Universidad de La Frontera

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

Este trabajo de investigación tiene como objetivo el realizar una propuesta para el fortalecimiento de las acciones de respuesta del plan de emergencias para el Centro de Formación Integral para el Trabajo (CEFIT). Esto debido a que a pesar de contar con la gestión documental y de implementación de un Plan de Preparación y Prevención de emergencias, se evidencia la necesidad de mejorar y optimizar mecanismos, estrategias y actividades que permitan a la institución dar cumplimiento a los requerimientos legales pertinentes, así como a la preservación de la salud y seguridad de la comunidad educativa, como requisito indispensable y dependiente en una articulación integral y eficaz de sus actores. Por lo que su proceso metodológico se apoya en cuatro fases; la primera de ellas que pretende diagnosticar el actual plan de emergencias de la institución respecto de sus componentes, la segunda evaluando el conocimiento y la percepción que tiene la comunidad educativa sobre dicho plan de emergencias, la tercera identificando las oportunidades de mejora respecto de los resultados de la fase 1 y 2, para finalmente en la cuarta fase proponer las estrategias que fortalecerán la respuesta ante emergencias para el CEFIT.

The biodiversity-productivity relationship (BPR) is foundational to our understanding of the global extinction crisis and its impacts on ecosystem functioning. Understanding BPR is critical for the accurate valuation and effective conservation of biodiversity. Using ground-sourced data from 777,126 permanent plots, spanning 44 countries and most terrestrial biomes, we reveal a globally consistent positive concave-down BPR, showing that continued biodiversity loss would result in an accelerating decline in forest productivity worldwide. The value of biodiversity in maintaining commercial forest productivity alone-US$166 billion to 490 billion per year according to our estimation-is more than twice what it would cost to implement effective global conservation. This highlights the need for a worldwide reassessment of biodiversity values, forest management strategies, and conservation priorities.

BACKGROUND: More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown. METHODS: We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years. RESULTS: The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P=0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001). CONCLUSIONS: Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. (Funded by the Population Health Research Institute and others.).

The Cronbach's alpha is the most widely used method for estimating internal consistency reliability. This procedure has proved very resistant to the passage of time, even if its limitations are well documented and although there are better options as omega coefficient or the different versions of glb, with obvious advantages especially for applied research in which the ítems differ in quality or have skewed distributions. In this paper, using Monte Carlo simulation, the performance of these reliability coefficients under a one-dimensional model is evaluated in terms of skewness and no tau-equivalence. The results show that omega coefficient is always better choice than alpha and in the presence of skew items is preferable to use omega and glb coefficients even in small samples.

Manganese is an essential element for plants, intervening in several metabolic processes, mainly in photosynthesis and as an enzyme antioxidant-cofactor.Nevertheless, an excess of this micronutrient is toxic for plants.Mn phytotoxicity is manifested in a reduction of biomass and photosynthesis, and biochemical disorders such as oxidative stress.Some studies on Mn toxicity and Mn translocation from soil to plant cells in Mn 2+ form have demonstrated their importance under low pH and redox potential conditions in the soil.When Mn is inside the cells, mechanisms that can tolerate this toxicity are also observed, being important the compartmentalization of this metal in different organelles of shoot and leaf plant cells.A key role of antioxidative systems in plants in relation to high Mn amounts has also been reported as a defense mechanism.The purpose of this review is to show the role of Mn as an essential micronutrient and as a toxic element to higher plants as well as to their transport and tolerance mechanisms.The forms and dynamics of this element in soils and the importance of the acidity for this dynamic and availability for plants are also given.

BACKGROUND: The optimal range of sodium intake for cardiovascular health is controversial. METHODS: We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events. RESULTS: The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome. CONCLUSIONS: In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.).

BACKGROUND: Higher levels of sodium intake are reported to be associated with higher blood pressure. Whether this relationship varies according to levels of sodium or potassium intake and in different populations is unknown. METHODS: We studied 102,216 adults from 18 countries. Estimates of 24-hour sodium and potassium excretion were made from a single fasting morning urine specimen and were used as surrogates for intake. We assessed the relationship between electrolyte excretion and blood pressure, as measured with an automated device. RESULTS: Regression analyses showed increments of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure for each 1-g increment in estimated sodium excretion. The slope of this association was steeper with higher sodium intake (an increment of 2.58 mm Hg in systolic blood pressure per gram for sodium excretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74 mm Hg per gram for <3 g per day; P<0.001 for interaction). The slope of association was steeper for persons with hypertension (2.49 mm Hg per gram) than for those without hypertension (1.30 mm Hg per gram, P<0.001 for interaction) and was steeper with increased age (2.97 mm Hg per gram at >55 years of age, 2.43 mm Hg per gram at 45 to 55 years of age, and 1.96 mm Hg per gram at <45 years of age; P<0.001 for interaction). Potassium excretion was inversely associated with systolic blood pressure, with a steeper slope of association for persons with hypertension than for those without it (P<0.001) and a steeper slope with increased age (P<0.001). CONCLUSIONS: In this study, the association of estimated intake of sodium and potassium, as determined from measurements of excretion of these cations, with blood pressure was nonlinear and was most pronounced in persons consuming high-sodium diets, persons with hypertension, and older persons. (Funded by the Heart and Stroke Foundation of Ontario and others.).

Forest restoration is being scaled up globally to deliver critical ecosystem services and biodiversity benefits; however, there is a lack of rigorous comparison of cobenefit delivery across different restoration approaches. Through global synthesis, we used 25,950 matched data pairs from 264 studies in 53 countries to assess how delivery of climate, soil, water, and wood production services, in addition to biodiversity, compares across a range of tree plantations and native forests. Benefits of aboveground carbon storage, water provisioning, and especially soil erosion control and biodiversity are better delivered by native forests, with compositionally simpler, younger plantations in drier regions performing particularly poorly. However, plantations exhibit an advantage in wood production. These results underscore important trade-offs among environmental and production goals that policy-makers must navigate in meeting forest restoration commitments.

Rhizobacteria are capable of stimulating plant growth through a variety of mechanisms that include improvement of plant nutrition, production and regulation of phytohormones, and suppression of disease causing organisms.While considerable research has demonstrated their potential utility, the successful application of plant growth promoting rhizobacteria (PGPR) in the field has been limited by a lack of knowledge of ecological factors that determine their survival and activity in the plant rhizosphere.To be effective, PGPR must maintain a critical population density of active cells.Inoculation with PGPR strains can temporarily enhance the population size, but inoculants often have poor survival and compete with indigenous bacteria for available growth substrates.PGPR often have more than one mechanism for enhancing plant growth and experimental evidence suggests that the plant growth stimulation is the net result of multiple mechanisms of action that may be activated simultaneously.The aim of this review is to describe PGPR modes of action and discuss practical considerations for PGPR use in agriculture.

Abstract. Since 2010 an uninterrupted sequence of dry years, with annual rainfall deficits ranging from 25 to 45 %, has prevailed in central Chile (western South America, 30–38° S). Although intense 1- or 2-year droughts are recurrent in this Mediterranean-like region, the ongoing event stands out because of its longevity and large extent. The extraordinary character of the so-called central Chile megadrought (MD) was established against century long historical records and a millennial tree-ring reconstruction of regional precipitation. The largest MD-averaged rainfall relative anomalies occurred in the northern, semi-arid sector of central Chile, but the event was unprecedented to the south of 35° S. ENSO-neutral conditions have prevailed since 2011 (except for the strong El Niño in 2015), contrasting with La Niña conditions that often accompanied past droughts. The precipitation deficit diminished the Andean snowpack and resulted in amplified declines (up to 90 %) of river flow, reservoir volumes and groundwater levels along central Chile and westernmost Argentina. In some semi-arid basins we found a decrease in the runoff-to-rainfall coefficient. A substantial decrease in vegetation productivity occurred in the shrubland-dominated, northern sector, but a mix of greening and browning patches occurred farther south, where irrigated croplands and exotic forest plantations dominate. The ongoing warming in central Chile, making the MD one of the warmest 6-year periods on record, may have also contributed to such complex vegetation changes by increasing potential evapotranspiration. We also report some of the measures taken by the central government to relieve the MD effects and the public perception of this event. The understanding of the nature and biophysical impacts of the MD helps as a foundation for preparedness efforts to confront a dry, warm future regional climate scenario.

Dear Editor, The measurement of malondialdehyde (MDA) content has long been used as a lipid peroxidation marker in studies related to oxidative stress and redox signaling, particularly in those studies focused on plant responses to abiotic and biotic stresses. A search for “malondialdehyde” and “plant*” in Scopus retrieves 9,000 publications from the last decade, with 1,221 of these published in 2018 (Scopus database, 2019). Unfortunately, however, there are major pitfalls in some of the current applications of this lipid peroxidation marker, including both (1) methodological aspects (a significant part of the scientific community still measures this compound using inadequate methodology), and (2) misinterpretation of results (mainly related to a misconception of oxidative stress, oxidative damage, and redox regulation). Life on our planet changed completely with the development of oxygenic photosynthesis by cyanobacteria ∼2.4 billion years ago (Harel et al., 2015). Higher oxygen tensions in the atmosphere brought about new opportunities for the diversification of complex life forms based on aerobic metabolism. Aerobic life implicitly afforded reactive oxygen species (ROS) a key role in the sophistication of acclimation mechanisms to a number of stresses, both of abiotic and biotic origin. Although ROS are part of aerobic life and play an essential role in stress acclimation and the regulation of plant development from germination to senescence, they are still today considered harmful molecules because of their high reactivity. Although ROS are indeed highly reactive and rapidly oxidize other target molecules leading to lipid peroxidation among many other biochemical reactions, it is important to keep in mind that both ROS production and lipid peroxidation are an intrinsic part of aerobic life and essential features of plant life. It is also important to bear in mind that lipid peroxidation not only is triggered by ROS, but can also result from increased lipoxygenase activity (e.g. as a result of a pathogen invasion or wounding attack). Therefore, both enzymatic and nonenzymatic lipid peroxidation processes may lead to the formation of MDA and other lipid peroxidation products in plants, such as jasmonates, which are an essential component of stress tolerance (Weber et al., 2004; Farmer and Mueller, 2013; Fig. 1A). Advantages and limitations of currently available methods for the measurement of MDA in plants. The most common extraction and analytical procedures for the analysis of MDA in plant samples are shown, indicating their advantages and limitations. (A) MDA is a secondary product of lipid peroxidation. (B) MDA exists in several different forms in aqueous solutions due to its pH-dependent tautometric chemical property. At higher pH than its pKa of 4.46, the enolic anion dominates, displaying a low chemical reactivity, whereas at lower pH (stress conditions), MDA appears in equilibrium between its protonated enol (⍺-β-unsaturated carbonyl) aldehyde form and the dialdehyde form: the high-reactive forms. (C) This chemical reactivity represents the basis for many MDA determination methods, which derivatize MDA prior to analysis and measure the complex formed by spectrophotometry, HPLC, or GC (in the latter two cases usually coupled to MS). LOOH, lipid hydroperoxide; OPDA, 12-oxo-phytodienoic acid; UHPLC, ultrahigh-performance liquid chromatography. Chemically, MDA is a small and reactive organic molecule that occurs ubiquitously among eukaryotes, formed by three carbon molecules with two aldehyde groups at the carbon 1 and carbon 3 positions. MDA exists in different forms in aqueous solutions due to its pH-dependent tautomeric chemical property. At higher pH than its pKa of 4.46, the dominate form is the enolic anion, which displays low chemical reactivity. However, at lower pH (expected under oxidative stress conditions), MDA appears in equilibrium between its protonated enol (α-β-unsaturated carbonyl) aldehyde and the dialdehyde form (Fig. 1B). These tautomers produced in acidic pH are chemically reactive, and MDA and other molecules with α-β-unsaturated carbonyl groups are known, including reactive electrophile species and reactive carbonyl species. Reactive electrophile species are known for the electrophilic character of the β-carbon that reacts with an electron-donor (nucleophilic) atom, whereas reactive carbonyl species are known for the high reactivity of the ⍺-β-unsaturated carbonyl groups resulting from the peroxidation of triunsaturated fatty acids, mostly linoleic acid, which is the in vivo source of up to 75% of MDA in Arabidopsis (Arabidopsis thaliana) leaves (Weber et al., 2004; Farmer and Mueller, 2013). Formation of MDA can be induced nonenzymatically by ROS or enzymatically by the activity of lipoxygenase (Farmer and Mueller, 2013). In both cases, the quantification of primary lipid hydroperoxide products is difficult due to their instability and reactivity. For this reason, quantification of lipid peroxidation is usually estimated by measuring the concentration of secondary oxidation products derived from these initial hydroperoxides (Davey et al., 2005), which are mostly aldehydes, such as MDA (Fig. 1C). Interestingly, both free and bound MDA are found in plant samples and a significant increase in free MDA was observed in Arabidopsis leaves under oxidative stress conditions (Weber et al., 2004). Several methods have been developed to assess MDA content using derivatization coupled with various separation and/or detection methods, which all take advantage of the electrophilic character of the MDA molecule. These methods include gas chromatography (GC), liquid chromatography (LC; with either UV or fluorescence detection) and mass spectrometry (MS; Fig. 1C). The thiobarbituric acid-reactive substances (TBARS) assay, first described five decades ago, is still the most commonly used method worldwide for both plant and animal samples. Heath and Packer (1968) described a very easy and quick method to estimate MDA generated by the polyunsaturated fatty acid (PUFA)-photoperoxidation process in isolated chloroplasts. This method is based on the electrophilic character of MDA, which binds readily at low pH and elevated temperature to the nucleophilic site of thiobarbituric acid (TBA). After extraction, plant extracts containing MDA are incubated with TBA at high temperatures, yielding an MDA(TBA)2 adduct of reddish color and green fluorescence with an absorbance maximum at 532 nm (Fig. 1). However, this rapid approach is particularly problematic when applied to plant samples that contain carbohydrates and anthocyanins (or other molecules rich in carbonyl groups), which are also susceptible to nucleophilic attack by TBA. These “artifacts” interfere with the absorbance measurements at 532 nm, resulting in an overestimation of MDA content (Taulavuori et al., 2001). Various approaches have been proposed to solve the problems with the Heath and Packer (1968) method, mainly (1) subtraction of the nonspecific absorbance by spectrophotometry in the TBARS assay (Hodges et al., 1999) and (2) the resolution of the resulting derivatization complex using HPLC or GC coupled or not with MS detection (Weber et al., 2004; Davey et al., 2005; Mendonça et al., 2017). Due to its simplicity and low cost, the Hodges et al. (1999) spectrophotometric method has since been extensively used. It provides an improved estimate of endogenous MDA in plant samples containing sugars, anthocyanins, and other interfering compounds, since it corrects a limitation of the Heath and Packer (1968) method by including a control assay solution without TBA and subtracting the absorbance of this at 532 nm from that of assay samples with TBA. Indeed, in addition to Hodges et al. (1999), Taulavuori et al. (2001) also compared the available spectrophotometric methods and clearly showed that MDA content is overestimated as a result of the absence of this correction in several plant tissues. However, because even such improved spectrophotometric measurements are not completely free of artifacts, alternative HPLC and GC techniques were introduced to specifically measure the MDA adducts formed, either with TBA or phenylhydrazines. The influence of possible interfering compounds in the spectrophotometric TBARS assay, such as high concentrations of stress-inducible compounds, was improved using reversed-phase HPLC coupled with UV detection, thus enhancing the specificity of MDA detection (Davey et al., 2005). However, specificity problems might still occur using this method, since other adducts formed could have the same retention time and be indistinguishable from MDA(TBA)2. One way to overcome this limitation is through the use of MS to identify peaks generated by GC after derivatization with pentafluorophenylhydrazine (Weber et al., 2004). Moreover, additional specific methods using other derivatizing chemicals to overcome the limitations of the TBA assay are currently available, among which the most sophisticated method (not yet applied to plant samples) comprises the sensitive and selective measurement of free and total plasmatic MDA using derivatization with 2,4-dinitrophenylhydrazine in ultra-HPLC (UHPLC) coupled to MS (Mendonça et al., 2017). This method solves the types of interference present in the aforementioned methods and can be used with any type of sample. Therefore, from a methodological point of view, two key aspects are essential considerations in MDA determination: (1) what type of sample will be analyzed and (2) what resources are available. The first method described by Heath and Packer (1968) is valid as a proxy of lipid peroxidation if isolated chloroplasts are used, in which neither sugars nor other interfering molecules are present. However, if the evaluation is of MDA in leaves or other plant tissues, the Heath and Packer (1968) method will overestimate MDA content, which will result not only from MDA-TBA adducts but also from the binding of TBA with other interfering compounds. This can be improved by the use of the Hodges et al. (1999) method to analyze MDA in leaves and other plant samples by spectrophotometry, although this method also has some limitations. Therefore, if the resources are available, it is better to use more specific and selective methods such as HPLC, UHPLC-MS, or GC-MS (Weber et al., 2004; Mendonça et al., 2017). Last but not least is the question of how we interpret MDA results. Since the bulk of MDA derives from the lipid peroxidation of PUFAs in plant membranes in response to oxidative stress (via ROS and/or lipoxygenase), MDA content is widely used as an indicator of damage in plant membranes. This holds true if MDA levels remain high, irreparably modifying proteins and nucleic acids. However, if the elimination of MDA and redox signaling regulation work correctly, MDA increases may represent acclimation processes rather than damage, since MDA can exert a positive role by activating regulatory genes involved in plant defense and development (defense and reproduction) and granting cell protection under oxidative stress conditions. In this respect, it has been suggested that MDA may act as a protection mechanism rather than being an indicator of damage. For instance, in observations of salt-stressed rosemary plants, MDA increased transiently in leaves, an antioxidant system to dissipate ROS was efficiently activated, and no signs of oxidative damage were observed (Tounekti et al., 2011). Figure 2 illustrates how MDA can trigger damage or protection depending on its cellular concentration and dynamics. Genetic evidence suggests that membranes rich in PUFAs act as supramolecular antioxidants that capture ROS, thereby limiting damage to proteins. This process constantly generates lipid fragmentation products including MDA (Schmid-Siegert et al., 2016). Other benefits of MDA relating to the signaling and regulation of essential biological functions (e.g. meristem activity and flower opening) have recently been proposed (Schmid-Siegert et al., 2012; Muñoz et al., 2018). Aldehyde compounds, such as MDA, have indeed been described as both toxic molecules and gene activators (Tagnon and Simeon, 2017). Therefore, the role of these compounds as damagers or protectors depends upon production, scavenging, and signaling modulation and thus relies on the enzymatic activity of aldehyde dehydrogenases (ALDHs; Fig. 2). Under environmental stress or developmental signals, MDA is produced from the lipid peroxidation of PUFAs by ROS attack or the activation of lipoxygenases. When aldehyde levels increase, protein carbonylation occurs, and this may either result in defense signaling if MDA accumulates transiently, or trigger cell death if there is sustained accumulation of MDA and carbonylated proteins accumulate in the cells. ALDH expression is induced to control the level of aldehyde compounds (such as MDA) by oxidizing them to their corresponding carboxylic acids, reestablishing low cellular levels so that they may serve as signals rather than cause harm to the cell (Tagnon and Simeon, 2017). Indeed, ALDHs are also major contributors to cellular redox homeostasis (Missihoun et al., 2018), providing the reducing agent NADPH essential for both the antioxidant activity of the ascorbate-glutathione cycle and photosynthesis (Yalcinkaya et al., 2019). Interestingly, ALDH activity is induced by H2O2 and abscisic acid, and its expression is regulated by the transcription factor Arabidopsis thaliana activating factor 1; hence, ALDH expression is induced by H2O2 (Zhao et al., 2018). Transient increases in MDA can induce abiotic and biotic stress-related genes, as has been specifically shown in Arabidopsis (Weber et al., 2004). However, in heat-stressed plants, sustained increases in MDA accumulation can also modify and inactivate PSII core proteins and Rubisco (Yamauchi et al., 2008; Yamauchi and Sugimoto, 2010). A negative correlation between MDA content and electron transport was described, implying that the function of PSII might be damaged by MDA modification of PSII proteins in heat-stressed plants (Yamauchi et al., 2008;Yamauchhi and Sugimoto, 2010). MDA generation is clearly implicated in the symptoms of environmentally stressed plants, and therefore further studies of MDA accumulation are necessary to better understand the physiological functions of MDA for plant survival under stress. MDA in plants: damage or protection? The balance between MDA production, elimination, and signaling is an important feature of redox biology and may determine plant survival under stress. ABA, abscisic acid; ATAF1, Arabidopsis thaliana activating factor 1. In conclusion, there is an urgent need in the scientific community to reduce common methodological pitfalls in the measurement of MDA content in plants and to improve the interpretation of results. It is essential that the scientific community as a whole operate at a level of precision far beyond that of the Heath and Packer (1968) method, evidence of whose inadequate use can be found in several recent examples in the literature, and carefully consider the optimal methodological approach for every scientific aim. Furthermore, it is very important that the MDA content in studies related to stress acclimation is correctly interpreted as a marker of lipid peroxidation, and that its limitations are considered alongside its advantages. In summary, to accurately estimate MDA content in plant samples and correctly interpret the results, we recommend that researchers do the following: Run a pilot experiment on a reduced sample size to test for the most accurate method to estimate MDA in line with your research goals. For example, the basic method by Heath and Packer (1968) can be a proxy for estimating MDA in isolated chloroplasts, but not for measuring MDA in complex plant samples. Choose the optimal methodology for your samples. Do not simply run the same protocol, as not all methods are appropriate for all sample types. Chromatography methods are especially recommended using adequate extraction processes, whereby the amount of material and solvent volume are adjusted in order to detect low MDA concentrations. Whenever possible, quantify free and bound MDA if your experimental design needs it by using sensitive and selective methods beyond the TBARS assay. Always keep in mind that whatever method is used, the determination of MDA will be an estimation of what the plant organ really contains and additional parameters must be used to confirm your results. Interpret your results with caution, taking into account that spectrophotometric methods have some limitations, whereas if you need a very precise determination it is better to use more specific and sensitive techniques (in particular chromatography coupled with MS).

Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status—wealth and education—differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. Findings Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96–1·58) for high-income countries, 1·59 (1·42–1·78) in middle-income countries, and 2·23 (1·79–2·77) in low-income countries (p interaction <0·0001). We observed similar results for all-cause mortality, with HRs of 1·50 (1·14–1·98) for high-income countries, 1·80 (1·58–2·06) in middle-income countries, and 2·76 (2·29–3·31) in low-income countries (p interaction <0·0001). By contrast, we found no or weak associations between wealth and these two outcomes. Differences in outcomes between educational groups were not explained by differences in risk factors, which decreased as the level of education increased in high-income countries, but increased as the level of education increased in low-income countries (p interaction <0·0001). Medical care (eg, management of hypertension, diabetes, and secondary prevention) seemed to play an important part in adverse cardiovascular disease outcomes because such care is likely to be poorer in people with the lowest levels of education compared to those with higher levels of education in low-income countries; however, we observed less marked differences in care based on level of education in middle-income countries and no or minor differences in high-income countries. Interpretation Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

AIMS: Atrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function. METHODS AND RESULTS: Baseline glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft-Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft-Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38-0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37-0.64), interaction P = 0.003]. CONCLUSION: In patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.

OBJECTIVE: The purpose of this article was to summarize the available evidence from systematic reviews on telerehabilitation in physical therapy. METHODS: We searched Medline/PubMed, EMBASE, and Cochrane Library databases. In addition, the records in PROSPERO and Epistemonikos and PEDro were consulted. Systematic reviews of different conditions, populations, and contexts-where the intervention to be evaluated is telerehabilitation by physical therapy-were included. The outcomes were clinical effectiveness depending on specific condition, functionality, quality of life, satisfaction, adherence, and safety. Data extraction and risk of bias assessment were carried out by a reviewer with non-independent verification by a second reviewer. The findings are reported qualitatively in the tables and figures. RESULTS: Fifty-three systematic reviews were included, of which 17 were assessed as having low risk of bias. Fifteen reviews were on cardiorespiratory rehabilitation, 14 on musculoskeletal conditions, and 13 on neurorehabilitation. The other 11 reviews addressed other types of conditions and rehabilitation. Thirteen reviews evaluated with low risk of bias showed results in favor of telerehabilitation versus in-person rehabilitation or no rehabilitation, while 17 reported no differences between the groups. Thirty-five reviews with unclear or high risk of bias showed mixed results. CONCLUSIONS: Despite the contradictory results, telerehabilitation in physical therapy could be comparable with in-person rehabilitation or better than no rehabilitation for conditions such as osteoarthritis, low-back pain, hip and knee replacement, and multiple sclerosis and also in the context of cardiac and pulmonary rehabilitation. It is imperative to conduct better quality clinical trials and systematic reviews. IMPACT: Providing the best available evidence on the effectiveness of telerehabilitation to professionals, mainly physical therapists, will impact the decision-making process and therefore yield better clinical outcomes for patients, both in these times of the COVID-19 pandemic and in the future. The identification of research gaps will also contribute to the generation of relevant and novel research questions.

Meat consumption is a major contributor to global warming. Given the worldwide growing demand of meat, and the severe impact of meat production on the planet, reducing animal protein consumption is a matter of food security and public health. Changing consumer food behavior is a challenge. Taste preferences, culinary traditions and social norms factor into food choices. Since behavioral change cannot occur without the subject's positive attitude based on reasons and motivations, a total of 34 papers on consumer attitudes and behavior towards meat consumption in relation to environmental concerns were examined. The results show that consumers aware of the meat impact on the planet, willing to stop or significantly reduce meat consumption for environmental reasons, and who have already changed their meat intake for ecological concerns are a small minority. However, environmental motives are already appealing significant proportions of Westerners to adopt certain meat curtailment strategies. Those who limit meat intake for environmental reasons are typically female, young, simply meat-reducer (not vegan/vegetarian), ecology-oriented, and would more likely live in Europe and Asia than in the U.S.

Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors-in-chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.

PURPOSE: To assess the prevalence of refractive error and related visual impairment in school-aged children in an urban population in New Delhi, India. METHODS: Random selection of geographically defined clusters was used to identify a sample of children 5 to 15 years of age. From December 2000 through March 2001, children in 22 selected clusters were enumerated through a door-to-door survey and examined at a local facility. The examination included visual acuity measurements, ocular motility evaluation, retinoscopy and autorefraction under cycloplegia, and examination of the anterior segment, media, and fundus. Myopia was defined as spherical equivalent refractive error of at least -0.50 D and hyperopia as +2.00 D or more. Children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance in four of the clusters. RESULTS: A total of 7008 children from 3426 households were enumerated, and 6447 (92.0%) examined. The prevalence of uncorrected, baseline (presenting), and best corrected visual acuity of 20/40 or worse in the better eye was 6.4%, 4.9%, and 0.81%, respectively. Refractive error was the cause in 81.7% of eyes with vision impairment, amblyopia in 4.4%, retinal disorders in 4.7%, other causes in 3.3%, and unexplained causes in the remaining 5.9%. There was an age-related shift in refractive error from hyperopia in young children (15.6% in 5-year-olds) toward myopia in older children (10.8% in 15-year-olds). Overall, hyperopia was present in 7.7% of children and myopia in 7.4%. Hyperopia was associated with female gender. Myopia was more common in children of fathers with higher levels of education. CONCLUSIONS: Reduced vision because of uncorrected refractive error is a major public health problem in urban school-aged children in India. Cost-effective strategies are needed to eliminate this easily treated cause of vision impairment.

BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

Light is one of the most important environmental factors affecting flavonoid biosynthesis in plants. The absolute dependency of light to the plant development has driven evolvement of sophisticated mechanisms to sense and transduce multiple aspects of the light signal. Light effects can be categorized in photoperiod (duration), intensity (quantity), direction and quality (wavelength) including UV-light. Recently, new information has been achieved on the regulation of light-controlled flavonoid biosynthesis in fruits, in which flavonoids have a major contribution on quality. This review focuses on the effects of the different light conditions on the control of flavonoid biosynthesis in fruit producing plants. An overview of the currently known mechanisms of the light-controlled flavonoid accumulation is provided. R2R3 MYB transcription factors are known to regulate by differential expression the biosynthesis of distinct flavonoids in response to specific light wavelengths. Despite recent advances, many gaps remain to be understood in the mechanisms of the transduction pathway of light-controlled flavonoid biosynthesis. A better knowledge on these regulatory mechanisms is likely to be useful for breeding programs aiming to modify fruit flavonoid pattern.