Association between a lifestyle score and all-cause mortality: a prospective analysis of the Chilean National Health Survey 2009-2010.

OBJECTIVE: To investigate the association between a lifestyle score and all-cause mortality in the Chilean population. DESIGN: Prospective study. SETTINGS: The score was based on seven modifiable behaviours: salt intake, fruit and vegetable intake, alcohol consumption, sleep duration, smoking, physical activity and sedentary behaviours. 1-point was assigned for each healthy recommendation. Points were summed to create an unweighted score from 0 (less healthy) to 7 (healthiest). According to their score, participants were then classified into: less healthy (0-2 points), moderately healthy (3-4 points) and the healthiest (5-7 points). Associations between the categories of lifestyle score and all-cause mortality were investigated using Cox proportional hazard models adjusted for confounders. Nonlinear associations were also investigated. PARTICIPANTS: 2706 participants from the Chilean National Health Survey 2009-2010. RESULTS: After a median follow-up of 10·9 years, 286 (10·6 %) participants died. In the maximally adjusted model, and compared with the healthiest participants, those less healthy had 2·55 (95 % CI 1·75, 3·71) times higher mortality risk due to any cause. Similar trends were identified for the moderately healthy group. Moreover, there was a significant trend towards increasing the mortality risk when increasing unhealthy behaviours (hazard ratio model 3: 1·61 (95 % CI 1·34, 1·94)). There was no evidence of nonlinearity between the lifestyle score and all-cause mortality. CONCLUSION: Individuals in the less healthy lifestyle category had higher mortality risk than the healthiest group. Therefore, public health strategies should be implemented to promote adherence to a healthy lifestyle across the Chilean population.

Identification of Structural Determinants of the Transport of the Dehydroascorbic Acid Mediated by Glucose Transport GLUT1.

GLUT1 is a facilitative glucose transporter that can transport oxidized vitamin C (i.e., dehydroascorbic acid) and complements the action of reduced vitamin C transporters. To identify the residues involved in human GLUT1's transport of dehydroascorbic acid, we performed docking studies in the 5 Å grid of the glucose-binding cavity of GLUT1. The interactions of the bicyclic hemiacetal form of dehydroascorbic acid with GLUT1 through hydrogen bonds with the -OH group of C3 and C5 were less favorable than the interactions with the sugars transported by GLUT1. The eight most relevant residues in such interactions (i.e., F26, Q161, I164, Q282, Y292, and W412) were mutated to alanine to perform functional studies for dehydroascorbic acid and the glucose analog, 2-deoxiglucose, in Xenopus laevis oocytes. All the mutants decreased the uptake of both substrates to less than 50%. The partial effect of the N317A mutant in transporting dehydroascorbic acid was associated with a 30% decrease in the Vmax compared to the wildtype GLUT1. The results show that both substrates share the eight residues studied in GLUT1, albeit with a differential contribution of N317. Our work, combining docking with functional studies, marks the first to identify structural determinants of oxidized vitamin C's transport via GLUT1.

[Effect of Sedentary behaviors on the Interaction Between the FTO Gene and Adiposity Levels in Chilean Adults - Results from the GENADIO Study]. / Efecto del sedentarismo sobre la interacción entre el gen FTO y niveles de adiposidad en adultos chilenos - Resultados del Estudio GENADIO.

BACKGROUND: The Fat-mass and obesity-associated-gene (FTO gene) and sedentary behavior time are associated with obesity. However, whether sedentary behavior time can modify the genetic predisposition to obesity in the Chilean population is unknown. Therefore, this study investigated the association between sedentary behavior, adiposity markers, and the FTO gene. METHODS: This cross-sectional study included 409 participants from the Genes, Environment, Diabetes, and Obesity (GENADIO) study. Adiposity markers studied included body weight, body mass index (BMI), waist circumference (WC), and fat mass. Sedentary behaviors were measured using accelerometers. Using multiple regression, we evaluated the interaction between sedentary behaviors and the FTO gene (rs9939609) on adiposity markers. RESULTS: Sedentary behaviors and the FTO genotype were positively associated with higher body weight, BMI, WC, and fat mass. However, the association between time of sedentary behavior and adiposity markers was higher in carriers of the risk variant for the FTO gene. For each hour of increment in sedentary behaviors, body weight increases by 1.36 kg ([95% CI: 0.27; 2.46], p = 0.015) and 2.95 kg ([95%CI: 1.24; 4.65], p = 0.001) in non-risk carriers (TT) versus risk carriers (AA), respectively. We observed similar results for WC, BMI, and body fat, but the interaction was significant only for WC. CONCLUSION: The association between sedentary behaviors and adiposity markers, especially body weight and WC, is higher in individuals who carry the risk variant of the FTO gene.

Cell-specific expression of functional glucose transporter 8 in mammary gland.

Differentiated mammary epithelial cells are responsible for milk synthesis during lactation, supporting early postnatal life in mammals. These cells are found in the terminal alveoli of a secretory epithelium, which is surrounded by myoepithelial cells and a stroma rich in fatty tissue. The aim of this study was to explore the cell-specific expression of the glucose transporter GLUT8 in mammary gland and evaluate its functionality for glucose transport, in order to confirm its role in lactose synthesis. Our histological results revealed that GLUT8 is expressed in adipocytes and the epithelial and myoepithelial cells in mammary gland, with a predominant intracellular granular pattern. Colocalization studies of endogenous and green fluorescent protein fused GLUT8 revealed their expressions in lysosome and Golgi, respectively, with Pearson's coefficient correlations of 0.82 ± 0.05 and 0.68 ± 0.16. Functional studies of dileucine to dialanine mutant of GLUT8 showed a fructose-sensitive 2-deoxy glucose uptake at a rate of 83.3 pmoles/(min∗106 cells), 7 folds over empty vector, with a 60 ± 4 and 72 ± 6% decline in 2-deoxy glucose in the presence of 20 and 50 mM fructose, respectively. We concluded that functional GLUT8 is expressed in mammary gland, localizing in mammary epithelial and myoepithelial cells, and adipocytes. In lactation, GLUT8 is expressed mainly in luminal epithelial cells, at the compartments of the endomembrane system. It is necessary to explore the physiological/pathological functions of GLUT8 in mammary gland, including its role in lactation.

Chitosan nanoparticles as a promising tool in nanomedicine with particular emphasis on oncological treatment.

The study describes the current state of knowledge on nanotechnology and its utilization in medicine. The focus in this manuscript was on the properties, usage safety, and potentially valuable applications of chitosan-based nanomaterials. Chitosan nanoparticles have high importance in nanomedicine, biomedical engineering, discovery and development of new drugs. The manuscript reviewed the new studies regarding the use of chitosan-based nanoparticles for creating new release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity of drugs. Nowadays, effective cancer treatment is a global problem, and recent advances in nanomedicine are of great importance. Special attention was put on the application of chitosan nanoparticles in developing new system for anticancer drug delivery. Pre-clinical and clinical studies support the use of chitosan-based nanoparticles in nanomedicine. This manuscript overviews the last progresses regarding the utilization, stability, and bioavailability of drug nanoencapsulation with chitosan and their safety.

[Association of adiposity and diabetes mellitus type 2 by education level in the Chilean population]. / Asociación entre adiposidad y diabetes mellitus tipo 2 según nivel educacional en población chilena: resultados de la Encuesta Nacional de Salud 2016-2017.

BACKGROUND: Adiposity and education are two independent risk factors for type 2 diabetes (T2D). However, there is limited evidence whether both education and adiposity are associated with T2D in an additive manner in the Chilean population. AIM: To investigate the joint association between adiposity and education with T2D in the Chilean adult population. MATERIAL AND METHODS: Analysis of data of the Chilean National Health Survey 2016-2017, which included 5,033 participants with a mean age of 43 years, (51% women). Poisson regression analyses with robust standard error were used to investigate the joint association of the education level and general and central adiposity with T2D. The results were reported as Prevalence Ratio and their 95% confidence intervals (PR, 95% CI). RESULTS: Obesity was associated with a higher probability of having T2D in men than in women, however central adiposity was associated with a higher probability of having T2D in women than in men. Compared with men who had higher education (> 12 years) and had normal body weight, those with the same educational level and who were obese had 2.3-times higher probability of having T2D (PR: 2.35 [95% CI: 1.02; 5.39]). For women, having a low education and being obese was associated with 4.4-times higher probability of having T2D compared to those with higher education and normal body mass index (BMI) (PR: 4.47 [95% IC: 2.12; 9.24]). Similar results were observed when waist circumference was used as a marker of obesity rather than BMI. CONCLUSIONS: Women and men with higher BMI and low education had a higher risk of T2D. However, this risk was higher in women than in men.

[Total sugar consumption and its association with obesity in Chilean adults]. / Consumo de azúcares totales y su asociación con obesidad en población chilena - Resultados del estudio GENADIO.

BACKGROUND: Sugar intake is a risk factor for the development of obesity. AIM: To investigate the association between total sugar intake and obesity markers in Chilean adults. MATERIAL AND METHODS: This cross-sectional study included 396 participants of the GENADIO study. Anthropometric measurements (body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio, and % body fat) were measured through standardized protocols. Total sugar intake was determined from a 7-days weighted food daily. Sugar intake expressed in g/day was categorized into quartiles. RESULTS: Higher sugar intake was associated with a higher BMI, WC and HC but not with body fat %. One quartile increment in sugar intake was associated with 1.50 kg [95% confidence interval (CI): 0.49; 2.50] higher body weight, 0.34 kg/m2 [95% CI: 0.01; 0.69] higher BMI, 1.23 cm [95% CI: 0.11; 2.34] higher WC, 1.39 cm [95% CI: 0.28; 2.50] higher HC and 0.02 the waist-to-hip ratio [95% C: 0.01; 0.02]. CONCLUSIONS: Total sugar intake was associated with higher adiposity levels in these Chilean adults.

[Association between cognitive impairment and depression in Chilean older adults]. / Diagnóstico médico de depresión se asocia a sospecha de deterioro cognitivo en adultos mayores.

BACKGROUND: Depression has been previously associated with cognitive impairment in high income country populations. However, its association in the Chilean population has not been investigated. AIM: To investigate the association between depression and cognitive impairment. MATERIAL AND METHODS: Data from 1384 Chilean adults aged > 60 years, participating in the National Health Survey 2009-2010 was analyzed. Cognitive impairment was assessed using the Mini Mental Examination score. The medical diagnosis of depression was self-reported. The association between depression and cognitive impairment was assessed using a logistic regression. RESULTS: Depression was positively associated with cognitive impairment. However, the magnitude of the association was higher in men (Odds ratio (OR) = 4.02 [95% confidence intervals (CI): 1.44; 6.61], p < 0.01]) than in women (OR = 2.23 [95%CI: 1.03; 3.43], p = 0.04). Older adults who were diagnosed for the first time with depression after 65 years of age, showed a stronger association with cognitive impairment (OR = 6.65 [95% CI: 2.39; 10.9], p < 0.01) than those diagnosed before 55 years. CONCLUSIONS: Our study confirms the association between depression and cognitive impairment. Further research is needed to elucidate the nature and potential mechanisms that link depression with cognitive impairment.

[Association between FTO gene rs9939609 and adiposity markers in Chilean children]. / Asociación entre el polimorfismo rs9939609 del gen FTO y marcadores de adiposidad en población infantil chilena.

INTRODUCTION: Obesity is considered a chronic inflammatory disease with an important genetic component. Although several studies have reported an association between the FTO (fat-mass associated gene) and adiposity in children, there is limited evidence in the Chilean population. OBJECTIVE: To deter mine the association between the polymorphism rs9939609 of the FTO gene and markers of adipo sity in Chilean children. PATIENTS AND METHOD: Cross-sectional study which included 361 children aged between 6 and 11 years (50% were girls). Between March and June 2008, clinical data and blood sample collection was carried out. The rs9939609 single-nucleotide polymorphism (SNP) of the FTO gene, was determined using the genomic DNA extracted from leukocytes, using the QIAamp DNA Blood Mini Kit (Qiagen GmbH, Hilden, Germany).The adiposity markers included were body mass index (BMI), waist circumference (WC), body fat, and WC/H index; which were later compared adjusted by sex, age, and Tanner stage. Linear regression analyses were conducted to detect the association between the polymorphism and obesity markers. RESULTS: After adjusting the models by age, sex, and Tanner stage, we found a significant association between the polymorphism and markers of adiposity. For each extra copy of the risk allele, we found an increase of 2.47 kg body weight (95% CI: 1.39-3.55); 1.06 kg/m2 BMI (95% CI: 0.56-1.54); 2.55 cm WC, (95% CI: 1.26-3.85); and 1.98% body fat (95% CI: 0.78-3.19). When converting adiposity markers to z-score, we found that WC/height index shows the strongest association with the risk allele FTO. CONCLUSION: This study supports the association between the rs9939609 SNP of the FTO gene and overall and central adiposity markers in Chilean children.

[Association of the TCF7L2 (RS7903146) genotype with adiposity and metabolic markers in the Chilean adult population]. / Asociación del polimorfismo rs7903146, del gen TCF7L2, con marcadores de adiposidad y metabólicos en población chilena - resultados del estudio GENADIO.

BACKGROUND: Type 2 diabetes etiology has a strong genetic component. More than 20 genetic variants have been associated with diabetes and other metabolic markers. However, the polymorphism rs7903146 of the TCF7L2 gene has shown the strongest association. AIM: To investigate the association of TCF7L2 (rs7903146) genotype with adiposity and metabolic markers in the Chilean adult population. MATERIAL AND METHODS: The association of TCF7L2 (rs7093146) with adiposity and metabolic markers was studied in 301 participants. The outcomes of the study were adiposity markers (body weight, body mass index (BMI), fat mass and waist circumference) and metabolic markers (blood glucose, insulin, HOMA-IR, lipid profile, high sensitivity C-reactive protein (CRP), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT) and leptin). RESULTS: There was an association between the polymorphism TCF7L2 genotype and fasting blood glucose. The latter increased by 4.86 mg/dl per each copy of the risk allele [(95% confidence intervals (CI): 0.48; 9.24), p = 0.03] in the unadjusted adjusted model. However, this association was slightly attenuated in the fully adjusted model [4.38 mg/dl (95% IC: 0.16; 8.60), p = 0.04)]. There were no associations between the TCF7L2 genotype and any other metabolic or adiposity outcome. CONCLUSIONS: These findings confirm the association between the TCF7L2 (rs7903146) and fasting glucose in the Chilean population. However, further studies are needed to confirm the association between the TCF7L2 and diabetes risk in the Chilean population.

[Association between adiposity and asthma]. / ¿Existe asociación entre asma y adiposidad en la población adulta chilena?

BACKGROUND: In people with asthma, adiposity is associated with more symptoms and less control of the disease whereas on those without asthma adiposity is associated with a higher risk of developing the disease. AIM: To investigate the association between asthma and adiposity markers in Chilean adults. MATERIAL AND METHODS: Data from 5,499 adults older than 15-years-old from the Chilean National Health Survey 20162017 were analyzed. Quintiles of body-mass index (BMI) and waist circumference (WC) were used as a proxy of adiposity. The association between asthma and quintiles of BMI and WC was determined by logistic regression. RESULTS: A higher BMI and WC was associated with a higher odds for asthma. This trend remained significant even after adjusting the models for socio-demographic factors, physical activity and smoking (Odds Ratio [OR] BMI: 1.13 [95% confidence intervals (CI): 1.04; 1.22], p < 0.01 and OR WC: 1.15 [95% IC: 1.06; 1.25], p < 0.01). CONCLUSIONS: A higher BMI and WC were positively associated with asthma.

[Factors associated with cognitive impairment in older adults in Chile]. / Factores asociados al deterioro cognitivo en personas mayores en Chile.

BACKGROUND: The risk factors for the development of cognitive impairment are not well known. AIM: To identify socio-demographic, lifestyle and health-related factors associated with cognitive impairment in older Chilean adults. MATERIAL AND METHODS: Data analysis of 1,384 participants ≥ 60 years who participated in the National Health Survey of Chile 2009-2010. Sociodemographic, lifestyle and health-related factors were used as exposure variables of interest. Cognitive impairment was assessed using an abbreviated version of the Mini Mental test and defined as a score < 13 points of a maximum of 19. A logistic regression was used to identify factors associated with cognitive impairment. RESULTS: In this sample, the prevalence of cognitive impairment was 11.6 [95% confidence intervals (CI): 8.8; 15.2]. The factors associated with cognitive impairment were age (Odds ratio (OR) for > 76 years: 4.89, p < 0.01), male sex (OR: 2.42, p = 0.02), lower education (OR: 21.6, p < 0.01), physical inactivity (OR: 2.07, p = 0.02), sedentary behavior (OR: 2.23, p = 0.01), sleeping > 9/hours/day (OR: 2.98, p = 0.01), consumption of < 5 portions/day of fruit and vegetables (OR: 2.02, p = 0.05), having an unhealthy lifestyle (OR: 6.10, p = 0.0001), being underweight (OR: 3.67, p < 0.01), obesity (OR: 3.32, p = 0.03), having hearing impairment (OR: 2.26, p = 0.02), having a visual impairment (OR: 3.89, p < 0.01), a history of depression (OR: 3.03, p = 0.01) and having a physical disability (OR: 5.63, p < 0.01). CONCLUSIONS: We identified 14 factors associated with cognitive impairment. Although some of these factors were non-modifiable such as age and sex, most of them could be modified by implementing prevention programs aiming to improve lifestyle behaviors in older adults in Chile.

[Association between sleep duration and cognitive impairment in older people]. / ¿Cuál es la asociación entre el tiempo destinado a dormir y el desarrollo de deterioro cognitivo en adultos mayores chilenos?

Background Sleep duration may be a risk factor for cognitive impairment. Aim To investigate the association between sleep duration and cognitive function in Chilean older adults. Material and Methods We analyzed information from 1,384 participants aged > 60 years participating in the National Health Survey 2009-2010 who were assessed with the Mini Mental State Examination (MMSE) and self-reported their average daily sleep hours. Logistic regression analysis was performed to investigate the association between MMSE and sleep duration. Results Compared to those participants who reported sleeping 7 hours per day, those that reported sleeping < 5 hours had a higher odd for cognitive impairment (Odds ratio (OR): 3.66 [95% confidence intervals (CI: 1.69; 7.95], p < 0.01). Similarly, those who reported sleeping > 8 hours per day also showed a higher odd for cognitive impairment (OR: 2.56 [95% CI: 1.32; 4.95], p < 0.01). This association was even stronger for people who reported more than 10 hours of sleep per day (OR: 4.46 [95% CI: 1.32; 4.95], p < 0.01). Conclusions Long and short sleep duration is associated with cognitive impairment in older adults in Chile independent of major confounding factors.

[Physical activity and sedentary behaviours are associated with cognitive impairment in Chilean older adults]. / Actividad física y tiempo sedente se asocian a sospecha de deterioro cognitivo en población adulta mayor chilena.

BACKGROUND: Lifestyle factors could promote healthy ageing. AIM: To investigate the association between physical activity (PA), sedentary behavior and cognitive impairment in Chilean older adults. MATERIAL AND METHODS: We included 1,390 participants from the National Health Survey (2009-2010). The Mini-Mental State Examination was used to diagnose cognitive impairment. Physical activity and sedentary behavior were assessed with the Global Physical Activity Questionnaire (GPAQ). Logistic regression was performed to investigate the associations. RESULTS: Compared with older adults with lower levels of PA (< 48 min/day), those with middle (48-248 min/day) and higher (>248 min/day) levels of PA had lower odds for cognitive impairment (Odds ratio (OR): 0.57 [95% confidence intervals (CI): 0.33; 0.82], p < 0.01 and 0.58 [95% CI: 0.32; 0.83], p < 0.01, respectively). Participants who reported spending more than 8 hours/day sitting had a high odds for cognitive impairment compared to those who spent < 4 hours/day (OR: 3.70 [95% CI: 1.37; 6.03], p = 0.01). CONCLUSIONS: Both PA and sedentary behavior were independently associated with cognitive decline independent of major confounding factors in Chilean older adults.

[Association between FTO (ns9939609) genotype and adiposity markers in Chilean adults]. / Asociación entre el polimorfismo rs9939609 del gen FTO y marcadores de adiposidad en población adulta chilena.

BACKGROUND: Numerous studies have identified the role of Fat-mass-associated-gene (FTO) in the development of obesity. AIM: To investigate the association of FTO gene with adiposity markers in Chilean adults. MATERIAL AND METHODS: 409 participants were included in this cross-sectional study. The association between FTO (rs9939609) genotype and adiposity markers was determined using linear regression analyses. Adiposity markers included were: body weight, body mass index, fat mass, waist circumference, hip circumference and waist/hip ratio. RESULTS: A fully adjusted model showed a significant association between FTO genotype and body weight (2.16 kg per each extra copy of the risk allele [95% confidence intervals (CI): 0.45 to 3.87], p = 0.014), body mass index (0.61 kg.m-2 [95% CI: 0.12 to 1.20], p = 0.050) and fat mass (1.14% [95% CI: 0.39 to 1.89], p = 0.010). The greater magnitude of association was found between the FTO gene and fat mass when the outcomes were standardized to z-score. CONCLUSIONS: This study confirms an association between the FTO gene and adiposity markers in Chilean adults, which is independent of major confounding factors.

[Effect of a high-fat diet on cholesterol gallstone formation]. / Efecto de una dieta alta en grasas en el proceso de formación de cálculos biliares de colesterol.

BACKGROUND: It is known that some nutrients play an important role in the development of cholelithiasis. Cholesterol is carried by micelles and vesicles in the bile. During the first stage of gallstone formation, cholesterol crystals derive from thermodynamically unstable vesicles. AIM: To determine the effect of a high fat diet on blood lipids and bile composition, and its implication in the formation of gallstones. MATERIAL AND METHODS: Two groups of 15 BALB/c mice each, coming from the same litter, were treated with a control or with a high-fat diet (64% fat and 0.14% cholesterol). After two months, the animals were sacrificed, blood and bile samples were obtained. Serum glucose and the corresponding lipid profiles were measured. In bile samples, cholesterol and phospholipid levels were analyzed, and cholesterol transporters (vesicles and micelles) were separated by gel filtration chromatography. RESULTS: Treated animals showed an 87% increase in serum total cholesterol (p < 0.01), a 97% increase in HDL-cholesterol (p < 0.05) and a 140% increase in LDL-cholesterol (p < 0.05). No changes in serum triglycerides or glucose were observed. In bile, a 13% increase in biliary cholesterol (p < 0.05) was observed but no change in biliary phospholipids. Also, an increase in biliary vesicular transporters and an increase of cholesterol/phospholipid ratio in vesicular transporters were observed. CONCLUSIONS: A high fat diet may contribute to the formation of gallstones in our experimental model.

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells.

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells.