Understanding the Origins of Bacterial Resistance to Aminoglycosides through Molecular Dynamics Mutational Study of the Ribosomal A-Site

Paromomycin is an aminoglycosidic antibiotic that targets the RNA of the bacterial small ribosomal subunit. It binds in the A-site, which is one of the three tRNA binding sites, and affects translational fidelity by stabilizing two adenines (A1492 and A1493) in the flipped-out state. Experiments have shown that various mutations in the A-site result in bacterial resistance to aminoglycosides. In this study, we performed multiple molecular dynamics simulations of the mutated A-site RNA fragment in explicit solvent to analyze changes in the physicochemical features of the A-site that were introduced by substitutions of specific bases. The simulations were conducted for free RNA and in complex with paromomycin. We found that the specific mutations affect the shape and dynamics of the binding cleft as well as significantly alter its electrostatic properties. The most pronounced changes were observed in the U1406C∶U1495A mutant, where important hydrogen bonds between the RNA and paromomycin were disrupted. The present study aims to clarify the underlying physicochemical mechanisms of bacterial resistance to aminoglycosides due to target mutations

Dairy products, surrogate markers, and cardiovascular disease; a sex-specific analysis from the ATTICA prospective study

Background and aims: Dairy products are a very diverse food group with multiple effects on the cardiac health of men and women. The aim of this work was to evaluate the sex-specific association between dairy products (total and subtypes) and 10-year first fatal/nonfatal cardiovascular disease (CVD) incidence. Methods and results: In 2001–2002, n = 1514 men and n = 1528 women (>18 years old) from greater Athens area, Greece, were enrolled. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. Dairy product consumption was examined in relation to 10-year CVD incidence. Follow-up (2011–2012) was achieved in n = 2020 participants (n = 317 CVD cases). Ranking from lowest (<1 serving/day) to highest (>2 servings/day) total dairy intake, CVD incidence in men was 17.8%, 15.0%, and 10.9% (p = 0.41), while in women it was 14%, 6.0%, and 5.7% (p = 0.02). Multiadjusted analysis revealed that total dairy intake protected against CVD only in women [Hazard Ratio (HR) = 0.48 and 95% Confidence Interval (95% CI) (0.23, 0.90)], irrespective of the fat content. Further analysis revealed that only fermented products (yogurt and cheese), protected against CVD. For per 200 g/day yogurt consumption, CVD risk was 20%–30% lower with this claim being more evident in women, while for per 30 g/day cheese intake, about 5% lower risk was observed particularly in men. As for butter, nonsignificant associations were highlighted. These associations were mainly retained in the case of hepatic steatosis, insulin resistance, and systemic inflammation. Conclusions: This work provides incentives for researchers to elucidate the diversity of ingredients and mechanisms through which dairy products exert their effect on cardiac health separately for men and women. © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II Universit

Effects of alcohol consumption and the metabolic syndrome on 10-year incidence of diabetes: The ATTICA study

Aim: The purpose of this prospective study was to investigate the effect of alcohol consumption on the 10-year diabetes incidence. Methods: In 2001-2002, a random sample of 1514 men (18-89 years old) and 1528 women (18-87 years old) was selected to participate in the ATTICA study (Athens metropolitan area, Greece). Among various other characteristics, average daily alcohol intakes (abstention, low, moderate, high) and type of alcoholic drink were evaluated. Diabetes was defined according to American Diabetes Association criteria. During 2011-2012, the 10-year follow-up was performed. Results: The 10-year incidence of diabetes was 13.4% in men and 12.4% in women. After making various adjustments, those who consumed up to 1 glass/day of alcohol had a 53% lower diabetes risk (RR = 0.47; 95% CI: 0.26, 0.83) compared with abstainers, while trend analysis revealed a significant U-shaped relationship between quantity of alcohol drunk and diabetes incidence (P< 0.001 for trend). Specific types of drinks were not associated with diabetes incidence; however, a one-unit increase in ratio of wine/beer/vodka vs. other spirits was associated with an 89% lower risk of diabetes (RR = 0.11; 95% CI: 0.02, 0.67). The protective effect of low alcohol consumption on diabetes incidence was more prominent among individuals with stricter adherence to the Mediterranean diet (RR = 0.08; 95% CI: 0.011, 0.70) and without the metabolic syndrome (RR = 0.34; 95% CI: 0.16, 0.70). Conclusion: This work revealed the protective effect of modest alcohol consumption of particularly wine and beer against the long-term incidence of diabetes, possibly due to their pleiotropic health effects. © 2014 Elsevier Masson SAS

Exploring the path of Mediterranean diet on 10-year incidence ofcardiovascular disease: The ATTICA study (2002-2012)

Background and aims: A Mediterranean diet has been associated with lower all-cause and cardiovascular disease (CVD) morbidity and mortality, but the clinical and behavioral pathway has not been well understood and appreciated. The aim of this work was to explore the path between adherence to a Mediterranean-type diet, lifestyle behaviors, clinical status, and a 10-year incidence of CVD. Methods and results: The ATTICA study was carried out in the Athens area during 2001-2002 and included 3042 participants free of CVD at baseline (49.8% men, aged 18-89). Adherence to a Mediterranean diet was assessed using the MedDietScore (range 0-55). During 2011-2012, 2583 out of the 3042 participants were found during the 10-year follow-up (15% lost to follow-up). Adherence to a Mediterranean diet decreased CVD risk (relative Risk (RR) per 1/55 unit = 0.96, 95% confidence interval (CI): 0.93, 1.00), independently of various sociodemographic, lifestyle, and clinical factors. Subgroup analyses revealed that participants with an unhealthy lifestyle (i.e., smokers, and obese and sedentary persons) remained protected from CVD through a greater adherence to a Mediterranean diet (RR for smokers = 0.92, 95%CI: 0.88, 0.97; RR for obese participants = 0.90, 95%CI: 0.82, 0.979; and RR for sedentary participants = 0.95, 95%CI: 0.90, 0.99). Path analysis revealed that adherence to a Mediterranean diet not only decreases the levels of C-reactive protein and interleukin-6 but also has an independent protective role against CVD risk per se (total effect of the MedDietScore on CVD = -0.003, 95%CI: -0.005 to 0.000). Conclusion: Adherence to a Mediterranean diet confers a considerable reduction on CVD risk, independent of various factors. Therefore, even subjects with unhealthy lifestyle behaviors may benefit from adherence to this diet, suggesting another dimension to prevention strategies. © 2014 Elsevier B.V

Dietary patterns and 10-year (2002-2012) incidence of type 2 diabetes: Results from the ATTICA cohort study

AIM: To identify dietary patterns among apparently healthy individuals and to determine their long-term effect on diabetes incidence. METHODS: During 2001-2002, a random sample of 3,042 men and women (18-89 years old), living in greater Athens, was randomly selected to participate in the study. During 2011-2012, the 10-year follow-up was performed in 2,583 participants (15% drop-out rate). After excluding participants with diabetes at baseline and those for whom no information on diabetes status was available at follow- up, the working sample consisted of 1,485 participants. Dietary habits were assessed by means of a validated semiquantitative, food frequency questionnaire. Factor analysis was performed to extract dietary patterns from 18 food groups. RESULTS: Diabetes diagnosis at follow-up was made in 191 participants, yielding an incidence rate of 12.9%. Six factors (i.e. dietary patterns) were identified that explained 54% of the variation in consumption. After adjusting for major confounders, and stratification by age-group, logistic regression revealed that the most healthful pattern consisted of the consumption of fruits, vegetables, legumes, bread, rusk, and pasta which reduced the 10-year diabetes risk by 40%, among participants aged 45-55 years. The association reached marginal statistical significance (95% CI: 0.34, 1.07), while no significant association was observed for the other age-groups. When the analysis was additionally adjusted for carbohydrate percentage, statistical significance was lost completely, suggesting a possibly mediating effect of this macronutrient. CONCLUSIONS: The results confirm the potentially protective effect of a plant-based dietary pattern in the primary prevention of diabetes, in particular among middle-aged people. Carbohydrate content may be a specific factor in this relationship; other micronutrients found in plant-based food groups may also play a role. © by Lab & Life Press/SBDR

Mediterranean diet and 10-year (2002-2012) incidence of diabetes and cardiovascular disease in participants with prediabetes: The ATTICA study

BACKGROUND: Prediabetes has been related to an increased risk of developing diabetes and cardiovascular disease (CVD). AIM: The aim of the present study was to examine the effect of the Mediterranean diet on diabetes and CVD risk in subjects with impaired fasting glucose (IFG, i.e. fasting plasma glucose 100-125 mg/dl). METHODS: During 2001-2002, 3042 men and women (>18y) were enrolled for the study. The participants showed no clinical evidence of CVD or any other chronic disease, and were living in the greater Athens (Greece) area. In 2011 and 2012, the 10-year follow-up examinations were performed, including a working sample of n = 1875 participants without diabetes at baseline. Adherence to the Mediterranean diet at baseline evaluation was assessed using the MedDietScore (range 0-55). RESULTS: The prediabetic subjects (n = 343) had a significantly higher incidence of diabetes (25% vs. 10%, p < 0.001) and CVD (17.8% vs. 12.3%, p = 0.007) compared with subjects with normal glucose values. A significant trend towards lower diabetes and CVD incidence was observed with medium and high adherence to the Mediterranean diet compared with low adherence (p < 0.001). High adherence to the Mediterranean diet (>35/55 score) was associated with lower 10-year incidence of diabetes and CVD. In multiple logistic regression models, participants with high levels of adherence to the Mediterranean diet were significantly less affected by diabetes and CVD than those with low adherence levels. CONCLUSION: High adherence to the Mediterranean diet is associated with a low risk of developing diabetes and CVD in prediabetic subjects. © by Lab & Life Press/SBDR

Metabolic syndrome, adherence to the Mediterranean diet and 10-year cardiovascular disease incidence: The ATTICA study

Background and aims: To better understand the metabolic syndrome (MS) spectrum through principal components analysis and further evaluate the role of the Mediterranean diet on MS presence. Methods: During 2001-2002, 1514 men and 1528 women (>18y) without any clinical evidence of CVD or any other chronic disease, at baseline, living in greater Athens area, Greece, were enrolled. In 2011-2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal CVD was defined according to WHO-ICD-10 criteria. MS was defined by the National Cholesterol Education Program Adult Treatment panel III (revised NCEP ATP III) definition. Adherence to the Mediterranean diet was assessed using the MedDietScore (range 0-55). Results: Five principal components were derived, explaining 73.8% of the total variation, characterized by the: a) body weight and lipid profile, b) blood pressure, c) lipid profile, d) glucose profile, e) inflammatory factors. All components were associated with higher likelihood of CVD incidence. After adjusting for various potential confounding factors, adherence to the Mediterranean dietary pattern for each 10% increase in the MedDietScore, was associated with 15% lower odds of CVD incidence (95%CI: 0.71-1.06). For the participants with low adherence to the Mediterranean diet all five components were significantly associated with increased likelihood of CVD incidence. However, for the ones following closely the Mediterranean pattern positive, yet not significant associations were observed. Conclusion: Results of the present work propose a wider MS definition, while highlighting the beneficial role of the Mediterranean dietary pattern. © 2015 Elsevier Ireland Ltd

Adherence to mediterranean diet offers an additive protection over the use of statin therapy: Results from the ATTICA study (2002-2012)

Background and Aims: The protective role of Mediterranean diet on cardiovascular disease (CVD) risk has been extensively discussed in the literature, but its incremental effect over the use of CVD risk reducing agents (such as hypolipidemic treatment) has rarely been evaluated. Methods: The ATTICA study was carried out in the Athens area during 2001-2002 and included 3042 participants free of CVD at baseline (49.8% men, aged 18-89 years). Adherence to Mediterranean diet was assessed using the MedDietScore (range 0-55) and statin use was recorded for all subjects. During 2011-2012, 2583 out of the 3042 baseline participants attended the 10-year follow-up of the ATTICA study (15% lost-to-follow-up) and CVD development was recorded. Results: Adherence to Mediterranean diet (highest tertile) decreased CVD risk by 29.3% (Hazard Ratio (HR): 0.707, 95% Confidence Intervals (CI): 0.537-0.831) as compared with the lowest tertile, independently of statin use. Patients with hyperlipidemia on a statin that adopted unhealthy dietary habits (lowest tertile) had 75% increased CVD risk than normolipidemic subjects with healthy dietary habits (HR=1.75, 95%CI: 1.33-2.29). The addition of Mediterranean diet tertiles in the multivariable model reclassified 46.7% of the participants to CVD risk categories. Conclusion: Adherence to Mediterranean diet confers a considerable reduction in CVD risk, independently of gender, age, family history of CVD, diabetes mellitus, smoking status, hypertension and physical activity status. Therefore, CVD prevention strategies should involve the implementation of a Mediterranean diet in both the general population and patients on a statin. © 2015 Bentham Science Publishers