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El ejercicio docente ha permitido detectar falencias en cuanto al aprendizaje de fracciones, y todos los ejercicios numéricos que la componen; por lo que se propone el desarrollo de una guía didáctica para la enseñanza de este tema por medio del uso de la plataforma Moodle Cloud y metodologías de la gamificación. De esta manera, se busca mejorar la percepción de los conocimientos por parte de los estudiantes a través del cambio en la aproximación metodológica, ya que el uso de herramientas digitales permite al cuerpo docente la experimentación e innovación desde lo pedagógico y procedimental. En ese sentido, Moodle Cloud permite una integración de recursos que pueden ser utilizados para incidir en la percepción dinámica de esta rama de operaciones matemáticas.

Acknowledgments: These results would not have been achieved without the selfless collaboration of the staff from Santa Ana and San Cecilio Hospitals and the participants who took part in the study. Juan Pedro Arrebola is under contract within the Ramón y Cajal Program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain)., To identify bioaccumulation patterns of α-, β- hexachlorocyclohexane (HCH) and dicofol in relation to sociodemographic, dietary, and lifestyle factors, adipose tissue samples of 387 subjects from GraMo cohort in Southern Spain were analyzed. Potential predictors of these organochlorine pesticides (OCP) levels were collected by face-to-face interviews and assessed by multivariable linear and logistic regression. OCPs were detected in 84.2% (β-HCH), 21.7% (α-HCH), and 19.6% (dicofol) of the population. β-HCH levels were positively related to age, body mass index (BMI), mother’s occupation in agriculture during pregnancy, living in Poniente and Alpujarras, white fish, milk and water consumption, and negatively related to being male, living near to an agricultural area, working ≥10 years in agriculture, and beer consumption. Detectable α-HCH levels were positively related to age, BMI, milk consumption, mother’s occupation in agriculture during pregnancy, and negatively with residence in Poniente and Alpujarras, Granada city, and Granada Metropolitan Area. Residence near to an agricultural area, smoking habit, white fish and water consumption, and living in Poniente and Alpujarras, Granada city and Granada Metropolitan Area were negatively associated with detectable dicofol levels. Our study revealed different bioaccumulation patterns of α, β-HCH and dicofol, probably due to their dissimilar period of use, and emphasize the need for assessing the exposure to frequently overlooked pollutants., CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III PI16/01858, PI18/01573, PI20/01568, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España

This study was supported by research grants from CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Spain (PI16/01858, PI18/01573, PI20/01568), co-funded by European Union (ERDF), "A way to make Europe"., Supplementary data to this article can be found online at https://doi. org/10.1016/j.envint.2021.106734, Background Despite restrictions on their production and use, most of the population is still exposed to Persistent Organic Pollutants (POPs), including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). These chemicals are thought to contribute to the aetiology of highly prevalent chronic conditions, such as cardiovascular diseases (CVDs), although current evidences are still controversial. Objectives To explore the potential contribution of historical POP exposure to 15-year pharmaceutical consumption in relation to CVD. Methods This study is framed within GraMo adult cohort. Participants (n = 387) were recruited in two hospitals in Granada province, Southern Spain (2003–2004). Historical exposure to 5 OCPs and 3 non-dioxine-like PCBs was estimated by analysing adipose tissue concentrations at recruitment. Pharmaceutical consumption from recruitment until year 2017 was quantified by reviewing dispensation databases. Average consumption increase (ACI) in CVD medication was calculated by subtracting average consumption in 2002 to the average yearly consumption during follow-up. ACI was expressed as Defined Daily Dose (DDD)/year units. Data analyses were carried out using a multivariable multinomial logistic regression and weighted quantile sum regression (WQS), with ACI categorized in quartiles (Q) as the dependent variable. Results Concentrations of most pollutants showed a positive trend with the quartiles of ACI. Particularly, PCB-153 showed increasing and statistically significant odds ratios (ORs) for Q2 (OR: 1.27, 95% confidence interval (CI): 1.07–1.52), Q3 (OR: 1.49, 95 %CI: 1.17–1.88) and Q4 (OR: 1.42, 95 %CI: 1.13–1.78) vs Q1. Similarly, beta-hexachlorocyclohexane (β-HCH) also showed increasing ORs, that reached statistical significance in Q4 (OR: 1.36, 95 %CI: 1.06–1.74) vs Q1. These findings were corroborated by WQS analyses, that revealed a significant mixture effect, predominantly accounted for by PCB-153 and β-HCH. Discussion Our results suggest that long-term POP exposure might represent a modifiable risk factor for CVD. These findings are relevant for public health campaigns and management, since pharmaceutical consumption is considered an indicator of both morbidity and health expenditure., CIBER de Epidemiología y Salud Pública, Santa Ana and San Cecilio Hospitals RYC-2016-20155, European Commission, Instituto de Salud Carlos III PI16/01858, PI18/01573, PI20/01568 ISCIII Ministerio de Economía, Industria y Competitividad, Gobierno de España, European Regional Development Fund, Ministerio de Economía, Industria y Competitividad, Gobierno de España

Adipose tissue has been recently highlighted as a promising matrix for evaluation of cadmium's (Cd) long-term exposure although not frequently considered in epidemiological studies. The association between Cd exposure and type 2 Diabetes Mellitus (T2DM) remains unclear. This work aimed to explore the association between adipose tissue Cd levels and T2DM incidence over a 16-year follow-up in an adult cohort from Southern Spain considering smoking status. We also performed complementary cross-sectional analyses focused on subclinical markers of glucose homeostasis at recruitment. Clinical information was obtained from hospital databases. Socio-demographic characteristics, lifestyle and diet were collected by face-to-face interviews. Homeostatic model assessment (HOMA) values of insulin sensitivity/resistance and β-cell function were calculated using fasting serum glucose, insulin, and C-peptide levels at recruitment. Adipose tissue Cd concentrations were quantified by inductively coupled plasma mass spectrometry. Statistical analyses were performed by means of Cox-regression and multivariable linear regression models. Participants in the 4th quartile (Q4) of Cd concentrations showed a non statistically-significant increased T2DM risk (Hazard Ratio (HR) Q4 vs Q1: 1.97; 95% Confidence Interval (CI): 0.69, 5.66). This association was particularly strong and suggestive in current smokers (HR: 2.19; 95% CI: 0.98, 4.98). Interestingly, smokers in the 2nd tertile (T2) of adipose tissue Cd levels showed increased log-transformed insulin resistance (beta T2 vs T1: 0.52; 95% CI: 0.07, 0.97), as well as higher log-transformed insulin levels (beta T2 vs T1: 0.52; 95% CI: 0.08, 0.95). We found evidences supporting that Cd exposure, particularly from tobacco smoking, could be a risk factor for T2DM. In addition, our results support the potential relevance of adipose tissue as a matrix for Cd exposure assessment.

The assessment of the health implications of human exposure to low doses of multiple environmental chemical pollutants represents an important challenge for environmental epidemiology. Current studies must go beyond simple exposure-disease associations and need further characterization of a complete exposure disease continuum, including exposure routes, adverse outcome pathways, potential subclinical effects, interactions between chemicals, and intra-individual susceptibility. This needs an effective synergism with basic sciences, which can enrich epidemiologic findings with very detailed information at a molecular level, but also with clinicians, who would help to provide accurate diagnoses and interpretation in a real-world scenario. On the other hand, environmental exposures can affect the general population at different levels, including economic and social dimensions, which have been frequently overlooked. These approaches would require specific methodologies that are relatively novel in the field of environmental epidemiology, such as cost-benefit analyses and qualitative techniques. Public health campaigns can clearly benefit from these mixed approaches.

Background: Adipose tissue has been acknowledged as a potential target of obesogenic pollutants, including metals. However, the presence of these chemicals in the adipose tissue has been poorly characterized. Assessment of adipose tissue metal content may provide valuable information for the study of metabolic disturbances related to human exposure to metals. Objective: To examine the distributions of adipose tissue concentrations of five toxic metals (i.e., arsenic [As], nickel [Ni], lead [Pb], tin [Sn], and titanium [Ti]) in adults, and potential socio- demographic and lifestyle factors associated with metal concentrations. Methods: The study population consisted of a subsample of 228 subjects from GraMo cohort in Southern Spain (N=387). Adipose tissue samples were intra- operatively collected from adults recruited in 2003-2004 in two public hospitals, and concentrations of metals in adipose tissue were analyzed in 2015 by High-Resolution Inductively Coupled Plasma Mass Spectrometry. Data on socio-demographic and lifestyle factors were obtained by baseline questionnaire completion. Linear and multinomial regression was used to identify factors associated with metal levels. Results: Ni, Pb, Sn, and Ti were detected in all adipose tissue samples, and As in 51%. Ni was the metal showing the highest median concentration (0.56 µg/g), followed by Ti (0.31 µg/g), Pb (0.08 µg/g), Sn (0.06 µg/g), and As (0.003 µg/g). Predictors of As levels included area of residence, social class, and oily fish intake ; for Ni: area of residence and consumption of cheese, meat, eggs, and canned food ; for Pb: vegetables intake and industrial occupation ; for Sn: age, body mass index, and consumption of lean fish, eggs, and milk ; and cheese intake for Ti. Some of these predictors were sex-specific, particularly those regarding dietary intake. Conclusions: This exploratory study provides the first evidence of the wide occurrence of Ni, Pb, Sn, Ti, and As in adipose tissue from adult population, and highlights the potential of this tissue as a biological matrix for studying exposure levels and chronic health effects of toxic metals.

This study was conceived as a first step to evaluate the suitability of adipose tissue cadmium (Cd) concentrations as a biomarker for the assessment of long-term exposure. Specifically, the aim of this work was to explore the socio-demographic, dietary, and lifestyle determinants of adipose tissue Cd concentrations. The study population is a subsample of GraMo cohort. Adipose tissue samples were intraoperatively collected from 226 adult volunteers recruited in two public hospitals from Granada, Spain. Cd concentrations in adipose tissue were analyzed by High-Resolution Inductively Coupled Plasma Mass Spectrometry (HR-ICP-MS). Data on socio-demographic characteristics, lifestyle, diet and health status were collected by face-to-face interviews. Predictors of Cd concentrations were assessed by multivariable linear regression with a stepwise variable selection. We found detectable levels of Cd in the adipose tissue of all the study participants, with a mean concentration (±standard deviation) of 12.66 ± 18.91 μg/kg. Smoking habit at recruitment was associated with increased adipose tissue Cd concentrations (β for smokers = 0.669 p 0.001; β for former smokers = 0.502, p 0.001; reference = non-smokers). Age was positively associated with Cd concentrations (β = 0.014, p 0.001), and men showed lower concentrations than women (β = -0.424, p 0.001). Obesity, measured as Body Mass Index (BMI), showed an inverse association with Cd concentrations (β = -0.038, p 0.001). Egg consumption ≥2 portions/week (β = 0.241, p = 0.025) was positively associated with Cd concentrations. Perceived exposure to paints was also positively associated with Cd concentrations. The observed associations with age, smoking habit, BMI, and egg and meat consumption did not substantially change after sex/gender stratification. Our results are consistent with currently-known Cd sources and suggest other potential pathways, which might be population-specific. As a whole, our findings underline the potential relevance of adipose tissue as a biological matrix for exposure characterization to Cd, as well as for the assessment of long-term clinical implications of the exposure, particularly in obesity-related diseases.