Cause-Specific Excess Mortality During the COVID-19 Pandemic (2020-2021) in 12 Countries of the C-MOR Consortium.

BACKGROUND: This study investigated cause-specific mortality rates in 12 countries during the COVID-19 pandemic in 2020 and 2021. METHODS: We collected weekly cause-specific mortality data from respiratory disease, pneumonia, cardiovascular disease (CVD) and cancer from national vital statistic databases. We calculated excess mortality for respiratory disease (excluding COVID-19 codes), pneumonia, and CVD in 2020 and 2021 by comparing observed weekly against expected mortality based on historical data (2015-2019), accounting for seasonal trends. We used multilevel regression models to investigate the association between country-level pandemic-related variables and cause-specific mortality. RESULTS: Significant reductions in cumulative mortality from respiratory disease and pneumonia were observed in 2020 and/or 2021, except for Georgia, Northern Ireland, Kazakhstan, and Ukraine, which exhibited excess mortality for one or both causes. Australia, Austria, Cyprus, Georgia, and Northern Ireland experienced excess cumulative CVD mortality in 2020 and/or 2021. Australia, Austria, Brazil, Cyprus, Georgia, Northern Ireland, Scotland and Slovenia, experienced increased crude cumulative cancer mortality during 2020 and/or 2021 compared to previous years. Among pandemic-related variables, reported COVID-19 incidence was negatively associated with increased cancer mortality, excess respiratory, (2020) and pneumonia (2021) mortality, and positively associated with respiratory and CVD mortality (2021). Stringency of control measures were negatively associated with excess respiratory disease, CVD, and increased cancer mortality (2021). CONCLUSIONS: This study provides evidence of substantial excess mortality from CVD, and notable reductions in respiratory disease and pneumonia in both years across most countries investigated. Our study also highlights the beneficial impact of stringent control measures in mitigating excess mortality from most causes in 2021.

Barriers and facilitators for adopting healthy lifestyles in breast cancer survivors: a scoping review protocol.

OBJECTIVE: This scoping review will identify barriers and facilitators for the adoption of 7 healthy lifestyle components by female breast cancer survivors. This will be achieved by mapping the World Cancer Research Fund/American Institute for Cancer Research recommendations and the Lifestyle Medicine pillars. INTRODUCTION: Adherence to healthy lifestyle components (including weight management, physical activity, healthy diet, restorative sleep, avoidance of risky substances, forming and maintaining healthy relationships, and stress management) may improve the quality of life of breast cancer survivors and reduce the risk of adverse patient outcomes. However, cancer survivors' adherence to recommendations of multiple healthy lifestyle components is low, and decreases over time. INCLUSION CRITERIA: The review will consider peer-reviewed studies investigating barriers and facilitators for adopting any of the 7 healthy lifestyle components by female adult (18+ years old) breast cancer survivors (ie, from the time of diagnosis) in community, hospital, and/or cancer care settings, without any geographical restrictions. All study designs and articles published in English will be included. METHODS: The review will follow the JBI methodology for scoping reviews. Databases to be searched will include MEDLINE (PubMed), Embase, CINAHL (EBSCOhost), PsycINFO (Ovid), and the Cochrane Library databases. Articles published from 2007 to the present will be considered since this was the year in which the World Cancer Research Fund/American Institute for Cancer Research recommendations were published. Two independent reviewers will screen the retrieved articles and extract the data. Barriers and facilitators for each lifestyle component will be grouped according to the Theoretical Domain Framework. A narrative summary will explicate the charted data. REVIEW REGISTRATION: Open Science Framework https://osf.io/cn3va.

Lifestyle habits of adults during the COVID-19 pandemic lockdown in Cyprus: evidence from a cross-sectional study.

BACKGROUND: The COVID-19 pandemic and the widespread adoption of virus control measures have inevitably disrupted efforts to address lifestyle risk factors for non-communicable diseases (NCD). This study aimed to explore the effects of COVID-19 lockdown on all lifestyle medicine pillars, namely diet, physical activity, sleep, stress, social support and use of risky substances. METHODS: This was a cross-sectional study on a convenient sample of adults who resided in Cyprus during the Spring 2020 lockdown. Participants completed an anonymous online questionnaire comprised of six validated tools regarding the following lifestyle behaviours before and during lockdown: adherence to the Mediterranean diet, physical activity, stress and social support levels, sleep pattern and use of risky substances such as smoking and alcohol. Paired before and during lockdown comparisons for each lifestyle pillar were undertaken using Wilcoxon Signed-Rank test and Bowker symmetry Test where response was numerical (non-parametric data) and categorical respectively. Furthermore, stratified analyses for sociodemographic characteristics were performed. RESULTS: Out of 745 participants, 74% were female and median age was 39 years. Overall participants reported significantly higher perceived stress score (22 v 25, p <  0.01), lower social support score (71 v 68, p <  0.001), and worse sleep quality score (4 v 5, p <  0.01) during lockdown. Mediterranean diet (MD) adherence was moderate and increased significantly only in those practicing religious fasting (score of 6 v 7, p <  0.01). Total minutes spent sitting increased (120 v 180, p <  0.01) although overall physical activity score did not significantly change. Smoking intensity increased during lockdown whilst frequency of alcohol consumption decreased (ptrend = 0.03 and <  0.01, respectively). CONCLUSION: Various lifestyle factors were adversely affected by the COVID-19 lockdown in Cyprus. Evidence from this study supports development of holistic lifestyle interventions during and following the pandemic to reduce short and long-term NCD risks by building on lifestyle behaviour strengths and addressing longstanding and emerging gaps and needs.

Developing a holistic contingency plan: Challenges and dilemmas for cancer patients during the COVID-19.

During the first quarter of 2020 the world is experiencing a pandemic of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), a novel beta coronavirus that is responsible for the 2019 novel coronavirus disease (COVID-19). The COVID-19 pandemic revealed that healthcare systems around the world were not prepared to deal with either the direct effects of the pandemic or with the indirect effects that are imposed on the health of patients with chronic disorders such as cancer patients. Some challenges and dilemmas currently faced during the pandemic include the management of cancer patients during the treatment and follow-up phases, the assessment of the safety of treatments currently used for the management of SARS-CoV-2 for use in cancer patients, the development of psychoeducation and emotional support for cancer patients and the safe conduct of clinical trials involving participation of cancer patients. Evidence from the literature supports the need for the urgent development of a holistic contingency plan which will include clear guidelines for the protection and comprehensive care of cancer patients. The implementation of such a plan is expected to have many beneficial effects by mainly minimizing the increased morbidity and mortality of cancer patients that could result as an adverse consequence of the COVID-19 or future pandemics.

The Effects of Diet and Dietary Interventions on the Quality of Life among Breast Cancer Survivors: A Cross-Sectional Analysis and a Systematic Review of Experimental Studies.

There is an ongoing need for solid evidence about the effects of healthy behaviors, and particularly diet, on the quality of life (QoL) among breast cancer survivors. We first conducted a cross-sectional study on 68 Italian stage I-III breast cancer survivors, to investigate the association of adherence to the Mediterranean diet (MD), physical activity and weight status with QoL. Adherence to MD and physical activity was assessed using structured questionnaires. QoL was assessed using the European Organization for the Research and Treatment of Cancer Quality-of-Life tools. We showed that low consumption of red meat and carbonated beverages, daily consumption of wine and high consumption of dishes seasoned with sofrito had beneficial effects on several QoL subscales. By contrast, using olive oil as the main culinary fat, low consumption of commercial sweets and high consumption of nuts were associated with negative effects. Overall, these findings resulted in a null effect of adherence to MD on QoL. Furthermore, we observed better QoL sub-scores among women who performed moderate physical activity (i.e., diarrhea) and those who were underweight/normal weight (i.e., physical functioning and dyspnea) if compared with their counterparts (p-values ≤ 0.003 after correction for multiple comparison). Next, we performed a systematic review of nine experimental studies to summarize whether dietary interventions might improve QoL among breast cancer patients. All the studies demonstrated significant improvements in overall QoL and/or its subscales after the interventions. However, differences in study design, interventions and tools used for QoL assessment did not allow us to provide an overall estimate. Moreover, only a single-arm trial evaluated the effect of an exclusive dietary-based intervention, while others combined dietary recommendations with physical activity and weight loss programs. For these reasons, our study encourages more efforts to improve the robustness of current evidence, through more homogenous tools, larger population-based studies and further randomized controlled trials.

Dietary Patterns are Associated with Leukocyte LINE-1 Methylation in Women: A Cross-Sectional Study in Southern Italy.

Bioactive food compounds have different effects on global DNA methylation, an epigenetic mechanism associated with chromosomal stability and genome function. Since the diet is characterized by a mixture of foods, we aimed to identify dietary patterns in women, and to evaluate their association with long interspersed nuclear elements (LINE-1) methylation, a surrogate marker of global DNA methylation. We conducted an observational cross-sectional study of 349 women from Southern Italy, with no history of severe diseases. Dietary patterns were derived by food frequency questionnaire and principal component analysis. LINE-1 methylation of leukocyte DNA was assessed by pyrosequencing. We observed that intake of wholemeal bread, cereals, fish, fruit, raw and cooked vegetables, legumes, soup, potatoes, fries, rice, and pizza positively correlated with LINE-1 methylation levels. By contrast, vegetable oil negatively correlated with LINE-1 methylation levels. Next, we demonstrated that adherence to a prudent dietary pattern-characterized by high intake of potatoes, cooked and raw vegetables, legumes, soup and fish-was positively associated with LINE-1 methylation. In particular, women in the 3rd tertile exhibited higher LINE-1 methylation level than those in the 1st tertile (median = 66.7 %5mC; IQR = 4.67 %5mC vs. median = 63.1 %5mC; IQR = 12.3 %5mC; p < 0.001). Linear regression confirmed that women in the 3rd tertile had higher LINE-1 methylation than those in the 1st tertile (ß = 0.022; SE = 0.003; p < 0.001), after adjusting for age, educational level, employment status, smoking status, use of folic acid supplement, total energy intake and body mass index. By contrast, no differences in LINE-1 methylation across tertiles of adherence to the Western dietary pattern were evident. Interestingly, women who exclusively adhered to the prudent dietary pattern had a higher average LINE-1 methylation level than those who exclusively or preferably adhered to the Western dietary pattern (ß = 0.030; SE = 0.004; p < 0.001; ß = 0.023; SE = 0.004; p < 0.001; respectively), or those with no preference for a specific dietary pattern (ß = 0.013; SE = 0.004; p = 0.002). Our study suggested a remarkable link between diet and DNA methylation; however, further mechanistic studies should be encouraged to understand the causal relationship between dietary intake and DNA methylation.

Mediterranean Diet and Particulate Matter Exposure Are Associated With LINE-1 Methylation: Results From a Cross-Sectional Study in Women.

Emerging evidence suggests that air pollution increases the risk of cardiovascular disease (CVD) and metabolic disorders, adding to the global burden of disease attributable to lifestyle and behavioral factors. Although long interspersed nucleotide elements 1 (LINE-1) methylation has been associated with these disorders, no studies have simultaneously examined the effects of diet and air pollution exposure on DNA methylation. Herein, we evaluated the association of particulate matter (PM with aerodynamic diameters of less than 10 mm) exposure and adherence to Mediterranean Diet (MD) with LINE-1 methylation. Healthy women (n = 299), aged 15 to 80 years, were enrolled in a cross-sectional study. Dietary data and adherence to MD were assessed by a Food Frequency Questionnaire (FFQ) and Mediterranean Diet Score (MDS). PM10 levels during 1-month before recruitment were recorded by monitoring stations and assigned to each woman based on their residential address and day of recruitment. LINE-1 methylation in blood samples was assessed by pyrosequencing and reported as percentage of 5-methylcytosine (5mC). The Mann-Whitney U test, Spearman's rank correlation test and linear regression models were applied. Our results demonstrated, for the first time, an inverse association between adherence to MD and exposure to PM10 with LINE-1 methylation: while higher monthly PM10 exposure decreases LINE-1 methylation level (ß = -0.121; p = 0.037), the adherence to MD increases it (ß = 0.691; p < 0.001). MDS seemed to interact with PM10 levels (p = 0.002) on LINE-1 methylation, as such we confirmed that the effect of MD decreased with increasing PM10 levels (ß = 0.657; p < 0.001 in the first tertile; ß = 0.573; p < 0.001 in the second tertile; ß = 0.551; p < 0.001 in the third tertile). Thus, we suggest that LINE-1 methylation is a possible mechanism underpinning environment-related health effects, and encourage further research to evaluate whether the adherence to the MD could counteract the negative effect of PM10 exposure.

The Association of Dietary Patterns with High-Risk Human Papillomavirus Infection and Cervical Cancer: A Cross-Sectional Study in Italy.

Specific foods and nutrients help prevent the progression of persistent high-risk human papillomavirus (hrHPV) infection to cervical cancer (CC). The aim of this study was to investigate dietary patterns which may be associated with hrHPV status and the risk of high-grade cervical intraepithelial neoplasia (CIN2+). Overall, 539 eligible women, including 127 with CIN2+, were enrolled in a cross-sectional study, and tested for hrHPV infection. Food intake was estimated using a food frequency questionnaire. Logistic regression models were applied. Using the Mediterranean Diet Score, we demonstrated that, among 252 women with a normal cervical epithelium, medium adherence to the Mediterranean diet decreased the odds of hrHPV infection when compared to low adherence (adjOR = 0.40, 95%CI = 0.22-0.73). Using the principal component analysis, we also identified two dietary patterns which explained 14.31% of the variance in food groups intake. Women in the third and fourth quartiles of the "Western pattern" had higher odds of hrHPV infection when compared with first quartile (adjOR = 1.77, 95% CI = 1.04-3.54 and adjOR = 1.97, 95%CI = 1.14-4.18, respectively). Adjusting for hrHPV status and age, women in the third quartile of the "prudent pattern" had lower odds of CIN2+ when compared with those in the first quartile (OR = 0.50, 95%CI = 0.26-0.98). Our study is the first to demonstrate the association of dietary patterns with hrHPV infection and CC and discourages unhealthy habits in favour of a Mediterranean-like diet.

Potential testing of reprocessing procedures by real-time polymerase chain reaction: A multicenter study of colonoscopy devices.

BACKGROUND: Reprocessing of endoscopes is key to preventing cross-infection after colonoscopy. Culture-based methods are recommended for monitoring, but alternative and rapid approaches are needed to improve surveillance and reduce turnover times. A molecular strategy based on detection of residual traces from gut microbiota was developed and tested using a multicenter survey. METHODS: A simplified sampling and DNA extraction protocol using nylon-tipped flocked swabs was optimized. A multiplex real-time polymerase chain reaction (PCR) test was developed that targeted 6 bacteria genes that were amplified in 3 mixes. The method was validated by interlaboratory tests involving 5 reference laboratories. Colonoscopy devices (n = 111) were sampled in 10 Italian hospitals. Culture-based microbiology and metagenomic tests were performed to verify PCR data. RESULTS: The sampling method was easily applied in all 10 endoscopy units and the optimized DNA extraction and amplification protocol was successfully performed by all of the involved laboratories. This PCR-based method allowed identification of both contaminated (n = 59) and fully reprocessed endoscopes (n = 52) with high sensibility (98%) and specificity (98%), within 3-4 hours, in contrast to the 24-72 hours needed for a classic microbiology test. Results were confirmed by next-generation sequencing and classic microbiology. CONCLUSIONS: A novel approach for monitoring reprocessing of colonoscopy devices was developed and successfully applied in a multicenter survey. The general principle of tracing biological fluids through microflora DNA amplification was successfully applied and may represent a promising approach for hospital hygiene.

LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia.

BACKGROUND: Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women. METHODS: Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion. RESULTS: Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01-1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%). CONCLUSIONS: LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations are necessary to propose and validate a novel methylation biomarker panel, based on LINE-1 methylation and other differentially methylated regions, for the screening of women at risk of CC.

DAPK1 Promoter Methylation and Cervical Cancer Risk: A Systematic Review and a Meta-Analysis.

OBJECTIVE: The Death-Associated Protein Kinase 1 (DAPK1) gene has been frequently investigated in cervical cancer (CC). The aim of the present study was to carry out a systematic review and a meta-analysis in order to evaluate DAPK1 promoter methylation as an epigenetic marker for CC risk. METHODS: A systematic literature search was carried out. The Cochrane software package Review Manager 5.2 was used. The fixed-effects or random-effects models, according to heterogeneity across studies, were used to calculate odds ratios (ORs) and 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by histological type, assays used to evaluate DAPK1 promoter methylation, and control sample source. RESULTS: A total of 20 papers, published between 2001 and 2014, on 1929 samples, were included in the meta-analysis. DAPK1 promoter methylation was associated with an increased CC risk based on the random effects model (OR: 21.20; 95%CI = 11.14-40.35). Omitting the most heterogeneous study, the between study heterogeneity decreased and the association increased (OR: 24.13; 95% CI = 15.83-36.78). The association was also confirmed in all the subgroups analyses. CONCLUSIONS: A significant strong association between DAPK1 promoter methylation and CC was shown and confirmed independently by histological tumor type, method used to evaluate methylation and source of control samples. Methylation markers may have value in early detection of CC precursor lesions, provide added reassurances of safety for women who are candidates for less frequent screens, and predict outcomes of women infected with human papilloma virus.

Low fruit consumption and folate deficiency are associated with LINE-1 hypomethylation in women of a cancer-free population.

Several dietary agents, such as micronutrient and non-nutrient components, the so-called bioactive food components, have been shown to display anticancer properties and influence genetic processes. The most common epigenetic change is DNA methylation. Hypomethylation of long interspersed elements (LINE-1) has been associated with an increased risk of several cancers, although conflicting findings have also been observed. The aim of the present study was to test the hypothesis that a low adherence to the Mediterranean diet (MD) and folate deficiency may cause LINE-1 hypomethylation in blood leukocytes of healthy women, and thus genomic instability. One hundred and seventy-seven non-pregnant women were enrolled. Mediterranean diet score (MDS) and folate intake were calculated using a food frequency questionnaire. LINE-1 methylation level was measured by pyrosequencing analysis in three CpG sites of LINE-1 promoter. According to MDS, only 9.6 % of subjects achieved a high adherence to MD. Taking into account the use of supplements, there was a high prevalence of folate deficiency (73.4 %). Women whose consumption of fruit was below the median value (i.e., <201 gr/day) were 3.7 times more likely to display LINE-1 hypomethylation than women whose consumption was above the median value (OR 3.7; 95 % CI 1.4-9.5). Similarly, women with folate deficiency were 3.6 times more likely to display LINE-1 hypomethylation than women with no folate deficiency (OR 3.6; 95 % CI 1.1-12.1). A dietary pattern characterized by low fruit consumption and folate deficiency is associated with LINE-1 hypomethylation and with cancer risk.

Risk of surgical site infection in older patients in a cohort survey: targets for quality improvement in antibiotic prophylaxis.

The aims of the present study were to: (1) assess surgical site infection (SSI) incidence in a cohort of surgical patients and (2) estimate the compliance with national guidelines for perioperative antibiotic prophylaxis (PAP). SSIs, among the most common health care-associated infections, are an important target for surveillance and an official priority in several European countries. SSI commonly complicates surgical procedures in older people and is associated with substantial attributable mortality and costs. The implementation of PAP guidelines is difficult among surgeons, and failure to comply with the standard of care has been widely reported. A 12-month prospective survey was performed in accordance with the methods, protocols, and definitions of the Hospital in Europe Link for Infection Control through Surveillance (HELICS) protocol. The compliance of the current PAP practices with the published national guidelines was assessed. A total of 249 patients were enrolled. The cumulative SSI incidence was 3.2 per 100 operative procedures. Cumulative compliance for PAP was 12.4%. Overall, only infection risk index ≥ 1 was confirmed as a significant risk factor for SSI (odds ratio, 6.65; 95% confidence interval, 1.04-42.59; P = 0.045). When only older patients (age >65 years) were considered, no significant risk factors for SSI were identified. Our study indicates an overall inadequate compliance with PAP recommendations, thus highlighting the need to develop multimodal and targeted intervention programs to improve compliance with PAP guidelines.

LINE-1 hypomethylation in blood and tissue samples as an epigenetic marker for cancer risk: a systematic review and meta-analysis.

OBJECTIVE: A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other tissues as an epigenetic marker for cancer risk. METHODS: A systematic literature search in the Medline database, using PubMed, was conducted for epidemiological studies, published before March 2014. The random-effects model was used to estimate weighted mean differences (MDs) with 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by sample type (tissue or blood samples), cancer types, and by assays used to measure global DNA methylation levels. The Cochrane software package Review Manager 5.2 was used. RESULTS: A total of 19 unique articles on 6107 samples (2554 from cancer patients and 3553 control samples) were included in the meta-analysis. LINE-1 methylation levels were significantly lower in cancer patients than in controls (MD: -6.40, 95% CI: -7.71, -5.09; p<0.001). The significant difference in methylation levels was confirmed in tissue samples (MD -7.55; 95% CI: -9.14, -65.95; p<0.001), but not in blood samples (MD: -0.26, 95% CI: -0.69, 0.17; p = 0.23). LINE-1 methylation levels were significantly lower in colorectal and gastric cancer patients than in controls (MD: -8.33; 95% CI: -10.56, -6.10; p<0.001 and MD: -5.75; 95% CI: -7.75, -3.74; p<0.001) whereas, no significant difference was observed for hepatocellular cancer. CONCLUSIONS: The present meta-analysis adds new evidence to the growing literature on the role of LINE-1 hypomethylation in human cancer and demonstrates that LINE-1 methylation levels were significantly lower in cancer patients than in control samples, especially in certain cancer types. This result was confirmed in tissue samples, both fresh/frozen or FFPE specimens, but not in blood. Further studies are needed to better clarify the role of LINE-1 methylation in specific subgroups, considering both cancer and sample type, and the methods of measurement.

Tumor necrosis factor-alpha -308 G>A polymorphism, adherence to Mediterranean diet, and risk of overweight/obesity in young women.

The present study was conducted in order to (i) characterize the adherence to the Mediterranean diet (MD) pattern and fatty acids (FAs) intakes and (ii) explore interactions between TNFA -308 G>A polymorphism and adherence to MD and FAs intakes, respectively, on overweight/obesity risk. From 2010 to 2013, 380 healthy women were enrolled, and MD score (MDS) and FAs intakes were evaluated by a Food Frequencies Questionnaire in relation to nutritional status. TNFA -308 G/A polymorphism was characterized using PCR-RFLP. A total of 32.6% of women were overweight or obese. Lower mean MDS values were more observed in the younger age group than in the older age group (3.60 versus 4.45). The risk of being overweight/obese was 3.5-fold increased due to poor adherence to MD and was about twofold increased in less educated women. Furthermore, younger age was associated with poor adherence to MD. No evidence for an independent effect of the polymorphism on overweight/obesity risk was found. There was no evidence of biological interaction from the gene-diet interaction analyses. Young women, less educated and with poor adherence to MD, are a target group for the nutritional interventions that aimed to control the obesity risk, thus improving the adherence to MD and particularly the intake of unsaturated FAs.

Folate deficiency is not associated with increased mitochondrial genomic instability: results from dietary intake and lymphocytic mtDNA 4977-bp deletion in healthy young women in Italy.

The mitochondrial DNA (mtDNA) 4977-bp deletion is a biomarker of mitochondrial genomic instability. It is frequently detected in a number of sporadic diseases, and it accumulates in many tissues during aging. Folic acid plays an important role in the maintenance of genomic stability in mammals. The aim of the present cross-sectional study was to characterise the levels of the mtDNA deletion in the lymphocytes of healthy young women, taking into account folate intake, red blood cell (RBC) folate levels and the distribution of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism. Folate intake was estimated by a food frequency questionnaire. Determination of the MTHFR C677T polymorphism and of the mtDNA deletion was performed by real-time polymerase chain reaction analysis. A total of 476 women were enrolled. Low levels of deletion were found (mean ΔCt = 1.24). After multivariate analysis, results did not show any significant relationship between age, smoking habits, pregnancy status, nutritional status, inadequate folate intake, folate deficiency, use of folic acid supplements, MTHFR C677T polymorphism and mtDNA 4977-bp deletions. The lack of association between inadequate folate intake, folate deficiency and mitochondrial genomic instability was confirmed also considering reference values of folate based on DNA damage prevention. Our results indicate that mtDNA 4977-bp deletions are maintained at low levels in lymphocytes of young healthy women despite the wide range of variation of folate intakes and folate status. Future studies, carefully designed to address limits and methodological issues related to variation of this biomarker as an effect of different dietary patterns and of folate status, could provide further insight on the specific mechanisms that are acting in lymphocytes of healthy subjects under observed folate intake.