argentina

Evidence has implicated oxidative stress (OS) and inflammation as drivers of neurodegenerative pathologies. We previously reported on the beneficial effects of (-)-epicatechin (Epi) treatment on aging-induced OS and its capacity to restore modulators of mitochondrial biogenesis in the prefrontal cortex of 26-month-old male mice. In the present study using the same mouse model of aging, we examined the capacity of Epi to mitigate hippocampus OS, inflammation, hyperphosphorylation of tau protein, soluble β-amyloid protein levels, cell survival, memory, anxiety-like behavior levels and systemic inflammation. Mice were subjected to 4 weeks of Epi treatment (1 mg kg-1 day-1) and samples of the hippocampus were obtained. Assessments of the OS markers, protein carbonyls, and malondialdehyde levels demonstrated their significant increase (∼3 fold) with aging that were partially suppressed by Epi. The protein levels of the glial fibrillary acidic protein, inflammatory factor 1 (Iba1), pro-inflammatory cytokines, interleukins (IL-1β, IL-3, 5, 6 and 15), cyclooxygenase 2, tumor necrosis factor α, nuclear factor-activated B cells and interferon γ increase with aging and were also significantly decreased with Epi treatment. However, anti-inflammatory cytokines, IL-1ra, IL-10 and 11 decrease with aging and were restored with Epi. Epi also reversed the aging effects on the hyperphosphorylation of tau, increased soluble β-amyloid levels (∼2 fold), cellular death (as per caspase 3 and 9 activity), and reduced nerve growth factor and triggering receptor expressed on myeloid cells 2 levels. Measures of anxiety like-behavior and memory demonstrated improvements with Epi treatment. Indicators of systemic inflammation increase with aging and Epi was capable of decreasing blood inflammatory markers. Altogether, the results show a significant capacity of Epi to mitigate hippocampus OS and inflammation leading to improved brain function.

Aquaculture is an expanding economic sector that nourishes the world’s growing population due to its nutritional significance over the years as a source of high-quality proteins. However, it has faced severe challenges due to significant cases of environmental pollution, pathogen outbreaks, and the lack of traceability that guarantees the quality assurance of its products. Such context has prompted many researchers to work on the development of novel, affordable, and reliable technologies, many based on nanophotonic sensing methodologies. These emerging technologies, such as surface plasmon resonance (SPR), localised SPR (LSPR), and fibre-optic SPR (FO-SPR) systems, overcome many of the drawbacks of conventional analytical tools in terms of portability, reagent and solvent use, and the simplicity of sample pre-treatments, which would benefit a more sustainable and profitable aquaculture. To highlight the current progress made in these technologies that would allow them to be transferred for implementation in the field, along with the lag with respect to the most cutting-edge plasmonic sensing, this review provides a variety of information on recent advances in these emerging methodologies that can be used to comprehensively monitor the various operations involving the different commercial stages of farmed aquaculture. For example, to detect environmental hazards, track fish health through biochemical indicators, and monitor disease and biosecurity of fish meat products. Furthermore, it highlights the critical issues associated with these technologies, how to integrate them into farming facilities, and the challenges and prospects of developing plasmonic-based sensors for aquaculture.

Summary: Dysregulated inflammation following myocardial infarction (MI) promotes left ventricular (LV) remodeling and loss of function. Targeting inflammation resolution by activating formyl peptide receptors (FPRs) may limit adverse remodeling and progression towards heart failure. This study characterized the cellular and signaling properties of Compound 43 (Cmpd43), a dual FPR1/FPR2 agonist, and examined whether Cmpd43 treatment improves LV and infarct remodeling in rodent MI models. Cmpd43 stimulated FPR1/2-mediated signaling, enhanced proresolution cellular function, and modulated cytokines. Cmpd43 increased LV function and reduced chamber remodeling while increasing proresolution macrophage markers. The findings demonstrate that FPR agonism improves cardiac structure and function post-MI. Key Words: agonist, Compound 43, formyl peptide receptor, heart failure, myocardial infarction

Turbojet applications benefit from accurate performance models. The aim of this study is to explore the applicability of data-mining algorithms to determine relationships between the generated thrust, the environmental conditions (free stream air-speed, inlet temperature and pressure) and the operating conditions (input fuel flow and shaft angular speed). For this purpose, experimental tests were carried out within wind-tunnel facilities using an experimental single-spool turbojet test bench. It is well-known that a large set of data-mining approaches relies on establishing linear correlations among input and output variables. The scope of this article is to assess the applicability of correlational data-mining approaches by i) an exploratory data analysis to find underlying data patterns and ii) principal component regressions to obtain a suitable predictive model for the generated thrust. Validation experiments demonstrated that the data-based model allows capturing the effects of the environmental and operating conditions with good accuracy (Root Mean Squared Error RMSE = 3.5100%), while maintaining a low complexity in the resulting structure. These results show that it is possible to generate turbojet experimental performance maps through data-mining algorithms with a correlational approach.

Nonalcoholic fatty liver disease (NAFLD) is characterized by a spectrum of diseases, ranging from simple steatosis to hepatocellular carcinoma. The main factors for NAFLD are closely related to obesity, insulin resistance, intestinal microbiota alterations, hyperinsulinism, low-grade systemic inflammation, nitroxidative stress, lipid peroxidation, and mitochondrial dysfunction. Currently, the treatment of NAFLD is based on diet and exercise because, to date, there is no specific pharmacological agent, already approved, that raises the need for new therapeutic strategies. Nutraceuticals, such as polyphenols, have potential beneficial effects for health. In this article, the beneficial effects of epigallocatechin-3-gallate (EGCG) and (−)-epicatechin (EC) are discussed. EGCG is the main catechin in green tea, which has shown in various studies its potential effect preventing and treating NAFLD since it has shown antihyperlipidemic, anti-inflammatory, antifibrotic, antioxidant, and improvement of liver lipid metabolism. However, it has been found that excessive consumption may cause hepatotoxicity. EC is widely distributed in nature (fruits and vegetables). This flavanol has shown many beneficial effects, including antihypertensive, anti-inflammatory, anti-hyperglycemic, antithrombotic, and antifibrotic properties. It increases mitochondrial biogenesis, and it also has effects on the regulation of synthesis and metabolism of lipids. This flavanol is a nontoxic substance; it has been classified by the United States Food and Drug Administration as harmless. The EC-induced effects can be useful for the prevention and/or treatment of NAFLD.

Sarcopenia is a progressive and generalized age-related skeletal muscle (SkM) disorder characterized by the accelerated loss of muscle mass (atrophy) and function. SkM atrophy is associated with increased incidence of falls, functional decline, frailty and mortality. In its early stage, SkM atrophy is associated with oxidative stress, increased pro-inflammatory cytokine levels and proteasome-mediated protein degradation. These processes also link to the activation of atrophy associated factors and signaling pathways which lack any approved, targeted pharmacotherapy. We have characterized the capacity of flavanols specifically, epicatechin to favorably modulate SkM mass and function in animal models of SkM disease and in proof of concept studies in humans including muscular dystrophies. In this study we wished to evaluate the capacity of this flavanol to ameliorate aging associated sarcopenia. Using 24-month-old male rats a 4 week oral administration of the flavanol (+)-epicatechin (1mg/kg/day) was implemented while control rats only received vehicle (water). SkM strength (grip) and endurance (treadmill walk), muscle size, (muscle mass, cross sectional area of fibers), ubiquitin-proteasome atrophic pathway (including myostatin, Murf1 and Atrogin1 by Western blots) and markers of oxidative stress and inflammation in gastrocnemius were quantified. We also analyzed a relevant protein synthesis pathway (IGF/AKT/mTOR). The use of (+)-epicatechin in aged rats led to significant changes as follows: 1) improved SkM mass and function, 2) downregulation of atrophic pathway, 3) reduced levels of oxidative stress and proinflammatory cytokines and, 4) upregulation of protein synthesis pathway. Given its safety and tolerance profile this agent warrant its rigorous investigation in clinical trials.

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Cardiac fibrosis is one of the hallmarks of a diabetic cardiomyopathy. When activated, cardiac fibroblasts (CFs) increase the production of extracellular matrix proteins. Transforming growth factor (TGF)