Dietary restriction and hepatic cancer: Systematic review and meta-analysis of animal studies.

The effect of calorie restriction, fasting, and ketogenic diets on the treatment of liver cancer remains uncertain. Therefore, we conducted a systematic review to evaluate the effect of restrictive diets on the development and progression of liver cancer in animal models. We did a meta-analysis using the Cochrane Collaboration's Review Manager software, with the random effects model and the inverse variance technique. We examined 19 studies that were conducted between 1983 and 2020. Of these, 63.2% investigated calorie restriction, 21.0% experimented with a ketogenic diet, and 15.8% investigated the effects of fasting. The intervention lasted anything from 48 h to 221 weeks. Results showed that restrictive diets may reduce tumor incidence and progression, with a significant reduction in the risk of liver cancer development. Thereby, our results suggest that putting limits on what you eat may help treat liver cancer in more ways than one.

Treadmill Exercise Reverses the Adverse Effects of Intermittent Fasting on Behavior and Cortical Spreading Depression in Young Rats.

Intermittent fasting (IF) and physical exercise (PE) have beneficial psychological and physiological effects, improving memory and anxiety-like behavior. However, the impact of this combination on brain electrophysiological patterns is unknown. We aimed to evaluate the behavior and parameters of a brain excitability-related phenomenon named cortical spreading depression (CSD) in young rats (31-87 days of life) submitted to IF and treadmill PE for eight weeks. Sixty-four male and female Wistar rats aged 24 days were randomized into control, IF, PE, and IF+PE groups. Behavioral tests (open field (OF), object recognition, and elevated plus maze (EPM)) were performed, and the CSD propagation features were recorded. IF caused behavioral responses indicative of anxiety (lower number of entries and time spent in the OF center and EPM open arms). IF also reduced the discrimination index for object recognition memory tests and increased the propagation velocity of CSD. PE rats displayed more entries into the OF center and lowered CSD propagation speed. Data suggest that IF worsens anxiety-like behavior and memory and accelerates CSD in young rats. In contrast, PE reverted the unfavorable effects of IF. The brain effects of IF and PE at younger ages are recommended for study.

Physical exercise alleviates oxidative stress in brown adipose tissue and causes changes in body composition and nutritional behavior in rats with polycystic ovary syndrome.

AIM: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder in women. We investigate the effect of physical exercise on body composition, nutritional parameters, and oxidative stress in rats with PCOS. METHODS: Female rats were into three groups: Control, PCOS, and PCOS + Exercise. PCOS was induced by letrozole (1 mg/kg via p.o.) for 21 days consecutively. Physical exercise was swimming, for 21 consecutive days, 1 h/day with 5 % load. In all groups, we assessed the nutritional and murinometric parameters, body composition, thermography, and oxidative stress in brown adipose tissue (BAT) and peri-ovarian adipose tissue (POAT). KEY FINDINGS: In PCOS we observed an increase (P < 0.05) in body weight vs. the Control group. But, the PCOS + Exercise group prevent this weight gain (P < 0.05). The temperature in BAT, decrease (P < 0.05) in the PCOS group vs. Control group. PCOS + Exercise prevented this reduction (P < 0.05) in BAT temperature vs. PCOS groups. We observed decreases (P < 0.05) in Lee Index and BMI in POS + Exercise vs. PCOS group. In PCOS rats, we observed an increase (P < 0.05) in murinometric (SRWG, EI, and FE) and body composition parameters (TWB, ECF, ICF, and FFM) vs. the Control group. The PCOS + Exercise prevents (P < 0.05) these changes in all groups, compared with PCOS. Regarding the BAT, we observe an increase (P < 0.05) in MPO and MDA levels in the PCOS vs. Control group. PCOS + Exercise prevents (P < 0.05) these increases vs. the PCOS group. SIGNIFICANCE: PCOS modifies body composition, and nutritional parameters, and induces changes in oxidative stress in BAT. Physical exercise prevented these alterations.

Bromelain supplementation and inflammatory markers: A systematic review of clinical trials.

BACKGROUND AND AIMS: The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance. Therefore, the aim was to assess whether bromelain supplementation exerts anti-inflammatory effects in adults. METHODS: The systematic review was registered in PROSPERO (n° CRD42020221395), and the search was performed in MEDLINE, Scopus, Web of Science, and Cochrane Library. The terms used in the search were: "bromelains", "bromelain", "randomized clinical trial", and "clinical trial". Eligibility criteria were: randomized clinical trials with participants aged 18 years or over, of both sexes, who received supplementation with bromelain alone or in combination with other oral compounds, with an evaluation of inflammatory parameters as primary and secondary outcomes, published in English, Portuguese or Spanish. RESULTS: 1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1ß, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks. Markers associated with inflammation varied between studies, including IL-2, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ and MCP-1, PGE-2, CRP and fibrinogen. Eleven (11) participants experienced side effects, and two discontinued treatment in the studies. The reported adverse effects were mainly gastrointestinal but well tolerated. CONCLUSION: The general effect of bromelain supplementation on inflammation is inconsistent because of population heterogeneity, doses used, treatment duration, and parameters evaluated. The observed effects are punctual and isolated, and further standardization is needed to establish doses, supplementation time, and which type of inflammatory condition is indicated.

Consumption and supplementation of vitamin E in breast cancer risk, treatment, and outcomes: A systematic review with meta-analysis.

BACKGROUND: Robust evidence have shown diet or dietary components in playing a direct role on cancer chemoprevention such as breast cancer (BC), and also prevention against cancer therapy side effects. In this context, vitamin E isoforms have been associated with tumor suppression pathways, mainly related to proliferation, invasion, metastasis, tumor metabolism and chemoresistance. OBJECTIVE: Therefore, we performed a systematic review with meta-analysis to assess the effects of vitamin E consumption and/or supplementation on breast cancer risk, treatment, and outcomes. METHODS: The studies were selected in the electronic databases PubMed, Science Direct, Scopus and Web of Science. RESULTS: A total of 22 articles were selected, which nine manuscripts we perform the meta-analysis. The summary effect estimate did not indicate any significant association between consumption versus non-consumption of total vitamin E and breast cancer risk. After assessing the effects of vitamin E supplementation on breast cancer risk, only two had data for comparison and vitamin E supplementation presented no impact on breast cancer risk. However, the summary effect estimate from the included studies indicated that vitamin E consumption was inversely associated with breast cancer recurrence in the control group. There are no significant results regarding dietary or supplemental vitamin E intake and BC risk reduction. CONCLUSION: Finally, regarding recurrence, survival, and mortality, the results indicated that vitamin E consumption was inversely associated with breast cancer recurrence, although no association was found for breast cancer mortality.

α-tocopherol as a selective modulator of toxicogenic damage induced by antineoplastic agents cyclophosphamide and doxorubicin.

The aim of this study was to determine the oxidative/antioxidative effects, modulatory and selective potential of α-tocopherol (vitamin E) on antineoplastic drug-induced toxicogenetic damage. The toxicity, cytotoxicity and genotoxicity induced by antineoplastic agents cyclophosphamide (CPA) and doxorubicin (DOX) was examined utilizing as models Saccharomyces cerevisiae, Allium cepa, Artemia salina and human peripheral blood mononuclear cells (PBMCs) in the presence of α-tocopherol. For these tests, concentrations of α- tocopherol 100 IU/ml (67mg/ml), CPA 20 µg/ml, DOX 2 µg/ml were used. The selectivity of α-tocopherol was assessed by the MTT test using human mammary gland non-tumor (MCF10A) and tumor (MCF-7) cell lines. Data showed cytoplasmic and mitochondrial oxidative damage induced by CPA or DOX was significantly diminished by α-tocopherol in S. cerevisiae. In addition, the toxic effects on A. salina and cytotoxic and mutagenic effects on A. cepa were significantly reduced by α-tocopherol. In PBMCs, α-tocopherol alone did not markedly affect these cells, and when treated in conjunction with CPA or DOX, α-tocopherol reduced the toxicogenetic effects noted after antineoplastic drug administration as evidenced by decreased chromosomal alterations and lowered cell death rate. In human mammary gland non-tumor and tumor cell lines, α-tocopherol produced selective cytotoxicity with 2-fold higher effect in tumor cells. Evidence indicates that vitamin E (1) produced anti-cytotoxic and anti-mutagenic effects against CPA and DOX (2) increased higher selectivity toward tumor cells, and (3) presented chemoprotective activity in PBMCs.

Chemopreventive and anti-tumor potential of vitamin E in preclinical breast cancer studies: A systematic review.

BACKGROUND: Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity. OBJECTIVE: Therefore, this systematic review aimed to evaluate antitumor and chemopreventive activity of different vitamin E isoforms (tocopherols and tocotrienols) through in vitro and in vivo studies. METHOD: The systematic review was registered in PROSPERO (No. CRD4202126207) and the search was carried out in four electronic databases (PubMed, Science Direct, Scopus and Web of Science) in June 2021 by three independent reviewers. The search equation used was: "Supplementation" AND ("Vitamin E" OR Tocopherol OR Tocotrienol) AND "breast cancer" AND (chemotherapy OR therapy OR prevention). In vitro studies and animal models of breast cancer supplemented with tocopherol or tocotrienol vitamers, alone or in combination, were included. RESULTS: The results revealed 8546 relevant studies that were initially identified in our search. After analysis, a total of 12 studies were eligible for this systematic review. All studies included animal models, and 5 of them also performed in vitro experiments on cancer cell lines. The studies performed supplementation with tocopherols, mixtures (tocopherols and tocotrienols) and synthetic vitamin E forms. There was an significant association of estradiol, dendritic cells and pterostilbene in combined therapy with vitamin E. Vitamin E delayed tumor development, reduced tumor size, proliferation, viability, expression of anti-apoptotic and cell proliferation genes, and upregulated pro-apoptotic genes, tumor suppressor genes and increased immune response. The effects on oxidative stress markers and antioxidant activity were conflicting among studies. Only one study with synthetic vitamin E reported cardiotoxicity, but it did not show vitamin E genotoxicity. CONCLUSION: In conclusion, vitamin E isoforms, isolated or associated, showed antitumor and chemopreventive activity. However, due to studies heterogeneity, there is a need for further analysis to establish dose, form, supplementation time and breast cancer stage.

Reliability and Validity Estimate of the Pro-Inflammatory/Anti-Inflammatory Food Intake Score in South American Pediatric Population: SAYCARE Study.

Chronic low-grade inflammation may be associated with the development of chronic non-communicable diseases in young populations, often lasting to adulthood. Studies show that the diet is related to chronic inflammation. The Pro-inflammatory/Anti-inflammatory Food Intake Score (PAIFIS) is an indicator that measures the inflammatory potential of the diet, with the help of validated tools that assess food consumption. The validation of tools that assess inflammatory dietary patterns in young populations to produce valid and reliable results is essential to guide disease prevention strategies for adulthood. METHODS: This study aimed to estimate the Pro-inflammatory/Anti-inflammatory Food Intake Score (PAIFIS) in children and adolescents in South America and to test its reliability and validity using a food frequency questionnaire (FFQ) and an inflammatory biomarker. This work consists of a validation study in a sample of children and adolescents conducted in South America (SAYCARE Study). The habitual consumption of food contributing to calculating the PAIFIS was obtained through an FFQ and 24 h Dietary Recall (24HDR). Reliability was tested using the FFQ (FFQ1 × FFQ2), using Spearman's correlation coefficient to estimate the agreement between measurements. The validity of the PAIFIS was tested using 24HDR and the inflammatory biomarker C-reactive protein (CRP) using Spearman's correlation and multilevel linear regression. RESULTS: For children and adolescents, pro- and anti-inflammatory food groups showed Spearman's correlation coefficients ranging from 0.31 to 0.66, convergent validity ranging from 0.09 to 0.40, and criterion validity for a reliability range from -0.03 to 0.18. The PAIFIS showed Spearman's correlation coefficients for reliability ranging from 0.61 to 0.69, convergent validity from 0.16 to 0.23, and criterion validity from -0.03 to 0.24. CONCLUSION: The PAIFIS showed acceptable reliability, weak convergent validity, and weak criterion validity in children and adolescents.

RELATIONSHIP BETWEEN SELENIUM NUTRITIONAL STATUS AND MARKERS OF LOW-GRADE CHRONIC INFLAMMATION IN OBESE WOMEN.

Low-grade chronic inflammation is one of the main disorders that characterize adipose tissue dysfunction in obesity and is an important element in the pathogenesis of several comorbidities. In this context, selenium is an essential micronutrient that exerts important anti-inflammatory functions, and the role of selenium in controlling inflammation associated with obesity is not well defined. Thus, this study aimed to evaluate the relationship between markers of the nutritional status of selenium and low-grade chronic inflammation in obese women. This cross-sectional study included 81 women aged between 18 and 50 years, who were divided into two groups according to body mass index (BMI): the obesity group (n = 38) and normal weight group (n = 43). Selenium intake was assessed by 3-day diet records. The plasma, erythrocyte, and urinary selenium concentrations were determined using inductively coupled plasma optical emission spectrometry. The analysis of serum cytokines interleukin (IL)-8, IL-1ß, IL-6, IL-10, and tumor necrosis factor alpha (TNFα) was performed using flow cytometry. The results of this study revealed that the obese women had higher dietary intake of selenium than eutrophic women. However, obese participants showed decreased selenium concentrations in plasma and erythrocytes, in parallel with increased concentrations of selenium in the urine. Regarding the inflammatory parameters, obese women exhibited higher concentrations of IL-6 and lower concentrations of the cytokines IL-8, IL-1ß, and TNFα than eutrophic women. In the binary logistic regression analysis, erythrocyte selenium was considered an independent predictor of the serum concentrations of cytokine IL-8 in obese women, reflecting the anti-inflammatory action of this micronutrient.

Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic

Abstract We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients.

Cellular reprogramming, chemoresistance, and dietary interventions in breast cancer.

Breast cancer (BC) diagnosis has been associated with significant risk factors, including family history, late menopause, obesity, poor eating habits, and alcoholism. Despite the advances in the last decades regarding cancer treatment, some obstacles still hinder the effectiveness of therapy. For example, chemotherapy resistance is common in locally advanced or metastatic cancer, reducing treatment options and contributing to mortality. In this review, we provide an overview of BC metabolic changes, including the impact of restrictive diets associated with chemoresistance, the therapeutic potential of the diet on tumor progression, pathways related to metabolic health in oncology, and perspectives on the future in the area of oncological nutrition.

Improvement of 2,2'-Azobis(2-Methylpropionamidine) Dihydrochloride-Induced Hepatic Redox Imbalance in Swiss Mice and HepG2 Cells by Rutin.

Redox imbalance can lead to irreversible damages to biological functions. In this context, rutin stands out for its antioxidant potential. The objective of this study was to evaluate the acute and chronic effect of rutin on the hepatic redox imbalance. The study was performed according to three different protocols. First, healthy male Swiss mice were divided into two groups: control and rutin, the second of which received chronic oral supplementation of rutin (10 mg/kg). The second involved evaluation of the generation of reactive oxygen species (ROS) by HepG2 cells, incubated or not with rutin (20 and 40 µg/mL) for 3 h. The final protocol involved assessment of the acute effect of rutin (10 mg/kg) in mice with oxidative stress induced by 2,2'-azobis(2-methylpropionamidine) dihydrochloride (ABAP). After the in vivo treatments, the livers were collected to analyze the oxidative damage by thiol, and the antioxidant defense by catalase, superoxide dismutase, and glutathione peroxidase. In the HepG2 cells, the following probes were employed to assess the ROS production: dichlorofluorescein, MitoSOX, dihydroethidium, and Amplex Red. Rutin administered chronically improved the antioxidant defense in healthy animals, and when administered acutely both inhibited the increased production of ROS in HepG2 cells and improved the redox imbalance parameters in mice with induced oxidative stress. This study suggests rutin as a protective agent for restoration of hepatic redox homeostasis in redox injury induced by ABAP in Swiss mice and HelpG2 cells.

Evaluation of the Validity of a Food Frequency Questionnaire and 24-Hour Dietary Recall to Assess Dietary Iron Intake in Children and Adolescents from the South American Youth/Child Cardiovascular and Environmental Study.

BACKGROUND: A food frequency questionnaire (FFQ) for South American children and adolescents was developed, but its validity for assessing dietary iron intake has not been evaluated. OBJECTIVE: To evaluate the validity of the FFQ and 24-hour dietary recalls (24h-DR) for assessing dietary iron intake in children and adolescents. DESIGN: The South American Youth/Child Cardiovascular and Environmental study is a multicenter observational study, conducted in five South American cities: Buenos Aires (Argentina), Lima (Peru), Medellin (Colombia), Sao Paulo, and Teresina (Brazil). The FFQ assessed dietary intake over the previous 3 months, and the 24h-DR was completed three times (2 weekdays and 1 weekend day) with a minimum 5-day interval between recalls. Blood samples were collected to assess serum iron, ferritin, and hemoglobin levels. PARTICIPANTS AND SETTING: Data of 99 children (aged 3 to 10 years) and 50 adolescents (aged 11 to 17 years) from public and private schools were collected during 2015 to 2017. MAIN OUTCOME MEASURES: Dietary iron intake calculated from the FFQ (using the sum of daily iron intake in all food/food groups) and 24h-DR (mean of 3 days using the multiple source method). STATISTICAL ANALYSES PERFORMED: Dietary iron intake in relation to blood biomarkers were assessed using Spearman rank correlations adjusted for sex, age, and total energy intake, and the quadratic weighted κ coefficients for agreement. RESULTS: Spearman correlations showed very good coefficients (range = 0.78 to 0.85) for the FFQ in both age groups; for the 24h-DR, the coefficients were weak in children and adolescents (range = 0.23 to 0.28). The agreement ranged from 59.9% to 72.9% for the FFQ and from 63.9% to 81.9% for the 24h-DR. CONCLUSION: The South American Youth/Child Cardiovascular and Environmental study FFQ exhibited good validity to rank total dietary iron intake in children and adolescents, and as well as the 24h-DR, presented good strength of agreements when compared with serum iron and ferritin levels.

24 h movement behavior and metabolic syndrome study protocol: A prospective cohort study on lifestyle and risk of developing metabolic syndrome in undergraduate students from low-income regions during a pandemic.

Introduction: Obesity and its comorbidities are increasingly prevalent in Latin America, with a more rapid growth in individuals with lower income. The composition of movement behaviors within a 24 h period may have important implications for obesity, metabolic and mental health in cross-sectional data. However, a longitudinal study is needed to confirm the findings from the primarily cross-sectional evidence. The COVID-19 pandemic has been associated with cardiometabolic outcomes and has impeded healthy behavior. Objectives: The first objective is to evaluate the time elapsed since the diagnosis of not meeting 24 h movement guidelines and the potential subsequent onset of metabolic syndrome in undergraduate students from low-income regions within 4 years of follow up. The second objective is to test the association between 24 h movement, mental wellbeing, eating behaviors, and abdominal obesity in the period of this pandemic. Methods: The 24 h movement behavior and metabolic syndrome (24 h-MESYN) study is a multicentre cohort study that will include participants from two Brazilian cities within the 2022-2025 period to asses the first objective, and also a nested case-control study at the baseline will be carried out to evaluate the second objective. Previously, we conducted a feasibility study in the academic year of 2021 to assessing the psychometric properties of subjective tools, refine our study protocol, and adjust the epidemiological conditions of the cohort's subsequent phases (like as prevalence of exposure of interest, sampling process, and study adherence). Statistical tests as Cohen's kappa agreement; factorial analysis; logistic, Poisson and linear regression; and Kaplan-Meier analysis will be performed, in accordance with the objectives.

Reliability and validity of the dutch eating behavior questionnaire in an online format for university students from low-income regions in a pandemic context: A 24†hour MESYN study.

Objective: To test the reliability and validity of the Dutch Eating Behavior Questionnaire (DEBQ) in an online format in university students from low-income regions. Methods: We applied the questionnaire to a sample of 195 and 117 university students from a low-income region (Gini index of 0.56) to study validity and reliability, respectively. The DEBQ consists of 33 items on eating behavior in three dimensions/factors: emotional eating, restrained eating and external eating. The questionnaire was administered twice at 2-week intervals. We tested the reliability via temporal stability and internal consistency and construct validity via exploratory and confirmatory factor analysis. Results: For reliability, we identified an acceptable Spearman correlation coefficient (rho > 0.30 and p < 0.05) and Cronbach's alpha (α ≥ 0.70) for all DEBQ items. In the exploratory analysis, we identified 6 factors representing a mix of original and additional factors, with an explained variance of 69.1%. In the confirmatory analysis with structural equation modeling, we observed better global model adjustment for the 6-factor model with the Tucker-Lewis index and comparative fit index closer to one, as well as root mean square error of approximation closer to zero than the original (3-factor) model. Using generalized structural equation modeling, we also observed a better fit in latent class modeling for the 6-factor model (AIC: 16990.67; BIC. 17874.38) than for the 3-factor model (AIC: 17904.09; BIC: 18342.67). Conclusion: The online format of the DEBQ has acceptable reliability and validity for measuring eating behavior in university students from low-income regions.

Food consumption of branched chain amino acids and insulin resistance: A systematic review of observational studies in humans.

This review systematically investigated observational studies in humans that evaluated the dietary intake of branched-chain amino acids (BCAA) and its association with insulin resistance. A search implemented through the electronic databases of PubMed, Scopus, and Web of Science. The evaluation of insulin resistance or the risk of developing insulin resistance in humans were the variables of interest in the search for articles. After using the selection criteria, three studies included in this review. The Food Frequency Questionnaire (FFQ) was the instrument used to evaluate the diet in all of the selected studies. Overall, 1940 studies identified and three thoroughly reviewed. We found only one study with positive effects of BCAA on insulin resistance; the other two reviewed studies did not demonstrate positive effects of the dietary intake of BCAA, individually or the sum of three amino acids on variables of interest. In this sense, the associations between BCAA and insulin resistance are inconsistent, potentially due to other longitudinal outcomes.

Sampling and processing blood samples within the South American Youth/Child cARdiovascular and Environmental (SAYCARE) Study.

Obesity and overweight in children and adolescents is increasing rapidly worldwide; however, scarce data have been reported from South America countries. With the purpose of assessing hyperlipidemia, insulin resistance and chronic inflammation, the evaluation of blood biomarkers such as glucose, lipoproteins and chronic inflammation proteins is required. In the context of the SAYCARE study, in children and adolescents (3 to 18 years) from seven South American cities, our aim was to assess the impact of pre analytical conditions on different biomarkers evaluated in 474 fresh serum samples, in different country centers. We also evaluated the stability according to time and frozen storage within this study across the concordance of the results obtained from the 49 blood samples measured in three different centers. Significant correlations as well as concordance were observed in TG, Total-C, HDL-C and glucose between Buenos Aires and São Paulo. The samples evaluated in Teresina and São Paulo presented similar results, with exception of total cholesterol. We observed acceptable concordance between Buenos Aires vs São Paulo and Teresina vs São Paulo, suggesting that samples could be processed in each of these centers. This concordance is a consequence of the strict pre analytical conditions previously established in the SAYCARE study.

Oral Pharmacological Activation of Hypothalamic Guanylate Cyclase 2C Receptor Stimulates Brown Fat Thermogenesis to Reduce Body Weight.

Linaclotide is a synthetic peptide approved by the FDA for the treatment of constipation-predominant irritable bowel syndrome and chronic constipation. Linaclotide binds and activates the transmembrane receptor guanylate cyclase 2C (Gucy2c). Uroguanylin (UGN) is a 16 amino acid peptide that is mainly secreted by enterochromaffin cells in the duodenum and proximal small intestine. UGN is the endogenous ligand of Gucy2c and decreases body weight in diet-induced obese (DIO) mice via the activation of the thermogenic program in brown adipose tissue. Therefore, we wanted to evaluate whether oral linaclotide could also improve DIO mice metabolic phenotype. In this study, we have demonstrated that DIO mice orally treated with linaclotide exhibited a significant reduction of body weight without modifying food intake. Linaclotide exerts its actions through the central nervous system, and more specifically, via Gucy2c receptors located in the mediobasal hypothalamus, leading to the activation of the sympathetic nervous system to trigger the thermogenic activity of brown fat stimulating energy expenditure. These findings indicate for first time that, in addition to its effects at intestinal level to treat irritable bowel syndrome with constipation and chronic constipation, linaclotide also exerts a beneficial effect in whole body metabolism.

Reliability and validity of an FFQ for South American children and adolescents from the SAYCARE study.

OBJECTIVE: The purpose of this study was to analyse the reliability and validity of a semi-quantitative FFQ to assess food group consumption in South American children and adolescents. DESIGN: The SAYCARE (South American Youth/Child cARdiovascular and Environmental) study is an observational, multicentre, feasibility study performed in a sample of 3- to 18-year-old children and adolescents attending private and public schools from six South American countries. Participants answered the FFQ twice with a two-week interval and three 24-h dietary recalls. Intraclass and Spearman's correlations, weighted Cohen's kappa (κw), percentage of agreement and energy-adjusted Pearson's correlation coefficients were calculated. SETTING: Seven cities in South America (Buenos Aires, Lima, Medelin, Montevideo, Santiago, Sao Paulo and Teresina). SUBJECTS: A sample of 200 children and 244 adolescents for reliability analyses and 252 children and 244 adolescents for validity analyses were included. RESULTS: Depending on the food group, for children and adolescents, reliability analyses resulted in Spearman's coefficients from 0·47 to 0·73, intraclass correlation coefficients from 0·66 to 0·99, κw coefficients from 0·35 to 0·63, and percentage of agreement between 72·75 and 83·52 %. In the same way, validity analyses resulted in Spearman's coefficients from 0·17 to 0·37, energy-adjusted Pearson's coefficients from 0·17 to 0·61, κw coefficients from 0·09 to 0·24, and percentages of agreement between 45·79 and 67·06 %. CONCLUSION: The SAYCARE FFQ achieved reasonable reliability and slight-moderate validity for almost all food groups intakes. Accordingly, it can be used for the purpose of ranking the intake of individuals within a population.