Autophagy modulation in lymphocytes from COVID-19 patients. new therapeutic target in SARS-COV-2 infection

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the “cytokine storm.” Among these, interleukin (IL)-6, tumor necrosis factor‐α (TNF‐α), and IL-1β seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNF‐α, and IL-1β in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection

Dual-source computed tomography coronary artery imaging in children

Computed tomography (CT) has a well-established diagnostic role in the assessment of coronary arteries in adults. However, its application in a pediatric setting is still limited and often impaired by several technical issues, such as high heart rates, poor patient cooperation, and radiation dose exposure. Nonetheless, CT is becoming crucial in the noninvasive approach of children affected by coronary abnormalities and congenital heart disease. In some circumstances, CT might be preferred to other noninvasive techniques such as echocardiography and MRI for its lack of acoustic window influence, shorter acquisition time, and high spatial resolution. The introduction of dual-source CT has expanded the role of CT in the evaluation of pediatric cardiovascular anatomy and pathology. Furthermore, technical advances in the optimization of low-dose protocols represent an attractive innovation. Dual-source CT can play a key role in several clinical settings in children, namely in the evaluation of children with suspected congenital coronary artery anomalies, both isolated and in association with congenital heart disease. Moreover, it can be used to assess acquired coronary artery abnormalities, as in children with Kawasaki disease and after surgical manipulation, especially in case of transposition of the great arteries treated with arterial switch operation and in case of coronary re-implantation

LIFE Med Hiss: An innovative cohort design for public health

The aim of MED HISS methodology was to test the effectiveness of a low-cost approach to study long-term effects of air pollution, applicable in all European countries. This approach is potentially exportable to other environmental issues where a cohort representative of the country population is needed. The cohort is derived from the National Health Interview Survey, compulsory in European countries, which has information on individual lifestyle factors. In Life Med Hiss approach, subjects recruited have been linked at individual level with health data and have been then followed-up for mortality and hospital admissions outcomes. Exposure values of air pollution (PM2.5 and NO 2 ) have been assigned using national dispersion models, enhanced by the information derived from monitoring station with data fusion techniques, and then upscaled at municipality level (highest level of detail achievable for the Italian Survey). Results for mortality have been used to test the effectiveness of this methodology and are encouraging if compared with European ones. The advantages of this technique are summarized below: • It uses a cohort already available and compulsory in European countries• It uses air quality modelling data, available for most of the countries• It permits to implement versatile environmental surveillance system

Blood flow characteristics after aortic valve neocuspidization in paediatric patients: a comparison with the Ross procedure.

AIMS: The aortic valve (AV) neocuspidization (Ozaki procedure) is a novel surgical technique for AV disease that preserves the natural motion and cardiodynamics of the aortic root. In this study, we sought to evaluate, by 4D-flow magnetic resonance imaging, the aortic blood flow characteristics after AV neocuspidization in paediatric patients. METHODS AND RESULTS: Aortic root and ascending aorta haemodynamics were evaluated in a population of patients treated with the Ozaki procedure; results were compared with those of a group of patients operated with the Ross technique. Cardiovascular magnetic resonance studies were performed at 1.5 T using a 4D flow-sensitive sequence acquired with retrospective electrocardiogram-gating and respiratory navigator. Post-processing of 4D-flow analysis was performed to calculate flow eccentricity and wall shear stress. Twenty children were included in this study, 10 after Ozaki and 10 after Ross procedure. Median age at surgery was 10.7 years (range 3.9-16.5 years). No significant differences were observed in wall shear stress values measured at the level of the proximal ascending aorta between the two groups. The analysis of flow patterns showed no clear association between eccentric flow and the procedure performed. The Ozaki group showed just a slightly increased transvalvular maximum velocity. CONCLUSION: Proximal aorta flow dynamics of children treated with the Ozaki and the Ross procedure are comparable. Similarly to the Ross, Ozaki technique restores a physiological laminar flow pattern in the short-term follow-up, with the advantage of not inducing a bivalvular disease, although further studies are warranted to evaluate its long-term results

Long term effect of air pollution on incident hospital admissions: Results from the Italian Longitudinal Study within LIFE MED HISS project

Background: The LIFE MED HISS project aims at setting up a surveillance system on the long term effects of air pollution on health, using data from National Health Interview Surveys and other currently available sources of information in most European countries. Few studies assessed the long term effect of air pollution on hospital admissions in European cohorts. Objective: The objective of this paper is to estimate the long term effect of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) on first-ever (incident) cause-specific hospitalizations in Italy. Methods: We used data from the Italian Longitudinal Study (ILS), a cohort study based on the 1999–2000 National Health Interview Survey (NHIS), followed up for hospitalization (2001–2008) at individual level. The survey contains information on crucial potential confounders: occupational/educational/marital status, body mass index (BMI), smoking habit and physical activity. Annual mean exposure to PM2.5 and NO2 was assigned starting from simulated gridded data at spatial resolution of 4 × 4 km2 firstly integrated with data from monitoring stations and then up-scaled at municipality level. Statistical analyses were conducted using Cox proportional hazard models with robust variance estimator. Results: For each cause of hospitalization we estimated the hazard ratios (HRs) adjusted for confounders with 95% Confidence Interval (CI) related to a 10 μg/m3 increase in pollutants. For PM2.5 and NO2, respectively, we found positive associations for circulatory system diseases [1.05(1.03–1.06); 1.05(1.03–1.07)], myocardial infarction [1.15(1.12–1.18); 1.15(1.12–1.18)], lung cancer [1.18(1.10–1.26); 1.20(1.12–1.28)], kidney cancer [1.24(1.11–1.29); 1.20(1.07–1.33)], all cancers (but lung) [1.06(1.04–1.08); 1.06(1.04–1.08)] and Low Respiratory Tract Infections (LRTI) [1.07 (1.04–1.11); 1.05 (1.02–1.08)]. Discussion: Our results add new evidence on the effects of air pollution on first-ever (incident) hospitalizations, both in urban and rural areas. We demonstrated the feasibility of a low-cost monitoring system based on available data

Creazione di una Banca dati ed elaborazione dei dati pregressi dello stato qualitativo della Sacca di Goro

Provincia di Ferrara Servizio Risorse idriche e Tutela Ambientale U:O:P:C: Acque costiere ed economia ittic

Compressed Sensing Cardiac Cine Imaging Compared with Standard Balanced Steady-State Free Precession Cine Imaging in a Pediatric Population

Purpose: To compare real-time compressed sensing (CS) and standard balanced steady-state free precession (bSSFP) cardiac cine imaging in children. Materials and Methods: Twenty children (mean age, 15 years ± 5 [SD], range, 7-21 years; 10 male participants) with biventricular congenital heart disease (n = 11) or cardiomyopathy (n = 9) were prospectively included. Examinations were performed with 1.5-T imagers by using both bSSFP and CS sequences in all participants. Quantification of ventricular volumes and function was performed for all images by two readers blinded to patient diagnosis and type of sequence. Values were correlated with phase-contrast flow measurements by one reader. Intra- and interreader agreement were analyzed. Results: There were no significant differences between ventricular parameters measured on CS compared with those of bSSFP (P >.05) for reader 1. Only ejection fraction showed a significant difference (P =.02) for reader 2. Intrareader agreement was considerable for both sequences (bSSFP: mean difference range, +1 to -2.6; maximum CI, +7.9, -13; bias range, 0.1%-4.1%; intraclass correlation coefficient [ICC] range, 0.931-0.997. CS: mean difference range, +7.4 to -5.6; maximum CI, +37.2, -48.8; bias range, 0.5%-7.5%; ICC range, 0.717-0.997). Interreader agreement was acceptable but less robust, especially for CS (bSSFP: mean difference range, +2.6 to -5.6; maximum CI, +60.7, -65.3; bias range, 1.6%-6.2%; ICC range, 0.726-0.951. CS: mean difference range, +10.7 to -9.1; maximum CI, +87.5, -84.6; bias range, 1.1%-17.3%; ICC range, 0.509-0.849). The mean acquisition time was shorter for CS (20 seconds; range, 17-25 seconds) compared with that for bSSFP (160 seconds; range, 130-190 seconds) (P <.001). Conclusion: CS cardiac cine imaging provided equivalent ventricular volume and function measurements with shorter acquisition times compared with those of bSSFP and may prove suitable for the pediatric population

Tofacitinib Decreases Autophagy of Fibroblast-Like Synoviocytes From Rheumatoid Arthritis Patients

The pathway of Janus tyrosine kinases (JAKs) has a central role in the pathogenesis of Rheumatoid Arthritis (RA) by regulating multiple immune functions and cytokine production. The JAK inhibitor tofacitinib is effective in RA patients not responding to methotrexate or TNF-inhibitors. Since hyperactive autophagy has been associated with impaired apoptosis of RA fibroblast-like synoviocytes (FLS), we aimed to investigate the role of tofacitinib in modulating autophagy and apoptosis in these cells. FLS isolated from RA biopsies were cultured with tofacitinib in presence of autophagy inducer rapamycin and in serum deprivation condition. Levels of autophagy, apoptosis, and citrullinated proteins were analyzed by western blot, flow cytometry, immunocytofluorescence, and Real-Time PCR. Rapamycin induced an increase in RA-FLS autophagy while the levels of autophagy marker LC3-II were reduced after in vitro treatment with tofacitinib. The analysis of autophagic flux by specific fluorescence dye confirmed the reduction of autophagy in RA FLS. The treatment with tofacitinib did not influence apoptosis of RA FLS. Modulation of the autophagic process by tofacitinib did not significantly change citrullination. The results of this study demonstrate that tofacitinib is able to modulate autophagy of FLS contributing to its effectiveness in RA patients