Diabetes and COVID-19: The potential role of mTOR.

Diabetes is the most frequent comorbidity among patients with COVID-19. COVID-19 patients with diabetes have a more severe prognosis than patients without diabetes. However, the etiopathogenetic mechanisms underlying this more unfavorable outcome in these patients are not clear. Probably the etiopathogenetic mechanisms underlying diabetes could represent a favorable substrate for a greater development of the inflammatory process already dysregulated in COVID-19 with a more severe evolution of the disease. In the attempt to shed light on the possible etiopathogenetic mechanisms, we wanted to evaluate the possible role of mTOR (mammalian Target Of Rapamycin) pathway in this context. We searched the PubMed and Scopus databases to identify articles involving diabetes and the mTOR pathway in COVID-19. The mTOR pathway could be involved in this etiopathogenetic mechanism, in particular, the activation and stimulation of this pathway could favor an inflammatory process that is already dysregulated in itself, while its inhibition could be a way to regulate this dysregulated inflammatory process. However, much remains to be clarified about the mechanisms of the mTOR pathway and its role in COVID-19. The aim of this review is to to understand the etiopathogenesis underlying COVID-19 in diabetic patients and the role of mTOR pathway in order to be able to search for new weapons to deal with this disease.

OVERVIEW OF NEUTRON MEASUREMENTS IN JET FUSION DEVICE.

The design and operation of ITER experimental fusion reactor requires the development of neutron measurement techniques and numerical tools to derive the fusion power and the radiation field in the device and in the surrounding areas. Nuclear analyses provide essential input to the conceptual design, optimisation, engineering and safety case in ITER and power plant studies. The required radiation transport calculations are extremely challenging because of the large physical extent of the reactor plant, the complexity of the geometry, and the combination of deep penetration and streaming paths. This article reports the experimental activities which are carried-out at JET to validate the neutronics measurements methods and numerical tools used in ITER and power plant design. A new deuterium-tritium campaign is proposed in 2019 at JET: the unique 14 MeV neutron yields produced will be exploited as much as possible to validate measurement techniques, codes, procedures and data currently used in ITER design thus reducing the related uncertainties and the associated risks in the machine operation.

Benchmarking of Monte Carlo based shutdown dose rate calculations for applications to JET.

The calculation of dose rates after shutdown is an important issue for operating nuclear reactors. A validated computational tool is needed for reliable dose rate calculations. In fusion reactors neutrons induce high levels of radioactivity and presumably high doses. The complex geometries of the devices require the use of sophisticated geometry modelling and computational tools for transport calculations. Simple rule of thumb laws do not always apply well. Two computational procedures have been developed recently and applied to fusion machines. Comparisons between the two methods showed some inherent discrepancies when applied to calculation for the ITER while good agreement was found for a 14 MeV point source neutron benchmark experiment. Further benchmarks were considered necessary to investigate in more detail the reasons for the different results in different cases. In this frame the application to the Joint European Torus JET machine has been considered as a useful benchmark exercise. In a first calculational benchmark with a representative D-T irradiation history of JET the two methods differed by no more than 25%. In another, more realistic benchmark exercise, which is the subject of this paper, the real irradiation history of D-T and D-D campaigns conducted at JET in 1997-98 were used to calculate the shut-down doses at different locations, irradiation and decay times. Experimental dose data recorded at JET for the same conditions offer the possibility to check the prediction capability of the calculations and thus show the applicability (and the constraints) of the procedures and data to the rather complex shutdown dose rate analysis of real fusion devices. Calculation results obtained by the two methods are reported below, comparison with experimental results give discrepancies ranging between 2 and 10. The reasons of that can be ascribed to the high uncertainty on the experimental data and the unsatisfactory JET model used in the calculation. A new dedicated JET benchmark experiment will be performed trying to solve these issues.

FLUKA simulation of TEPC response to cosmic radiation.

The aircrew exposure to cosmic radiation can be assessed by calculation with codes validated by measurements. However, the relationship between doses in the free atmosphere, as calculated by the codes and from results of measurements performed within the aircraft, is still unclear. The response of a tissue-equivalent proportional counter (TEPC) has already been simulated successfully by the Monte Carlo transport code FLUKA. Absorbed dose rate and ambient dose equivalent rate distributions as functions of lineal energy have been simulated for several reference sources and mixed radiation fields. The agreement between simulation and measurements has been well demonstrated. In order to evaluate the influence of aircraft structures on aircrew exposure assessment, the response of TEPC in the free atmosphere and on-board is now simulated. The calculated results are discussed and compared with other calculations and measurements.

A mathematical model of aircraft for evaluating the effects of shielding structure on aircrew exposure.

To investigate the influence of the aircraft structures and contents on the exposure of aircrew to the galactic component of cosmic rays, a mathematical model of an aeroplane has been developed. The irradiation of the mathematical model in the cosmic ray environment has been simulated using the Monte Carlo transport code FLUKA. Effective dose andambient dose-equivalent rates have been determined inside the aircraft at several locations along the fuselage at a typicaI civil aviation altitude. A significant effect of the shielding of aircraft structures has been observed on the ambient dose-equivalent rates, while the impact on the effective dose rates seems to be minor. Care should be taken in positioning the detectors onboard when the measurements are aimed at validating the codes.

Monte Carlo calculation of the angular distribution of cosmic rays at flight altitudes.

The angular distribution of the secondary radiation produced by the galactic component of cosmic rays has been determined by simulating the penetration of the primary spectra in the Earth's atmosphere. The simulations have been carried out with the latest version of the FLUKA code. Particles have been scored at various altitudes according to their angle of incidence for some significant values of vertical cut-off rigidity and solar modulation parameter. The calculated results at typical cruise altitudes for a civil aircraft are presented. The data at 10.7 km have been fitted with simple mathematical equations. It has been demonstrated that the major contribution to the doses at aviation altitudes arises from downward-directed particles. The isotropic irradiation usually assumed for the evaluation of aircrew exposure could be a very poor approximation.

Evaluation of the influence of aircraft shielding on the aircrew exposure through an aircraft mathematical model.

In order to investigate the influence of aircraft shielding on the galactic component of cosmic rays, an aircraft mathematical model has been developed by the combinatorial geometry package of the Monte-Carlo transport code FLUKA. The isotropic irradiation of the aircraft in the cosmic ray environment has been simulated. Effective dose and ambient dose equivalent rates have been determined inside the aircraft at several locations along the fuselage, at a typical civil aviation altitude (10 580 m), for vertical cut-off rigidity of 0.4 GV (poles) and 17.6 GV (equator) and deceleration potential of 465 MV. The values of both quantities were generally lower than those in the free atmosphere. They depend, in an intricate manner, on the location within the aircraft, quantity of fuel, number of passengers, etc. The position onboard of crew members should be taken into account when assessing individual doses. Likewise due consideration must be taken when positioning detectors which are used to measure H*(10). Care would be needed to avoid ambiguity when comparing the results of calculation with the experimental data.

Hepatitis B immunisation with a reduced number of doses in newborn babies and children.

74 healthy babies born to mothers positive for hepatitis B surface antigen (HBsAg) were randomly divided at birth to receive either HB immunoglobulin and 2 doses of HB vaccine 2 months apart, or HB immunoglobulin and 3 doses of HB vaccine 1 month apart. 80 healthy babies born to HBsAg, anti-HBs, and anti-HB core (c) negative mothers were randomly divided at birth to receive either 2 doses of vaccine 2 months apart or 3 doses 1 month apart. The seroconversion rates and the geometric means of anti-HBs titres were lower in both groups of babies given 2 doses of vaccine than in the groups given 3 doses. 60 pairs of children at risk, aged 1 to 12 years and HBsAg, anti-HBs, and anti-HBc negative, were randomly divided to receive either the 2-dose regimen or the 3-dose regimen. The seroconversion rates and the geometric means of anti-HBs titres were satisfactory in both groups.

[Effect of methadone administration on MHV-3 virus-induced experimental hepatitis in the mouse]. / Effetto della somministrazione di metadone sulla epatite sperimentale del topo da virus MHV-3.

Mice treated with 15 mg/Kg/day methadone and infected with MHV-3 virus after 7 days did not show increased susceptibility to MHV-3 virus infection, did not develop more serious forms of hepatitis and not mortality did not increase with respect to the controls. Drug administration was continued for the duration of the experiment.