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• PM 10 exposure negatively affects parameters of folliculogenesis during assisted reproduction procedures. • Rapid changes of ambient PM 10 concentration have been associated with cumulative pregnancy rates. • Particulate matter may affect the results of assisted reproduction procedures in the Lombardy region, north-west Italy. The harmful effect of polluted air on spontaneous fertility has been consistently reported. However, the specific pollutants involved in determining this effect are still to be clarified. The study of Assisted Reproductive Technology (ART) populations is particularly helpful in this context since it allows to monitor the key events of the reproductive process. We analyzed the medical records of 2122 patients who underwent fresh or frozen ART cycles during 2014–2017 in the Lombardy region, north-west Italy. Each subject was assigned the daily PM 10 estimates concentration, at the municipality of residence, during the induction of multiple follicular growth. A multivariable linear regression model with a repeated-measures design was used to estimate the association between short-term exposure to PM 10 and ART outcomes, A reduction in the number of retrieved oocytes in association with 10 μg/m3 increment of the pollutant estimated at 13–14 days before oocyte retrieval (Day 0) and a decrease in the percentage of metaphase II oocytes for 1-week and 2-weeks mean exposure before day 0 were observed. For cumulative pregnancies, a significant lag time change effect for PM 10 exposure (Day -9−0) has been detected, by means of multivariable logistic regression models. An increase in PM 10 exposure was associated with a decrease in clinical and ongoing pregnancies while a decrease in PM 10 exposure was associated with a significant increase in pregnancy rates. In a population living in a highly polluted area in Italy, we added suggestive evidence of a negative association between ART outcomes and PM 10 exposure after controlling for known risk factors for ART success rate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The association between obesity and cardiovascular disease (CVD) is proven, but why some adults with obesity develop CVD while others remain disease-free is poorly understood. Here, we investigated whether mitochondrial DNA (mtDNA) methylation in platelets is altered prior to CVD development in a population of adults with overweight and obesity. Methods: We devised a nested case-control study of 200 adults with overweight or obesity who were CVD-free at baseline, of whom 84 developed CVD within 5 years, while 116 remained CVD-free. Platelet mtDNA was isolated from plasma samples at baseline, and mtDNA methylation was quantified in mitochondrially encoded cytochrome-C-oxidase I (MT-CO1; nt6797 and nt6807), II (MT-CO2; nt8113 and nt8117), and III (MT-CO3; nt9444 and nt9449); tRNA leucine 1 (MT-TL1; nt3247 and nt3254); D-loop (nt16383); tRNA phenylalanine (MT-TF; nt624); and light-strand-origin-of-replication (MT-OLR; nt5737, nt5740, and nt5743) by bisulfite-pyrosequencing. Logistic regression was used to estimate the contribution of mtDNA methylation to future CVD risk. ROC curve analysis was used to identify the optimal mtDNA methylation threshold for future CVD risk prediction. A model was generated incorporating methylation at three loci (score 0, 1, or 2 according to 0, 1, or 2–3 hypermethylated loci, respectively), adjusted for potential confounders, such as diastolic and systolic blood pressure, fasting blood glucose, and cholesterol ratio. mtDNA methylation at MT-CO1 nt6807 (OR = 1.08, 95% CI 1.02–1.16; P = 0.014), MT-CO3 nt9444 (OR = 1.22, 95% CI 1.02–1.46, P = 0.042), and MT-TL1 nt3254 (OR = 1.30, 95% CI 1.05–1.61, P = 0.008) was higher at baseline in those who developed CVD by follow-up, compared with those who remained CVD-free. Combined use of the three loci significantly enhanced risk prediction, with hazard ratios of 1.38 (95% CI 0.68–2.78) and 2.68 (95% CI 1.41–5.08) for individuals with score 1 or 2, respectively (P = 0.003). Methylation at these sites was independent of conventional CVD risk factors, including inflammation markers, fasting blood glucose concentration, and blood pressure. Conclusions: Methylations of MT-CO1, MT-CO3, and MT-TL1 are, together, strong predictors of future CVD incidence. Since methylation of these mtDNA domains was independent of conventional CVD risk factors, these markers may represent a novel intrinsic predictor of CVD risk in adults with overweight and obesity. [ABSTRACT FROM AUTHOR]

Background Overweight and obesity are becoming more widespread with alarming projections for the coming years. Obesity may increase susceptibility to the adverse effects of PM exposure, exacerbating the effects on cardiovascular diseases and altering the biomarkers of vascular inflammation. The associated biological mechanisms have not been fully understood yet; the common denominator in the pathogenesis of the co-morbidities of obesity is the presence of an active, low-grade inflammatory process. DNA methylation has been shown to regulate inflammatory pathways that are responsible for the development of cardiovascular diseases. Objectives The aim of the study was to investigate, in a population of overweight/obese subjects, the effects of PM on blood DNA methylation in genes associated to inflammatory response. Methods Using bisulfite pyrosequencing, we measured DNA methylation in peripheral blood mononuclear cells from 186 overweighted/obese subjects. In particular, we quantified DNA methylation in a set of 3 candidate genes, including CD14, TLR4 and TNF-α, because of the important roles that these genes play in the inflammatory pathway. Personal exposure to PM 10 was estimated for each subject based on the local PM 10 concentrations, measured by monitoring stations at residential address. Repeated measure models were used to evaluate the association of PM10 with each genes, accounting for possible correlations among the genes that regulate the same inflammatory pathway. Results We found an inverse association between the daily PM 10 exposure and the DNA methylation of inflammatory genes, measured in peripheral blood of healthy overweight/obese subjects. Considering different exposure time-windows, the effect on CD14 and TLR4 methylation was observed, respectively, in days 4–5-6, and days 6–7-8. TNF-α methylation was not associated to PM 10 . Conclusions Our findings support a picture in which PM 10 exposure and transcriptional regulation of inflammatory gene pathway in obese subjects are associated. [ABSTRACT FROM AUTHOR]

• Short-term PM 10 and PM 2.5 exposures were associated with increased concentrations of plasmatic EVs. • Increased Sync-1 + EV levels were associated with the plasmatic decrease of the circulating endothelial dysfunction biomarker sVCAM-1. • The EV-miRNA dysregulated in response to both PM 10 and PM 2.5 exposures exhibited putative roles in inflammation, gestational hypertension, and pre-eclampsia. The impact of exposure to respirable particulate matter (PM) during pregnancy is a growing concern, as several studies have associated increased risks of adverse pregnancy and birth outcomes, and impaired intrauterine growth with air pollution. The molecular mechanisms responsible for such effects are still under debate. Extracellular vesicles (EVs), which travel in body fluids and transfer microRNAs (miRNAs) between tissues (e.g., pulmonary environment and placenta), might play an important role in PM-induced risk. We sought to determine whether the levels of PM with aerodynamic diameters of ≤10 µm (PM 10) and ≤2.5 µm (PM 2.5) are associated with changes in plasmatic EV release and EV-miRNA content by investigating 518 women enrolled in the INSIDE study during the first trimester of pregnancy. In all models, we included both the 90-day averages of PM (long-term effects) and the differences between the daily estimate of PM and the 90-day average (short-term effects). Short-term PM 10 and PM 2.5 were associated with increased concentrations of all seven EV types that we assayed (positive for human antigen leukocyte G (HLA-G), Syncytin-1 (Sync-1), CD14, CD105, CD62e, CD61, or CD25 determinants), while long-term PM 10 showed a trend towards decreased EV concentrations. Increased Sync-1 + EV levels were associated with the plasmatic decrease of sVCAM-1, but not of sICAM-1, which are circulating biomarkers of endothelial dysfunction. Thirteen EV-miRNAs were downregulated in response to long-term PM 10 and PM 2.5 variations, while seven were upregulated (p-value < 0.05, false discovery rate p-value (qFDR) < 0.1). Only one EV-miRNA (hsa-miR-221-3p) was downregulated after short-term variations. The identified PM-modulated EV-miRNAs exhibited putative roles in inflammation, gestational hypertension, and pre-eclampsia, as highlighted by miRNA target analysis. Our findings strongly support the hypothesis that EVs have an important role in modulating PM exposure effects during pregnancy, possibly through their miRNA cargo. [ABSTRACT FROM AUTHOR]

Maternal exposure to air pollutants has been associated with pregnancy complications and adverse birth outcomes. Endothelial dysfunction, an imbalance in vascular function, during pregnancy is considered a key element in the development of pre-eclampsia. Environmental exposure to particulate matter (PM) during the first trimester of pregnancy might increase maternal inflammatory status thus affecting fetal growth, possibly leading to preterm delivery. The purpose of the study was to evaluate possible effects of PM 10 and PM 2.5 exposure on fetal growth in healthy pregnant women at the end of the first trimester of pregnancy by investigating the relationship between circulating biomarkers of inflammation (IL-6), early systemic prothrombotic effects (CRP, plasma fibrinogen, PAI-1) and endothelial dysfunction (sICAM-1 and sVCAM-1). 295 pregnant women were recruited. Individual PM exposure was assigned to each subject by calculating the mean of PM 10 and PM 2.5 daily values observed during the 30, 60, and 90 days preceding enrolment (long-term) and single lag days back to fourteen days (short-term), and circulating plasma biomarkers were determined. For long-term exposure, we observed an increase in sVCAM-1 and a decrease of PAI-1 levels for each 10 μg/m3 increase in PM 10 concentration. Decreases in IL-6 and CRP levels were associated with each 10 μg/m3 PM 2.5 increase. For short-term exposure, the levels of sVCAM-1 and PAI-1 were found to be associated with PM 10 exposure, whereas fibrinogen levels were associated with PM 2.5 exposure. Maternal plasmatic fibrinogen levels were negatively associated with the crown-rump length (p-value = 0.008). The present study showed that both long- and short-term exposures to PM are associated with changes in circulating levels of biomarkers in pregnant women reflecting systemic inflammation and endothelial dysfunction/activation. Our findings support the hypothesis that inflammation and endothelial dysfunction might have a central role in modulating the detrimental effects of air pollution exposure during pregnancy. • Maternal exposure to PM during pregnancy may affect fetal growth. •Systemic inflammation and endothelial dysfunction are the underlying mechanisms. •sVCAM-1 and PAI-1 levels were associated with PM10 concentration. •Decreases in IL-6 and CRP levels were associated with PM2.5. •Maternal plasmatic fibrinogen was negatively associated with the crown-rump length. [ABSTRACT FROM AUTHOR]

Background: Despite epidemiological findings showing increased air pollution related cardiovascular diseases (CVD), the knowledge of the involved molecular mechanisms remains moderate or weak. Particulate matter (PM) produces a local strong inflammatory reaction in the pulmonary environment but there is no final evidence that PM physically enters and deposits in blood vessels. Extracellular vesicles (EVs) and their miRNA cargo might be the ideal candidate to mediate the effects of PM, since they could be potentially produced by the respiratory system, reach the systemic circulation and lead to the development of cardiovascular effects. The SPHERE (“Susceptibility to Particle Health Effects, miRNAs and Exosomes”) project was granted by ERC-2011-StG 282413, to examine possible molecular mechanisms underlying the effects of PM exposure in relation to health outcomes. Methods/design: The study population will include 2000 overweight (25 < BMI < 30 kg/cm2) or obese (BMI ≥ 30 kg/cm2) subjects presenting at the Center for Obesity and Work (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy). Each subject donates blood, urine and hair samples. Extensive epidemiological and clinical data are collected. Exposure to PM is assigned to each subject using both daily PM10 concentration series from air quality monitors and pollutant levels estimated by the FARM (Flexible air Quality Regional Model) modelling system and elaborated by the Regional Environmental Protection Agency. The recruitment period started in September 2010 and will continue until 2015. At December 31, 2013 we recruited 1250 subjects, of whom 87% lived in the province of Milan. Primary study outcomes include cardiometabolic and respiratory health effects. The main molecular mechanism we are investigating focuses on EV-associated microRNAs. Discussion: SPHERE is the first large study aimed to explore EVs as a novel potential mechanism of how air pollution exposure acts in a highly susceptible population. The rigorous study design, the availability of banked biological samples and the potential to integrate epidemiological, clinical and molecular data will also furnish a powerful base for investigating different complementary molecular mechanisms. Our findings, if confirmed, could lead to the identification of potentially reversible alterations that might be considered as possible targets for new diagnostic and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: A number of studies have focused on possible relationships between characteristics of female endocrine status and melanoma (CM) risk; however, the link between melanoma, oral contraceptive (OC) and hormonal replacement therapy (HRT) use, and reproductive factors remains controversial. A comprehensive, systematic bibliographic search of the medical literature was conducted to identify relevant studies. Random effects models were used to summarise results. Subgroup, meta-regression and sensitivity analyses have been carried out to explore sources of between-study variation and bias. We included thirty-six observational studies published in the last 30years. Summarising a total of 5626 melanoma cases, we did not find any significant melanoma risk associated with OC and HRT use. Several reproductive factors were also investigated, summarising data on 16787 melanoma cases. We found a significantly increased melanoma risk for late age at first birth, and women with more than one child may be at a lower risk for melanoma; however, socio-economic confounders were found to play a significant role in explaining this association. This study confirmed no increased risk of CM with the use of oral contraceptives and hormone replacement therapy: exogenous female hormones do not contribute to an increased risk of CM. In contrast, significant associations of CM with parity and age at first pregnancy were observed in this meta-analysis finds and warrant further research. [Copyright &y& Elsevier]

Background: ABO blood type has been associated with various malignancies, including pancreatic cancer. Our aim was to study this association using data from a hospital-based tumour registry. Methods: From the tumour registry, we retrieved data from 15,359 cancer patients treated during 2000–2003 at the European Institute of Oncology (Milan, Italy), with defined ABO blood type. We performed a case-control analysis, comparing the distribution of ABO blood types of patients with each specific form of cancer against that of patients with other forms of cancer. We also reviewed the literature and performed a meta-analysis on the association between ABO blood group and pancreatic cancer. Results: We observed a significantly lower frequency of blood type O in patients with exocrine pancreatic cancer compared to patients with other forms of cancer (29% versus 44%; P <0.001; odds ratio (OR), 0.53; 95% confidence intervals (CI), 0.33–0.83). This association was confirmed by the meta-analysis of seven prior studies (summary relative risk, 0.79; 95% CI, 0.70–0.90). No association was found for endocrine pancreatic cancer or for cancer originating in other organs. Conclusions: Our data suggest that the association between ABO blood group and cancer is limited to exocrine pancreas malignancy. [Copyright &y& Elsevier]

The article presents a meta-analysis of observational studies which examined the association of cigarette smoking and colorectal cancer. Independent articles which contained the minimum information necessary to estimate colorectal cancer risk related to cigarette smoking were used for the study. The search was performed on PubMed, ISI Web of Science, and EMBASE databases to May of 2008. The analysis of incidence included one hundred six observational studies. Adjusted risk estimates for ever smokers versus never smokers were obtained from twenty six studies. Researchers found a significant association between cigarette smoking and colorectal cancer.

Smoking is a recognized risk factor for pancreatic cancer. The aim of this study was to perform a meta-analysis to provide a robust estimate of the strength of the association between smoking and pancreatic cancer, to determine the risk of pipe and cigar smoking, and to estimate the duration of an elevated risk after smoking cessation. We performed a meta-analysis of 82 published studies containing epidemiologic information about smoking and pancreatic cancer. Information on studies published between 1950 and 2007 was abstracted and prepared for analysis using standard meta-analytic procedures. The overall risk of pancreatic cancer estimated from the combined results for current and former smokers was, respectively, 1.74 (95% CI 1.61–1.87) and 1.2 (95% CI 1.11–1.29). The risk of pancreatic cancer for current and former pipe and/or cigar smokers was respectively 1.47 (95% CI 1.17–1.83) and 1.29 (95% CI 0.68–2.45). For former cigarette smokers, the risk remains elevated for a minimum of 10 years after cessation. Based on estimates from four continents, smoking cigarettes causes a 75% increase in the risk of pancreatic cancer compared to non-smokers, and the risk persists for a minimum of 10 years after smoking cessation. This implies that in a population where the prevalence of smoking is 30%, the population’s attributable risk (the proportion of pancreatic cancer explained by smoking) is estimated to be 20%. [ABSTRACT FROM AUTHOR]

Background: During COVID‐19 outbreak, Italy was the first country in Europe to be heavily affected with an intensive care unit mortality of 26%. In order to reduce this percentage, physicians should establish clear and objective criteria to stratify COVID‐19 patients at high risk of in‐hospital death. Thus, the aim has been to test a large spectrum of variables ranging from clinical evaluation to laboratory biomarkers to identify which parameter would best predict all‐cause in‐hospital mortality in COVID‐19 patients. Design: observational study. Results: Multivariate Cox regression analysis showed that each 5 years of increase in age corresponded to a hazard ratio (HR) of 1.28 (95% CI 1.00‐1.65, P =.050); each increment of 803 ng/L of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) corresponded to a HR of 1.24 (95% CI 1.11‐1.39, P <.001); each increment of 58 ng/L of interleukin (IL)‐6 corresponded to a HR of 1.23 (95% CI 1.09‐1.40, P <.001), and each increment of 250 U/L of lactate dehydrogenase (LDH) corresponded to a HR of 1.23 (95% CI 1.10‐1.37, P <.001). According to the calculated cut‐points for age (≥70 years), NT‐proBNP (≥803 ng/L), IL‐6 (≥58 ng/L) and LDH (≥371 U/L) when 2 out of these 4 were overcome, the HR was 2.96 (95% CI 1.97‐4.45, P <.001). Conclusion: In COVID‐19 patients, besides age, the evaluation of three biochemical parameters, available in few hours after hospital admission can predict in‐hospital mortality regardless of other comorbidities. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the connection of antibodies group (ABO) blood type to pancreatic cancer.

Simple Summary: In this study, we aim to shed light on a fascinating new aspect of cellular communication involving extracellular vesicles (EVs) and their cargo of microRNAs (EV-miRNAs). These EVs were once thought of as cellular waste but are now known to play a crucial role in transferring vital information between cells. We investigated how EV-miRNAs respond to various environmental and lifestyle factors and how this might be linked to the development and progression of cancer. By analyzing the associations between these factors and specific miRNAs related to common cancers (oncomiRs), we aim to better understand the complex regulatory networks of miRNAs in response to exogenous influences. The findings could revolutionize our understanding of cancer development and have important implications for future exposome studies in the research community. Intercellular communication has been transformed by the discovery of extracellular vesicles (EVs) and their cargo, including microRNAs (miRNAs), which play crucial roles in intercellular signaling. These EVs were previously disregarded as cellular debris but are now recognized as vital mediators of biological information transfer between cells. Furthermore, they respond not only to internal stimuli but also to environmental and lifestyle factors. Identifying EV-borne oncomiRs, a subset of miRNAs implicated in cancer development, could revolutionize our understanding of how environmental and lifestyle exposures contribute to oncogenesis. To investigate this, we studied the plasma levels of EV-borne oncomiRs in a population of 673 women and 238 men with a body mass index > 25 kg/m2 (SPHERE population). The top fifty oncomiRs associated with the three most common cancers in women (breast, colorectal, and lung carcinomas) and men (lung, prostate, and colorectal carcinomas) were selected from the OncomiR database. Only oncomiRs expressed in more than 20% of the population were considered for statistical analysis. Using a Multivariate Adaptive Regression Splines (MARS) model, we explored the interactions between environmental/lifestyle exposures and EV oncomiRs to develop optimized predictor combinations for each EV oncomiR. This innovative approach allowed us to better understand miRNA regulation in response to multiple environmental and lifestyle influences. By uncovering non-linear relationships among variables, we gained valuable insights into the complexity of miRNA regulatory networks. Ultimately, this research paves the way for comprehensive exposome studies in the future. [ABSTRACT FROM AUTHOR]

Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two blood samples were collected from 231 pregnant women at 11–13 weeks of gestation and in the perinatal period. At each time point, SARS-CoV-2 antibodies and neutralizing antibody titers were measured by ELISA and microneutralization (MN) assays, respectively. Plasmatic NLRP3 was determined by ELISA. Fourteen miRNAs selected for their role in inflammation and/or pregnancy were quantified by qPCR and further investigated by miRNA-gene target analysis. NLRP3 levels were positively associated with nine circulating miRNAs, of which miR-195-5p was increased only in MN+ women (p-value = 0.017). Pre-eclampsia was associated with a decrease in miR-106a-5p (p-value = 0.050). miR-106a-5p (p-value = 0.026) and miR-210-3p (p-value = 0.035) were increased in women with gestational diabetes. Women giving birth to small for gestational age babies had lower miR-106a-5p and miR-21-5p (p-values = 0.001 and 0.036, respectively), and higher miR-155-5p levels (p-value = 0.008). We also observed that neutralizing antibodies and NLRP3 concentrations could affect the association between APOs and miRNAs. Our findings suggest for the first time a possible link between COVID-19, NLRP3-mediated pyroptosis, inflammation, and APOs. Circulating miRNAs might be suitable candidates to gain a comprehensive view of this complex interplay. [ABSTRACT FROM AUTHOR]

Abstract: The etiology of colorectal cancer is complex and multifactorial. Tobacco smoke has been found to be associated both with colorectal adenoma and cancer development. It was hypothesized that tobacco smoking could interact with genetic factors, providing different risk estimates according to different genetic predisposition. We reviewed and summarized by a meta-analytic approach the evidence from the literature on the interaction of smoking with the five most studied gene polymorphisms (GSTM1, GSTT1, mEH3, mEH4, NAT2). We calculated pooled Odds Ratios for each gene–smoking combination by random effects models, and provided a pooled P-value for gene–smoking interaction. Heterogeneity among studies was evaluated by the Q statistic and I 2. Overall, 27 case–control studies or nested case–control studies are included in this review: 12 presented data on GSTM1 polymorphism, eight on GSTT1, seven on mEH3, mEH4, and 10 on NAT2. We found a weak suggestion of an antagonistic effect of mEH3 low or medium metabolizer with smoking on colorectal adenoma risk (pooled P-value for the interaction: 0.02): smokers carriers of mEH3 low or medium metabolizer had slightly lower risk (Odds Ratio; 95% Confidence Interval: 1.6; 1.2–2.1) than smokers with mEH3 high metabolizer (1.8; 1.4–2.4). A non-significant positive interaction between GSTT1 null genotype and smoking was suggested for colorectal adenoma risk. None of the other common genetic polymorphisms involved in tobacco carcinogens metabolism seemed to modify the smoking-related risk of colorectal adenoma or cancer. [Copyright &y& Elsevier]

Human exposure to air pollutants, and specifically to particulate matter (PM) and volatile organic compounds (VOCs), may pose a relevant risk on human health. To evaluate the personal exposure of adults living and working in Milan (Italy) by environmental and biological monitoring. Personal exposure of 51 volunteer adults to PM 2.5 , PM 2.5 – 10 and selected VOCs, including benzene, toluene, ethylbenzene, o-xylene, m + p-xylene, methyl tert-butyl ether, naphthalene, hexane, cyclohexane, heptane, and limonene was assessed along a 24-h period via personal cascade impactors and radial diffusive samplers. Urine spot samples were collected to investigate the corresponding urinary biomarkers. Time-activity patterns were filled in by participants to explore the performed activities. Multiple regression models were applied to investigate the association between personal exposure, biomarker levels, and tobacco smoke, traffic exposure, commuting mode, cooking activities, and personal characteristics. Median personal exposure to PM 2.5 , PM 2.5 – 10 , benzene, toluene, ethylbenzene o-xylene, m + p-xylene, methyl tert-butyl ether, naphthalene, hexane, cyclohexane, heptane, and limonene were 36.1, 7.8, 2.3, 7.8, 2.1, 1.8, 4.7, 0.8, 0.3, 1.4, 2.5, 1.6, and 59.9 μg/m3, respectively. Median levels of urinary benzene, toluene, ethylbenzene o-xylene, m + p-xylene, naphthalene, hexane, and heptane were 78.0, 88.1, 21.5, 15.2, 43.9, 21.0, 11.0, and 22.5 ng/L, respectively. For personal exposure, multiple regression models explained up to 67% (PM 2.5) and 61% (benzene) of variability, with major contribution from commuting mode and environmental exposure. For biological monitoring, multiple regression analysis explained up to 74% of urinary benzene, with a major contribution given by creatinine, and secondary contributions by commuting mode, personal exposure to airborne benzene and smoking. Personal exposure to air pollutants was lower than that measured in the past in Milan. Personal exposure was mainly driven by traffic variables, while internal dose was mainly driven by personal characteristics and smoking habit. Unlabelled Image • General population personal exposure was investigated by environmental monitoring. • Biological monitoring was applied to assess urinary unmetabolized VOC. • VOC exposure was lower than in the past. • Commuting mode affected personal exposure to air pollutants. • Personal characteristics, smoking and air exposure were main biomarker determinants. [ABSTRACT FROM AUTHOR]

Background: In COVID-19 patients, aldosterone via angiotensin-converting enzyme-2 deregulation may be responsible for systemic and pulmonary vasoconstriction, inflammation, and oxidative organ damage. Aim: To verify retrospectively the impact of the mineralcorticoid receptor antagonist canrenone i.v. on the need of invasive ventilatory support and/or all-cause in-hospital mortality. Methods: Sixty-nine consecutive COVID-19 patients, hospitalized for moderate to severe respiratory failure at Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico of Milan, received two different therapeutic approaches in usual care according to the personal skills and pharmacological management experience of the referral medical team. Group A (n = 39) were given vasodilator agents or renin–angiotensin–aldosterone system (RAAS) inhibitors and group B (n = 30) were given canrenone i.v. Results: Among the 69 consecutive COVID-19 patients, those not receiving canrenone i.v. (group A) had an event-free rate of 51% and a survival rate of 64%. Group B (given a mean dose of 200 mg/q.d. of canrenone for at least two days of continuous administration) showed an event-free rate of 80% with a survival rate of 87%. Kaplan–Meier analysis for composite outcomes and mortality showed log rank statistics of 0.0004 and 0.0052, respectively. Conclusions: The novelty of our observation relies on the independent positive impact of canrenone on the all-cause mortality and clinical improvement of COVID-19 patients ranging from moderate to severe diseases. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated the association between air pollution and different medical conditions including respiratory and cardiovascular diseases. Air pollutants might have a role also in the etiology of mental disorders in the light of their toxicity on central nervous system. Purpose of the present manuscript was to review and summarize available data about an association between psychiatric disorders and air pollution. A research in the main database sources has been conducted to identify relevant papers about the topic. Different air pollutants and in particular PM and nitric oxides have been associated with poor mental health; long exposition to PM 2.5 has been associated with an increased risk of new onset of depressive symptoms (Cohen's effect size d: 0.05–0.81), while increased concentration of nitric dioxide in summer with worsening of existing depressive conditions (Cohen's effect size d: 0.05–1.77). However, the interpretation of these finding should take into account the retrospective design of most of studies, different periods of observations, confounding factors such as advanced age or medical comorbidity. Further studies with rigorous methodology are needed to confirm the results of available literature about this topic. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to explore whether the Variable Lifting Index (VLI) can be corrected for cumulative mass and thus test its efficacy in predicting the risk of low-back pain (LBP). Background A validation study of the VLI method was published in this journal reporting promising results. Although several studies highlighted a positive correlation between cumulative load and LBP, cumulative mass has never been considered in any of the studies investigating the relationship between manual material handling and LBP. Method Both VLI and cumulative mass were calculated for 2,374 exposed subjects using a systematic approach. Due to high variability of cumulative mass values, a stratification within VLI categories was employed. Dummy variables (1-4) were assigned to each class and used as a multiplier factor for the VLI, resulting in a new index (VLI_CMM). Data on LBP were collected by occupational physicians at the study sites. Logistic regression was used to estimate the risk of acute LBP within levels of risk exposure when compared with a control group formed by 1,028 unexposed subjects. Results Data showed greatly variable values of cumulative mass across all VLI classes. The potential effect of cumulative mass on damage emerged as not significant ( p value = .6526). Conclusion When comparing VLI_CMM with raw VLI, the former failed to prove itself as a better predictor of LBP risk. Application To recognize cumulative mass as a modifier, especially for lumbar degenerative spine diseases, authors of future studies should investigate potential association between the VLI and other damage variables. [ABSTRACT FROM AUTHOR]

Background Inhaled particles have been shown to produce systemic changes in DNA methylation. Global hypomethylation has been associated to viral sequence reactivation, possibly linked to the activation of pro-inflammatory pathways occurring after exposure. This observation provides a rationale to investigate viral sequence (both exogenous and endogenous) methylation in association to metal-rich particulate matter exposure. To verify this hypothesis, we chose the Wp promoter of the Epstein-Barr Virus (EBV-Wp) and the promoter of the human-endogenous-retrovirus w (HERV-w), respectively as a paradigm of an exogenous and an endogenous retroviral sequence, to be investigated by bisulfite PCR Pyrosequencing. We enrolled 63 male workers in an electric furnace steel plant, exposed to high level of metal-rich particulate matter. Results Comparing samples obtained in the first day of a work week (time 0-baseline, after 2 days off work) and the samples obtained after 3 days of work (time 1-post exposure), the mean methylation of EBV-Wp was significantly higher at baseline compared to post-exposure (mean baseline = 56.7%5mC; mean post-exposure = 47.9%5mC; p-value = 0.009), whereas the mean methylation of HERV-w did not significantly differ. Individual exposure to inhalable particles and metals was estimated based on measures in all working areas and time spent by the study subjects in each area. In a regression model adjusted for age, body mass index and smoking, PM and metal components had a positive association with EBV-Wp methylation (i.e. PM10: β = 5.99, p-value < 0.038; nickel: β = 17.82, p-value = 0.02; arsenic: β = 13.59, p-value < 0.015). Conclusions The difference observed comparing baseline and post-exposure samples may be suggestive of a rapid change in EBV methylation induced by air particles, while correlation between EBV methylation and PM/metal exposure may represent a more stable adaptive mechanism. Future studies investigating a larger panel of viral sequences could better elucidate possible mechanisms and their role in pro-inflammatory pathways leading to systemic health effects. [ABSTRACT FROM AUTHOR]

Aims Exposure to particulate air pollution is associated with increased blood pressure (BP), a well-established risk factor for cardiovascular disease. To elucidate the mechanisms underlying this relationship, we investigated whether the effects of particulate matter of less than 10 μm in aerodynamic diameter (PM 10 ) on BP are mediated by microRNAs. Methods and results We recruited 90 obese individuals and we assessed their PM 10 exposure 24 and 48 h before the recruitment day. We performed multivariate linear regression models to investigate the effects of PM 10 on BP. Using the TaqMan® Low-Density Array, we experimentally evaluated and technically validated the expression levels of 377 human miRNAs in peripheral blood. We developed a mediated moderation analysis to estimate the proportion of PM 10 effects on BP that was mediated by miRNA expression. PM 10 exposure 24 and 48 h before the recruitment day was associated with increased systolic BP ( β =1.22 mmHg, P =0.019; β =1.24 mmHg, P =0.019, respectively) and diastolic BP ( β =0.67 mmHg, P =0.044; β =0.91 mmHg, P =0.007, respectively). We identified nine miRNAs associated with PM 10 levels 48 h after exposure. A conditional indirect effect (CIE=−0.1431) of PM 10 on diastolic BP, which was mediated by microRNA-101, was found in individuals with lower values of mean body mass index. Conclusions Our data provide evidence that miRNAs are a molecular mechanism underlying the BP-related effects of air pollution exposure, and indicate miR-101 as epigenetic mechanism to be further investigated. [ABSTRACT FROM AUTHOR]

Purpose: Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of Lu-DOTATATE in multiple cycles. Methods: Fifty-one consecutive patients with unresectable/metastatic sst-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. Results: No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. Conclusion: Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. [ABSTRACT FROM AUTHOR]

A number of studies have highlighted important alterations of the lipid profile in COVID-19 patients. Besides the well-known atheroprotective function, HDL displays anti-inflammatory, anti-oxidative, and anti-infectious properties. The aim of this retrospective study was to assess the HDL anti-inflammatory and antioxidant features, by evaluation of HDL-associated Serum amyloid A (SAA) enrichment and HDL-paraoxonase 1 (PON-1) activity, in a cohort of COVID-19 patients hospitalized at the Cardiorespiratory COVID-19 Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan. COVID-19 patients reached very low levels of HDL-c (mean ± SD: 27.1 ± 9.7 mg/dL) with a marked rise in TG (mean ± SD: 165.9 ± 62.5 mg/dL). Compared to matched-controls, SAA levels were significantly raised in COVID-19 patients at admission. There were no significant differences in the SAA amount between 83 alive and 22 dead patients for all-cause in-hospital mortality. Similar findings were reached in the case of PON-1 activity, with no differences between alive and dead patients for all-cause in-hospital mortality. In conclusion, although not related to the prediction of in-hospital mortality, reduction in HDL-c and the enrichment of SAA in HDL are a mirror of SARS-CoV-2 positivity even at the very early stages of the infection. [ABSTRACT FROM AUTHOR]

Context: Colorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. The association between cigarette smoking and colorectal cancer has been inconsistent among studies.Objective: To clarify the association of cigarette smoking and colorectal cancer, we performed a comprehensive literature search and a meta-analysis of observational studies considering both incidence and mortality.Data Sources: We performed a literature search using PubMed, ISI Web of Science (Science Citation Index Expanded), and EMBASE to May 2008, with no restrictions. We also reviewed references from all retrieved articles.Study Selection: All articles that were independent and contained the minimum information necessary to estimate the colorectal cancer risk associated with cigarette smoking and a corresponding measure of uncertainty.Data Extraction: Articles were reviewed and data were extracted and cross-checked independently by 3 investigators, and any disagreement was resolved by consensus among all 3.Results: One hundred six observational studies were included in the analysis of incidence. Twenty-six studies provided adjusted risk estimates for ever smokers vs never smokers, leading to a pooled relative risk of 1.18 (95% confidence interval [CI], 1.11-1.25). Smoking was associated with an absolute risk increase of 10.8 cases per 100,000 person-years (95% CI, 7.9-13.6). We found a statistically significant dose-relationship with an increasing number of pack-years and cigarettes per day. However, the association was statistically significant only after 30 years of smoking. Seventeen cohort studies were included in the analysis of mortality. The pooled risk estimate for ever vs never smokers was 1.25 (95% CI, 1.14-1.37). Smoking was associated with an absolute risk increase of 6.0 deaths per 100,000 person-years (95% CI, 4.2-7.6). For both incidence and mortality, the association was stronger for cancer of the rectum than of the colon.Conclusion: Cigarette smoking is significantly associated with colorectal cancer incidence and mortality. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are important components of the metastatic niche and are crucial in infiltration, metastasis, and immune tolerance processes during tumorigenesis. We hypothesized that human endogenous retroviruses (HERV) positive EVs derived from tumor cellsmay have a role in modulating the innate immune response. The study was conducted in two different colorectal cancer cell lines, representing different stages of cancer development: Caco-2, derived from a non-metastatic colorectal adenocarcinoma, and SK-CO-1, derived from metastatic colorectal adenocarcinoma (ascites). Both cell lines were treated with decitabine to induce global hypomethylation and to reactivate HERV expression. EVs were quantified by nanoparticle tracking analysis, and HERV-positive EV concentrations were measured by flow cytometry. The effect of EVs isolated from both untreated and decitabine-treated cells on the innate immune response was evaluated by injecting them in zebrafish embryos and then assessing Interleukin 1β (IL1-β), Interleukin 10 (IL-10), and the myeloperoxidase (mpx) expression levels by real-time qPCR. Interestingly, HERV-K positive EVs concentrations were significantly associated with a reduced expression of IL1-β and mpx, supporting our hypothesis that HERV-positive EVs may act as immunomodulators in tumor progression. The obtained results open new perspectives about the modulation of the immune response in cancer therapy. [ABSTRACT FROM AUTHOR]