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Mechanization management in sugarcane production bases today faces difficulties such as the obsolescence of machinery with an average age for tractors higher than 30 years. The high dependence on external services, the duality of the harvesting system where external services are received from modern combines. and a park of old machines is operated by sugar cane production bases such as cooperatives, fragmented into teams of very low productivity, which affects the organization of logistics, technical assistance and the use of transportation. This paper theoretically demonstrates the advantages in machinery management achieved by forming labor fronts with the equipment of two or more bases, to jointly harvest the sugarcane areas. Likewise, the advantages of using the fronts as operational centers for other tasks that can be fulfilled with high quality in unison with the harvest or immediately after it is executed. The implementation of the fronts in the 2021 - 2022 harvest is described, resulting greater productivity for the harvesters grouped in the new system and demonstrating the possibility of achieving greater sugar yield. [ABSTRACT FROM AUTHOR]

The associations between circulating vitamin D concentrations and total and site-specific colorectal cancer (CRC) incidence have been examined in several epidemiological studies with overall inconclusive findings. The aim of this systematic review and meta-analysis of both case-control and prospective cohort studies was to evaluate the association between CRC and circulating levels of vitamin D. The main exposure and outcome were circulating total 25(OH)D and CRC, respectively, in the overall population (i.e., all subjects). Two reviewers, working independently, screened all the literature available to identify studies that met the inclusion criteria (e.g., case-control or prospective cohort studies, published in English, and excluding non-original papers). Data were pooled by the generic inverse variance method using a random or fixed effect model, as approriate. Heterogeneity was identified using the Cochran's Q-test and quantified by the I2 statistic. Results were stratified by study design, sex, and metabolite of vitamin D. Sensitivity and subgroup analyses were also performed. A total of 28 original studies were included for the quantitative meta-analysis. Meta-analyses comparing the highest vs lowest categories, showed a 39% lower risk between levels of total 25(OH)D and CRC risk (OR (95% CI): 0.61 (0.52; 0.71); 11 studies) in case-control studies; whereas a 20% reduced CRC risk in prospective cohort studies (HR (95% CI): 0.80 (0.66; 0.97); 6 studies). Results in women mirrored main results, whereas results in men were non-significant in both analyses. Our findings support an inverse association between circulating vitamin D levels and CRC risk. [ABSTRACT FROM AUTHOR]

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Background Epidemiologic studies have reported a modest inverse association between dairy consumption and the risk of type 2 diabetes (T2D). Whether plasma metabolite profiles associated with dairy consumption reflect this relationship remains unknown. Objectives We aimed to identify the plasma metabolites associated with total and specific dairy consumption, and to evaluate the association between the identified multi-metabolite profiles and T2D. Methods The discovery population included 1833 participants from the Prevención con Dieta Mediterránea (PREDIMED) trial. The confirmatory cohorts included 1522 PREDIMED participants at year 1 of the trial and 4932 participants from the Nurses' Health Studies (NHS), Nurses' Health Study II (NHSII), and Health Professionals Follow-Up Study US-based cohorts. Dairy consumption was assessed using validated FFQs. Plasma metabolites (n  = 385) were profiled using LC-MS. We identified the dairy-related metabolite profiles using elastic net regularized regressions with a 10-fold cross-validation procedure. We evaluated the associations between the metabolite profiles and incident T2D in the discovery and the confirmatory cohorts. Results Total dairy intake was associated with 38 metabolites. C14:0 sphingomyelin (positive coefficient), C34:0 phosphatidylethanolamine (positive coefficient), and γ-butyrobetaine (negative coefficient) were associated in a directionally similar fashion with total and specific (milk, yogurt, cheese) dairy consumption. The Pearson correlation coefficients between self-reported total dairy intake and predicted total dairy intake based on the corresponding multi-metabolite profile were 0.37 (95% CI, 0.33–0.40) in the discovery cohort and 0.16 (95% CI, 0.13–0.19) in the US confirmatory cohort. After adjusting for T2D risk factors, a higher total dairy intake–related metabolite profile score was associated with a lower T2D risk [HR per 1 SD; discovery cohort: 0.76 (95% CI, 0.63–0.90); US confirmatory cohort: 0.88 (95% CI, 0.78–0.99)]. Conclusions Total dairy intake was associated with 38 metabolites, including 3 consistently associated with dairy subtypes (C14:0 sphingomyelin, C34:0 phosphatidylethanolamine, γ-butyrobetaine). A score based on the 38 identified metabolites showed an inverse association with T2D risk in Spanish and US populations. [ABSTRACT FROM AUTHOR]

Background Previous meta-analyses, with some methodological controversies, have assessed the relation between nut consumption and type 2 diabetes (T2D) risk and pointed to contradictory results, making desirable the performance of an updated meta-analysis. Objectives We aimed to systematically review and meta-analyze all the published studies investigating the relations of total nuts and different types of nuts—i.e. walnuts, peanuts, peanut butter, and total tree nuts—with the prevalence and incidence of T2D. Methods A systematic search was conducted in the PubMed and Cochrane databases through 12 August, 2020. The inverse variance method with fixed-effect models was used to pool data across studies, expressed as risk ratios (RRs) or ORs and 95% CIs for prospective cohort and cross-sectional studies, respectively. The Cochran Q test and I 2 statistics were used to test and quantify heterogeneity, respectively. Dose-response meta-analysis was also conducted. Results Eight studies (5 prospective and 3 cross-sectional) were included in the quantitative synthesis. Meta-analyses of cross-sectional studies and prospective cohort studies, comparing the highest with the lowest categories, revealed a nonsignificant association between total nut consumption and T2D. Meta-analyses of prospective cohort studies showed an inverse association between peanut butter consumption and T2D incidence (RR: 0.87; 95% CI: 0.77, 0.98; I 2 = 50.6%; P heterogeneity = 0.16), whereas no association was observed between peanuts or tree nuts and T2D. There was no evidence of a linear dose-response or nonlinear dose-response gradient for total nut and peanut consumption in prospective cohort studies. The certainty of the evidence using NutriGrade was very low for all the exposures. Conclusions Current results do not demonstrate an association of total nut, peanut, or tree nut consumption with T2D. Peanut butter consumption may be inversely associated with this disease. This review protocol was registered at www.crd.york.ac.uk/prospero/ as CRD42020149756. [ABSTRACT FROM AUTHOR]

Background: Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases.Objectives: The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD.Methods: The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training-validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models.Results: A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P < 0.001).Conclusions: A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: The quality of carbohydrate consumed, assessed by the glycemic index (GI), glycemic load (GL), or carbohydrate quality index (CQI), affects the postprandial glycemic and insulinemic responses, which have been implicated in the etiology of several chronic diseases. However, it is unclear whether plasma metabolites involved in different biological pathways could provide functional insights into the role of carbohydrate quality indices in health.Objectives: We aimed to identify plasma metabolomic profiles associated with dietary GI, GL, and CQI.Methods: The present study is a cross-sectional analysis of 1833 participants with overweight/obesity (mean age = 67 y) from 2 case-cohort studies nested within the PREDIMED (Prevención con Dieta Mediterránea) trial. Data extracted from validated FFQs were used to estimate the GI, GL, and CQI. Plasma concentrations of 385 metabolites were profiled with LC coupled to MS and associations of these metabolites with those indices were assessed with elastic net regression analyses.Results: A total of 58, 18, and 57 metabolites were selected for GI, GL, and CQI, respectively. Choline, cotinine, γ-butyrobetaine, and 36:3 phosphatidylserine plasmalogen were positively associated with GI and GL, whereas they were negatively associated with CQI. Fructose-glucose-galactose was negatively and positively associated with GI/GL and CQI, respectively. Consistent associations of 21 metabolites with both GI and CQI were found but in opposite directions. Negative associations of kynurenic acid, 22:1 sphingomyelin, and 38:6 phosphatidylethanolamine, as well as positive associations of 32:1 phosphatidylcholine with GI and GL were also observed. Pearson correlation coefficients between GI, GL, and CQI and the metabolomic profiles were 0.30, 0.22, and 0.27, respectively.Conclusions: The GI, GL, and CQI were associated with specific metabolomic profiles in a Mediterranean population at high cardiovascular disease risk. Our findings may help in understanding the role of dietary carbohydrate indices in the development of cardiometabolic disorders. This trial was registered at isrctn.com as ISRCTN35739639. [ABSTRACT FROM AUTHOR]

Background: Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown.Objectives: We examined associations of glutamate, glutamine, and the glutamine-to-glutamate ratio with AF and HF incidence in a Mediterranean population at high cardiovascular disease (CVD) risk.Methods: The present study used 2 nested case-control studies within the PREDIMED (Prevención con Dieta Mediterránea) study. During ∼10 y of follow-up, there were 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma concentrations of glutamate and glutamine were semiquantitatively profiled with LC-tandem MS. ORs were estimated with multivariable conditional logistic regression models.Results: In fully adjusted models, per 1-SD increment, glutamate was associated with a 29% (95% CI: 1.08, 1.54) increased risk of HF and glutamine-to-glutamate ratio with a 20% (95% CI: 0.67, 0.94) decreased risk. Glutamine-to-glutamate ratio was also inversely associated with HF risk (OR per 1-SD increment: 0.80; 95% CI: 0.67, 0.94) when comparing extreme quartiles. Higher glutamate concentrations were associated with a worse cardiometabolic risk profile, whereas a higher glutamine-to-glutamate ratio was associated with a better cardiometabolic risk profile. No associations between the concentrations of these metabolites and AF were observed.Conclusions: Our findings suggest that high plasma glutamate concentrations possibly resulting from alterations in the glutamate-glutamine cycle may contribute to the development of HF in Mediterranean individuals at high CVD risk.This trial was registered at www.isrctn.com as ISRCTN35739639. [ABSTRACT FROM AUTHOR]

Background Telomere attrition may play an important role in the pathogenesis and severity of type 2 diabetes (T2D), increasing the probability of β cell senescence and leading to reduced cell mass and decreased insulin secretion. Nutrition and lifestyle are known factors modulating the aging process and insulin resistance/secretion, determining the risk of T2D. Objectives The aim of this study was to evaluate the effects of pistachio intake on telomere length and other cellular aging-related parameters of glucose and insulin metabolism. Methods Forty-nine prediabetic subjects were included in a randomized crossover clinical trial. Subjects consumed a pistachio-supplemented diet (PD, 50 E% [energy percentage] carbohydrates and 33 E% fat, including 57 g pistachios/d) and an isocaloric control diet (CD, 55 E% carbohydrates and 30 E% fat) for 4 mo each, separated by a 2-wk washout period. DNA oxidation was evaluated by DNA damage (via 8-hydroxydeoxyguanosine). Leucocyte telomere length and gene expression related to either oxidation, telomere maintenance or glucose, and insulin metabolism were analyzed by multiplexed quantitative reverse transcriptase-polymerase chain reaction after the dietary intervention. Results Compared with the CD, the PD reduced oxidative damage to DNA (mean: −3.5%; 95% CI: −8.07%, 1.05%; P  = 0.009). Gene expression of 2 telomere-related genes (TERT and WRAP53) was significantly upregulated (164% and 53%) after the PD compared with the CD (P  = 0.043 and P  = 0.001, respectively). Interestingly, changes in TERT expression were negatively correlated to changes in fasting plasma glucose concentrations and in the homeostatic model assessment of insulin resistance. Conclusions Chronic pistachio consumption reduces oxidative damage to DNA and increases the gene expression of some telomere-associated genes. Lessening oxidative damage to DNA and telomerase expression through diet may represent an intriguing way to promote healthspan in humans, reversing certain deleterious metabolic consequences of prediabetes. This study was registered at clinicaltrials.gov as NCT01441921. [ABSTRACT FROM AUTHOR]

Background Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D). Objectives The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D. Methods We used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography–tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR–related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models. Results We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors. Conclusions The multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D. [ABSTRACT FROM AUTHOR]

Background: High glucose and insulin concentrations seem to have a negative impact on bone health. However, the relation between the dietary glycemic index (DGI) and the dietary glycemic load (DGL), which has proved to be effective at modulating blood glucose concentrations after carbohydrate consumption, has yet to be explored in relation to bone health. Objective: The aim of the study was to examine the associations between the DGI or DGL and the risk of osteoporotic-related fractures in an elderly Mediterranean population. Design: The study was conducted in 870 subjects aged 55-80 y at high cardiovascular disease risk participating in the PREvención con DIeta MEDiterránea (PREDIMED)-Reus study. The DGI and DGL were estimated from validated food-frequency questionnaires with the use of the international glycemic index and glycemic load values, with glucose as reference. Data on osteoporotic fractures were acquired from a systematic review of medical records. We used Cox proportional hazard models to assess the risk of osteoporotic fracture according to tertiles of average DGI and DGL. Results: A total of 114 new cases of osteoporotic-related fractures were documented after a mean follow-up of 8.9 y. Participants in the highest tertile of DGI and DGL had a significantly higher risk of osteoporotic fractures than those in the lowest tertile after adjusting for potential confounders (HR: 1.80; 95% CI: 1.03, 3.15 and HR: 3.20; 95% CI: 1.25, 8.18, respectively). Conclusions: A high DGI and DGL are associated with a higher risk of osteoporosis-related fractures in an elderly Mediterranean population at high cardiovascular disease risk. This trial was registered at isrctn.com as ISRCTN35739639. [ABSTRACT FROM AUTHOR]

Magnesium (Mg) is an essential dietary element for humans involved in key biological processes. A growing body of evidence from epidemiological studies, randomized controlled trials (RCTs) and meta-analyses have indicated inverse associations between Mg intake and cardiovascular diseases (CVD). The present review aims to summarize recent scientific evidence on the topic, with a focus on data from epidemiological studies assessing the associations between Mg intake and major cardiovascular (CV) risk factors and CVD. We also aimed to review current literature on circulating Mg and CVD, as well as potential biological processes underlying these observations. We concluded that high Mg intake is associated with lower risk of major CV risk factors (mainly metabolic syndrome, diabetes and hypertension), stroke and total CVD. Higher levels of circulating Mg are associated with lower risk of CVD, mainly ischemic heart disease and coronary heart disease. Further, RCTs and prospective studies would help to clarify whether Mg intake and Mg circulating levels may also protect against other CVDs and CVD death. [ABSTRACT FROM AUTHOR]

The specific nutritional composition of nuts could affect different metabolic pathways involved in a broad range of metabolic diseases. We therefore investigated whether chronic consumption of pistachio nuts modifies the urine metabolome in prediabetic subjects. We designed a randomized crossover clinical trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Nuclear magnetic resonance (NRM) was performed to determine changes in 24-h urine metabolites. Significant changes in urine metabolites according to the different intervention periods were found in uni- and multivariate analysis. Score plot of the first two components of the multilevel partial least squares discriminant analysis (ML-PLS-DA) showed a clear separation of the intervention periods. Three metabolites related with gut microbiota metabolism (i.e., hippurate, p-cresol sulfate and dimethylamine) were found decreased in PD compared with CD (P<.05). Moreover, cis-aconitate [intermediate of the tricarboxylic acid (TCA)] was also found decreased following PD compared with CD. Intragroup analysis showed that creatinine levels were significantly increased in PD (P=.023), whereas trimethylamine N-oxide (TMAO) was found significantly reduced following PD (P=.034). Our results suggest that chronic pistachio consumption may modulate some urinary metabolites related to gut microbiota metabolism and the TCA cycle; all associated with metabolic derangements associated with insulin resistance and Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Nuts and dried fruit are essential foods in the Mediterranean diet. Their frequent consumption has been associated with the prevention and/or the management of such metabolic conditions as type 2 diabetes (T2D), metabolic syndrome and cardiovascular diseases. Several previous reviews of epidemiological studies and clinical trials have evaluated the associations of nuts and/or dried fruit with various metabolic disorders. However, no reviews have focused on the mechanisms underlying the role of nuts and/or dried fruit in insulin resistance and T2D. This review aims to report nut and dried-fruit nutritional interventions in animals and humans, and to focus on mechanisms that could play a significant role in the prevention and treatment of insulin resistance and T2D. [ABSTRACT FROM AUTHOR]

Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53−/− MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53−/− cells but not in isogenic p53+/+ cells, indicating gene-specific adaptation. However, full-length sequencing revealed no obvious or previously described genetic changes associated with oncolytic activity. Half-maximal effective dose (EC50) assays in mouse p53-positive colon cancer (CT26) and p53-deficient breast cancer (4T1) cells indicated that the evolved viruses were more effective against 4T1 cells than the parental virus or a reference oncolytic VSV (MΔ51), but showed no increased efficacy against CT26 cells. In vivo assays using 4T1 syngeneic tumor models showed that one of the evolved lines significantly delayed tumor growth compared to mice treated with the parental virus or untreated controls, and was able to induce transient tumor suppression. Our results show that RNA viruses can be specifically adapted typical cancer features such as p53 inactivation, and illustrate the usefulness of experimental evolution for oncolytic virotherapy. [ABSTRACT FROM AUTHOR]

Telomere length (TL) has been associated with aging and is determined by lifestyle. However, the mechanisms by which a dietary pattern such as the Mediterranean diet (MedDiet) affects TL homeostasis are still unknown. Our aim was to analyse the effect of an energy-restricted MedDiet with physical activity promotion (intervention group) versus an unrestricted-caloric MedDiet with no weight-loss advice (control group) on TL and 8-hydroxydeoxyguanosine (8-OHdG) plasma levels. In total, 80 non-diabetic participants with metabolic syndrome were randomly selected from the PREDIMED (PREvención con DIeta MEDiterránea)-Plus-Reus study. TL was measured by a hybridisation method and 8-OHdG levels by ELISA at baseline and after one year of intervention. Linear mixed models (LMM)—raw and after adjusting for potential confounders—were used to examine the associations between TL or 8-OHdG plasma levels by intervention group and/or time. A total of 69 subjects with available DNA samples were included in the analyses. A significant β-coefficient was found for time towards increasing values through the year of follow-up for TL (unadjusted β of 0.740 (95% CI: 0.529 to 0.951), and multivariable model β of 0.700 (95% CI: 0.477 to 0.922)). No significant βs were found, neither for the intervention group nor for the interaction between the intervention group and time. Regarding 8-OHdG plasma levels, no significant βs were found for the intervention group, time, and its interaction. Our results suggest that MedDiet could have an important role in preventing telomere shortening, but calorie restriction and exercise promotion did not provide an additional advantage concerning telomere length after one year of MedDiet intervention. [ABSTRACT FROM AUTHOR]

The increased prevalence of atrial fibrillation (AF) and heart failure (HF) highlights the need to better understand the mechanisms underlying these cardiovascular diseases (CVDs). In the present study, we aimed to evaluate the association between glycolysis-related metabolites and the risk of AF and HF in a Mediterranean population at high risk of CVD. We used two case–control studies nested within the PREDIMED trial. A total of 512 incident AF cases matched to 734 controls, and 334 incident HF cases matched to 508 controls, were included. Plasma metabolites were quantified by using hydrophilic interaction liquid chromatography coupled with high-resolution negative ion mode MS detection. Conditional logistic regression analyses were performed. The results showed no association between baseline plasma glycolysis intermediates and other related metabolites with AF. Only phosphoglycerate was associated with a higher risk of HF (OR for 1 SD increase: 1.28; 95% CI: 1.06, 1.53). The present findings do not support a role of the glycolysis pathway in the pathogenesis of AF. However, the increased risk of HF associated with phosphoglycerate requires further studies. [ABSTRACT FROM AUTHOR]

Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascular risk. The 2018 WCRF/AICR and LRL scores were calculated. Multivariable Cox proportional regression models were fitted to estimate the HRs (hazard ratios) and 95% confidence intervals (CIs) for incident CRC events. During a median interquartile range (IQR) follow-up of 6.0 (4.4–7.3) years, 97 CRC events were considered. A significant linear association was observed between each 1-point increment in the WCRF/AICR score (score range from 0 to 7) and CRC risk (HR (95% CI) = 0.79 (0.63–0.99)). Similarly, each 1-point increment in the LRL score (score range from 0 to 5) was associated with a 22% reduction in CRC risk (0.78 (0.64–0.96)). Adhering to emergent lifestyle scores might substantially reduce CRC incidence in elderly individuals. Further longitudinal studies, which take different lifestyle indexes into account, are warranted in the future. [ABSTRACT FROM AUTHOR]

Background: The interaction between obesity and genetic traits on high density lipoprotein (HDL) levels has been extensively studied. The variance of serum HDL has a strong genetic heritability, although the studied variant only explains a small part of this variation. The goal of this study was to investigate the associations between the apolipoprotein type 2 (APOA2) rs3813627 single nucleotide polymorphism (SNP) and anthropometric and biochemical variables, though body mass index (BMI). Methods: This study included 153 subjects (91 overweight/obese (BMI ≥ 25 kg/m2) and 62 non-obese individuals (BMI < 25 kg/m2)). The APOA2 rs3813627 SNP was selected and genotyped. Genotype analysis was performed to analyze the associations between APOA2 SNPs and anthropometric and biochemical variables through BMI. Results: The APOA2 rs3813627 TT genotype was associated with low HDL levels in comparison with the APOA2 rs3813627 GG and GT genotype in overweight/obese individuals, but not in the non-obese subjects (p < 0.05). The same trend was observed in the apolipoprotein type 1 (APOA1) protein levels (p < 0.05). Correlation analysis revealed a negative correlation between HDL and APOA1 levels and APOA2 rs3813627 SNP under recessive model (p < 0.05). The odds ratio for low HDL levels was 3.76 and 3.94 for low APOA1 levels. The mediation analysis of APOA2 rs3813627 SNP through BMI showed a full mediation on HDL and partial mediation on APOA1 levels (p < 0.05). Bioinformatic analysis showed that rs3813627 lies in the APOA2 promoter and overlaps motifs for several bound transcription factors. Conclusions: On the basis of these data, the APOA2 rs3813627 SNP is associated with low HDL and APOA1 levels susceptibility, and this effect was mediated by an increased BMI. [ABSTRACT FROM AUTHOR]

Obesity is well accepted as crucial risk factor that plays a critical role in the initiation and progression of colorectal cancer (CRC). More specifically, visceral adipose tissue (VAT) in people with obesity could produce chronic inflammation and an altered profile expression of key transcription factors that promote a favorable microenvironment to colorectal carcinogenesis. For this, the aim of this study was to explore the relationship between adipogenic and inflammatory transcription factors in VAT from nonobese, obese, and/or CRC patients. To test this idea, we studied the expression and methylation of CCAAT-enhancer binding protein type alpha (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in VAT from non-obese control, non-obese CRC subjects, overweight/obese control, and overweight/obese CRC patients and their correlation with anthropometric and biochemical variables. We found decreased expression of C/EBP-α in overweight/obese CRC patients in comparison with overweight/obese control subjects. PGC-1α and NF-κB were overexpressed in CRC patients independently of the BMI. NF-κB promoter was hypomethylated in overweight/obese CRC patients when compared to overweight/obese control individuals. In addition, multiple significant correlations between expression, methylation, and biochemical parameters were found. Finally, linear regression analysis showed that the expression of C/EBP-α and NF-κB and that NF-κB methylation were associated with CRC and able to explain up to 55% of CRC variability. Our results suggest that visceral adipose tissue may be a key factor in tumor development and inflammatory state. We propose C/EBP-α, PGC-1α and NF-κB to be interesting candidates as potential biomarkers in adipose tissue for CRC patients. [ABSTRACT FROM AUTHOR]

Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56–0.64), 0.78 (95% CI 0.75–0.81) and 0.52 (95% CI 0.49–0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption. [ABSTRACT FROM AUTHOR]

Introduction: Background: to date, gluten-free (GF) diet is the only treatment available for individuals with celiac disease. Both individual and collective food intake assessments are a challenge because a food composition database of GF products (GFPs) is lacking. Objectives: to describe the process of developing a food composition database of GFPs, and to compare the nutritional profile and price of some GFPs and non-GFPs. Methods: initially, a total of 216 brands of GFPs marketed in Spain were recorded. Nutritional information was collected from nutritional labels and product fact sheets that had been provided by food companies or collected first-hand by researchers. Then, the nutritional profile and price of the cereal and cereal byproducts foodstuff groups, including 19 types of products, were compared. Statistical analyses were performed using the SPSS statistical program (22.0 edition; SPSS, Chicago, IL, USA). Results: a total of 2,247 GFPs from 126 different foodstuff brands were included in the food composition database of GFPs (CELIAC-BASE). We classified these products into 14 foodstuff groups. The protein content of the GFPs studied was significantly lower, and the price was higher, than that of their non-GFP counterparts. Some, but not all, GFPs had a higher content of fat and sugar, and a lower content of dietary fiber as compared to their non-GFP counterparts. Some GFPs were up to 6 times more expensive than the corresponding non-GFPs. Conclusions: CELIAC-BASE is a pioneering tool for dietitians. Many GFPs have poor nutritional profiles and should be consumed only occasionally in a balanced GF diet. [ABSTRACT FROM AUTHOR]

Background and Aims: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk., Methods and Results: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time., Conclusion: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk., Competing Interests: Declaration of competing interest J.S.-S. reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council, and Eroski Foundation. Reports serving in the Executive Committee of the Instituto Danone Spain and on the Scientific Committee of the Danone International Institute. He has received research support from Patrimonio Comunal Olivarero, Spain; and Borges SA, Spain. Reports receiving consulting fees or travel expenses from Danone; Eroski Foundation, Instituto Danone—Spain, and Abbot Laboratories., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background & Aims: The Portfolio and Dietary Approaches to Stop Hypertension (DASH) diets have been shown to lower cardiometabolic risk factors in randomized controlled trials (RCTs). However, the Portfolio diet has only been assessed in RCTs of hyperlipidemic patients. Therefore, to assess the Portfolio diet in a population with metabolic syndrome (MetS), we conducted a longitudinal analysis of one-year data of changes in the Portfolio and DASH diet scores and their association with cardiometabolic risk factors in Prevención con Dieta Mediterránea (PREDIMED)-Plus trial., Methods: PREDIMED-Plus is an ongoing clinical trial (Trial registration: ISRCTN89898) conducted in Spain that includes 6874 older participants (mean age 65 y, 48% women) with overweight/obesity fulfilling at least three criteria for MetS. Data for this analysis were collected at baseline, six months and one year. Adherence to the Portfolio and DASH diet scores were derived from a validated 143-item food frequency questionnaire. We used linear mixed models to examine the associations of 1-SD increase and quartile changes in the diet scores with concomitant changes in cardiometabolic risk factors., Results: After adjusting for several potential confounders, a 1-SD increase in the Portfolio diet score was significantly associated with lower HbA1c (β [95% CI]: -0.02% [-0.02, -0.01], P < 0.001), fasting glucose (-0.47 mg/dL [-0.83, -0.11], P = 0.01), triglycerides (-1.29 mg/dL [-2.31, -0.28], P = 0.01), waist circumference (WC) (-0.51 cm [-0.59, -0.43], P < 0.001), and body mass index (BMI) (-0.17 kg/m 2 [-0.19, -0.15], P < 0.001). A 1-SD increase in the DASH diet score was significantly associated with lower HbA1c (-0.03% [-0.04, -0.02], P < 0.001), glucose (-0.84 mg/dL [-1.18, -0.51], P < 0.001), triglycerides (-3.38 mg/dL [-4.37, -2.38], P < 0.001), non-HDL-cholesterol (-0.47 mg/dL [-0.91, -0.04], P = 0.03), WC (-0.69 cm [-0.76, -0.60 cm], P < 0.001), BMI (-0.25 kg/m 2 [-0.28, -0.26 kg/m 2 ], P < 0.001), systolic blood pressure (-0.57 mmHg [-0.81, -0.32 mmHg], P < 0.001), diastolic blood pressure (-0.15 mmHg [-0.29, -0.01 mmHg], P = 0.03), and with higher HDL-cholesterol (0.21 mg/dL [0.09, 0.34 mg/dL, P = 0.001]). Similar associations were seen when both diet scores were assessed as quartiles, comparing extreme categories of adherence., Conclusions: Among older adults at high cardiovascular risk with MetS, greater adherence to the Portfolio and DASH diets showed significant favourable prospective associations with several clinically relevant cardiometabolic risk factors. Both diets are likely beneficial for cardiometabolic risk reduction., Competing Interests: Conflict of interest AJG has done consulting work for SoLo GI Nutrition and has received an honorarium from the Soy Nutrition Institute. CWCK has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri-Foods Canada (AAFC), Almond Board of California, American Peanut Council, Barilla, Canadian Institutes of Health Research (CIHR), Canola Council of Canada, International Nut and Dried Fruit Council, International Tree Nut Council Research and Education Foundation, Loblaw Brands Ltd, Pulse Canada and Unilever. He has received in-kind research support from the Almond Board of California, American Peanut Council, Barilla, California Walnut Commission, Kellogg Canada, Loblaw Companies, Nutrartis, Quaker (PepsiCo), Primo, Unico, Unilever, WhiteWave Foods/Danone. He has received travel support and/or honoraria from the American Peanut Council, Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International Nut and Dried Fruit Council, International Pasta Organization, Lantmannen, Loblaw Brands Ltd, Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, Peanut Institute, Pulse Canada, Sun-Maid, Tate & Lyle, Unilever and White Wave Foods/Danone. He has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organization, McCormick Science Institute and Oldways Preservation Trust. He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD), is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the EASD and is a Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. DJAJ has received research grants from Loblaw Companies Ltd., the Almond Board of California, Soy Nutrition Institute (SNI), and the Canadian Institutes of Health Research (CIHR). He has received in-kind supplies for trials as a research support from the Almond board of California, Walnut Council of California, American Peanut Council, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge Limited, Kellogg Canada, WhiteWave Foods. He has been on the speaker's panel, served on the scientific advisory board and/or received travel support and/or honoraria from the Loblaw Companies Ltd, Diet Quality Photo Navigation (DQPN), Better Therapeutics (FareWell), Verywell, True Health Initiative (THI), Heali AI Corp, Institute of Food Technologists (IFT), Soy Nutrition Institute (SNI), Herbalife Nutrition Institute (HNI), Herbalife International, Pacific Health Laboratories, Nutritional Fundamentals for Health (NFH), the Soy Foods Association of North America, the Nutrition Foundation of Italy (NFI), the Toronto Knowledge Translation Group (St. Michael's Hospital), the Canadian College of Naturopathic Medicine, The Hospital for Sick Children, the Canadian Nutrition Society (CNS), and the American Society of Nutrition (ASN). He is a member of the International Carbohydrate Quality Consortium (ICQC). His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry, his 2 daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the low glycemic index plant foods advocated here, The Portfolio Diet for Cardiovascular Risk Reduction (Academic Press/Elsevier 2020 ISBN:978-0-12-810510-8)and his sister, Caroline Brydson, received funding through a grant from the St. Michael's Hospital Foundation to develop a cookbook for one of his studies. ER has received research funding through his institution from the California Walnut Commission, Folsom, CA, USA; was a paid member of its Health Research Advisory Group; and is a nonpaid member of its Scientific Advisory Council. He has also received research support through his institution from Alexion and serves on its Scientific Advisory board, received fees for scientific presentations and travel support from Danone, and travel support from the International Nut Council. JS-S serves on the board of (and receives grant support through his institution from) the International Nut and Dried Fruit Council and the Eroski Foundation. He also serves on the Executive Committee of the Instituto Danone, Spain, and on the Scientific Committee of the Danone International Institute. He has received research support from the Patrimonio Comunal Olivarero, Spain, and Borges S.A., Spain. He receives consulting fees or travel expenses from Danone, the Eroski Foundation, the Instituto Danone Spain, and Abbot Laboratories. RE reports grants from Cerveza y Salud, Spain, Fundacion Dieta Mediterranea, Spain and Interprofesional del Vino, Spain. Also, personal fees for given lectures from Brewers of Europe, Belgium, Fundacion Cerveza y Salud, Spain, Pernaud-Ricard, Mexico, Instituto Cervantes, Alburquerque, USA; Instituto Cervantes, Milan, Italy, Instituto Cervantes, Tokyo, Japan, Lilly Laboratories, Spain, and Wine and Culinary International Forum, Spain, and non-financial support to organize a National Congress on Nutrition. Also feeding trials with product from Grand Fountain and Uriach Laboratories, Spain. JLS has received research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of Ontario Ministry of Research and Innovation and Science, Canadian Institutes of health Research (CIHR), Diabetes Canada, PSI Foundation, Banting and Best Diabetes Centre (BBDC), American Society for Nutrition (ASN), INC International Nut and Dried Fruit Council Foundation, National Dried Fruit Trade Association, National Honey Board, International Life Sciences Institute (ILSI), Pulse Canada, Quaker, The Tate and Lyle Nutritional Research Fund at the University of Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), and The Nutrition Trialists Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council). He has received in-kind food donations to support a randomized controlled trial from the Almond Board of California, California Walnut Commission, American Peanut Council, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods/Danone, and Nutrartis. He has received travel support, speaker fees and/or honoraria from Diabetes Canada, Dairy Farmers of Canada, FoodMinds LLC, International Sweeteners Association, Nestlé, Pulse Canada, Canadian Society for Endocrinology and Metabolism (CSEM), GI Foundation, Abbott, General Mills, Biofortis, ASN, Northern Ontario School of Medicine, INC Nutrition Research & Education Foundation, European Food Safety Authority (EFSA), Comité Européen des Fabricants de Sucre (CEFS), Nutrition Communications, International Food Information Council (IFIC), Calorie Control Council, and Physicians Committee for Responsible Medicine. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, Wirtschaftliche Vereinigung Zucker e.V., Danone, and Inquis Clinical Research. He is a member of the European Fruit Juice Association Scientific Expert Panel and Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular Society (CCS), and Obesity Canada. He serves or has served as an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Technical Committee on Carbohydrates of ILSI North America. He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His wife is an employee of AB InBev. All other authors declare no conflicts., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations., Methods: Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models., Results: After adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30-2.63) and 1.57 (1.09-2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99-1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03-1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57-4.03), 1.65 (1.00-2.71) and 1.65 (1.04-2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF., Conclusions: Our findings support the role of the choline metabolic pathway in the pathogenesis of AF and HF., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: High nut consumption has been previously associated with decreased prevalence of metabolic syndrome (MetS) regardless of race and dietary patterns., Objectives: The aim of this study was to assess whether changes in nut consumption over a 1-y follow-up are associated with changes in features of MetS in a middle-aged and older Spanish population at high cardiovascular disease risk., Methods: This prospective 1-y follow-up cohort study, conducted in the framework of the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial, included 5800 men and women (55-75 y old) with overweight/obesity [BMI (in kg/m2) ≥27 and <40] and MetS. Nut consumption (almonds, pistachios, walnuts, and other nuts) was assessed using data from a validated FFQ. The primary outcome was the change from baseline to 1 y in features of MetS [waist circumference (WC), glycemia, HDL cholesterol, triglyceride (TG), and systolic and diastolic blood pressure] and excess weight (body weight and BMI) according to tertiles of change in nut consumption. Secondary outcomes included changes in dietary and lifestyle characteristics. A generalized linear model was used to compare 1-y changes in features of MetS, weight, dietary intakes, and lifestyle characteristics across tertiles of change in nut consumption., Results: As nut consumption increased, between each tertile there was a significant decrease in WC, TG, systolic blood pressure, weight, and BMI (P < 0.05), and a significant increase in HDL cholesterol (only in women, P = 0.044). The interaction effect between time and group was significant for total energy intake (P < 0.001), adherence to the Mediterranean diet (MedDiet) (P < 0.001), and nut consumption (P < 0.001). Across tertiles of increasing nut consumption there was a significant increase in extra virgin olive oil intake and adherence to the MedDiet; change in energy intake, on the other hand, was inversely related to consumption of nuts., Conclusions: Features of MetS and excess weight were inversely associated with nut consumption after a 1-y follow-up in the PREDIMED-Plus study cohort. This trial was registered at isrctn.com as ISRCTN89898870., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55-75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible to improve significantly their dietary quality, assessed by adherence to Mediterranean diet, DII and both healthful and unhealthful provegetarian patterns. People at maximum weight are the most benefitted in the short term by a weight management program. Long term weight loss efforts may also reduce the effect of a weight management program.