The first genome-wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease.

INTRODUCTION: Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS: We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS: We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio  = 2.93 [2.37-3.63], P = 2.6 × 10-23 ). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. DISCUSSION: We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. HIGHLIGHTS: This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values.

A 12-week evaluation of annatto tocotrienol supplementation for postmenopausal women: safety, quality of life, body composition, physical activity, and nutrient intake.

BACKGROUND: Evidence suggests that tocotrienols may benefit bone health in osteopenic women. However, their safety in this population has never been investigated. This study was to evaluate the safety of a 12-week supplementation of annato tocotrienol in postmenopausal osteopenic women, along with effects of the supplementation on quality of life, body composition, physical activity, and nutrient intake in this population. METHODS: Eighty nine postmenopausal osteopenic women were randomly assigned to 3 treatment arms: (1) Placebo (430 mg olive oil/day), (2) Low tocotrientol (Low TT) (430 mg tocotrienol/day from DeltaGold 70 containing 300 mg tocotrienol) and (3) High tocotrienol (High TT) (860 mg tocotrienol/day from DeltaGold 70 containing 600 mg tocotrienol) for 12 weeks. DeltaGold 70 is an extract from annatto seed with 70% tocotrienol consisting of 90% delta-tocotrienol and 10% gamma-tocotrienol. Safety was examined by assessing liver enzymes (aspartate aminotransferase, alanine aminotransferase), alkaline phosphatase, bilirubin, kidney function (blood urea nitrogen and creatinine), electrolytes, glucose, protein, albumin, and globulin at 0, 6, and 12 weeks. Serum tocotrienol and tocopherol concentrations were assessed and pills counted at 0, 6, and 12 weeks. Quality of life, body composition, physical activity, and dietary macro- and micro-nutrient intake were evaluated at 0 and 12 weeks. A mixed model of repeated measures ANOVA was applied for analysis. RESULTS: Eighty seven subjects completed the study. Tocotrienol supplementation did not affect liver or kidney function parameters throughout the study. No adverse event due to treatments was reported by the participants. Tocotrienol supplementation for 6 weeks significantly increased serum delta-tocotrienol level and this high concentration was sustained to the end of study. There was no difference in serum delta-tocotrienol levels between the Low TT and the High TT groups. No effects of tocotrienol supplementation were observed on quality of life, body composition, physical activity, and nutrient intake. CONCLUSIONS: Annatto-derived tocotrienol up to 600 mg per day for 12 weeks appeared to be safe in postmenopausal osteopenic women, particularly in terms of liver and kidney functions. Tocotrienol supplementation for 12 weeks did not affect body composition, physical activity, quality of life, or intake of macro- and micro-nutrients in these subjects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02058420 . TITLE: Tocotrienols and bone health of postmenopausal women.

An insight into the role of magnesium in the immunomodulatory properties of mesenchymal stem cells.

Magnesium (Mg2+) is a mineral with the ability to influence cell proliferation and to modulate inflammatory/immune responses, due to its anti-inflammatory properties. In addition, mesenchymal stem cells (MSCs) modulate the function of all major immune cell populations. Knowing that, the current work aimed to investigate the effects of Mg2+ enrichment, and its influence on the immunomodulatory capacity of MSCs. Murine C3H/10T1/2 MSCs were cultivated in media with different concentrations of Mg2+ (0, 1, 3 and 5 mM), in order to evaluate the effects of Mg2+ on MSC immunomodulatory properties, cell proliferation rates, expression of NFκB and STAT-3, production of IL-1ß, IL-6, TGF-ß, IL-10, PGE2 and NO, and TRPM7 expression. The results showed that TRPM7 is expressed in MSCs, but Mg2+, in the way that cells were cultivated, did not affect TRPM7 expression. Additionally, there was no difference in the intracellular concentration of Mg2+. Mg2+, especially at 5 mM, raised proliferation rates of MSCs, and modulated immune responses by decreasing levels of IL-1ß and IL-6, and by increasing levels of IL-10 and PGE2 in cells stimulated with LPS or TNF-α. In addition, MSCs cultured in 5 mM Mg2+ expressed lower levels of pNFκB/NFκB and higher levels of pSTAT-3/STAT-3. Furthermore, conditioned media from MSCs reduced lymphocyte and macrophage proliferation, but Mg2+ did not affect this parameter. In addition, conditioned media from MSCs cultured at 5 mM of Mg2+ modulated the production profile of cytokines, especially of IL-1ß and IL-6 in macrophages. In conclusion, Mg2+ is able to modulate some immunoregulatory properties of MSCs.

Effects of consumption of mauritia flexuosa fruits on renal and hepatic functions in growing rats

INTRODUCTION: Previous studies have reported that buriti (Mauritia flexuosa L. f.) is a typical fruit from the Brazilian cerrado ecosystem and an important food source for low-income populations. Its composition is rich in carotenoid polyphenols, monounsaturated fatty acids, and ascorbic acid. However, studies on the biological effects resulting from the consumption of this fruit are scarce. OBJECTIVE: To evaluate the effects of a diet supplemented with buriti (Mauritia flexuosa L. f.) on kidney and liver functions in growing rats. METHODS: Determination of centesimal composition, carotenoids, and fatty acids content for buriti pulp, standard chow, and butiti-supplemented chow were performed. Then, Wistar rats of both sexes were fed a standard diet or supplemented with buriti pulp. Blood samples were collected at the end of the experiment to determine biochemical parameters. The unpaired t-test was applied, and differences were considered significant when p<0.05. RESULTS: A diet enriched with buriti pulp did not interfere with kidney function and most markers of liver function in animals. Alkaline phosphatase showed significantly higher plasma concentration in female rats, and albumin and uric acid showed lower concentrations in male rats in both experimental groups. CONCLUSION: The changes observed in biochemical markers did not provide evidence of adverse effects of buriti pulp supplementation on liver function. Thus, the intake of buriti pulp can be encouraged as it is a low-cost food source for the general population.

IN VITRO AND IN VIVO ANTIOXIDANT ACTIVITY OF BURITI FRUIT (MAURITIA FLEXUOSA L.F.).

INTRODUCTION: studies have shown high concentration of monounsaturated fatty acids, carotenoids, polyphenols and ascorbic acid in Buriti fruit (Mauritia flexuosa L.f.). This study evaluated the in vitro and in vivo antioxidant activities of buriti fruit (Mauritia flexuosa L.f.). METHODS: the chemical composition and total phenolic and carotenoid contents of the buriti pulp and the feed rations were determined, and the in vitro antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay. Wistar rats (21 days old) were randomly allocated (n=10) into a control groups and experimental groups (feed enriched with buriti pulp). After 60 days, the in vivo antioxidant activity was evaluated through the determination of the catalase activity and non-protein sulfhydryl (NPSH) groups in the liver and quantification of malondialdehyde (MDA) in the plasma and tissues. RESULTS: high contents of oleic fatty acids (73.3%), phenolic compounds (192 ± 0.3 mg/100 g) and carotenoids (23.9 ± 0.5 mg/100 g) as well as elevated in vitro antioxidant activity were found in the buriti pulp. The enriched diet had higher contents of phenols and carotenoids as well as higher antioxidant activity compared with the standard feed (p < 0.05). There were no differences between the groups regarding catalase activity in the liver and MDA concentrations in the plasma, liver and kidneys. The male rats of the experimental group had higher liver concentrations of NPSH compounds (p < 0.05). CONCLUSION: these results may corroborate the claim that buriti fruit is an antioxidant functional food and support its utilization in a nutritionally balanced diet.

Introducción: estudios previos han demostrado que la fruta Burití (Mauritia flexuosa L.f). posee una alta concentración de ácidos grasos monoinsaturados, carotenoides, polifenoles y ácido ascórbico. Este estudio evaluó la actividad antioxidante in vitro e in vivo del Burití. Métodos: fueron determinadas la composición química, el contenido de compuestos fenólicos y de carotenoides tanto de la pulpa del Burití como de las raciones de alimento. La actividad antioxidante in vitro fue analizada utilizando el ensayo del radical 2,2-difenil-1-picrilhidrazil (DPPH). Ratas Wistar (21 días de edad) fueron asignadas al azar (n = 10) en grupos controles y grupos experimentales (alimentación enriquecida con pulpa de Burití). Después de 60 días, la actividad antioxidante in vivo se evaluó mediante la actividad enzimática de la catalasa y grupos sulfhidrílo no proteico (NPSH) en el hígado, y se cuantificó el malondialdehído (MDA) en plasma y tejidos. Resultados: la pulpa del Burití presentó alto contenido de ácido graso oleico (73,3%), compuestos fenólicos (192 ± 0,3 mg/100 g) y carotenoides (23,9 ± 0,5 mg/100 g), así como una elevada actividad antioxidante in vitro. La dieta enriquecida tenía mayor contenido de fenoles y carotenoides, y una mayor actividad antioxidante en comparación con la alimentación estándar (p < 0,05). No se observaron diferencias entre los grupos con respecto a la actividad de la catalasa en el hígado y las concentraciones de MDA en plasma, hígado y riñones. Las ratas macho del grupo experimental tuvieron concentraciones hepáticas más altas de NPSH (p < 0,05). Conclusión: estos resultados pueden corroborar la hipótesis de que la fruta Burití es un alimento funcional antioxidante y su consumo es conveniente en una dieta nutricionalmente equilibrada.

Magnesium Status and Its Relationship with C-Reactive Protein in Obese Women.

This study assessed the relationship between magnesium status and C-reactive protein concentration in obese and nonobese women. This cross-sectional study included 131 women, aged between 20 and 50 years, who were divided into two groups: obese (n=65) and control (n=66) groups. Magnesium intake was monitored using 3-day food records and NutWin software version 1.5. The plasma, erythrocyte, and urinary magnesium concentrations were determined by flame atomic absorption spectrophotometry. C-reactive protein concentration in serum was measured by immunoturbidimetric assay. The mean values of the magnesium content in the diet were lower than those recommended, though there was no significant difference between groups (p>0.05). The mean concentrations of plasma and erythrocyte magnesium were within the normal range, with no significant difference between groups (p>0.05). Urinary excretion of this mineral was less than the reference values in both groups, with no significant difference (p>0.05). The mean concentration of serum C-reactive protein was within the normal range in both groups, with no significant difference (p>0.05). There was a positive correlation between urinary magnesium and serum C-reactive protein (p=0.015). Obese patients ingest low dietary magnesium content, which seems to induce hypomagnesuria as a compensatory mechanism to keep plasma concentrations of the mineral at adequate levels. The study shows a positive correlation between urinary magnesium concentrations and serum C-reactive protein, suggesting the influence of hypomagnesuria on this inflammatory protein in obese women.

Mg status in inflammation, insulin resistance, and associated conditions

Magnesium (Mg), an essential ion for the human body, is involved in various enzymatic reactions, particularly those related to energy transfer, storage, and transport. Longitudinal studies show that hypomagnesaemia (Mg serum concentration <0.75 mmol/L) and Mg dietary inadequacy (daily intake < EAR (Estimated Average Requirement) for age/gender) are conditions related to metabolic disorders of the immune and cardiovascular system and often occur in obese and diabetic individuals. Poor eating habits, reduced Mg content in food and water are the main causes of the decrease in Mg intake by the general population. In clinical practice, the serum concentration of this mineral is the most widely used marker for diagnosing deficiency. However, the serum concentration does not reflect the nutritional Mg status since it can be maintained by mobilization of body storage, mainly the bone. Thus, the use of serum concentration as the only routine biomarker of Mg status may hinder the diagnosis of Mg deficiency. In clinical and experimental research, different methods for Mg status assessment are proposed (plasma, erythrocyte, urine), but they are seldom used in clinical routine. In some countries (such as USA and Brazil) the average daily Mg dietary ingestion of more than 60% of the adult population is lower than the Estimated Average Requirement for age and gender, and these data are not too different for individuals with chronic non-communicable diseases. It is unclear whether it is an actual reduction of Mg consumption or if the recommendations are overestimated. If we assume that the recommendations are correct, the question is if this condition constitutes a risk factor for chronic diseases or the hypomagnesemia described in some diseases is a consequence of physiopathological changes. This review has the latest information of human and animal studies about Mg status evaluated from plasma, erythrocyte and urine, dietary inadequacy, and its relation to inflammation and to components of metabolic syndrome.

A formação do profissional nutricionista na percepção do docente / Professional nutritionists education from the perception of the teacher / La formación del profesional nutricionista en la percepción del docente

Este estudo avaliou a formação do profissional de nutrição na percepção dos docentes nutricionistas de uma instituição de Ensino Superior do nordeste brasileiro. Trata-se de pesquisa qualitativa realizada com vinte professores nutricionistas que ministraram disciplinas do ciclo profissional no período de 1980 a 2008. A principal limitação foi a deficiência de infraestrutura física, de material e de equipamentos, sobretudo para a realização de aulas práticas. Limitações relacionadas à atividade docente e ao conhecimento adquirido pelos estudantes foram mencionadas. Apesar das dificuldades apontadas, melhorias estruturais foram referidas. Adequações adicionais são necessárias na infraestrutura, bem como medidas voltadas para melhor planejamento do trabalho docente e para conscientização do corpo discente do seu papel no processo ensino-aprendizagem, possibilitando a formação de profissionais mais capacitados para o mercado de trabalho.

This study evaluated the nutrition professionals education from the perception of nutrition teachers at a higher education institution in northeastern Brazil. This was a qualitative study among twenty nutrition teachers who were giving classes within disciplines in the professional cycle between 1980 and 2008. The main limitations faced were deficiencies in physical infrastructure, material and equipment, especially for conducting practical classes. Limitations relating to teaching activities and the knowledge acquired by students were mentioned. In spite of the difficulties, structural improvements were reported. Additional adjustments to infrastructure are required, along with measures aimed at better planning of teaching work and greater awareness among students regarding their role in the teaching-learning process, thereby enabling the education of professionals who are better qualified for the labor market.

Este estudio evaluó la formación del profesional de nutrición en la percepción de los docentes nutricionistas de una institución de Enseñanza Superior del nordeste brasileño. Se trata de encuesta cualitativa realizada con veinte profesores nutricionistas que dictaran asignaturas del ciclo de profesionalización en el período de 1980 a 2008. La principal limitación fue la deficiencia de infraestructura física, de material y de equipos, principalmente para la realización de clases prácticas. Se mencionaron las limitaciones relacionadas con la actividad docente y con el conocimiento adquirido por los estudiantes. A pesar de las dificultades señaladas, se refirieron mejoras estructurales. Son necesarias adecuaciones adicionales en la infraestructura, así como medidas enfocadas en una mejor planificación del trabajo docente y para la toma de conciencia del cuerpo discente de su papel en el proceso enseñanza-aprendizaje, posibilitando la formación de profesionales más capacitados para el mercado de trabajo.

Restrição dietética de magnésio associada à dieta hiperlipídica: implicações sobre a homeostase do mineral e sensibilidade à insulina / Dietary magnesium restriction associated with a high-fat diet: implications on mineral homeostasis and insulin sensitivity

A resistência dos tecidos à ação da insulina é uma das principais complicações do excesso de peso. O aumento da gordura corporal, decorrente do consumo excessivo de nutrientes, é acompanhado por um quadro de inflamação crônica de baixa intensidade que está relacionado com a fisiopatologia da resistência à insulina. O magnésio (Mg) é um mineral envolvido com diversos processos fisiológicos e bioquímicos, especialmente aqueles relacionados ao metabolismo energético e ao controle glicêmico. Apesar de a deficiência deste mineral estar relacionada com condições pré-diabéticas, não está claro se a inadequação dietética promove alterações na sensibilidade à insulina e/ou se condições de resistência à insulina causam distúrbios na homeostase de Mg. O objetivo deste trabalho foi investigar os efeitos da restrição dietética de Mg e sua associação com o excesso de lipídios sobre a homeostase do mineral e a sensibilidade à insulina. Ratos Wistar, machos, com peso entre 97-123 g, permaneceram em gaiolas individuais por 24 semanas. Os animais receberam rações normolipídicas (CON, 7% de lipídios) ou hiperlipídicas (HL, 32% de lipídios), adequadas (CON e HL Mg; 500 mg de Mg/kg de ração; n = 6 para cada grupo) ou com restrição de Mg (Mg[50] e HL Mg[50]; 50 mg de Mg/kg de ração; n = 6 para cada grupo). O consumo da dieta HL promoveu maior acúmulo de tecido adiposo e maior ganho de peso corporal (p < 0,05). Os animais que consumiram rações com restrição de Mg apresentaram hipomagnesemia (p<0,01), menor excreção urinária (p < 0,01) e fecal (p < 0,001) de Mg e menor concentração óssea desse mineral (p < 0,001). No entanto, não foram observadas alterações no Mg muscular (p > 0,05). O grupo HL Mg[50] apresentou maior concentração de Mg no eritrócito quando comparado aos outros grupos. A restrição dietética de Mg, isoladamente, não promoveu alterações na sensibilidade à insulina (avaliada pelo teste de tolerância à insulina). Quando associada à dieta hiperlipídica, resultou em aumento da glicemia de jejum e em redução da sensibilidade à insulina, após 16 semanas (p < 0,01). Em nível molecular, a fosforilação da proteína quinase B (Akt) no músculo e no fígado foi significantemente menor no grupo HL Mg[50] (p < 0,05). A restrição dietética de Mg induziu ao aumento do conteúdo proteico dos canais TRPM6 e TRPM7 no rim, independentemente da sensibilidade à insulina. Os resultados deste estudo apontam que a deficiência de Mg tende a agravar as repercussões metabólicas do consumo de dietas hiperlipídicas na sensibilidade à insulina e que a resistência à insulina altera a compartimentalização do Mg

Insulin resistance is one of the main complications of overweight. Increase body fat, due to excessive consumption of nutrients is accompanied by a chronic low-grade inflammation related to insulin resistance pathophysiology. Magnesium (Mg) is a mineral involved in many physiological and biochemical processes, especially those related to energy metabolism and glycemic control. Although Mg deficiency is related to pre-diabetic conditions, it is unclear whether dietary inadequacy promotes changes in insulin sensitivity and/or if conditions of insulin resistance cause disturbances in Mg homeostasis. This work aimed to investigate the effects of dietary Mg restriction and its association with high-fat diet on mineral homeostasis and insulin sensitivity. Male Wistar rat (97-123 g) remained in individual cages for 24 weeks. Animals received normolipid diet (CON, 7% lipid) or high-fat diet (HF, 32% lipid), adequate (CON and HF, 500 mg Mg / kg diet, n = 6 for each group) or Mg restricted (Mg[50] and HF Mg[50], 50 mg of Mg / kg of diet, n = 6 for each group). High-fat diet promoted a greater adipose tissue excess and body weight gain (p<0.05). Animals with Mg restricted diet had hypomagnesemia (p<0.01), lower Mg urinary (p<0.01) and faecal loss (p<0.001) and lower bone Mg concentration (p<0.001). However, no changes were observed in muscle Mg (p>0.05). HF Mg[50] group presented higher concentration of erythrocyte Mg when compared to the other groups. Singly, dietary Mg restriction did not induce changes in insulin sensitivity (as assessed by the insulin tolerance test). When associated with high-fat diet, dietary Mg restriction resulted in higher fasting glycemia and lower insulin sensitivity after 16 weeks (p<0.01). At the molecular level, protein kinase B (Akt) phosphorylation in muscle and liver was significantly lower in HFMg [50] group (p<0.05). Dietary Mg restriction induced increased protein content of renal TRPM6 and TRPM7 channels, regardless of insulin sensitivity. The results of this study indicate that Mg deficiency worsens metabolic effects of high-fat diet on insulin sensitivity. In addition, insulin resistance changes Mg compartmentalization