A Mediterranean diet improves glycation markers in healthy people and in those with chronic diseases: a systematic review of clinical trials.

CONTEXT: Consumption of the Mediterranean diet (MedDiet) has beneficial effects on cardiometabolic health and aging. OBJECTIVE: This systematic review aimed to critically investigate the effect of the MedDiet on glycation markers in healthy or overweight individuals with type 2 diabetes or cardiovascular disease. DATA SOURCES: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched, using the terms "Mediterranean diet" AND "glycation end products, advanced". DATA EXTRACTION: Three randomized and 3 nonrandomized clinical trials, containing data on 2935 adult and elderly individuals with normal weight or overweight, were included. All extracted data were compiled, compared, and critically analyzed. DATA ANALYSIS: The authors of most of the studies demonstrated a reduction in serum concentrations of advanced glycation end products (AGEs), such as εN-carboxymethyllysine and methylglyoxal, and in skin autofluorescence levels after at least 4 weeks of adherence to the MedDiet. The MedDiet also led to positive effects on gene expression of receptors for AGEs, as RAGE and AGER1, and an enzyme involved in detoxification (glyoxalase I). There is no evidence that short-term adherence affects glycation markers. CONCLUSIONS: Glycation markers improved in response to the MedDiet. The possible mechanisms involved may be related to the low AGE and refined sugars content of the diet, as well as its high monounsaturated fatty acid, phenolic compound, and dietary fiber contents. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021284006.

Dietary advanced glycation end products, body composition, and anthropometric measures: A cross-sectional analysis in women with excess body weight.

BACKGROUND AND AIMS: To assess the association between dietary advanced glycation end products (dAGEs) versus body composition and anthropometric variables. METHODS AND RESULTS: Body composition (dual-energy X-ray absorptiometry), anthropometry, and habitual food intake were cross-sectionally evaluated in women with excess body weight and body fat. Mean dAGEs content was estimated using a database containing the Nԑ-(carboxymethyl)lysine (CML) content of 549 foods, which was adjusted by mean energy intake, and categorized into low, medium, and high dAGEs, by the 10th and 50th percentiles of the sample. Associations were tested by linear regression adjusted for age, education, marital status, and physical activity level. Eighty participants had mean ± standard deviation dAGEs 7.85 ± 2.65 AGEs kU/kcal. Compared with high dAGEs, women with low dAGEs ingested more carbohydrate (62% vs. 50% of calories, p < 0.001) and fiber (≈25 g vs. ≈18 g, p = 0.027) and less protein (13% vs. 17% of calories, p = 0.006) and fat (26% vs. 33% of calories, p = 0.011). Women with low dAGEs had waist/hip ratio 0.05 higher than those with high dAGEs (R2 = 0.256, p = 0.005). Low dAGEs relative to medium (p = 0.009) and high (p = 0.002) dAGEs was associated with a ≈5% gynoid fat reduction (R2 = 0.164). CONCLUSION: Low dAGEs was associated with a higher waist/hip ratio and lower percentage of gynoid fat in women with excess body weight and excess body fat. REGISTRATION NUMBER: RBR-7z358j.

Ecological integrity of tropical secondary forests: concepts and indicators.

Naturally regenerating forests or secondary forests (SFs) are a promising strategy for restoring large expanses of tropical forests at low cost and with high environmental benefits. This expectation is supported by the high resilience of tropical forests after natural disturbances, yet this resilience can be severely reduced by human impacts. Assessing the characteristics of SFs and their ecological integrity (EI) is essential to evaluating their role for conservation, restoration, and provisioning of ecosystem services. In this study, we aim to propose a concept and indicators that allow the assessment and classification of the EI of SFs. To this end, we review the literature to assess how EI has been addressed in different ecosystems and which indicators of EI are most commonly used for tropical forests. Building upon this knowledge we propose a modification of the concept of EI to embrace SFs and suggest indicators of EI that can be applied to different successional stages or stand ages. Additionally, we relate these indicators to ecosystem service provision in order to support the practical application of the theory. EI is generally defined as the ability of ecosystems to support and maintain composition, structure and function similar to the reference conditions of an undisturbed ecosystem. This definition does not consider the temporal dynamics of recovering ecosystems, such as SFs. Therefore, we suggest incorporation of an optimal successional trajectory as a reference in addition to the old-growth forest reference. The optimal successional trajectory represents the maximum EI that can be attained at each successional stage in a given region and enables the evaluation of EI at any given age class. We further suggest a list of indicators, the main ones being: compositional indicators (species diversity/richness and indicator species); structural indicators (basal area, heterogeneity of basal area and canopy cover); function indicators (tree growth and mortality); and landscape proxies (landscape heterogeneity, landscape connectivity). Finally, we discuss how this approach can assist in defining the value of SF patches to provide ecosystem services, restore forests and contribute to ecosystem conservation.

Susceptibility of Candida albicans Strains Isolated from Vaginal Secretion in Front of the Mycocins of Wickerhamomyces anomalus.

Mycocins are substances that have the potential to affect other sensitive yeasts or microorganisms. Wickerhamomyces anomalus is a yeast that produces mycocins that have great biotechnological potential, being highly competitive in many habitats, as it is adaptable to a wide range of environmental conditions. Thus, they are targets for studies in different areas, including the environment, industry, and medical sciences. Yeasts of the genus Candida are of great importance due to the high frequency with which they colonize and infect the human host. Yeast infections are often difficult to treat due to the acquisition of resistance against antifungals, leading to studies focusing in new treatment alternatives. This work aims to verify the inhibition of Candida albicans isolated from vaginal secretion by mycocins produced by Wickerhamomyces anomalus. Tests were carried out in solid medium and microdilution tests, where mycocins proved to be efficient in inhibiting the growth of C. albicans, hemolysis, and irritation in an organotypic model, which showed that the mycocins produced by W. anomalus are safe and non-irritating. Thus, the results of this work can provide scientific evidence for the application of mycocins in the production of new antifungal alternatives.

Effect of dietary advanced glycation end-products restriction on type 2 diabetes mellitus control: a systematic review.

CONTEXT: Reducing dietary advanced glycation end-products (AGEs) may favor diabetes control. OBJECTIVE: Critically analyze studies about the effect of dietary AGEs restriction on inflammation, oxidative stress, and glycemic control in patients with type 2 diabetes mellitus (DM2). DATA SOURCE: This systematic review was conducted according to PRISMA methodology. The PubMed, Web of Science, LILACS, and Cochrane Library databases were searched, using the terms "type 2 diabetes," "advanced glycation end products" and "diet." DATA EXTRACTION: Seven original studies were included in this review. The duration of the studies ranged from 1 day to 16 weeks. All extracted data were compiled, compared, and critically analyzed. DATA ANALYSIS: Glycemic variables were considered the primary outcomes. The secondary outcomes were glycation, inflammatory, and oxidative stress markers. CONCLUSION: Although serum insulin, homeostasis model assessment of insulin resistance, and glycated hemoglobin values were lower after the consumption of AGEs restricted diets in most studies, there was a lack of unanimity regarding dietary AGEs' positive effect on inflammation, oxidative stress, and blood glucose. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020152640.

Does dietary fat affect advanced glycation end products and their receptors? A systematic review of clinical trials.

CONTEXT: Dietary fat seems to affect advanced glycation end products (AGEs) and their receptors. This systematic review assesses studies that evaluated the effect of dietary fat on markers of glycation. OBJECTIVE: The aim of this systematic review was to analyze the effect of dietary fat on markers of glycation and to explore the mechanisms involved. DATA SOURCES: This study was conducted according to PRISMA guidelines. PubMed, Cochrane, and Scopus databases were searched, using descriptors related to dietary fat, AGEs, and the receptors for AGEs. STUDY SELECTION: Studies were selected independently by the 3 authors. Divergent decisions were resolved by consensus. All studies that evaluated the effects of the quantity and quality of dietary fat on circulating concentrations of AGEs and their receptors in adults and elderly adults with or without chronic diseases were included. Initially, 9 studies met the selection criteria. DATA EXTRACTION: Three authors performed data extraction independently. Six studies were included. RESULTS: Consumption of a Mediterranean diet rich in monounsaturated fatty acids (MUFAs) and low in dietary AGEs reduced serum concentrations of AGEs, reduced expression of the receptor for AGE (RAGE), and increased expression of the AGE receptor 1 (AGER1) when compared with consumption of a Western diet rich in saturated fatty acids and dietary AGEs. Supplementation with omega-3 polyunsaturated fatty acids (PUFAs) resulted in decreased concentrations of fluorescent AGEs and decreased expression of RAGE as well as increased expression of AGER1. CONCLUSIONS: Increased consumption of MUFAs and omega-3 PUFAs and reduced consumption of saturated fatty acids seem to be effective strategies to beneficially affect glycation markers, which in turn may prevent and control chronic diseases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021220489.

The role of land-use history in driving successional pathways and its implications for the restoration of tropical forests.

Secondary forests are increasingly important components of human-modified landscapes in the tropics. Successional pathways, however, can vary enormously across and within landscapes, with divergent regrowth rates, vegetation structure and species composition. While climatic and edaphic conditions drive variations across regions, land-use history plays a central role in driving alternative successional pathways within human-modified landscapes. How land use affects succession depends on its intensity, spatial extent, frequency, duration and management practices, and is mediated by a complex combination of mechanisms acting on different ecosystem components and at different spatial and temporal scales. We review the literature aiming to provide a comprehensive understanding of the mechanisms underlying the long-lasting effects of land use on tropical forest succession and to discuss its implications for forest restoration. We organize it following a framework based on the hierarchical model of succession and ecological filtering theory. This review shows that our knowledge is mostly derived from studies in Neotropical forests regenerating after abandonment of shifting cultivation or pasture systems. Vegetation is the ecological component assessed most often. Little is known regarding how the recovery of belowground processes and microbiota communities is affected by previous land-use history. In published studies, land-use history has been mostly characterized by type, without discrimination of intensity, extent, duration or frequency. We compile and discuss the metrics used to describe land-use history, aiming to facilitate future studies. The literature shows that (i) species availability to succession is affected by transformations in the landscape that affect dispersal, and by management practices and seed predation, which affect the composition and diversity of propagules on site. Once a species successfully reaches an abandoned field, its establishment and performance are dependent on resistance to management practices, tolerance to (modified) soil conditions, herbivory, competition with weeds and invasive species, and facilitation by remnant trees. (ii) Structural and compositional divergences at early stages of succession remain for decades, suggesting that early communities play an important role in governing further ecosystem functioning and processes during succession. Management interventions at early stages could help enhance recovery rates and manipulate successional pathways. (iii) The combination of local and landscape conditions defines the limitations to succession and therefore the potential for natural regeneration to restore ecosystem properties effectively. The knowledge summarized here could enable the identification of conditions in which natural regeneration could efficiently promote forest restoration, and where specific management practices are required to foster succession. Finally, characterization of the landscape context and previous land-use history is essential to understand the limitations to succession and therefore to define cost-effective restoration strategies. Advancing knowledge on these two aspects is key for finding generalizable relations that will increase the predictability of succession and the efficiency of forest restoration under different landscape contexts.

The High "Cost" of Experimental Drugs Obtained Through Health Litigation in Brazil.

BACKGROUND: Brazilian patients have legal right to access unlicensed medicines undergoing clinical research, if there is evidence of efficacy and safety. This study investigated the occurrence of serious adverse events related to very high-cost medicines from clinical studies, expanded access and compassionate use programs, obtained by patients though health litigation. METHODS: A descriptive study using secondary data investigated unlicensed medicines obtained through lawsuits from 2010 to 2017, costing more than 1 million Brazilian reais (BRL), adjusted by the Brazilian Consumer Index to July 2017. Data sources were the Brazilian Health Surveillance Agency Registry (DATAVISA) and Adverse Events in Clinical Studies (NotivisaEC) Databases. Medicines were categorized by the Anatomical Therapeutic Chemical classification to level 03 and events by the WHO Adverse Drug Reaction Terminology. The study received ethical approval by the University of Brasilia Institutional Research Board. RESULTS: In the period, 812 drugs were obtained through litigation, and of these, 78 exceeded cost of 1 million BRL; 44 of them presented reports of 1,248 serious adverse events. Total Brazilian Government expenditure with these drugs was 3.2 billion BRL. Class L04A (n=7) showed greater expenditures (over 1.8 billion BRL). One hundred ninety-six deaths occurred and L01X was the most involved category (49.5%). Most other serious events (n=419) and sequelae (n=10) were related to L01X. CONCLUSION: Very high-cost drugs paid for by the government and obtained through health litigation presented deaths and serious adverse events in expanded access and compassionate use programs in Brazil.

Antibiotic Activity of Wickerhamomyces anomalus Mycocins on Multidrug-Resistant Acinetobacter baumannii.

To evaluate the susceptibility of multidrug-resistant Acinetobacter baumannii to mycocins produced by Wickerhamomyces anomalus and to verify the cytotoxicity of these compounds. Three culture supernatants of W. anomalus (WA40, WA45, and WA92), containing mycocins (WA40M1, WA45M2, and WA92M3), were tested on A. baumannii using broth microdilution methods, solid medium tests, and cytotoxicity tests in human erythrocytes and in Artemia saline Leach. W. anomalus was able to produce high antimicrobial mycocins, as even at high dilutions, they inhibited A. baumannii. In a solid medium, it was possible to observe the inhibition of A. baumannii, caused by the diffusion of mycocins between agar. Finally, the three supernatants were not cytotoxic when tested on human erythrocytes and Artemia salina. According to the evidence in this study, the mycocins of W. anomalus have been effective and could be used in the development of new antimicrobial substances.

Can advanced glycation end-products and their receptors be affected by weight loss? A systematic review.

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of most chronic diseases. Therefore, identification of treatments that can attenuate the effects of these compounds and prevent cardiometabolic complications is of extreme public health interest. Recently, body weight management interventions showed positive results on reducing serum AGE concentrations. Moreover, the soluble receptor for advanced glycation end products (sRAGE) is considered to be a novel biomarker to identify patients with obesity most likely to benefit from weight management interventions. This systematic review aimed to critically analyze papers evaluating the effects of weight loss on serum AGEs and its receptors in adults with excess body weight. MEDLINE, Cochrane, Scopus, and Lilacs databases were searched. Three studies evaluating the response of AGEs to energy-restricted diets and six assessing sRAGE as the primary outcome were included. Energy-restricted diets and bariatric surgery reduced serum AGE concentrations, but effects on endogenous secretory RAGE (esRAGE) and sRAGE concentrations are conflicting. These results may be associated with mechanisms related to changes in dietary intake and limiting endogenous AGE formation. Therefore, the role of energy-restricted diets and bariatric surgery on lowering serum AGE concentrations, as well as its effects on AGEs receptors, deserves further investigation.

Effect of reducing dietary advanced glycation end products on obesity-associated complications: a systematic review.

CONTEXT: Consumption of dietary advanced glycation end products (AGEs) is associated with oxidative stress, inflammation, and other chronic conditions commonly associated with obesity. OBJECTIVE: To analyze the effects of dietary AGEs on complications associated with obesity. DATA SOURCES: This systematic review was conducted and reported according to PRISMA guidelines. The PubMed, Cochrane, and Scopus databases were searched, using the terms "advanced glycation end products," "overweight," and "obesity." The last search was performed in October 2018. DATA EXTRACTION: Six studies that evaluated the effects of low-AGE and high-AGE diets were included in the review. The duration of the studies ranged from 1 day to 12 weeks. A comparison of all the compiled data was conducted by the authors. DATA ANALYSIS: Circulating and urinary AGE markers, besides soluble receptor for AGEs, were considered as the primary outcomes. The secondary outcomes were cardiometabolic, inflammatory, glycemic, anthropometric, and renal markers. CONCLUSIONS: AGE-RAGE interactions can activate the NF-κB (nuclear factor kappa B) signaling pathway and inhibit the PI3K-AKT pathway in adipocytes, which may explain their association with chronic diseases. This interaction can be considered as a novel explanation for the pathogenesis of obesity. AGEs can also be used as a biomarker for monitoring responses to dietary interventions in overweight and obese people. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42018082745.

Biodiversity recovery of Neotropical secondary forests.

Old-growth tropical forests harbor an immense diversity of tree species but are rapidly being cleared, while secondary forests that regrow on abandoned agricultural lands increase in extent. We assess how tree species richness and composition recover during secondary succession across gradients in environmental conditions and anthropogenic disturbance in an unprecedented multisite analysis for the Neotropics. Secondary forests recover remarkably fast in species richness but slowly in species composition. Secondary forests take a median time of five decades to recover the species richness of old-growth forest (80% recovery after 20 years) based on rarefaction analysis. Full recovery of species composition takes centuries (only 34% recovery after 20 years). A dual strategy that maintains both old-growth forests and species-rich secondary forests is therefore crucial for biodiversity conservation in human-modified tropical landscapes.

Effect of increased calcium consumption from fat-free milk in an energy-restricted diet on the metabolic syndrome and cardiometabolic outcomes in adults with type 2 diabetes mellitus: a randomised cross-over clinical trial.

We investigated the effects of high-Ca fat-free milk phase (MD) (prescription of approximately 1500 mg of Ca/d) v. low-Ca phase (CD) (prescription of approximately 800 mg of Ca/d) in an energy-restricted diet on the metabolic syndrome (MetS) and cardiometabolic measures in individuals with type 2 diabetes mellitus (T2DM) and low habitual Ca consumption (<600 mg/d). In this randomised cross-over design, fourteen adults with T2DM (49·5 (sd 8·6) years, BMI 29·4 (sd 4·5) kg/m2) consumed either MD or CD for 12 weeks, with a washout of 18 weeks between phases. A breakfast shake containing 700 mg (MD) or 6·4 mg (CD) of Ca was consumed in the laboratory. In addition, energy-restricted diets were prescribed (800 mg of dietary Ca/d). Waist circumference (WC), fasting glucose, fasting TAG, systolic (SBP) and diastolic blood pressure (DBP), fasting total cholesterol, fasting LDL-cholesterol, fasting HDL-cholesterol, HDL:LDL ratio, HDL:TAG ratio and lipid accumulation product (LAP) index were assessed at baseline and after each phase. Ca consumption during the study was equivalent to 1200 mg/d during MD and 525 mg/d during CD. There was a greater reduction in WC, SBP, DBP and LAP index after MD compared with CD. HDL:LDL ratio increased and total cholesterol, LDL-cholesterol, SBP, DBP and LAP index decreased only in MD. The consumption of approximately 1200 mg of Ca/d (700 mg from fat-free milk+500mg from other dietary sources) associated with an energy-restricted diet decreased some of the MetS components and cardiometabolic measures in adults with T2DM.

An Amazonian rainforest and its fragments as a laboratory of global change.

We synthesize findings from one of the world's largest and longest-running experimental investigations, the Biological Dynamics of Forest Fragments Project (BDFFP). Spanning an area of ∼1000 km2 in central Amazonia, the BDFFP was initially designed to evaluate the effects of fragment area on rainforest biodiversity and ecological processes. However, over its 38-year history to date the project has far transcended its original mission, and now focuses more broadly on landscape dynamics, forest regeneration, regional- and global-change phenomena, and their potential interactions and implications for Amazonian forest conservation. The project has yielded a wealth of insights into the ecological and environmental changes in fragmented forests. For instance, many rainforest species are naturally rare and hence are either missing entirely from many fragments or so sparsely represented as to have little chance of long-term survival. Additionally, edge effects are a prominent driver of fragment dynamics, strongly affecting forest microclimate, tree mortality, carbon storage and a diversity of fauna. Even within our controlled study area, the landscape has been highly dynamic: for example, the matrix of vegetation surrounding fragments has changed markedly over time, succeeding from large cattle pastures or forest clearcuts to secondary regrowth forest. This, in turn, has influenced the dynamics of plant and animal communities and their trajectories of change over time. In general, fauna and flora have responded differently to fragmentation: the most locally extinction-prone animal species are those that have both large area requirements and low tolerance of the modified habitats surrounding fragments, whereas the most vulnerable plants are those that respond poorly to edge effects or chronic forest disturbances, and that rely on vulnerable animals for seed dispersal or pollination. Relative to intact forests, most fragments are hyperdynamic, with unstable or fluctuating populations of species in response to a variety of external vicissitudes. Rare weather events such as droughts, windstorms and floods have had strong impacts on fragments and left lasting legacies of change. Both forest fragments and the intact forests in our study area appear to be influenced by larger-scale environmental drivers operating at regional or global scales. These drivers are apparently increasing forest productivity and have led to concerted, widespread increases in forest dynamics and plant growth, shifts in tree-community composition, and increases in liana (woody vine) abundance. Such large-scale drivers are likely to interact synergistically with habitat fragmentation, exacerbating its effects for some species and ecological phenomena. Hence, the impacts of fragmentation on Amazonian biodiversity and ecosystem processes appear to be a consequence not only of local site features but also of broader changes occurring at landscape, regional and even global scales.