Mitochondrial DNA methylation is associated with Mediterranean diet adherence in a population of older adults with overweight and obesity.

AbstractIntroductionAdherence to the Mediterranean dietary pattern (MeDiet) and adiposity, respectively, decreases and increases the risk of multiple common age-related diseases through several mechanisms including inflammation, reactive oxygen species (ROS) production in the mitochondria, and DNA methylation. For example, adverse changes in platelets from obese and overweight adults include hyperaggregability and increased ROS. Since platelets are anuclear, their prothrombotic function is fully orchestrated by the mitochondria and the only DNA present is the mitochondrial DNA (mtDNA). In this study, we tested the hypothesis that MeDiet influences patterns of mtDNA methylation in platelets from older adults with greater adiposity.Material and methodsWe selected 134 participants with overweight or obesity (mean BMI = 35.5 ± 5.1 and age = 62 ± 10 years) from the "Susceptibility to particle health effects, miRNA and exosomes"(SPEHRE) Study. Dietary intake was assessed using a food frequency questionnaire and MeDiet adherence was calculated using the MeDiet Score described by Martínez-González et al.(2012). MtDNA was extracted from platelets, linearized, bisulfite converted and DNA methylation was quantified by pyrosequencing at 13 CpG in seven genes that encode for tRNAs (MT-TF and MT-TL1), regulatory regions (D-Loop and MT-OLR), and subunits of the electron-transport-chain (MT-CO1, MT-CO2, and MT-CO3).ResultsIn these participants, MeDiet score ranged from 3 to 12 (mean = 6.5), with higher scores reflecting greater MeDiet adherence. Regression analysis showed that higher MeDiet score was associated with lower D-loop (β = -0.031, P = 0.019) and higher MT-CO2 CpG1 (β = 0.040, P = 0.023) methylation. No associations were found between MeDiet Score and methylation level at MT-CO1(2 CpGs), MT-CO2(CpG2), MT-CO3(2 CpGs), MT-TL1(2 CpGs), MT-TF(CpG1), MT-OLR(3 CpGs).In addition, there was no association between mtDNA methylation and BMI.DiscussionThe D-loop is critical for mitochondrial function since it initiates mtDNA replication and transcription. Increased D-loop methylation has been associated with reduced mitochondrial functionality, and insulin resistance. Our results suggest that higher adherence to MeDiet lowers D-loop methylation which may protect against obesity-related comorbidities (e.g. insulin resistance).Higher MeDiet scores are associated with MT-CO2 CpG1 hypermethylation. MT-CO2 encodes for a subunit of the Cytochrome-C-oxidase, a highly regulated enzyme involved in the oxidative metabolism. MT-CO2 demethylation, induced by Valproic-Acid administration, has been reported to be associated with increased ROS production. Our results suggest a possible role of MeDiet in mitochondrial ROS regulation via methylation of MT-CO2.For the first time, we observed associations between MeDiet adherence and mtDNA methylation. Validation of these findings in independent cohorts is required

Superoxide Dismutase-1 intracellular content in T lymphocytes associates with increased Regulatory T Cell level in Multiple Sclerosis subjects undergoing immune-modulating treatment.

Reactive oxygen species (ROS) participate in the T-cell activation processes. ROS-dependent regulatory networks are usually mediated by peroxides, which are more stable and able to freely migrate inside cells. Superoxide dismutase (SOD)-1 represents the major physiological intracellular source of peroxides. We found that antigen-dependent activation represents a triggering element for SOD-1 production and secretion by human T lymphocytes. A deranged T-cell proinflammatory response characterizes the pathogenesis of multiple sclerosis (MS). We previously observed a decreased SOD-1 intracellular content in leukocytes of MS individuals at diagnosis, with increasing amounts of such enzyme after interferon (IFN)-b 1b treatment. Here, we analyzed in depth SOD-1 intracellular content in T cells in a cohort of MS individuals undergoing immune-modulating treatment. Higher amounts of the enzyme were associated with increased availability of regulatory T cells (Treg) preferentially expressing Foxp3-exon 2 (Foxp3-E2), as described for effective Treg. In vitro administration of recombinant human SOD-1 to activated T cells, significantly increased their IL-17 production, while SOD-1 molecules lacking dismutase activity were unable to interfere with cytokine production by activated T cells in vitro. Furthermore, hydrogen peroxide addition was observed to mimic, in vitro, the SOD-1 effect on IL-17 production. These data add SOD-1 to the molecules involved in the molecular pathways contributing to re-shaping the T-cell cytokine profile and Treg differentiation

Towards operationalizing UNESCO Recommendations on “Historic Urban Landscape”: a position paper

<p>This position paper critically analyses the process to implement the UNESCO Recommendation on the Historic Urban Landscape (2011), exploring evaluation tools, innovative business / management models and financing tools for the conservation and regeneration of Historic Urban Landscape (HUL), to make it operational in the perspective of a circular economy model of sustainable development for city / territory system regeneration. Through evaluation tools, it is possible to pass from general principles to operational practices; to produce empirical evidence of the economic, social and environmental benefits of HUL integrated conservation and regeneration. The challenge of generating a symbiosis between conservation and transformation issues requires adequate evaluation methods, business, management and financing tools, engaging civil society and local stakeholders, capturing both HUL tangible and intangible values to turn the historic urban landscape into a driver of sustainable growth. The analysis carried out in this paper shows that through the suggested tools it is possible to make operational the UNESCO Recommendations, transforming conflicts into opportunities, producing economic attractiveness and strengthen social awareness and cohesion.</p

Effects of the Emissions of Vehicles Ahead on In-Car Exposure to Traffic-Related Air Pollutants: A Multiple Statistical Analysis Approach

Traffic-related air pollutants inside vehicle cabins are often extremely high compared to background pollution concentrations. The study of the determinants of these concentrations is particularly important for professional drivers and commuters who spend long periods in vehicles. This study is aimed at identifying and quantifying the effect of several exposure determinants on carbon monoxide (CO), equivalent black carbon (eBC), two particulate matter (PM) fractions (PM0.3–1 and PM1–2.5), and ultrafine particle (UFP) concentrations inside a passenger car cabin. The novelty of this work consists in examining the effects of the emissions of the first vehicle ahead (henceforth called “leading vehicle”) on pollutant concentrations inside the cabin of the following vehicle (i.e., the car that was equipped with the air monitoring devices), with particular emphasis on the role of the leading vehicle characteristics (e.g., emission reduction technologies). The real-time instrumentation was placed inside the cabin of a petrol passenger car, which was driven by the same operator two times per day on the same route in real driving conditions. The in-cabin ventilation settings were set as follows: windows closed, air conditioning and recirculation modes off, and the fanned ventilation system on. The measurements were conducted over a total of 10 weekdays during two different seasons (i.e., summer and autumn). A video camera fixed to the windscreen was used to retrieve information about traffic conditions and leading vehicle characteristics through careful video analysis. The associations among pollutant concentrations and their potential determinants were evaluated using generalized estimating equation univariate and multiple models. The results confirmed the significant impact of several well-known determinants such as seasonality, microclimatic parameters, traffic jam situations, and route characteristics. Moreover, the outcomes shed light on the key role of leading vehicle emissions as determinant factors of the pollutant concentrations inside car cabins. Indeed, in the tested cabin ventilation conditions, it was demonstrated that in-cabin pollutant concentrations were significantly higher with leading vehicles ahead (from +14.6% to +67.5%) compared to empty road conditions, even though the introduction of newer technologies with better emissions reduction helped mitigate their effect. Additionally, diesel-fuelled leading vehicles compared to petrol-fuelled leading vehicles were impactful on in-cabin CO (−7.2%) and eBC (+45.3%) concentrations. An important effect (+30.4%) on in-vehicle PM1–2.5 concentrations was found with heavy-duty compared to light-duty leading vehicles. Finally, this research pointed out that road-scale factors are more important determinant factors of in-cabin concentrations than local pollution and meteorological conditions

Velocity of Ultrasonic Waves in Solutions of Electrolytes

List of the genes involved in CVDs according to DisGeNET database. For each gene all the related diseases and the putative EV-MiRNAs targeting it are indicated both as list and as number of occurrences. (PDF 1206 kb

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists