Extracellular Vesicles and Immunity: At the Crossroads of Cell Communication.

Extracellular vesicles (EVs), comprising exosomes and microvesicles, are small membranous structures secreted by nearly all cell types. They have emerged as crucial mediators in intercellular communication, playing pivotal roles in diverse physiological and pathological processes, notably within the realm of immunity. These roles go beyond mere cellular interactions, as extracellular vesicles stand as versatile and dynamic components of immune regulation, impacting both innate and adaptive immunity. Their multifaceted involvement includes immune cell activation, antigen presentation, and immunomodulation, emphasising their significance in maintaining immune homeostasis and contributing to the pathogenesis of immune-related disorders. Extracellular vesicles participate in immunomodulation by delivering a wide array of bioactive molecules, including proteins, lipids, and nucleic acids, thereby influencing gene expression in target cells. This manuscript presents a comprehensive review that encompasses in vitro and in vivo studies aimed at elucidating the mechanisms through which EVs modulate human immunity. Understanding the intricate interplay between extracellular vesicles and immunity is imperative for unveiling novel therapeutic targets and diagnostic tools applicable to various immunological disorders, including autoimmune diseases, infectious diseases, and cancer. Furthermore, recognising the potential of EVs as versatile drug delivery vehicles holds significant promise for the future of immunotherapies.

Exposure profiles in pregnant women from a birth cohort in a highly contaminated area of southern Italy.

Protecting the health of pregnant women from environmental stressors is crucial for reducing the burden of non-communicable diseases. In industrially contaminated sites, this action is particularly challenging due to the heterogeneous pollutant mixtures in environmental matrices. The aim of this study was to evaluate distribution patterns of mercury, hexachlorobenzene and polychlorobiphenyls in the serum of 161 pregnant women recruited in the framework of the Neonatal Environment and Health Outcomes (NEHO) cohort and living both inside and outside the National Priority Contaminated Site (NPCS) of Priolo. Food macro-categories were determined, and serum levels of contaminants were used to perform k-means cluster analysis and identify the role of food in pollutant transfer from the environment. Two groups of mothers with high and low measured pollutant levels were distinguished. Concentrations in mothers in the high-exposure cluster were at least twofold for all the evaluated pollutants (p < 0.0001) and included mothers living inside and outside NPCS, with a predominance of individuals from the NPCS (p = 0.045). Fish consumption was higher in the high-exposure cluster (p = 0.019). These findings suggest a link between contamination of environmental matrices such as sediment with maternal exposure, through the intake of local food. Such consideration appears poorly investigated in the context of contaminated sites.

Extracellular vesicles from PBDE-47 treated M(LPS) THP-1 macrophages modulate the expression of markers of epithelial integrity, EMT, inflammation and muco-secretion in ALI culture of airway epithelium.

AIMS: The lung epithelial cells form a physical barrier to the external environment acting as the first line of defence against potentially harmful environmental stimuli. These cells interact with several other cellular components, of which macrophages are some of the most relevant. We analysed the effects of the PBDE-47 on the microRNA cargo of THP-1 macrophage like derived small Extracellular Vesicles (sEVs) and the effects on A549 lung epithelial cells. MAIN METHODS: sEVs from M(LPS) THP-1 macrophage-like cells after PBDE-47 treatment (sEVsPBDE+LPS) were characterized by nanoparticle tracking analysis and their microRNA cargo studied by qPCR. Confocal microscopy was applied to study sEVs cellular uptake by A549 cells. The expression of tight junctions (TJs), adhesion molecules, inflammation markers and mucus production in A549 cultured in air liquid interface (ALI) conditions were studied by Real Time PCR and confocal microscopy. KEY FINDINGS: sEVsPBDE+LPS microRNA cargo analysis showed that the PBDE-47 modulated the expression of the miR-15a-5p, miR29a-3p, miR-143-3p and miR-122-5p. Furthermore, ALI cultured A549 cells incubated with sEVsPBDE+LPS showed that zonula occludens-1 (p ≤ 0.04), claudin (p ≤ 0.02), E-cadherin (p ≤ 0.006) and Vimentin (p ≤ 0.0008) mRNAs were increased in A549 cells after sEVsPBDE+LPS treatment. Indeed, Interleukin (IL)-8 (p ≤ 0.008) and mucin (MUC5AC and MUC5B) (p ≤ 0.03 and p ≤ 0.0001) mRNA expression were up- and down-regulated, respectively. SIGNIFICANCE: PBDE-47 treated macrophages secrete sEVs with altered microRNA cargo that affect the mRNA expression of TJs, adhesion molecules, cytokines and EMT markers damaging the normal function of the lung epithelium, potentially contributing to the development of lung diseases.

Validation of a simplified-geometry model of inhaled formoterol pharmacodynamics in asthmatic patients.

PharmacoKinetics (PK) and PharmacoDynamics (PD) mathematical models of inhaled bronchodilators represent useful tools for understanding the mechanisms of drug action and for the individuation of therapy regimens. A PK/PD model for inhaled bronchoactive compounds was previously proposed, incorporating a simplified-geometry approach: the key feature of that model is a mixed compartmental and spatially distributed representation of the kinetics, with the direct computation of representative flow rates from Ohm's law and bronchial diameter profiles. The aim of the present work is the enrichment and validation of this simplified geometry modeling approach against clinical efficacy data. The improved model is used to compute airflow response to treatment for each single virtual patient from a simulated population and it is found to produce very good fits to observed FEV1 profiles. The model provides a faithful quantitative description of the increasing degree of improvement with respect to basal conditions with continuing administration and with increasing drug dosages, as clinically expected.

Investigating the Relationship between Parental Education, Asthma and Rhinitis in Children Using Path Analysis.

Parental socioeconomic position (SEP) is a known determinant of a child's health. We aimed to investigate whether a low parental education, as proxy of SEP, has a direct effect on physician-diagnosed asthma, current asthma and current allergic rhinitis in children, or whether associations are mediated by exposure to other personal or environmental risk factors. This study was a secondary data analysis of two cross-sectional studies conducted in Italy in 2006. Data from 2687 adolescents (10-14 years) were analyzed by a path analysis model using generalized structural equation modelling. Significant direct effects were found between parental education and family characteristics (number of children (coefficient = 0.6229, p < 0.001) and crowding index (1.1263, p < 0.001)) as well as with exposure to passive smoke: during pregnancy (maternal: 0.4697, p < 0.001; paternal: 0.4854, p < 0.001), during the first two years of children's life (0.5897, p < 0.001) and currently (0.6998, p < 0.001). An indirect effect of parental education was found on physician-diagnosed asthma in children mediated by maternal smoking during pregnancy (0.2350, p < 0.05) and on current allergic rhinitis mediated by early environmental tobacco smoke (0.2002; p < 0.05). These results suggest the importance of promotion of ad-hoc health policies for promoting smoking cessation, especially during pregnancy.

The Influence of Sociodemographic Factors, Lifestyle, and Risk Perception on Dietary Patterns in Pregnant Women Living in Highly Contaminated Areas: Data from the NEHO Birth Cohort.

During pregnancy, maternal nutrition and lifestyle play a critical role in influencing fetal development and newborn health outcomes. The aim of this study is to investigate the factors influencing the adherence to dietary patterns in pregnant women living in highly contaminated areas, and whether women with higher environmental risk perception manifest different nutritional behaviors during pregnancy. Food consumption data on 816 pregnant women from the Neonatal Environment and Health Outcomes (NEHO) residential birth cohort were analyzed. Dietary patterns were computed by principal component analysis. A multinomial logistic regression was also applied to identify sociodemographic, lifestyle, and pregnancy-related determinants of adherence to dietary patterns during pregnancy. Three patterns of food consumption-explaining 24.9% of the total variance-were identified as "prudent", "high energy", and "vegetarian" patterns. Results suggest that food choices during pregnancy follow a social gradient and align with other health behaviors during pregnancy: older, better educated, and physically active women with higher risk perception are more likely to follow healthier dietary patterns. Knowledge about what is eaten can contribute to dietary choices. Interventions to improve the prenatal nutrition knowledge of pregnant women are needed, especially concerning younger mothers and those with lower educational levels.

A multipollutant low-grade exposure regulates the expression of miR-30b, Let-7a and miR-223 in maternal sera: Evidence from the NEHO cohort.

There is growing evidence that environmental pollutants can induce epigenetic modifications altering the balance of miRNAs and inducing the onset of pathological conditions in animals. In this study, we measured the serum concentration of a suite of inorganic and organic pollutants (Cu, Zn, Se, Hg, HCB, p,p'-DDE, PCBs) and their association to serum miR-30b, miR-223 and Let-7a microRNA expression in 68 healthy pregnant women from the NEHO birth cohort sited in a highly industrialized area. The effects of the pollutants on the modulation of circulating miRNAs' expression were first investigated using linear continuous regression models with a single-compound approach showing that miR-223 expression was significantly associated with serum concentration of Se and Zn (pSe = 0.0336; pZn = 0.0225) and miR-30b was associated with Hg levels (pHg = 0.019). Furthermore, when contaminants were categorized into tertiles, miR-223 and miR-30b showed a positive association with higher tertiles of Zn, p,p'-DDE (pZn = 0.023; pDDE = 0.041) and Hg (pHg = 0.008), respectively. Moreover, Let-7a expression was exclusively influenced by medium tertiles levels of Se (low vs medium tertiles, p = 0.001). Simultaneous exposure to multi-pollutant mixture was approached by WQS regression model. Statistical analysis shows a driving effect of Zn, Se, Cu, Hg and HCB on significant increased expression of Let-7a (p = 0.045). Mercury and Se significantly amplified the expression for miR-30b (p = 0.038). Differently, the combined effect of p,p'-DDE, Zn and Se decreased miR-223 expression (p = 0.0001). The documented modified expression of circulating miRNAs in the serum of pregnant women, exposed to low-medium dose contaminants mixtures offers innovative early-warning approaches to human health risk assessment.

Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Evidence of effective smoking cessation interventions in patients with diabetes is limited. The unique behavioral and metabolic characteristics of smokers with type 2 diabetes warrants a randomized clinical trial of the smoking cessation drug varenicline. Objective: To evaluate the efficacy and safety of varenicline in patients with type 2 diabetes with an intention to quit smoking. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial recruited patients from 6 outpatient clinics in 5 hospitals in Catania, Italy. Patients with type 2 diabetes, who were smoking at least 10 cigarettes a day, and who intended to quit smoking were screened for eligibility. Eligible patients were randomized to either varenicline or placebo treatment. The trial consisted of a 12-week treatment phase followed by a 40-week follow-up, nontreatment phase. Intention-to-treat data analysis was performed from December 2020 to April 2021. Interventions: Varenicline, 1 mg, twice daily or matched placebo administered for 12 weeks. Patients in both treatment groups also received smoking cessation counseling. Main Outcomes and Measures: The primary efficacy end point of the study was the continuous abstinence rate (CAR) at weeks 9 to 24. Secondary efficacy end points were the CAR at weeks 9 to 12 and weeks 9 to 52 as well as 7-day point prevalence of abstinence at weeks 12, 24, and 52. Results: A total of 300 patients (mean [SD] age, 57.4 [0.8] years; 117 men [78.0%] in varenicline group and 119 men [79.3%] in placebo group) were randomized to receive varenicline (n = 150) or placebo (n = 150). The CAR at weeks 9 to 24 was significantly higher for the varenicline than placebo group (24.0% vs 6.0%; odds ratio [OR], 4.95; 95% CI, 2.29-10.70; P < .001). The CARs at weeks 9 to 12 (31.3% vs 7.3%; OR, 5.77; 95% CI, 2.85-11.66; P < .001) and weeks 9 to 52 (18.7% vs 5.3%; OR, 4.07; 95% CI, 1.79-9.27; P < .001) as well as the 7-day point prevalence of abstinence at weeks 12, 24, and 52 were also significantly higher for the varenicline vs placebo group. The most frequent adverse events occurring in the varenicline group compared with the placebo group were nausea (41 [27.3%] vs 17 [11.4%]), insomnia (29 [19.4%] vs 19 [12.7%]), abnormal dreams (19 [12.7%] vs 5 [3.4%]), anxiety (17 [11.4%] vs 11 [7.3%]), and irritability (14 [9.4%] vs 8 [5.4%]). Serious adverse events were infrequent in both groups and not treatment-related. Conclusions and Relevance: Results of this trial showed that inclusion of varenicline in a smoking cessation program is efficacious in achieving long-term abstinence without serious adverse events. Varenicline should be routinely used in diabetes education programs to help patients with type 2 diabetes stop smoking. Trial Registration: ClinicalTrials.gov Identifier: NCT01387425.

The effect of laboratory-verified smoking on SARS-CoV-2 infection: results from the Troina sero-epidemiological survey.

Previous research yielded conflicting results on the association between cigarette smoking and risk of SARS-CoV-2 infection. Since the prevalence of smoking is high globally, the study of its impact on COVID-19 pandemic may have considerable implications for public health. This study is the first to investigate the association between the SARS-CoV-2 antibody sero-positivity and biochemically verified smoking status, to refine current estimates on this association. SARS-CoV-2-specific IgG and serum cotinine levels (a well-known marker of tobacco exposure) were assessed in a large sero-epidemiological survey conducted in the town of Troina (Sicily, Italy). A propensity score matching was carried out to reduce the effect of possible factors on SARS-CoV-2 infection risk among study participants. Of the 1785 subjects included in our study, one-third was classified as current smokers, based on serum cotinine levels. The overall proportion of subjects with positive serology for SARS-CoV-2 IgG was 5.4%. The prevalence of SARS-CoV-2 antibody positivity and previous COVID-19 diagnosis were reduced in smokers. This reduced prevalence persisted after adjusting for possible confounders (such as sex, age, previous infection, chronic conditions, and risk group) at regression analyses, and the point estimates based on the PS-matched models resulted consistent with those for the unmatched population. This study found a lower proportion of positive SARS-CoV-2 serology among current smokers, using direct laboratory measures of tobacco exposure and thus avoiding possible bias associated with self-reported smoking status. Results may also serve as a reference for future clinical research on potential pharmaceutical role of nicotine or nicotinic-cholinergic agonists against COVID-19.

Association between greenspace and lung function in Italian children-adolescents.

BACKGROUND: Few studies have examined the impact of urban greenspace exposure on lung function in children-adolescents, and the available evidence is still inconsistent. The aim of the current study was to verify the hypothesis that the effects of greenspace exposure vary with differing levels of lung function of children-adolescents. METHODS: Between November 2005 and May 2006, 2150 children-adolescents (age-range: 10-15 years) living in the city of Palermo were enrolled in a cross-sectional survey. Parents were interviewed through a modified version of the Italian Studies on Respiratory Disorders in Children and the Environment (SIDRIA) questionnaire. All children-adolescents performed spirometry and were tested for allergic sensitization. Exposures to greenspace and grey space at the home addresses were measured using the CORINE land-cover classes. Parametric quantile regression models were applied for assessing the association between greenspace exposure and spirometry parameters, accounting for possible confounders and effect modifiers. A p-value lower than 0.05 was considered statistically significant. RESULTS: From the 1st to the 21st percentile, children-adolescents living within greenspace had higher FEV1 than those living within grey space. In particular, the estimated effects were: 1st (ß = 0.238 L, p = 0.01), 5th (ß = 0.140 L, p = 0.01), 10th (ß = 0.097 L, p = 0.015), and 15th (ß = 0.073 L, p = 0.025). Similarly, from the 1st to the 29th percentile, children-adolescents living within greenspace had higher FVC than those living within grey space. In particular, the estimated effects were: 1st (ß = 0.367 L, p = 0.0003), 5th (ß = 0.215 L, p = 0.0003), 10th (ß = 0.150 L, p = 0.0004), and 15th (ß = 0.112 L, p = 0.001). No significant associations were found for FEV1/FVC, FEF25-75 and FEF25-75/FVC. CONCLUSION: Quantile regression techniques may provide new insights into the evaluation of the association between greenspace exposure and lung function in children-adolescents, showing substantially heterogeneous effects from lower to higher quantiles of spirometry parameters. These results may help implementing policies for planning sustainable housing and surrounding greenspaces.

Repeatability of dental shade by digital spectrophotometry in current, former, and never smokers.

Cigarette smoking contributes to poor oral health and dental discoloration. Therefore, stopping smoking may translate into measurable amelioration of dental shade indices. We compared dental shade parameters by digital spectrophotometry among current, former, and never smokers and verified their repeatability at 7 and 30 days. Dental shade parameters (CIE L*a*b* and corresponding whiteness index for dentistry-WID) were measured in current, former, and never smokers with a digital spectrophotometer (Vita Easyshade V) on three separate study visits: at baseline (day 0), at day 7, and day 30. Dental shade parameters were analyzed in 18 current, 18 former, and 20 never smokers. The repeatability of shade parameters was consistent in current, former, and never smokers. L*, a*, b*, and WID show significant short and long-term repeatability (p < 0.0001, by regression analyses). The mean (± SD) WID score of 13.42 (± 4.9) in current smokers was significantly lower compared to the WID score of 20.38 (± 5.3) in never smokers (p = 0.001). No significant differences were observed between current and former smokers and between former smokers and former smokers. Dental shade measurements by digital spectrophotometry were highly reproducible and showed that teeth whiteness of current smokers is substantially inferior compared to never smokers. Objective discrimination of dental shade can be a valuable regulatory science endpoint for investigating oral hygiene and dental aesthetics of consumer care products, smoking cessation medications, and tar-free tobacco products (e-cigarettes, heated tobacco products, oral nicotine products) for cigarette substitution.Clinical trial registration: the study was not registered in ClinicalTrials.gov considering that it is a pilot study, parts of a larger project with ID: NCT04649645.

[Application of an algorithm for the validation of congenital anomaly cases using hospital discharge records]. / Applicazione di un algoritmo per la validazione dei casi di malformazione congenita provenienti dal flusso delle schede di dimissione ospedaliera.

OBJECTIVES: to evaluate and validate the adoption of an algorithm for the identification of cases of congenital anomalies (CAs) to improve the performance of the Congenital Malformations Registry of Sicily Region (Southern Italy). DESIGN: an algorithm was used to identify congenital anomalies on a sample of hospital discharge records (SDO) with ICD-9-CM code between 740-759 on any of the diagnoses within the first year of life, together with a sample of healthy births equal to 5% of total births for the same period. The identified cases were evaluated through the clinical record analysis. SETTING AND PARTICIPANTS: the analysed sample was composed of 4,271 cases identified between June 2013 and December 2014 along with 3,993 SDO without any code of MC (5% of the total volume of births in the same period). MAIN OUTCOME MEASURES: positive predictive value (VPP) and negative predictive value (VPN) were computed by means of the comparison between the algorithm outcomes and the clinical record verification. RESULTS: 4,271 potentially malformed records involving 3,381 subjects born in the Sicilian territory have been identified. Among the hospital discharge records that it was possible to verify, the application of the algorithm led to the exclusion of 924 cases: of these, 62 proved to be false negatives (VPN: 93.3). The valid cases were 1,179, while the cases to be evaluated 617: the comparison between algorithm and clinical record analysis led to a VPP of 91.7 and 72.1, respectively, for valid and to be evaluated. CONCLUSIONS: the tested algorithm proved to be a useful tool for identifying SDO potentially related to congenital anomalies. In the overall sample, the algorithm provided an outcome consistent with the clinical record assessment in 87.4% (2,379) of cases.

Relationship among Body Composition, Adipocytokines, and Irisin on Exercise Capacity and Quality of Life in COPD: A Pilot Study.

Adipose tissue is an endocrine organ that interferes with the severity of chronic obstructive pulmonary disease (COPD). Although inflammatory markers, body composition, and nutritional status have a significant impact on pulmonary function, the real contribution of adipocytokines and myokines in COPD is still controversial. We aimed to evaluate the role played by the body composition, leptin, adiponectin, haptoglobin, and irisin on the functional exercise capacity, respiratory function, and quality of life (QoL) in COPD. In 25 COPD (20% GOLD-1; 60% GOLD-2; 20% GOLD-3) patients and 26 matched control subjects, we find that leptin, total adiponectin and haptoglobin are significantly increased whereas the 6 min walk test (6MWT) and physical functioning scores are significantly decreased in COPD versus controls. A significant positive relationship is found between leptin and fat mass and between 6MWT and the good health indicators of nutritional status. A significant inverse relationship is found between 6MWT and leptin and fat mass, FEV1 and haptoglobin, and irisin and haptoglobin. Phase angle and leptin level are significant predictors for functional exercise capacity assessed with 6MWT. Taken altogether, the results of this pilot study further support the role played by body composition and adipocytokines on exercise capacity respiratory function and QoL in COPD.

Impact of the flame retardant 2,2'4,4'-tetrabromodiphenyl ether (PBDE-47) in THP-1 macrophage-like cell function via small extracellular vesicles.

2,2'4,4'-tetrabromodiphenyl ether (PBDE-47) is one of the most widespread environmental brominated flame-retardant congeners which has also been detected in animal and human tissues. Several studies have reported the effects of PBDEs on different health issues, including neurobehavioral and developmental disorders, reproductive health, and alterations of thyroid function. Much less is known about its immunotoxicity. The aim of our study was to investigate the effects that treatment of THP-1 macrophage-like cells with PBDE-47 could have on the content of small extracellular vesicles' (sEVs) microRNA (miRNA) cargo and their downstream effects on bystander macrophages. To achieve this, we purified sEVs from PBDE-47 treated M(LPS) THP-1 macrophage-like cells (sEVsPBDE+LPS) by means of ultra-centrifugation and characterized their miRNA cargo by microarray analysis detecting the modulation of 18 miRNAs. Furthermore, resting THP-1 derived M(0) macrophage-like cells were cultured with sEVsPBDE+LPS, showing that the treatment reshaped the miRNA profiles of 12 intracellular miRNAs. This dataset was studied in silico, identifying the biological pathways affected by these target genes. This analysis identified 12 pathways all involved in the maturation and polarization of macrophages. Therefore, to evaluate whether sEVsPBDE+LPS can have some immunomodulatory activity, naïve M(0) THP-1 macrophage-like cells cultured with purified sEVsPBDE+LPS were studied for IL-6, TNF-α and TGF-ß mRNAs expression and immune stained with the HLA-DR, CD80, CCR7, CD38 and CD209 antigens and analyzed by flow cytometry. This analysis showed that the PBDE-47 treatment does not induce the expression of specific M1 and M2 cytokine markers of differentiation and may have impaired the ability to make immunological synapses and present antigens, down-regulating the expression of HLA-DR and CD209 antigens. Overall, our study supports the model that perturbation of miRNA cargo by PBDE-47 treatment contributes to the rewiring of cellular regulatory pathways capable of inducing perturbation of differentiation markers on naïve resting M(0) THP-1 macrophage-like cells.

Seroepidemiological Survey on the Impact of Smoking on SARS-CoV-2 Infection and COVID-19 Outcomes: Protocol for the Troina Study.

BACKGROUND: After the global spread of SARS-CoV-2, research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. However, emerging results on the role of smoking in SARS-CoV-2 infection susceptibility or COVID-19 outcomes are conflicting, and their robustness remains uncertain. OBJECTIVE: In this context, this study aims at quantifying the proportion of SARS-CoV-2 antibody seroprevalence, studying the changes in antibody levels over time, and analyzing the association between the biochemically verified smoking status and SARS-CoV-2 infection. METHODS: The research design involves a 6-month prospective cohort study with a serial sampling of the same individuals. Each participant will be surveyed about their demographics and COVID-19-related information, and blood sampling will be collected upon recruitment and at specified follow-up time points (ie, after 8 and 24 weeks). Blood samples will be screened for the presence of SARS-CoV-2-specific antibodies and serum cotinine, being the latter of the principal metabolite of nicotine, which will be used to assess participants' smoking status. RESULTS: The study is ongoing. It aims to find a higher antibody prevalence in individuals at high risk for viral exposure (ie, health care personnel) and to refine current estimates on the association between smoking status and SARS-CoV-2/COVID-19. CONCLUSIONS: The added value of this research is that the current smoking status of the population to be studied will be biochemically verified to avoid the bias associated with self-reported smoking status. As such, the results from this survey may provide an actionable metric to study the role of smoking in SARS-CoV-2 infection and COVID-19 outcomes, and therefore to implement the most appropriate public health measures to control the pandemic. Results may also serve as a reference for future clinical research, and the methodology could be exploited in public health sectors and policies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32285.

Measuring Risk Perception in Pregnant Women in Heavily Polluted Areas: A New Methodological Approach from the NEHO Birth Cohort.

Risk perception (RP) evaluation during pregnancy and its relationship with lifestyles are considered useful tools for understanding communities living in high-risk areas and preventing dangerous exposure. It is well known that exposure to pollutants and less-healthy lifestyles may result in increased disease occurrence during life. Our work investigated environmental RP through ad hoc questionnaires administered to 611 mothers within the NEHO birth cohort, recruited in three heavily contaminated areas of Southern Italy. Four different RP indices, an exploratory factorial analysis (EFA), and a latent class analysis were evaluated from questionnaires. The highest values of risk perception index were observed in the Milazzo site (0.64 ± 0.16) and the lowest in the Crotone site (0.5 ± 0.18). EFA revealed four latent factors, including different items describing environmental pollution, and subjects were classified into four latent classes with different RP indices. Significant RP profiles were different among the sites (p < 0.001). Our results did not demonstrate any association between RP and lifestyles during pregnancy. Improving healthy lifestyle behaviours, particularly in polluted areas, would generate co-benefits by preventing further risk factors. As remediation interventions can take a long time, it needs to improve healthy lifestyles in residents until remediation is completed.

Lung Function Decline in Adult Asthmatics-A 10-Year Follow-Up Retrospective and Prospective Study.

Asthma may have an impact on lung function decline but conflicting results are reported in forced expiratory volume in one second (FEV1) decline. We aimed to describe the changes in FEV1 in lifelong non-smoking adult asthmatic outpatients during a 10-year follow-up comparing years 1-5 (1st period) with years 6-10 (2nd period) to assess factors affecting these changes. A total of 100 outpatients performed spirometry every 3 months during a 10-year survey. FEV1/Ht3 slope values of the 2nd period reduced significantly respect to the 1st period (p < 0.0001). FEV1 slopes of years 1-5 and 6-10 were inversely associated with FEV1 at enrolment (p = 0.02, p = 0.01, respectively). Reversibility and variability FEV1 showed a significant effect on the 1st period slopes (p = 0.01 and p < 0.04, respectively). Frequent exacerbators in the 1st year had steeper FEV1/Ht3 slopes in the 1st period (p = 0.01). The number of subjects using higher doses of ICS was significantly lower at the 10th years respect to the 5th and the 1st year (p < 0.001, p = 0.003, respectively). This study shows that FEV1 decline in treated adult asthmatics non-smokers, over 10-year follow-up, is not constant. In particular, it slows down over time, and is influenced by FEV1 at enrolment, reversibility, variability FEV1 and exacerbation score in the 1st year.

A mathematical model of cardiovascular dynamics for the diagnosis and prognosis of hemorrhagic shock.

A variety of mathematical models of the cardiovascular system have been suggested over several years in order to describe the time-course of a series of physiological variables (i.e. heart rate, cardiac output, arterial pressure) relevant for the compensation mechanisms to perturbations, such as severe haemorrhage. The current study provides a simple but realistic mathematical description of cardiovascular dynamics that may be useful in the assessment and prognosis of hemorrhagic shock. The present work proposes a first version of a differential-algebraic equations model, the model dynamical ODE model for haemorrhage (dODEg). The model consists of 10 differential and 14 algebraic equations, incorporating 61 model parameters. This model is capable of replicating the changes in heart rate, mean arterial pressure and cardiac output after the onset of bleeding observed in four experimental animal preparations and fits well to the experimental data. By predicting the time-course of the physiological response after haemorrhage, the dODEg model presented here may be of significant value for the quantitative assessment of conventional or novel therapeutic regimens. The model may be applied to the prediction of survivability and to the determination of the urgency of evacuation towards definitive surgical treatment in the operational setting.

Excessive Daytime Sleepiness in Obstructive Sleep Apnea Patients Treated With Continuous Positive Airway Pressure: Data From the European Sleep Apnea Database.

Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3-13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1-15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea-hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use <4 h, occurred with similar frequency in patients with and without EDS at follow-up. Prevalence of residual EDS was highest (40%) in patients with a first follow-up visit at 0-3 months, then it was 13-19% in patients with a first follow-up visit after 4 months to 2 years. The change in ESS (n = 2,190) was weakly correlated with CPAP use (R2 = 0.023, p < 0.0001). Logistic regression showed that an ESS score >10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment.

2,2'4,4'-Tetrabromodiphenyl Ether (PBDE-47) Modulates the Intracellular miRNA Profile, sEV Biogenesis and Their miRNA Cargo Exacerbating the LPS-Induced Pro-Inflammatory Response in THP-1 Macrophages.

The 2,2'4,4'-tetrabromodiphenyl ether (PBDE-47) is one of the most prominent PBDE congeners detected in the environment and in animal and human tissues. Animal model experiments suggested the occurrence of PBDE-induced immunotoxicity leading to different outcomes and recently we demonstrated that this substance can impair macrophage and basophil activities. In this manuscript, we decided to further examine the effects induced by PBDE-47 treatment on innate immune response by looking at the intracellular expression profile of miRNAs as well as the biogenesis, cargo content and activity of human M(LPS) macrophage cell-derived small extracellular vesicles (sEVs). Microarray and in silico analysis demonstrated that PBDE-47 can induce some epigenetic effects in M(LPS) THP-1 cells modulating the expression of a set of intracellular miRNAs involved in biological pathways regulating the expression of estrogen-mediated signaling and immune responses with particular reference to M1/M2 differentiation. In addition to the cell-intrinsic modulation of intracellular miRNAs, we demonstrated that PBDE-47 could also interfere with the biogenesis of sEVs increasing their number and selecting a de novo population of sEVs. Moreover, PBDE-47 induced the overload of specific immune related miRNAs in PBDE-47 derived sEVs. Finally, culture experiments with naïve M(LPS) macrophages demonstrated that purified PBDE-47 derived sEVs can modulate macrophage immune response exacerbating the LPS-induced pro-inflammatory response inducing the overexpression of the IL-6 and the MMP9 genes. Data from this study demonstrated that PBDE-47 can perturb the innate immune response at different levels modulating the intracellular expression of miRNAs but also interfering with the biogenesis, cargo content and functional activity of M(LPS) macrophage cell-derived sEVs.