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Gene-environment interaction studies are emerging as a promising tool to shed light on the reasons for the rapid increase in excess body weight (overweight and obesity). We aimed to investigate the influence of several polymorphisms on excess weight in Spanish children according to a short- and long-term exposure to bisphenols and parabens, combining individual approach with the joint effect of them. This case-control study included 144 controls and 98 cases children aged 3-12 years. Thirty SNPs in genes involved in obesity-related pathways, xenobiotic metabolism and hormone systems were genotyped using the GSA microchip technology and qPCRs with Taqman® probes. Levels of bisphenols and parabens in urine and hair were used to assess short- and long-term exposure, respectively, via UHPLC-MS/MS system. LEPR rs9436303 was identified as a relevant risk variant for excess weight (OR Dom:AAvsAG+GG =2.65, p<0.001), and this effect persisted across exposure-stratified models. For long-term exposure, GPX1 rs1050450 was associated with increased excess weight at low single paraben exposure (OR GvsA =2.00, p=0.028, p-interaction=0.016), whereas LEPR rs1137101 exhibited a protective function at high co-exposure (OR Dom:AAvsAG+GG =0.17, p=0.007, p-interaction=0.043). ESR2 rs3020450 (OR Dom:GGvsAG+AA =5.17, p=0.020, p-interaction=0.028) and CYP2C19 rs4244285 (OR Dom:GGvsAG+AA =3.54, p=0.039, p-interaction=0.285) were identified as predisposing variants at low and high co-exposure, respectively. In short-term exposure, higher odds were observed for INSIG2 rs7566605 at high bisphenol exposure (OR CvsG =2.97, p=0.035, p-interaction=0.017) and for GSTP1 rs1695 at low levels (OR Dom:AAvsAG+GG =5.38, p=0.016, p-interaction=0.016). At low and medium co-exposure, SH2B1 rs7498665 (OR AvsG =0.17, p=0.015, p-interaction=0.085) and MC4R rs17782313 (OR AvsG =0.10, p=0.023, p-interaction=0.045) displayed a protective effect, whereas ESR2 rs3020450 maintained its contributing role (OR GvsA =3.12, p=0.030, p-interaction=0.010). Our findings demonstrate for the first time that understanding the genetic variation in excess weight and how the level of exposure to bisphenols and parabens might interact with it, is crucial for a more in-depth comprehension of the complex polygenic and multifactorial aetiology of overweight and obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Over the past three decades, there has been a significant increase in the prevalence and incidence of overweight and obesity worldwide. The obesogen hypothesis suggests that certain external agents may affect pathways related to fat accumulation and energy balance by stimulating fat cell differentiation and proliferation. Previous research has indicated that exposure to bisphenol A (BPA) and some of its analogues may influence fat accumulation by promoting the transformation of preadipocytes into adipocytes. This study aimed to assess the possible contribution of dietary bisphenol exposure to the odds of developing overweight and obesity in a sample of Spanish children according to sex., Methods: Dietary and anthropometric data were collected from 179 controls and 124 cases schoolchildren aged 3-12 years. Dietary exposure to BPA and bisphenol S (BPS) was assessed using a food consumption frequency questionnaire. Logistic regression models were used to assess the influence of dietary exposure to bisphenols on overweight and obesity stratified by sex., Results: For females, cases had significantly higher exposure to BPA from meat and eggs compared to controls (median = 319.55, interquartile range (IQR) = 176.39-381.01 vs 231.79 (IQR) = 162.11-350.19, p-value = 0.046). Diet quality was higher for controls (6.21 (2.14) vs 4.80 (2.24) p < 0.001) among males independently of a high or low exposure to bisphenols. However, higher diet quality was observed for female controls with an high exposure of total bisphenols (6.79 (2.04) vs 5.33 (2.02) p = 0.031). Females exposed to high levels of BPA from meat and eggs had higher likelihood of being overweight and obese (adjusted Odds Ratio = 2.70, 95% confidence interval = 1.00 - 7.32). However, no consistent associations were found in males., Conclusions: High BPA levels from meat and eggs were positively associated with overweight and obesity in females. The dietary intake of BPA in the schoolchildren in the present study was much higher than the acceptable daily intake established by EFSA for the last year., (© 2024. The Author(s).)

Introduction: Vaccine-induced immunity against COVID-19 generates antibody and lymphocyte responses. However, variability in antibody titers has been observed after vaccination, and the determinants of a better response should be studied. The main objective of this investigation was to analyze the inflammatory biomarker response induced in healthcare workers vaccinated with BNT162b2, and its association with anti-Spike (a SARS-CoV-2 antigen) antibodies measured throughout a 1-year follow-up., Methods: Anti-spike antibodies and 92 biomarkers were analyzed in serum, along with socio-demographic and clinical variables collected by interview or exploration., Results: In our study, four biomarkers (ADA, IL-17C, CCL25 and CD8α) increased their expression after the first vaccine dose; and 8 others (uPA, IL-18R1, EN-RAGE, CASP-8, MCP-2, TNFβ, CD5 and CXCL10) decreased their expression. Age, body mass index (BMI), smoking, alcohol consumption, and prevalent diseases were associated with some of these biomarkers. Furthermore, higher baseline levels of T-cell surface glycoprotein CD6 and hepatocyte growth factor (HGF) were associated with lower mean antibody titers at follow-up, while levels of monocyte chemotactic protein 2 (MCP-2) had a positive association with antibody levels. Age and BMI were positively related to baseline levels of MCP-2 (β=0.02, 95%CI 0.00-0.04, p=0.036) and HGF (β=0.03, 95%CI 0.00-0.06, p=0.039), respectively., Conclusion: Our findings indicate that primary BNT162b2 vaccination had a positive effect on the levels of several biomarkers related to T cell function, and a negative one on some others related to cancer or inflammatory processes. In addition, a higher level of MCP-2 and lower levels of HGF and CD6 were found to be associated with higher anti-Spike antibody titer following vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Leno-Duran, Serrano-Conde, Salas-Rodríguez, Salcedo-Bellido, Barrios-Rodríguez, Fuentes, Viñuela, García and Requena.)

Background: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food., Objective: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study., Methods: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI., Results: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [β-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m 2 (0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up., Discussion: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular disease, i.e. obesity, insulin resistance, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-c) levels and arterial hypertension. Phthalates are environmental chemicals which might influence the risk of the aforementioned disturbances, although the evidence is still controversial. The objective of this work was to synthesize the evidence on the association between human phthalate exposure and metabolic syndrome or any of its components. In this systematic review, the PRISMA guidelines were followed and the literature was search in PubMed, Web of Science and Scopus. Longitudinal and cross-sectional studies were included, the later only if a subclinical marker of disease was evaluated. The methodological quality was assessed with the Newcastle Ottawa Scale and a checklist for Analytical Cross-Sectional Studies developed in the Joanna Briggs Institute. A total of 58 articles were identified that showed high heterogenicity in the specific phthalates assessed, time-window of exposure and duration of follow-up. The quality of the studies was evaluated as high (n = 46, score >7 points) or medium (n = 12, score 4-6). The most frequently studied phthalates were DEHP-MEHP, MBzP and MEP. The evidence revealed a positive association between prenatal (in utero) exposure to most phthalates and markers of obesity in the offspring, but contradictory results when postnatal exposure and obesity were assessed. Moreover, postnatal phthalate exposure showed positive and very consistent associations with markers of diabetes and, to a lesser extent, with triglyceride levels. However, fewer evidence and contradictory results were found for HDL-c levels and markers of hypertension. The suggested mechanisms for these metabolic effects include transcription factor PPAR activation, antagonism of thyroid hormone function, antiandrogenic effects, oxidative stress and inflammation, and epigenetic changes. Nevertheless, as the inconsistency of some results could be related to differences in the study design, future research should aim to standardise the exposure assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited., Objective: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population., Methods: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models., Results: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (β-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (β-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015)., Conclusion: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to metal(loid)s during critical developmental windows could result in permanent damage to the target organ system, increasing susceptibility to disease later in life. In view of the fact that metals(loid)s have been shown to work as obesogens, the aim of the present case-control study was to evaluate the modification effect of exposure to metal(loid)s on the association between SNPs in genes involved in metal(loid) detoxification and excess body weight among children. A total of 134 Spanish children aged 6-12 years old were included (88 controls and 46 cases). Seven SNPs (GSTP1 rs1695 and rs1138272; GCLM rs3789453, ATP7B rs1061472, rs732774 and rs1801243; and ABCC2 rs1885301) were genotyped on GSA microchips, and ten metal(loid)s were analysed in urine samples through Inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic regressions were conducted to assess the genetic and metal exposures' main association and interaction effects. GSTP1 rs1695 and ATP7B rs1061472 showed significant effects on excess weight increase in those children carrying two copies of the risk G allele and being highly exposed to chromium (ORa = 5.38, p = 0.042, p interaction = 0.028 for rs1695; and ORa = 4.20, p = 0.035, p interaction = 0.012 for rs1061472) and lead (ORa = 7.18, p = 0.027, p interaction = 0.031 for rs1695, and ORa = 3.42, p = 0.062, p interaction = 0.010 for rs1061472). Conversely, GCLM rs3789453 and ATP7B rs1801243 appeared to play a protective role against excess weight in those exposed to copper (ORa = 0.20, p = 0.025, p interaction = 0.074 for rs3789453) and lead (ORa = 0.22, p = 0.092, p interaction = 0.089 for rs1801243). Our findings provide the first proof that interaction effects could exist between genetic variants within GSH and metal transporting systems and exposure to metal(loid)s, on excess body weight among Spanish children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work presented in this paper. Graphical abstract was created with BioRender.com., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To analyse the Health-Related Quality of Life (HRQoL) at diagnosis of patients with prostate cancer (PCa) according to tumour extension and urinary symptomatology and to explore factors associated with HRQoL., Methods: 408 Controls and 463 PCa cases were included. Eligibility criteria were a new diagnosis of PCa (cases), 40-80 years of age, and residence in the participating hospitals' coverage area for ≥ 6 months before recruitment. HRQoL was evaluated using the 12-Item Short-Form Health Survey, Mental (MCS) and Physical Component Summaries (PCS), and urinary symptoms with the International Prostate Symptom Score. HRQoL scores for all PCa cases, according to tumour extension and urinary symptoms, were compared with controls. In addition, information about lifestyles and comorbidities was collected and its association with low HRQoL (lower scores) were explored using logistic regression models., Results: Overall cases had similar PCS score, but lower MCS score than controls. The lowest standardised scores for both PCS and MCS were reached by cases with severe urinary symptoms and a metastatic tumour [mean (SD); PCS: 41.9 (11.5), MCS: 42.3 (10.3)]. Having "below" PCS and MCS scores was associated with the presence of three or more comorbidities in the cases [aOR = 2.86 (1.19-6.84) for PCS and aOR = 3.58 (1.37-9.31) for MCS] and with severe urinary symptomatology [aOR = 4.71 (1.84-12.08) for PCS and aOR = 7.63 (2.70-21.58) for MCS]., Conclusion: The mental dimension of HRQoL at diagnosis of patients with PCa was lower than in controls, especially for cases with severe urinary symptoms and a metastatic tumour. Comorbidities and urinary symptoms were variables associated with the HRQoL of PCa cases., (© 2022. The Author(s).)

The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45-1.88) and mono-iso-butyl phthalate (3.07, 2.39-3.95), mono-ethyl phthalate (2.05, 1.62-2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1β, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1β. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Juan Pedro Arrebola reports financial support, article publishing charges, and equipment, drugs, or supplies were provided by Carlos III Health Institute., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The worldwide pandemic has exposed healthcare professionals to a high risk of infection, exacerbating the situation of uncertainty caused by COVID-19. The objective of this review was to evaluate the psychological impact of the COVID-19 pandemic on dental professionals and their patients. A literature review was conducted using Medline-Pubmed, Web of Science, and Scopus databases, excluding systematic reviews, narratives, meta-analyses, case reports, book chapters, short communications, and congress papers. A modified version of the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the selected studies. The search retrieved 3879 articles, and 123 of these were selected for the review (7 longitudinal and 116 cross-sectional studies). Elevated anxiety levels were observed in dental professionals, especially in younger and female professionals. Except for orthodontic treatments, patients reported a high level of fear that reduced their demand for dentist treatment to emergency cases alone. The results suggest that the COVID-19 pandemic has had psychological and emotional consequences for dental professionals and their patients. Further research is necessary to evaluate the persistence of this problem over time.

Background: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn., Objectives: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism., Methods: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn., Results: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women., Discussion: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The development of second primary tumours (SPTs) is one of the main causes of low survival in patients with head and neck cancer (HNC). The aim of this study was to review the evidence about factors associated with developing SPTs in patients with HNC., Methods: An updated systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and the search was performed in Pubmed and Scopus. Only original articles with a cohort or case-control design were included. Article quality was assessed with the Newcastle-Ottawa scale., Results: Thirty-six and two case-control studies were included, with quality medium (n = 5) to high (n = 33). Tobacco showed a significant association with SPT development, with risks ranging from 1.41 (95%CI: 1.04-1.91) to 5.52 (95%CI: 2.91-10.49). Regarding alcohol, risks ranged from 1.46 (95%CI: 1.12-1.91) to 21.3 (95%CI: 2.9-156). Location of the index tumour in the hypopharynx/oropharynx, absence of human papillomavirus and presence of a premalignant lesion also increased the risk of SPTs. More controversy was found for sex, age and other clinical factors of the tumour., Conclusion: Toxic lifestyle habits and clinical factors were associated with the risk of SPTs in HNC patients. These findings may improve individualised prevention strategies in its follow-up., (© 2022 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

Background: Polychlorinated biphenyls and organochlorine pesticides are persistent organic pollutants (POPs) that had been banned or restricted in many countries, including Spain. However, their ubiquity still poses environmental and human health threats., Objective: To longitudinally explore public healthcare costs associated with long-term exposure to a mixture of 8 POPs in a cohort of residents of two areas of Granada Province, Southern Spain., Methods: Longitudinal study in a subsample (n = 385) of GraMo adult cohort. Exposure assessment was performed by analyzing adipose tissue POP concentrations at recruitment. Average primary care (APC) and average hospital care (AHC) expenditures of each participant over 14 years were estimated using the data from their medical records. Data analyses were performed by robust MM regression, weighted quantile sum regression (WQS) and G-computation analysis., Results: In the adjusted robust MM models for APC, most POPs showed positive beta coefficients, being Hexachlorobenzene (HCB) significantly associated (β: 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (β: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semi-rural residents, where β-HCH was also marginally-significantly associated to APC (β: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (β: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by β-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (β: 0.23; 95%CI: -0.01, 0.48). No significant results were observed in G-Computation analyses., Conclusion: Long-term exposure to POP mixtures might represent a modifiable factor increasing healthcare costs, thus affecting the efficiency of the healthcare systems. However, and owing the complexity of the potential causal pathways and the limitations of the present study, further research is warranted to fully elucidate ascertain whether interventions to reduce human exposure should be considered in healthcare policies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The etiology of prostate cancer (PCa) remains uncertain, and the role of diet is unclear. We aimed to evaluate the role of diet, through dietary patterns, on PCa, considering tumor aggressiveness and extension. The CAPLIFE study is a population-based case-control study including a total of 428 incident PCa cases and 393 controls aged 40-80 years. Dietary information was collected through a validated food frequency questionnaire. Three dietary patterns were identified through principal component analysis: "Mediterranean," "Western," and "Unhealthy," which were categorized into tertiles according to the control group cutoff points. Tumor aggressiveness and extension was determined. Logistic regression models were used to assess the association between dietary patterns and PCa. High adherence to an unhealthy dietary pattern was associated with higher odds of PCa, OR T3vsT1 = 1.52 (95% CI 1.02-2.27), especially for cases with ISUP 1-2 and localized PCa tumors. This association was not observed with a Western or Mediterranean pattern. In conclusion, adherence to an unhealthy diet appears to be associated with higher odds of PCa, especially for cases with ISUP 1-2 and localized PCa tumors.

Several epidemiological studies have analyzed the effects of lifestyle modification on reducing the risk of gestational diabetes mellitus (GDM); however, their results remain inconsistent. This umbrella review aims to evaluate the effects of diet and/or physical activity interventions during pregnancy on preventing GDM. Systematic reviews and meta-analysis of randomized clinical trials reporting preventive effects of diet and/or physical activity in reducing the incidence of GDM were included from PubMed, Web of Science, Scopus and Cochrane library. Two authors independently assessed the overlapping and quality of the 35 selected reviews using AMSTAR 2. The results, although variable, tend to defend the protective role of diet and physical activity interventions separately and independently of each other in the prevention of GDM. However, the results for the combined interventions show a possible protective effect; however, it is not entirely clear because most of the analyzed meta-analyses tend to approach 1, and heterogeneity cannot be ruled out. Establishing conclusions about the most efficient type of intervention and a dose-effect relationship was not feasible given the low quality of systematic reviews (83% low to critically low) and the variability in reporting interventions. Therefore, more studies with better quality and definition of the interventions are required. The protocol was previously registered in PROSPERO as CRD42021237895.

A growing body of evidence supports that more than 900 single nucleotide polymorphisms (SNPs) and exposure to endocrine disrupting chemicals, such as bisphenols and parabens, are important contributors to the development of obesity. The aim of this study was to evaluate the way in which fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs9436303 variants contribute to variability in body mass index (BMI) according to estimated dietary exposure of bisphenols and parabens. This cross-sectional study included 101 Spanish participants (16-24 years). SNP genotyping assays were performed through quantitative PCRs (qPCRs) using Taqman® probes. Dietary exposure to bisphenols and parabens was calculated from food frequency questionnaire and chemical determination in food samples by ultra-high performance liquid chromatography-tandem mass spectrometry system. Linear regression models were conducted to address the association of genetic variants and BMI according to levels of bisphenols/parabens exposure. Risk G allele of LEPR rs9436303 was significantly positively associated with BMI (exp (β) = 1.20, 95% CI: 1.04-1.38, p = 0.011). In participants highly exposed to bisphenols, the LEPR rs9436303 G allele was related to a significant increased BMI (exp (β) = 1.27, 95% CI: 1.03-1.57, p = 0.024). A more relevant trend was observed with high exposure to parabens (exp (β) = 1.33, 95% CI: 1.08-1.63, p = 0.009). We provide the first evidence that interaction between LEPR polymorphism and dietary intake of bisphenols and parabens may be responsible for an increased BMI, suggesting a potential effect in obesity. Moreover, we proposed LEPR rs9436303 as a genetic marker of susceptibility to excess weight induced by exposure., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

The general population is continuously exposed to phthalates via various consumer products. Epidemiological research relating phthalate exposure to thyroid function during non-developmental periods is limited. This study aimed to investigate the associations between specific serum phthalate metabolites and indicators of thyroid function in adults. We measured 10 serum phthalate metabolites and thyroid hormones - total triiodothyronine (TT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) - in a subsample of 207 adults from the GraMo cohort. This subsample was made up of men and women (in equal proportions) of middle age (49 ± 17 years) and from Southern Spain (province of Granada). Data on age, sex, body mass index, residence area, tobacco use, alcohol consumption and attained education were obtained from a questionnaire. Phthalate metabolites were log-transformed and categorized into tertiles. Cross-sectional associations of each metabolite with thyroid hormones were analyzed using multivariable-adjusted linear regression models. The mixture effect of metabolite phthalates was assessed using weighted quantile sum regression. After multivariable-adjustment, the following phthalate metabolites were significantly associated with TT3 in a dose-response manner: MMP (β = 0.90: 95% confidence interval 0.68,1.12), MEP (β = 0.67: 0.44, 0.90), MiBP (β = 0.49: 0.21, 0.77), MiDP (β = 0.27: 0.03, 0.52), MBzP (β = 0.51: 0.28, 0.73), MEHP (β = -0.59: -0.82, -0.35) and MiNP (β = -0.43: -0.71, -0.14), when comparing highest vs. lowest exposed. The sum of all metabolites was also linked to FT4 levels. No significant associations were observed for TSH except for MiNP. Although phthalate metabolites with different molecular weight showed opposite associations, overall metabolite concentrations seem to associate with increased TT3 and FT4 serum levels. The cross-sectional nature of this analysis limits causal inference., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this work was to study the associations of adipose tissue trace element concentrations with type 2 diabetes (T2DM) incidence over a 16-year follow-up period in an adult cohort from Southern Spain. 16-year T2DM incidence was gathered from hospital records. Chemical analyses of Cr, V, Zn, Fe, Cu and Se in adipose tissue were performed using inductively coupled plasma mass spectrometry. Multivariable Cox-regression models were used. Complementary cross-sectional analyses with markers of glucose homeostasis at recruitment were performed by multivariable linear regression. Out of 214 participants, 39 developed T2DM during the follow-up. Adipose tissue concentrations of Fe (HR = 1.97, 95% CI: 0.99 to 2.58, p = 0.057), Cr (HR = 1.58, 95% CI: 1.07-2.33, p = 0.022) and Cu (HR = 1.61, 95% CI: 1.01-2.58, p = 0.046) were individually associated with T2DM incidence. When Fe, Cr and Cu were simultaneously entered in a model, only Cr was significantly associated with T2DM incidence (HR = 1.68, 95% CI: 1.02-2.76, p = 0.041). Furthermore, adipose tissue V (β = 0.283, p = 0.004) and Zn (β = 0.217, p = 0.028) concentrations were positively associated with β-pancreatic cell function (HOMA-β), while Se showed an inverse association (β = -0.049, p = 0.027). Although further research is warranted on the potential mechanisms of action, our results suggest that adipose tissue concentrations of certain trace elements (particularly Fe, Cr and Cu) are associated with the risk of incident T2DM, while V and Zn might have a protective effect. These biomarkers might complement prediction algorithms and contribute to identify patients with an increased risk of T2DM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Continuous exposure to low doses of persistent organic pollutant (POPs), such as those occurring in the general population, might contribute to the burden of type 2 diabetes mellitus (T2DM). However, evidences from longitudinal studies are scarce. We aimed to explore the associations of accumulated POP exposure with the development of T2DM by means of 1) longitudinal associations with the 16-year incidence of the disease, and 2) complementary cross-sectional analyses with markers of glucose homeostasis at recruitment. Organochlorine pesticide and polychlorinated biphenyl (PCB) concentrations were analyzed in adipose tissue samples and incident T2DM cases were retrieved from clinical records. Homeostatic model assessment values of insulin sensitivity/resistance and β-cell function at recruitment were calculated. Linear and Cox-regression models were performed. In individuals with normal weight/overweight (n = 293), we observed positive dose-response relationships between the studied POPs and T2DM risk, particularly for hexachlorobenzene (HCB) [hazard ratio (HR): 3.96 for 4th quartile versus 1st quartile (Q1); confidence interval (CI) 95%: 0.79, 19.71]. PCB-180 showed a positive but seemingly non-linear association with T2DM risk [HR of 3 er quartile (Q3) versus Q1: 6.48; CI 95%: 0.82, 51.29]. Unadjustment for body mass index considerably increased the magnitude of the associations. In the cross-sectional study (n = 180), HCB and PCB-180 were inversely associated with insulin sensitivity and positively associated with insulin resistance parameters. Our results suggest that a higher burden of specific POPs in adipose tissue may disrupt glucose homeostasis, possibly contributing to increase T2DM risk, especially in non-obese adults., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Parabens are alkyl esters of p-hydroxybenzoic acid which are extensively used in cosmetics, pharmaceuticals and foodstuffs due to their antimicrobial properties. The most commonly used parabens are methyl-(MeP), ethyl-(EtP), propyl-(PrP) and butyl-(BuP) paraben. Most human exposure to parabens is achieved through the consumption of food or pharmaceutical products and the use of personal care products. However, studies on dietary parabens exposure and the associated factors are very scarce. The main aim of the present study was to explore factors associated with dietary exposure to parabens in Spanish adolescents according to gender. Dietary data and anthropometric measures were collected from 585 adolescents (53.4% boys) aged 12-16 years. Parabens exposure through diet was assessed using a food frequency questionnaire with food products providing more than 95% of energy and macronutrient intake being included in analysis. Stepwise regression was used to identify the foods that most contributed to parabens intake. Logistic regression was used to evaluate factors predicting higher dietary exposure to parabens. The main contributors to dietary MeP, EtP, PrP and BuP exposure in adolescent boys were eggs (41.9%), canned tuna (46.4%), bakery and baked goods products (57.3%) and pineapple (61.1%). In adolescent girls, the main contributors were apples and pears (35.3%), canned tuna (42.1%), bakery and baked goods products (55.1%) and olives (62.1%). Overweight/obese girls were more likely to belong to the highest tertile of overall parabens intake (odds ratio [OR]: 3.32; 95% confidence interval [95% CI]: 1.21-9.15) and MeP (OR: 3.05; 95% CI: 1.14-8.12) than those with a body mass index lower than 25 kg/m 2 . These findings suggest a positive association between dietary exposure to parabens and overweight/obesity in adolescent girls., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Tocilizumab (TCZ) has been administered in SARS-CoV-2 pneumonia but the factors associated with mortality before and after treatment remain unclear. Cox regression models were used to estimate the predictors of time to death in a cohort of hospitalized patients with COVID-19 receiving TCZ. In addition, the mean differences between discharged and deceased patients in laboratory parameters measured before and 3, 6 and 9 days after TCZ administration were estimated with weighted generalized estimation equations. The variables associated with time to death were immunosuppression (Hazard Ratio-HR 3.15; 95% confidence interval-CI 1.17, 8.51), diabetes mellitus (HR 2.63; 95% CI 1.23-5.64), age (HR 1.05; 95% CI 1.02-1.09), days since diagnosis until TCZ administration (HR 1.05, 95% CI 1.00-1.09), and platelets (HR 0.27; 95% CI: 0.11, 0.69). In the post-TCZ analysis and compared to discharged patients, deceased patients had more lactate dehydrogenase ( p = 0.013), troponin I ( p = 0.013), C-reactive protein ( p = 0.013), neutrophils ( p = 0.024), and fewer platelets ( p = 0.013) and lymphocytes ( p = 0.013) as well as a lower average PaO 2 /FiO 2 ratio. In conclusion, in COVID-19 diagnosed patients receiving TCZ, early treatment decreased the risk of death, while age, some comorbidities and baseline lower platelet counts increased that risk. After TCZ administration, lower platelet levels were again associated with mortality, together with other laboratory parameters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sarabia De Ardanaz, Andreu-Ubero, Navidad-Fuentes, Ferrer-González, Ruíz del Valle, Salcedo-Bellido, Barrios-Rodríguez, Cáliz-Cáliz and Requena.)

Toenails have been used as biomarkers of exposure to toxic metals, but their validity for this purpose is not yet clear and might differ depending on the specific agent. To evaluate this issue, we reviewed the literature on: a) the time-window of exposure reflected by toenails; b) the reproducibility of toenail toxic-metal levels in repeated measures over time; c) their relationship with other biomarkers of exposure, and; d) their association with potential determinants (i.e. sociodemographic, anthropometric, or lifestyle characteristics) or with sources of exposure like diet or environmental pollution. Thus, we performed a systematic review, searching for articles that provided original data for levels of any of the following toxic metals in toenails: aluminum, beryllium, cadmium, chromium, mercury, nickel, lead, thallium and uranium. We identified 88 articles, reporting data from 67 different research projects, which were quite heterogeneous with regard to population profile, sample size and analytical technique. The most commonly studied metal was mercury. Concerning the time-window of exposure explored by toenails, some reports indicate that toenail cadmium, nickel and lead may reflect exposures that occurred 7-12 months before sampling. For repeated samples obtained 1-6 years apart, the range of intraindividual correlation coefficients of aluminum, chromium and mercury was 0.33-0.56. The correlation of toxic metal concentrations between toenails and other matrices was higher for hair and fingernails than for urine or blood. Mercury levels were consistently associated with fish intake, while other toxic metals were occasionally associated with specific sources (e.g. drinking water, place of residence, environmental pollution, and occupation). The most frequently evaluated health endpoints were cardiovascular diseases, cancer, and central nervous system diseases. Available data suggest that toenail mercury levels reflected long-term exposures and showed positive associations with fish intake. The lack of standardization in sample collection, quality control, analytical techniques and procedures - along with the heterogeneity and conflicting results among studies - mean it is still difficult to conclude that toenails are a good biomarker of exposure to toxic metals. Further studies are needed to draw solid conclusions about the suitability of toenails as biomarkers of exposure to toxic metals., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Obesogenic endocrine-disrupting chemicals, such as bisphenol A (BPA) and its analogue bisphenol S (BPS), seem to play an important role in the development of obesity, although contradictory results have been reported. The aim of the present study was to conduct a gender analysis of the factors associated with exposure to dietary bisphenols in 585 Spanish adolescents. Dietary BPA and BPS exposure was assessed using a food frequency questionnaire. Foods and macronutrients accounting for more than 95% of energy intake were selected for analysis. Stepwise regression was used to estimate the foods that most contributed to dietary bisphenol exposure in the sample. Gender-related factors associated with greater dietary bisphenol exposure were evaluated using multivariate logistic regression models. Canned tuna was the main dietary source of BPA and BPS in both adolescent boys and girls. Overweight/obese girls showed a higher risk of high dietary exposure to BPA (odds ratio (OR): 3.38, 95% confidence interval (CI): 1.25-9.07) and total bisphenols (OR: 2.81, 95% CI: 1.03-7.67) in comparison with girls with a BMI lower than 25 kg/m 2 . Present results indicate a positive association of dietary exposure to both total bisphenols and BPA with being overweight/obese in adolescent girls.

Objective: To estimate physical activity (PA) in healthy women before and during pregnancy and to evaluate the features associated with moderate PA (MPA)., Methods: A prospective cohort study was conducted on women selected 14 weeks of pregnancy during 2013-2015 in primary public health service centers in southern Spain. Type, duration, and frequency of PA (IPAQ questionnaire in first, second, and third trimesters [T1, T2, T3]) were measured. Variables associated with MPA were evaluated using multiple logistic regressions controlling for age, pre-pregnancy obesity, level of education, number of living children, pre-pregnancy PA, and adherence to Mediterranean diet (AMD)., Results: Out of 463 women, MPA was estimated in 64% pre-pregnancy, and 54%, 61%, and 59% in T1, T2, and T3, respectively. MPA was associated with greater AMD in T2 (adjusted odds ratio [aOR] 1.17, 95% confidence interval [CI] 1.04-1.33) and T3 (aOR 1.16, 95% CI 1.02-1.31), previous PA (aOR 13.5, 95% CI 8.12-22.5 in T1; aOR 2.61, 95% CI 1.72-3.96 in T2; aOR 2.59, 95% CI 1.65-4.05 in T3), and pre-pregnancy obesity (aOR 2.97, 95% CI 1.28-6.89 in T1; aOR 2.69, 95% CI 1.23-3.60 in T3)., Conclusion: PA decreased at the beginning of pregnancy, but compliance remained over 50%. MPA was associated with diet, pre-pregnancy PA, and obesity., (© 2020 International Federation of Gynecology and Obstetrics.)

This research aims to explore clusters of a mixture of 15 Persistent Toxic Substances (PTSs) in the adipose tissue of 227 individuals of an adult cohort from Granada Province (Southern Spain). Information about residence and occupation during participants lifetime was gathered by means of validated questionnaires. Clusters of pollutants in the study population were identified by Principal Component Analyses (PCA). PCA analyses revealed three major clusters of pollutants: PC1, representing predominantly an assortment of metal(loid)s, namely aluminium, arsenic, chromium, nickel and lead; PC2, including mostly Organochlorine Pesticides (OCPs), such as HCB, β-HCH and p,p'-DDE; and PC3, gathering mainly a mixture of Polychlorinated Biphenyls (PCB-138, PCB-153 and PCB-180) and metals (cadmium, cobalt and chromium). The patterns of distribution of individual pollutants and their mixtures were explored through Geographic Information Systems and multivariable linear regression models. Living in rural areas was associated with decreased levels of the mixture of PCBs and metals. Residents of industrial and heavy traffic areas showed increased levels of the mixture of metal(loid)s. Those living in rural and semi-rural areas at recruitment had decreased levels of the OCP mixture. Occupational history related to agriculture and food industry was associated with increased levels of the mixture of metal(loid)s, whereas those who had been involved in motor and industrial activities showed increased levels of the OCP mixture. Participants who had worked in cleaning and housekeeping activities for long periods showed decreased levels of the mixture of PCBs and metals. Our research revealed suggestive clusters of exposure, that emphasized the need for further epidemiological studies to address the effect of environmental pollutants from a mixture perspective. Results also highlight the potential of adipose tissue as a matrix for exposure assessment to combinations of different families of contaminants., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To analyze the association between prostate cancer (PCa) risk and night shift work, chronotype, and sleep duration in the context of a population-based case-control study of incident prostate cancer in Spain, a total of 465 PCa cases and 410 controls were analyzed. Selection criteria were: (i) age 40-80 years, and (ii) residence in the coverage area of the reference hospitals for ≥6 months before recruitment. Exposure variables were: (i) night shift work (permanent or rotating); (ii) chronotype: morning, neither, or evening (Munich ChronoType Questionnaire) and (iii) sleep duration according to the recommendations of the American National Sleep Foundation. PCa aggressiveness was determined according to the International Society of Urology Pathology classification. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were estimated using logistic regression models. Night shift work was associated with PCa, aOR = 1.47 (95% CI 1.02-2.11), especially for rotating night shifts, aOR = 1.73 (95% CI 1.09-2.75). The magnitude of the association between ever night work and PCa was higher in evening subjects with aOR = 3.14 (95% CI 0.91-10.76) than in morning chronotypes with an aOR = 1.25 (95% CI 0.78-2.00). Working night shifts, especially rotating night shifts, could increase PCa risk. This risk may be higher in people with an evening chronotype., Competing Interests: The authors declare no conflict of interest.

Dietary diversity (DD) is a key component of a high-quality diet, providing the adequate nutrient requirements. However, the role of DD on prostate cancer (PCa) is still uncertain. The aim of this study was to evaluate the relationship between DD, adequate nutrient intake and PCa, according to the aggressiveness of the tumor. The CAPLIFE (CAP: prostate cancer; LIFE: lifestyles) study is a population-based case-control study including a total of 402 incident PCa cases and 302 controls. The DD score (DDS), adjusted by total energy intake, was collected through a validated food frequency questionnaire. Nutrient adequacy was defined according to European Dietary Recommendation Intake for men. The aggressiveness of PCa was determined according to the International Society of Urology Pathology classification. The association between DDS, nutrient intake and PCa was assessed by logistic regression models with adjustment for potential confounding factors. DDS was similar for PCa cases and controls, independent of PCa aggressiveness. According to each food group DDS, the protein group showed the highest mean score in all the subgroups analyzed. However, no differences were observed for each of the DDS components. The DDS, the variety of the group's food intake, and the adequate nutrient intake, were not associated with PCa.

Background: Adipose tissue has been acknowledged as a potential target for obesogenic pollutants, including toxic metal(loid)s. However, the presence of these chemicals in the adipose tissue has been poorly characterized., Objective: To examine the distributions of adipose tissue concentrations of five toxic metal(loid)s (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(loid) 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 metal(loid)s 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(loid) levels., Results: Ni, Pb, Sn, and Ti were detected in all adipose tissue samples, and As in 51% of them. 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 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 metal(loid)s., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Backgound : Traditional anthropometrics such as body mass index (BMI) or waist circumference (WC) do not fully capture the complex biology of body fat (BF) in the elderly. The Clinica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index, based on BMI, is proposed as a better indicator of BF. However, its relation with BMI is not clear. The aim was to compare the agreement between CUN-BAE, BMI, and WC in those aged ≥50 years. Methods : A cross-sectional sample of 3153 Caucasian healthy adults was taken from the MCC-Spain study. The Pearson's correlation and its 95% confidence interval (CI), adiposity distribution, and Kappa Index (95%CI) were calculated. Results : The correlation of CUN-BAE with WC is 0.18 (95%CI 0.14-0.21) and that with BMI is moderate (r 0.58; 95%CI 0.55-0.60), but both increased strongly by sex. Agreement (normal weight/overweight/obesity) of CUN-BAE with BMI is 7% and with WC is 18%. Conclusions : The correlation and the degree of agreement of CUN-BAE with BMI and WC are low in individuals aged over 50, but it is higher by sex. Thus, this different criterion of obesity may have clinical applications. More studies with a gold standard are needed to evaluate the CUN-BAE in elderly adults.

The etiology of prostate cancer (PCa) remains largely unknown. Compliance with the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) cancer prevention recommendations and its relationship to PCa was evaluated. A total of 398 incident PCa cases and 302 controls were included. The selection criteria for both cases and controls were: (i) age between 40-80 years; and (ii) residence in the coverage area of the reference hospitals for 6 months or more prior to recruitment. A score to measure the compliance with the recommendations of 2018 WCRC/AICR criteria was built. The level of compliance was used as a continuous variable and categorized in terciles. The aggressiveness of PCa was determined according to the ISUP classification. Adjusted odds ratios (aOR) and their 95% confidence intervals (95% CI) were estimated using multivariable logistic regression models. A slight protective tendency was observed between the level of compliance with the preventive recommendations and PCa risk, aOR = 0.81 (95% CI 0.69-0.96) for the total cases of PCa. This association also was observed when the aggressiveness was considered. In addition, limiting consumption of "fast foods", sugar-sweetened drinks, and alcohol were independently associated with lower risk of PCa.

Maternal nutrition is recognized as one of the main determinants of fetal growth. We analyzed the risk of having a Small for Gestational Age (SGA) newborn according to maternal dairy intake during pregnancy. A matched case-control study was conducted in Spain. Dietary intake during pregnancy was assessed using a validated Food Frequency Questionnaire. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using conditional logistic regression models. 518 cases (SGA) and 518 controls (adequate birth weight) were included. Most study participants did not meet the current recommendations for dairy intake (78.6% cases and 80.2% controls). Intake of dairy products was not associated with a lower frequency of SGA, aOR Q4 vs. Q1  = 1.12 (95% CI 0.73, 1.70), and aOR Q5 vs. Q1  = 1.44 (95% CI 0.92, 2.26). Our results suggest that a low dairy intake during pregnancy is not associated with an increased risk of SGA; possibly due to the low consumption of dairy in both groups.

Health problems associated with essential trace metals can result from both inadequate (i.e., low intake) and excessive exposures (i.e., from environmental and/or occupational source). Thus, measuring the exposure level is a real challenge for epidemiologists. Among non-invasive biomarkers that intend to measure long-term exposure to essential trace metals, the toenail is probably the biological matrix with the greatest potential. This systematic review collects the current evidence regarding the validity of toenail clippings as exposure biomarker for trace metals such as boron, cobalt, copper, iron, manganese, molybdenum, selenium, silicon, vanadium and zinc. Special attention was paid to the time-window of exposure reflected by the toenail, the intraindividual variability in exposure levels over time in this matrix, and the relationship of toenail with other biomarkers, personal characteristics and environmental sources. Our search identified 139 papers, with selenium and zinc being the most studied elements. The variability among studies suggests that toenail levels may reflect different degrees of exposure and probably correspond to exposures occurred 3-12 months before sampling (i.e., for manganese/selenium). Few studies assessed the reproducibility of results over time and, for samples obtained 1-6 years apart, the correlation coefficient were between 0.26 and 0.66. Trace metal levels in toenails did not correlate well with those in the blood and urine and showed low-moderate correlation with those in the hair and fingernails. Available data suggests that for some elements (Se, Mn, Zn) toenail concentrations reflect long-term external exposures in fairly reproducible levels, while for other metals, this association has not yet been assessed. Among dietary factors, only toenail selenium showed clear associations with the intake of supplements or specific foods. The toenail levels could also represent occupational exposure, for instance, Mn exposure in welders. The scarcity of information on other essential trace elements, together with the great heterogeneity among studies makes the validation of the usage of toenails as biomarkers of exposure to these elements difficult. Standardization of sample collection, quality control, analytical techniques and reporting procedures might facilitate further research focused on the clear understanding of the significance of essential levels in this promising matrix and would enhance its utility in epidemiological research., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72-1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95-1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81-1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84-1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70-1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66-0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.

Background: In contrast to the recognized role of Helicobacter pylori in the etiology of non-cardia gastric cancer (GC), there is still insufficient epidemiological evidence for the involvement of Epstein-Barr virus (EBV) in gastric carcinogenesis. We aimed to evaluate the relation of antibody profile and antibody reactivity intensity against four individual EBV proteins to GC risk., Methods: We used information from 281 GC cases and 2071 age and sex frequency matched controls recruited in the frame of the MCC-Spain multicase-control study, between 2008 and 2013. Sociodemographic, lifestyle and environmental factors were assessed in face-to-face interviews. Antibody responses to four EBV proteins (EBNA-1, ZEBRA, EA-D, and VCA-p18) were analyzed by multiplex serology. Odds ratios (OR) and 95% confidence intervals were calculated by using logistic regression mixed models to evaluate the association of seropositivity and antibody reactivity against EBV proteins with GC, adjusting for GC risk factors. Stratified analyses by tumor location (cardia vs. non-cardia) and morphology (intestinal vs. diffuse) were done., Results: Among controls, seropositivity for EA-D, ZEBRA, EBNA-1 and VCA-p18 was 85%, 91%, 97% and 99%, respectively. Even though seropositivity for none of the studied proteins was associated with a higher GC risk, increasing antibody reactivity against EBNA-1 and VCA-p18 was associated with higher OR of GC. This association was present for cardia and non-cardia cancer cases, and for intestinal and diffuse types., Conclusion: Our results support the hypothesis that EBV may play a role in GC etiology, and highlight the importance of evaluating specific antibodies and the dose-response relations when studying widespread infections., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Studies of iron and its association with the risk of small for gestational age (SGA) show inconsistent results. Consuming iron supplements during pregnancy is controversial because of possible risks. This study assessed the association between iron intake and the risk of having an SGA newborn and whether iron intake is associated with gestational diabetes. A case-control study of 518 pairs of Spanish women who were pregnant and attending five hospitals was conducted. Groups were matched 1:1 for age (±2 years) and hospital. Cases were women with an SGA newborn at delivery. Controls were women with normal-sized newborns at delivery. Data were gathered on demographic characteristics, socio-economic status, adverse habits (like smoking), and diet. A 137-item food frequency questionnaire was completed. Iron intakes were categorized in quintiles (Q1-Q5). Crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (CIs) were estimated by conditional logistic regression. No significant relationship was found between dietary iron intake and SGA. A protective association was found for women receiving iron supplementation >40 mg/day and SGA versus women not taking supplements (aOR = 0.64, 95% CI [0.42, 0.99]). This association was identified in mothers both with (aOR = 0.57, 95% CI [0.40, 0.81]) and without (aOR = 0.64, 95% CI [0.64, 0.97]) anaemia. In women in the control group without anaemia, iron supplementation >40 mg/day was positively associated with gestational diabetes (aOR = 6.32, 95% CI [1.97, 20.23]). Iron supplementation in pregnancy may prevent SGA independently of existing anaemia but may also increase the risk of gestational diabetes., (© 2019 John Wiley & Sons Ltd.)