Nitrite Attenuates the In Vitro Inflammatory Response of Immune Cells to the SARS-CoV-2 S Protein without Interfering in the Antioxidant Enzyme Activation.

SARS-CoV-2 induces a hyperinflammatory reaction due to the excessive release of cytokines during the immune response. The bacterial endotoxin lipopolysaccharide (LPS) contributes to the low-grade inflammation associated with the metabolic syndrome, enhancing the hyperinflammatory reaction induced by the SARS-CoV-2 infection. The intake of sodium nitrate, a precursor of nitrite and nitric oxide, influences the antioxidant and pro-inflammatory gene expression profile after immune stimulation with LPS in peripheral blood mononuclear cells from metabolic syndrome patients. We aimed to assess the inflammatory and antioxidant responses of immune cells from metabolic syndrome patients to exposure to the SARS-CoV-2 spike protein (S protein) together with LPS and the effect of nitrite in these responses. Whole blood samples obtained from six metabolic syndrome patients were cultured for 16 h at 37 °C with four different media: control medium, control medium plus LPS (100 ng/mL), control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL), and control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL) plus nitrite (5 µM). Immune stimulation with the LPS/S protein enhanced nitrate biosynthesis from nitrite oxidation and probably from additional organic precursors. In vitro incubations with the LPS/S protein enhanced the expression and/or release of pro-inflammatory TNFα, IL-6, IL-1ß, and TLR4, as well as the expression of the anti-inflammatory IL-1ra and IL-10 and antioxidant enzymes. Nitrite attenuated the pro- and anti-inflammatory response induced by the S protein without interfering with the activation of TLR4 and antioxidant enzyme expression, raising the possibility that nitrite could have potential as a coadjutant in the treatment of COVID-19.

Water intake, hydration status and 2-year changes in cognitive performance: a prospective cohort study.

BACKGROUND: Water intake and hydration status have been suggested to impact cognition; however, longitudinal evidence is limited and often inconsistent. This study aimed to longitudinally assess the association between hydration status and water intake based on current recommendations, with changes in cognition in an older Spanish population at high cardiovascular disease risk. METHODS: A prospective analysis was conducted of a cohort of 1957 adults (aged 55-75) with overweight/obesity (BMI between ≥ 27 and < 40 kg/m2) and metabolic syndrome from the PREDIMED-Plus study. Participants had completed bloodwork and validated, semiquantitative beverage and food frequency questionnaires at baseline, as well as an extensive neuropsychological battery of 8 validated tests at baseline and 2 years of follow-up. Hydration status was determined by serum osmolarity calculation and categorized as < 295 mmol/L (hydrated), 295-299.9 mmol/L (impending dehydration), and ≥ 300 mmol/L (dehydrated). Water intake was assessed as total drinking water intake and total water intake from food and beverages and according to EFSA recommendations. Global cognitive function was determined as a composite z-score summarizing individual participant results from all neuropsychological tests. Multivariable linear regression models were fitted to assess the associations between baseline hydration status and fluid intake, continuously and categorically, with 2-year changes in cognitive performance. RESULTS: The mean baseline daily total water intake was 2871 ± 676 mL/day (2889 ± 677 mL/day in men; 2854 ± 674 mL/day in women), and 80.2% of participants met the ESFA reference values for an adequate intake. Serum osmolarity (mean 298 ± 24 mmol/L, range 263 to 347 mmol/L) indicated that 56% of participants were physiologically dehydrated. Lower physiological hydration status (i.e., greater serum osmolarity) was associated with a greater decline in global cognitive function z-score over a 2-year period (ß: - 0.010; 95% CI - 0.017 to - 0.004, p-value = 0.002). No significant associations were observed between water intake from beverages and/or foods with 2-year changes in global cognitive function. CONCLUSIONS: Reduced physiological hydration status was associated with greater reductions in global cognitive function over a 2-year period in older adults with metabolic syndrome and overweight or obesity. Future research assessing the impact of hydration on cognitive performance over a longer duration is needed. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Registry, ISRCTN89898870. Retrospectively registered on 24 July 2014.

Lifestyle behaviors clusters in a nationwide sample of Spanish children and adolescents: PASOS study.

BACKGROUND: Youth is a vulnerable period. To classify lifestyle behaviors and its relationship with health-related outcomes of Spanish children and adolescents. METHODS: Cross-sectional study including 3261 children aged 7.5-17.5 y (52.8% females). Physical activity (PA), screen-time, sleep time, adherence to Mediterranean diet (MD), weight status (WS) by validated methods. Cluster analysis was run considering chronological age. RESULTS: Six clusters were identified: C1: high screen time, low adherence to MD and sleep time (n = 431,13.20%); C2: high WS, medium adherence to MD,high sleep time, and low screen time (n = 466,14.30%); C3: young group with low screen time and high PA, adherence to MD and sleep (n = 537,16.40%); C4: worst profile regarding adherence to MD, PA, WS and sleep time (n = 609,18.70%); C5: low screen time and PA, high sleep time (n = 804,24.70%); C6: high PA and screen time, low WS (n = 414,12.70%). Mean absolute values were statistically different among PA levels, screen and sleep time, adherence to MD, age, and WS (all p < 0.001). CONCLUSIONS: The most prevalent pattern was low levels of PA, MD, and screen time, and high sleep time. The second most prevalent was characterized by very low levels of PA, sleep time, and adherence to MD, and high screen time, and WS in adolescents. IMPACT STATEMENT: The main identified lifestyle behavior was poor physical activity, low adherence to Mediterranean Diet and high screen and sleep time. Children should increase physical activity levels, adherence to Mediterranean diet, decrease screen and sleep the appropriate hours per day. Families, schools, and medical communities must work together to gloss over present and future diseases. Sleep time had not been previously included in cluster analysis with physical activity, sedentary behaviors, obesity, and nutritional status, thus the present data open a new perspective in Spanish population. Health policies should focus on promoting physical activity, Mediterranean diet, adequate sleep and reducing screen time.

Carbon dioxide (CO2) emissions and adherence to Mediterranean diet in an adult population: the Mediterranean diet index as a pollution level index.

BACKGROUND: Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment. AIM: To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population. DESIGN AND POPULATION: Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed. METHODS: Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expressed in kg/day: Q1 (≤2.01 kg CO2), Q2 (2.02-2.34 kg CO2), Q3 (2.35-2.79 kg CO2) and Q4 (≥2.80 kg CO2). RESULTS: More men than women induced higher dietary levels of CO2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference). CONCLUSIONS: The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO2 emissions. Mediterranean Diet index may be used as a pollution level index.

Vitamin K dietary intake is associated with cognitive function in an older adult Mediterranean population.

BACKGROUND: In the last years, evidence that dietary vitamin K could have a role in the cognitive domain has increased. However, data from large trials are limited. The objective of this study was to assess the association of 2 year changes in the dietary intake of vitamin K with cognitive function measured through neuropsychological performance tests. METHODS: In 5,533 participants of the multicentre PREDIMED-Plus study (48.1% women, age 65.1 ± 4.9 years with overweight/obesity and metabolic syndrome), we assessed the adjusted odds ratios of cognitive function decline according to 2 year changes in vitamin K intake. Participants answered a battery of cognitive function tests and Food Frequency Questionnaires (FFQs) in order to estimate the vitamin K dietary intake. RESULTS: After adjusting for potential cofounders, the highest tertile of change of dietary vitamin K intake (median [IQR]; 194.4 µg/d [120.9, 373.1]) was inversely associated with a Mini-Mental State Examination (MMSE) score ≤24 (OR [95% CI]; 0.53 [0.35, 0.79] P for trend = 0.002) compared with a decrease in the intake of vitamin K (median [IQR]; -97.8 µg/d [-292.8, -51.5]). A significant positive association between changes in dietary vitamin K intake and the semantic verbal fluency test scores (OR [95% CI]; 0.69 [0.51, 0.94] P for trend = 0.019) was found. CONCLUSIONS: An increase of the intake of dietary vitamin K was associated with better cognitive function scores, independently of recognised risk factors for cognitive decline, in an older adult Mediterranean population with high cardiovascular risk.

Comparison between Original and Reviewed Consensus of European Working Group on Sarcopenia in Older People: A Probabilistic Cross-Sectional Survey among Community-Dwelling Older People.

INTRODUCTION: The European Working Group on Sarcopenia in Older People (EWGSOP) published a consensus on sarcopenia in 2010 and updated it in 2019 (EWGSOP2) which included the use of specific cut-off points. The aim was to assess how much prevalence of sarcopenia differed between EWGSOP2 and EWGSOP, as well as the use of specific cut-off points to assess differences in presarcopenia versus probable sarcopenia. METHODS: Observational, transversal, and comparative study (n = 1,283 older adults; 57% women). Anthropometrics and handgrip strength were measured, and appendicular skeletal muscle mass equation was defined. Conceptual and methodological definitions of EWGSOP and EWGSOP2 consensus were applied to calculate prevalence of presarcopenia, probable sarcopenia, and sarcopenia. RESULTS: Using cut-off points recommended for European population, prevalence of sarcopenia with EWGSOP2 was lower (-6.6%; p < 0.001) than EWGSOP. The prevalence of probable sarcopenia (EWGSOP2) was higher (+7.8%; p < 0.001) than EWGSOP presarcopenia. The agreement between EGWGSOP and EWGSOP2 was moderated (K = 0.45; IC = 0.40-0.51). Using specific-population cut-off points for muscle strength and appendicular muscle mass, the prevalence of probable sarcopenia with EWGSOP2 was higher (46.5%; p < 0.001) than EWGSOP (1.8%). The agreement between EGWGSOP and EWGSOP2 was moderated (K = 0.48; IC = 0.42-0.52). CONCLUSION: The new EWGSOP2 consensus underestimates the prevalence of sarcopenia, compared with EWGSOP using conventional cut-off points. The prevalence of presarcopenia with EWGSOP (low muscle mass) was lower than probable sarcopenia (low muscle strength) with the new EWGSOP2. In both cases, agreements between EWGSOP2 and EWGSOP were moderated. Discrepancies between the original and new consensus have implications on the primary health setting for identifying old and new cases for prevention and treatment.

Fruit consumption and cardiometabolic risk in the PREDIMED-plus study: A cross-sectional analysis.

BACKGROUND AND AIMS: Total fruit consumption is important for cardiovascular disease prevention, but also the variety and form in which is consumed. The aim of the study was to assess the associations between total fruit, subgroups of fruits based on their color and fruit juices consumption with different cardiometabolic parameters. METHODS AND RESULTS: A total of 6633 elderly participants (aged 55-75 years) with metabolic syndrome from the PREDIMED-Plus study were included in this analysis. Fruit and fruit juice consumption was assessed using a food frequency questionnaire. Linear regression models were fitted to evaluate the association between exposure variables (total fruit, subgroups based on the color, and fruit juices) and different cardiometabolic risk factors. Individuals in the highest category of total fruit consumption (≥3 servings/d) had lower waist circumference (WC) (ß = -1.04 cm; 95%CI:-1.81, -0.26), fasting glucose levels (ß = -2.41 mg/dL; 95%CI(-4.19, -0.63) and LDL-cholesterol (ß = -4.11 mg/dL; 95%CI:-6.93, -1.36), but, unexpectedly, higher systolic blood pressure (BP) (ß = 1.84 mmHg; 95%CI: 0.37, 3.30) and diastolic BP (ß = 1.69 mmHg; 95%CI:0.83, 2.56) when compared to those in the lowest category of consumption (<1 servings/d). Participants consuming ≥1 serving/day of total fruit juice had lower WC (ß = -0.92 cm; 95%CI:-1.56, -0.27) and glucose levels (ß = -1.59 mg/dL; 95%CI:-2.95, -0.23) than those consuming <1 serving/month. The associations with cardiometabolic risk factors differed according to the color of fruits. CONCLUSION: Fruit consumption is associated with several cardiometabolic risk factors in Mediterranean elders with metabolic syndrome. The associations regarding BP levels could be attributed, at least partially, to reverse causality bias inherent to the cross-sectional design of the study.

Physical activity and metabolic syndrome severity among older adults at cardiovascular risk: 1-Year trends.

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.

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia.

BACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.

Effect of changes in adherence to Mediterranean diet on nutrient density after 1-year of follow-up: results from the PREDIMED-Plus Study.

BACKGROUND: The prevalence of overweight/obesity and related manifestations such as metabolic syndrome (MetS) is increasing worldwide. High energy density diets, usually with low nutrient density, are among the main causes. Some high-quality dietary patterns like the Mediterranean diet (MedDiet) have been linked to the prevention and better control of MetS. However, it is needed to show that nutritional interventions promoting the MedDiet are able to improve nutrient intake. OBJECTIVE: To assess the effect of improving MedDiet adherence on nutrient density after 1 year of follow-up at the PREDIMED-Plus trial. METHODS: We assessed 5777 men (55-75 years) and women (60-75 years) with overweight or obesity and MetS at baseline from the PREDIMED-Plus trial. Dietary changes and MedDiet adherence were evaluated at baseline and after 1 year. The primary outcome was the change in nutrient density (measured as nutrient intake per 1000 kcal). Multivariable-adjusted linear regression models were fitted to analyse longitudinal changes in adherence to the MedDiet and concurrent changes in nutrient density. RESULTS: During 1-year follow-up, participants showed improvements in nutrient density for all micronutrients assessed. The density of carbohydrates (- 9.0%), saturated fatty acids (- 10.4%) and total energy intake (- 6.3%) decreased. These changes were more pronounced in the subset of participants with higher improvements in MedDiet adherence. CONCLUSIONS: The PREDIMED-Plus dietary intervention, based on MedDiet recommendations for older adults, maybe a feasible strategy to improve nutrient density in Spanish population at high risk of cardiovascular disease with overweight or obesity.

A randomized controlled trial for overweight and obesity in preschoolers: the More and Less Europe study - an intervention within the STOP project.

BACKGROUND: Childhood overweight and obesity is a serious public health issue with an increase being observed in preschool-aged children. Treating childhood obesity is difficult and few countries use standardized treatments. Therefore, there is a need to find effective approaches that are feasible for both health care providers and families. Thus, the overall aim of this study is to assess the acceptance and effectiveness of a parent support program (the More and Less, ML) for the management of overweight and obesity followed by a mobile health (mHealth) program (the MINISTOP application) in a socially diverse population of families. METHODS/DESIGN: A two-arm, parallel design randomized controlled trial in 300 2-to 6-year-old children with overweight and obesity from Romania, Spain and Sweden (n = 100 from each). Following baseline assessments children are randomized into the intervention or control group in a 1:1 ratio. The intervention, the ML program, consists of 10-weekly group sessions which focus on evidence-based parenting practices, followed by the previously validated MINISTOP application for 6-months to support healthy eating and physical activity behaviors. The primary outcome is change in body mass index (BMI) z-score after 9-months and secondary outcomes include: waist circumference, eating behavior (Child Eating Behavior Questionnaire), parenting behavior (Comprehensive Feeding Practices Questionnaire), physical activity (ActiGraph wGT3x-BT), dietary patterns (based on metabolic markers from urine and 24 h dietary recalls), epigenetic and gut hormones (fasting blood samples), and the overall acceptance of the overweight and obesity management in young children (semi-structured interviews). Outcomes are measured at baseline and after: 10-weeks (only BMI z-score, waist circumference), 9-months (all outcomes), 15- and 21-months (all outcomes except physical activity, dietary patterns, epigenetics and gut hormones) post-baseline. DISCUSSION: This study will evaluate a parent support program for weight management in young children in three European countries. To boost the effect of the ML program the families will be supported by an app for 6-months. If the program is found to be effective, it has the potential to be implemented into routine care to reduce overweight and obesity in young children and the app could prove to be a viable option for sustained effects of the care provided. TRIAL REGISTRATION: ClinicalTrials.gov NCT03800823; 11 Jan 2019.

Effect of a Nutritional and Behavioral Intervention on Energy-Reduced Mediterranean Diet Adherence Among Patients With Metabolic Syndrome: Interim Analysis of the PREDIMED-Plus Randomized Clinical Trial.

Importance: High-quality dietary patterns may help prevent chronic disease, but limited data exist from randomized trials about the effects of nutritional and behavioral interventions on dietary changes. Objective: To assess the effect of a nutritional and physical activity education program on dietary quality. Design, Setting, and Participants: Preliminary exploratory interim analysis of an ongoing randomized trial. In 23 research centers in Spain, 6874 men and women aged 55 to 75 years with metabolic syndrome and no cardiovascular disease were enrolled in the trial between September 2013 and December 2016, with final data collection in March 2019. Interventions: Participants were randomized to an intervention group that encouraged an energy-reduced Mediterranean diet, promoted physical activity, and provided behavioral support (n = 3406) or to a control group that encouraged an energy-unrestricted Mediterranean diet (n = 3468). All participants received allotments of extra-virgin olive oil (1 L/mo) and nuts (125 g/mo) for free. Main Outcomes and Measures: The primary outcome was 12-month change in adherence based on the energy-reduced Mediterranean diet (er-MedDiet) score (range, 0-17; higher scores indicate greater adherence; minimal clinically important difference, 1 point). Results: Among 6874 randomized participants (mean [SD] age, 65.0 [4.9] years; 3406 [52%] men), 6583 (96%) completed the 12-month follow-up and were included in the main analysis. The mean (SD) er-MedDiet score was 8.5 (2.6) at baseline and 13.2 (2.7) at 12 months in the intervention group (increase, 4.7 [95% CI, 4.6-4.8]) and 8.6 (2.7) at baseline and 11.1 (2.8) at 12 months in the control group (increase, 2.5 [95% CI, 2.3-2.6]) (between-group difference, 2.2 [95% CI, 2.1-2.4]; P < .001). Conclusions and Relevance: In this preliminary analysis of an ongoing trial, an intervention that encouraged an energy-reduced Mediterranean diet and physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significantly greater increase in diet adherence after 12 months. Further evaluation of long-term cardiovascular effects is needed. Trial Registration: isrctn.com Identifier: ISRCTN89898870.

DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

Analysis of Lynch Syndrome Mismatch Repair Genes in Women with Endometrial Cancer.

OBJECTIVE: Endometrial cancer is the second most frequent neoplasm in women with Lynch syndrome (LS). We sought to assess whether analyzing women with endometrial cancer would identify families with LS not identified with current clinical criteria. METHODS: We included women diagnosed with endometrial cancer younger than 50 years and also older if they had a family cancer history associated with LS. In blood samples obtained, we analyzed mutations in mismatch repair (MMR) genes, as well as protein expression by immunohistochemistry and microsatellite instability (MSI) in tumour tissue. RESULTS: A total of 103 patients were enrolled. We detected 14 pathogenic mutations and 4 genetic variants of unknown clinical significance in MMR genes. We found MSI in 41.66% of the women with a pathogenic mutation. In this group, 76.92% showed loss of at least one MMR protein. Women with mutations were younger at diagnosis, but all of them had a family history compatible with LS. CONCLUSIONS: Analysis of the MMR genes, in particular MSH6, seems to be appropriate in women with endometrial cancer and a family history of tumours associated with LS.

Food Neophobias in Spanish Adults with Overweight or Obesity by Sex: Their Association with Sociodemographic Factors and the Most Prevalent Chronic Diseases.

Food neophobia has been defined as the reluctance to try new foods. Food neophobia is common in children and older people, but until now, scarce research has been carried out on food neophobia in the adult population. The aim of this study was to assess the most usual food neophobias in Spanish adults with overweight and obesity by sex, and their association with sociodemographic factors and the most prevalent chronic diseases. A cross-sectional observational study was carried out on adults (mean age of 43.5 ± 13.7 years old; n = 590; 50% female) with overweight or obesity. Their anthropometrics, adherence to the Mediterranean diet, age, educational level, economic level, smoking and sleeping habits, physical activity, chronic diseases, and food neophobias were assessed. The highest food neophobias in Spanish adults with overweight or obesity were directed toward vegetables, meat, fish, pulses, game meat, and fruits, mostly among females, with differences between sexes. Phobias of the soft texture of foods were also observed, without differences between sexes. Age, educational level, sleeping habits, and physical activity were directly related, and economical level and smoking were inversely related to food neophobia, mainly to healthy foods, and more obvious in males than in females. There were associations between body mass index (BMI) and chronic diseases and food neophobia. Adherence to the adaption of healthy and sustainable diets is low within food neophobics, increasing the risk of diet-related chronic diseases.

Development and Evaluation of the Reliability of a Semi-Quantitative Food Frequency Questionnaire to Assess the Intake in the Serbian Population.

Assessing dietary habits with validated questionnaires is crucial for achieving reliable results in health research. The aim of this study was the development and validation of a semi-quantitative food frequency questionnaire (FFQ) in an 18-30-year-old Serbian population. A total of 93 participants completed the FFQ and three 24 h dietary recalls (24 hR). Pearson and intraclass correlations between FFQ and 24 hR intakes were assessed and were de-attenuated and energy-adjusted. Bland-Altman plots were generated, and quintiles of energy, water, fiber, and macronutrient intake were analyzed with contingency tables. Adjustments for sex differences were included. The validity of the FFQ varied, with significant correlations for energy, carbohydrates, cholesterol, and vitamin B12, vitamin C and vitamin D. Misclassification rates were generally low. Bland-Altman plots indicated good agreement between methods. It can be concluded that the validated FFQ is a promising tool for dietary assessment in the Serbian population. Results for several nutrients align closely with previous studies. The new FFQ is a useful tool for dietary assessment in the Serbian population.

An HPLC-UV Method to Assess Human Plasma 25(OH)D3.

The aim of this study was to validate an HPLC-UV method to assess vitamin D status by determining the linearity and precision of the 25-hydroxyvitamin D3 (25(OH)D3) calibration curve, the limits of detection, quantitation and robustness of the method, and its accuracy. A second stock solution of 25(OH)D3 was prepared (500 ng/mL), and working dilutions (5, 10, 20, 30, 40, and 50 ng/mL) were prepared for a calibration curve. The HPLC equipment had a UV-Vis diode-array detector and utilized an AcclaimTM 120 C18 column (5 µm, 4.6 × 250 mm) with a flow rate of 1.2 mL/min, a column temperature of 30 °C, and the standards and samples were maintained at 4 °C, with an injection volume of 100 µL. Detection of 25(OH)D3 was determined at 265 nm, with a retention time of 4.0 min. The validation was conducted according to the FDA Validation of Analytical Procedures: Guidance for Industry. Vitamin D was extracted from plasma samples using acetonitrile (ACN)-0.1% formic acid (2:1 v/v), and the percentage of recovery was calculated. The proposed method conditions gave excellent linearity (R2 = 0.9989) and the linearity coefficient was R2 > 0.99 for 25(OH)D3. The detection and quantification limits were 1.1703 ng/mL and 3.5462 ng/mL, respectively. Decreasing or increasing the reading temperature by 1 °C decreased the response units (AU) of vitamin D, 25(OH)D3. When the current flow rate decreased by 0.2 mL/min (1.0 mL/min), the retention time increased to 4.913 min, whereas an increase of 0.2 mL/min of the proposed flow rate (1.4 mL/min) decreased the retention time to 3.500 min. The percentage of recovery varied from 92.2% to 97.1%. The proposed method to quantify a vitamin D metabolite (25(OH)D3) in human plasma samples was reliable and validated.

Long-Term Impact of Nutritional Intervention with Increased Polyphenol Intake and Physical Activity Promotion on Oxidative and Inflammatory Profiles in Patients with Metabolic Syndrome.

Obesity and overweight pose significant risks to health, contributing to the prevalence of chronic conditions like type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). The current study aimed to assess the impact of a 6-year nutritional and lifestyle intervention on oxidative and inflammatory markers in individuals aged 55 to 75, specifically those at high risk of CVD. A study was carried out in a group of 80 participants with metabolic syndrome (MetS) residing in Mallorca, Spain, who underwent nutritional intervention based on a low-calorie Mediterranean diet (MedDiet) and promotion of physical activity. Before and after the intervention, several parameters including anthropometric data, haematological factors, blood pressure, and physical activity level were measured. Oxidative and inflammatory biomarkers in plasma were analysed. After the 6-year intervention, participants who managed to reduce their body mass index (BMI) had greater reductions in abdominal obesity, waist to heigh ratio (WHtR), diastolic blood pressure, and glucose levels, and increased high density protein cholesterol (HDL-c) compared to those who did not reduce BMI. This higher reduction in BMI was related to reduced energy intake and increased adherence to MedDiet, with greater polyphenol intake, and total physical activity (PA). Furthermore, improvements in oxidative stress and proinflammatory status were observed in participants who reduced their BMI. Significant reductions in the activity of the prooxidant enzyme, myeloperoxidase (MPO), levels of the lipid oxidation marker, malondialdehyde (MDA), and the proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1,) were found in those who reduced their BMI. In contrast, participants who did not improve their BMI exhibited higher levels of proinflammatory markers such as MCP-1 and tumour necrosis factor α (TNFα), as well as increased activity of the antioxidant enzyme catalase (CAT). Current findings suggest that an effective way to reduce BMI is a hypocaloric MedDiet combined with tailored physical activity to improve oxidative stress and proinflammatory status, and potentially reducing the risk of CVD.

Effects of Regular Exercise on the Biochemical, Oxidative, and Inflammatory Profiles and Quality of Life in Older Spaniards with Metabolic Syndrome.

Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging and for controlling and preventing chronic diseases. To assess the effects of regular physical activity on the biochemical and inflammatory profiles, as well as the quality of life of older adults diagnosed with metabolic syndrome. Participants (aged 55-70 years; living in the Balearic Islands, Spain) were divided into two groups (n = 50 each) according to the degree of physical activity measured by metabolic equivalents of task (METs). Anthropometric parameters, blood pressure, biochemical and hematological parameters, and inflammatory biomarkers were measured. Beck Depression Inventory and adherence to the Mediterranean diet questionnaires, as well as the Dietary Inflammatory Index, chair test, health-related quality of life (HRQoL), and Rapid Assessment of Physical Activity, were also determined. The characterization of the patients was similar in both groups, showing a homogeneous sample. The group with the highest METs experienced a decrease in depression and an increase in the intensity of physical activity. Adherence to the Mediterranean diet and HRQoL physical dimensions increased in participants with the highest METs, also showing a decrease in glycemia and glycosylated hemoglobin values. Inflammatory biomarkers, including tumor necrosis factor alpha, interleukin-6, interleukin-1ß, and osteoprotegerin, decreased in patients practicing more physical activity. High levels of physical activity are related to a healthier lifestyle, characterized by high adherence to the Mediterranean diet, decreased depressive behavior, oxidative stress, and inflammatory status in older people with metabolic syndrome.

Impact of Adherence to the Mediterranean Diet on Antioxidant Status and Metabolic Parameters in NAFLD Patients: A 24-Month Lifestyle Intervention Study.

BACKGROUND: The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. OBJECTIVES: To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) of NAFLD patients following a 24-month lifestyle intervention based on the MedDiet. Adult patients (n = 40; aged 40-60 years) diagnosed with NAFLD by magnetic resonance imaging were divided into two groups based on their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Anthropometrics, biochemistry parameters, intrahepatic fat contents (IFC), antioxidants, and inflammatory biomarkers were measured in plasma and erythrocytes before and after the intervention. RESULTS: After the intervention, body mass index (BMI) and plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-chol), triglycerides, malondialdehyde (MDA), and cytokeratin-18 (CK18) decreased, and high-density lipoprotein cholesterol (HDL-chol) increased. Participants with high adherence to MedDiet showed lower IFC, hepatic enzyme (AST, ALT, and GGT), glycemia, oxidase LDL (oxLDL) plasma levels, and erythrocyte MDA levels. Higher antioxidant activity (erythrocyte catalase-CAT, superoxide dismutase-SOD, glutathione peroxidase-GPx, glutathione reductase-GRd, and total glutathione-GSH as well as PBMCs-CAT gene expression) was observed in these patients, along with a reduction of PBMCs reactive oxygen species production and Toll-like receptor 4 (TLR4) expression. Inverse associations were observed between adherence to the MedDiet and BMI, glycemia, AST, IFC, and CK18 plasma levels and oxLDL, CAT, SOD, and GRd activities in erythrocytes. A significant linear regression was observed between adherence to the MedDiet and antioxidant score. CONCLUSIONS: Adherence to the MedDiet is associated with improved plasma and PBMC antioxidant and inflammatory biomarker profiles and high antioxidant defences in erythrocytes.