Air quality trends and implications pre and post Covid-19 restrictions.

Air pollution causes millions of premature deaths every year. Thus, air quality assessment is essential to preserve human health and support authorities to identify proper policies. In this study, concentration levels of 6 air contaminants (benzene, carbon monoxide, nitrogen dioxide, ground level ozone, particulate matters) as monitored in 2019, 2020 and 2021 by 37 stations, located in Campania (Italy) were analysed. Particular attention has been paid to March-April 2020 period to get clues on the possible effects of the lockdown regulations, imposed in Italy from March 9th to May 4th to limit COVID-19 spread, on atmospheric pollution. Air Quality Index (AQI), an algorithm developed by the United States Environmental Protection Agency (US-EPA), allowed us to classify the air quality from moderately unhealthy to good for sensitive groups. The evaluation of air pollution impact on human health by using the AirQ+ software evidenced a significant decrement of adult mortality in 2020 respect to 2019 and 2021. Among the six pollutants considered, PM10 and PM2.5 resulted the less affected by the lockdown restrictions. Finally, a comparison between NO2 ground level concentration and the reprocessed Level 2 NO2 tropospheric column concentration obtained from satellite surveys highlighted as concentration measured at the ground level stations can be strongly influenced by the station position and its surroundings.

Parameters of the Earth's Free Core Nutation from Diurnal Strain Tides.

Earth deformation at the diurnal tidal frequencies includes the resonant tidal-forcing response caused by the Free Core Nutation (FCN), a retrograde mode related to the slight misalignment of the rotation axes of the outer core and mantle. We analyse data from four underground high-sensitivity laser extensometers, whose signal-to-noise ratio in the diurnal tidal band is particularly high, and provide an alternative independent estimate of the FCN complex frequency with respect to more usual techniques (nutation and gravity). Firstly, we differentiate displacements due to diurnal solid tides to obtain extension along any azimuthal direction in terms of three complex parameters (A, S, C) which depend on latitude and frequency. Then, we demonstrate that we can invert the FCN complex frequency and the sensitivity of Im(A) and Re(S) to the resonance from our data. Lastly we obtain the probability distributions of those four parameters. Our results are in full agreement with those from nutation and gravity, as well as with reference IERS (International Earth Rotation and Reference Systems Service) values. Sensitivities of Im(A) and Re(S) to the resonance are estimated here for the first time and are in agreement with values computed using reference Love and Shida numbers from IERS.

Immune and central nervous system-related miRNAs expression profiling in monocytes of multiple sclerosis patients.

It is widely recognized that monocytes-macrophages adopt a wide variety of phenotypes, influencing the inflammatory activity and demyelination in Multiple Sclerosis (MS). However, how the phenotype of human monocytes evolves in the course of MS is largely unknown. The aim of our preliminary study was to analyse in monocytes of relapsing-remitting and progressive forms of MS patients the expression of a set of miRNAs which impact monocyte-macrophage immune function and their communication with brain cells. Quantitative PCR showed that miRNAs with anti-inflammatory functions, which promote pro-regenerative polarization, are increased in MS patients, while pro-inflammatory miR-155 is downregulated in the same patients. These changes may indicate the attempt of monocytes to counteract neuroinflammation. miR-124, an anti-inflammatory marker but also of myeloid cell quiescence was strongly downregulated, especially in progressive MS patients, suggesting complete loss of homeostatic monocyte function in the progressive disease phase. Profiling of miRNAs that control monocyte polarization may help to define not only the activation state of monocytes in the course of the disease but also novel pathogenic mechanisms.

LFA-1 Controls Th1 and Th17 Motility Behavior in the Inflamed Central Nervous System.

Leukocyte trafficking is a key event during autoimmune and inflammatory responses. The subarachnoid space (SAS) and cerebrospinal fluid are major routes for the migration of encephalitogenic T cells into the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, and are sites of T cell activation before the invasion of CNS parenchyma. In particular, autoreactive Th1 and Th17 cell trafficking and reactivation in the CNS are required for the pathogenesis of EAE. However, the molecular mechanisms controlling T cell dynamics during EAE are unclear. We used two-photon laser microscopy to show that autoreactive Th1 and Th17 cells display distinct motility behavior within the SAS in the spinal cords of mice immunized with the myelin oligodendrocyte glycoprotein peptide MOG35-55. Th1 cells showed a strong directional bias at the disease peak, moving in a straight line and covering long distances, whereas Th17 cells exhibited more constrained motility. The dynamics of both Th1 and Th17 cells were strongly affected by blocking the integrin LFA-1, which interfered with the deformability and biomechanics of Th1 but not Th17 cells. The intrathecal injection of a blocking anti-LFA-1 antibody at the onset of disease significantly inhibited EAE progression and also strongly reduced neuro-inflammation in the immunized mice. Our results show that LFA-1 plays a pivotal role in T cell motility during EAE and suggest that interfering with the molecular mechanisms controlling T cell motility can help to reduce the pathogenic potential of autoreactive lymphocytes.

Effect of fingolimod action on the release of monocyte-derived microvesicles in multiple sclerosis patients.

Recently, microvesicles (MVs) were considered as important mediators of intercellular communication, especially in pathological conditions as Multiple Sclerosis (MS). In myeloid cells, MV shedding is induced by the receptor P2X7 with the involvement of acid sphingomyelinase (A-SMase) and release of the IL-1ß. In this study we evaluate how Fingolimod affects MVs production by the monocytes, as well as P2X7R, IL-1ß expression and A-SMase activity. Treatment decreased MVs production and IL-1ß expression. This effect was associated with the inhibition of A-SMase activity in BzATP-stimulated monocytes from MS patients. These evidences suggest monocyte MVs as a possible disease and drug-efficacy biomarkers.

New Insights Into Immune Cell-Derived Extracellular Vesicles in Multiple Sclerosis.

Extracellular vesicles (EVs) are small vesicles including microvesicles and exosomes which differ in their distinct size, density, biogenesis, and content. Until recently, EVs were considered as simply scrap products. Nowadays, they are engendering huge interest and their shedding plays a well-recognized role in intercellular communication, not only participating in many physiological processes, but also suspected of being involved in the pathogenesis of many diseases. The present review aims to summarize the latest updates on immune cell-derived EVs, focusing on the current status of knowledge in Multiple Sclerosis. Significant progress has been made on their physical and biological characterization even though many aspects remain unclear and need to be addressed. However, it is worth further investigating in order to deepen the knowledge of this unexplored and fascinating field that could lead to intriguing findings in the evaluation of EVs as biomarkers in monitoring the course of diseases and the response to treatments.

Molecular Characterization of Peripheral Extracellular Vesicles in Clinically Isolated Syndrome: Preliminary Suggestions from a Pilot Study.

Extracellular vesicles (EVs), nanoparticles originated from different cell types, seem to be implicated in several cellular activities. In the Central Nervous System (CNS), glia and neurons secrete EVs and recent studies have demonstrated that the intercellular communication mediated by EVs has versatile functional impact in the cerebral homeostasis. This essential role may be due to their proteins and RNAs cargo that possibly modify the phenotypes of the targeted cells. Despite the increasing importance of EVs, little is known about their fluctuations in physiological as well as in pathological conditions. Furthermore, only few studies have investigated the contents of contemporary EVs subgroups (microvesicles, MVs and exosomes, EXOs) with the purpose of discriminating between their features and functional roles. In order to possibly shed light on these issues, we performed a pilot study in which MVs and EXOs extracted from serum samples of a little cohort of subjects (patients with the first clinical evidence of CNS demyelination, also known as Clinically Isolated Syndrome and Healthy Controls) were submitted to deep small-RNA sequencing. Data were analysed by an in-home bioinformatics platform. In line with previous reports, distinct classes of non-coding RNAs have been detected in both the EVs subsets, offering interesting suggestions on their origins and functions. We also verified the feasibility of this extensive molecular approach, thus supporting its valuable use for the analysis of circulating biomarkers (e.g., microRNAs) in order to investigate and monitor specific diseases.

Multiple Sclerosis Treatments Affect Monocyte-Derived Microvesicle Production.

Microvesicles (MVs) are released by immune cells especially of the myeloid lineage upon stimulation with ATP on its cognate receptor P2X7, both in physiological and pathological conditions. In multiple sclerosis (MS) the role of MVs remains little investigated. We aimed to compare the release of MVs in peripheral blood monocytes from MS patients with healthy donors (HDs) and to see how current MS treatment may affect such a production. We also assessed the treatment effect on M1 and M2 monocyte polarization and on the inflammasome components. Spectrophotometric quantification was performed to compare monocyte-derived MVs from 20 untreated relapsing-remitting MS patients and 20 HDs and to evaluate the effect of different treatments. Subgroups of nine interferon-beta and of five teriflunomide-treated MS patients were evaluated at baseline and after 2, 6, and 12 months of treatment. Six MS patients taking Fingolimod, after switching from a first-line therapy, were included in the study and analyzed only at 12 months of treatment. MVs analysis revealed that monocytes from MS patients produced vesicles in higher amounts than controls. All treatments reduced vesicle production but only teriflunomide was associated with a downregulation of purinergic P2X7 receptor and inflammasome components expression. The therapies modulated mRNA expression of both M1 and M2 monocyte markers. Our results, suggesting new molecular targets for drugs currently used in MS, may potentially provide useful novel evidence to approach the disease.

Thermally-assisted Magma Emplacement Explains Restless Calderas.

Many calderas show repeated unrest over centuries. Though probably induced by magma, this unique behaviour is not understood and its dynamics remains elusive. To better understand these restless calderas, we interpret deformation data and build thermal models of Campi Flegrei caldera, Italy. Campi Flegrei experienced at least 4 major unrest episodes in the last decades. Our results indicate that the inflation and deflation of magmatic sources at the same location explain most deformation, at least since the build-up of the last 1538 AD eruption. However, such a repeated magma emplacement requires a persistently hot crust. Our thermal models show that this repeated emplacement was assisted by the thermal anomaly created by magma that was intruded at shallow depth ~3 ka before the last eruption. This may explain the persistence of the magmatic sources promoting the restless behaviour of the Campi Flegrei caldera; moreover, it explains the crystallization, re-melting and mixing among compositionally distinct magmas recorded in young volcanic rocks. Our model of thermally-assisted unrest may have a wider applicability, possibly explaining also the dynamics of other restless calderas.

Influence of desloratadine on oxidative stress markers in patients with chronic idiopathic urticaria.

BACKGROUND: Recent findings suggest the involvement of oxidative stress in the pathogenesis of chronic idiopathic urticaria (CIU). It has been demonstrated that desloratadine has an antioxidant activity in vitro. We evaluated the effects of desloratadine on markers of oxidative stress in patients with CIU. METHODS: Blood samples were obtained from 10 patients with CIU before and after 4 weeks of treatment with desloratadine. Blood samples from 10 healthy volunteers were used as controls. In platelets from both patients and controls, radical oxygen species (ROS) production was measured using spectrofluorimetric detection of dichloro-fluorescein oxidation, and superoxide dismutase (SOD) activity was determined by means of the xanthine-xanthine oxidase system. RESULTS: Radical oxygen species concentrations and SOD activity were significantly elevated in patients with CIU at baseline as compared with control subjects. Treatment with desloratadine caused a relevant reduction of ROS levels and SOD activity (P<0.005). CONCLUSIONS: These preliminary results suggest that desloratadine exerts antioxidant effects also in vivo.