Preventing Gestational Diabetes Mellitus by Improving Healthy Diet and/or Physical Activity during Pregnancy: An Umbrella Review

Supplementary Materials: The following are available online at https://www.mdpi.com/article/ 10.3390/nu14102066/s1, Tables S1–S3: Search strategy, Table S4: Excluded studies and justification, Figure S1: Quality of included reviews assessed by Amstar 2, Tables S5–S9: Overlapping assessment, Table S10: Description of physical activity intervention in included systematic reviews, Table S11: Description of diet intervention in included systematic reviews, Table S12: Description of mixed intervention in included systematic review.Acknowledgments: The authors thank Ingrid de Ruiter, MBChB, for English language and editing support. The results of this study are part of the doctoral thesis of Malak Kouiti.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

Dietary Diversity and Prostate Cancer in a Spanish Adult Population: CAPLIFE Study

The authors wish to thank all subjects who participated in the study as well as all CAPLIFE collaborators. The authors also thank Ingrid de Ruiter for English editing support.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.Regional Ministry of Health of Andalusia (Consejeria de Salud de la Junta de Andalucia) PI-0514-201

Compliance with the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and Prostate Cancer

We thank all subjects who participated in the study and all CAPLIFE collaborators and the Ingrid de Ruiter, MBChB, for English language and editing support. The results of this study are part of the doctoral thesis of Macarena Lozano-Lorca.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.This research was funded by Regional Ministry of Health of Andalusia/Consejería de Salud of the Junta de Andalucía (PI-0514-2016) and Instituto de Salud Carlos III-FEDER (PI15/00914)

Dietary Patterns and Prostate Cancer: CAPLIFE Study

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, ORT3vsT1 = 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 aWestern 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.Regional Ministry of Health and Families, Junta de Andalucia/Consejeria de Salud y Familias, Junta de Andalucia PI-0514-201

Health‑related quality of life in patients newly diagnosed with prostate cancer: CAPLIFE study

Funding Funding for open access charge: Universidad de Granada / CBUA. This research was funded by Regional Ministry of Health and Families of Andalusia/Consejería de Salud y Familias de la Junta de Andalucía (PI-0514-2016).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.Funding for open access charge: Universidad de Granada/CBUARegional Ministry of Health and Families of Andalusia/Consejería de Salud y Familias de la Junta de Andalucía (PI-0514-2016

Public healthcare costs associated with long-term exposure to mixtures of persistent organic pollutants in two areas of Southern Spain: A longitudinal analysis

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 (beta 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (beta: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semirural residents, where p-HCH was also marginally-significantly associated to APC (beta: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (beta: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by p-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (beta: 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.CIBER de Epidemiologia y Salud Publica (CIBERESP), Instituto de Salud Carlos III, Spain PI16/01858 PI18/01573 PI20/01568European CommissionRamon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-20,155PFIS (Instituto de Salud Carlos III, Spain) FI17/00310Universidad de Granada/CBU

Effect of Adherence to a Mediterranean Diet and Olive Oil Intake during Pregnancy on Risk of Small for Gestational Age Infants

To quantify the effect of a Mediterranean dietary pattern, as well as the consumption of olive oil (OO), on the risk of having a small for gestational age infants (SGA), a matched case-control study was conducted in Spain. Dietary intake during pregnancy was assessed using a validated food frequency questionnaire. Three indices were used to evaluate the adherence to Mediterranean diet (MD) (Predimed, Trichopoulou and Panagiotakos). Crude odds ratios (cOR) and adjusted odds ratios (aOR) and their 95% confidence intervals (CI) were estimated using conditional logistic regression models. Results were stratified by severity of SGA: moderate (percentiles 6–10), and severe (percentiles _5). For moderate, four or more points in the Predimed´s index was associated with a 41% reduction of having SGA compared with women with a score _3, aOR = 0.59 (95% CI 0.38–0.98); for severe, the reduction in risk was not statistically significant. Similar results were found when the other MD indexes were used. An intake of OO above 5 g/day was associated with a lower risk of SGA (aOR = 0.53, 95% CI 0.34–0.85); statistical significance was observed for moderate SGA (aOR = 0.53, 95% CI 0.30–0.96), but not for severe SGA (aOR = 0.51, 95% CI 0.24–1.07), although the magnitude of ORs were quite similar. Adherence to a MD and OO intake is associated with a reduced risk of SGA.This work was supported by a grant from the National Institute of Health Carlos III (PI11/02199)

Toxic metals in toenails as biomarkers of exposure: A review

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.This work was supported by FIS grants PI12/00150, PI17CIII/00034, PI18/00287 (Instituto de Salud Carlos III, State Secretary of R + D + I and European Union (ERDF/ESF, “Investing in your future")), P42ES010349 and P30ES009089 (National Institute of Environmental Health Sciences).S

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals