Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 ...(IL-6) levels and with disease severity and mortality in COVID-19. We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 + or - 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization. Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 + or - 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 + or - 8.5 ng/mL and 25.4 + or - 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit (ICU), 14.4 + or - 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively, than in those not requiring ICU admission 22.4 + or - 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively. Similar differences were found when comparing COVID-19 patients who died in hospital 13.2 + or - 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL with survivors 19.3 + or - 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (rho - 0.284, p = 0.004); ii) the subsequent need of the ICU admission relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011 regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count. In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.
Current energy drivers are pushing research in power generation materials towards improved efficiency and improved environmental impact. In the context of new generation ultra-supercritical (USC) ...power plant, this is represented by increased efficiency, service temperature reaching 750°C, pressures in the range of 35–37.5MPa and associated carbon capture technology. Ni base alloys are primary candidate materials for long term high temperature applications such as boilers. The transition from their current applications, which have required lower exposure times and milder corrosive environments, requires the investigation of their microstructural evolution as a function of thermo-mechanical treatment and simulated service conditions, coupled with modelling activities that are able to forecast such microstructural changes. The lack of widespread microstructural data in this context for most nickel base alloys makes this type of investigation necessary and novel. Alloy INCONEL 617 is one of the Ni-base candidate materials. The microstructures of four specimens of this material crept at temperatures in the 650–750°C range for up to 20,000h have been characterised and quantified. Grain structure, precipitate type and location, precipitate volume fraction, size and inter-particle spacing have been determined. The data obtained are used both as input for and validation of a microstructurally-based CDM model for forecasting creep properties.
Abstract
Translation of electron FLASH radiotherapy in clinical practice requires the use of high energy accelerators to treat deep tumours and Very High Electron Energy (VHEE) could represent a ...valid technique to achieve this goal. In this scenario, a VHEE FLASH linac is under study at the University La Sapienza of Rome (Italy) in collaboration with the Italian Institute for Nuclear Research (INFN) and the Institut Curie (France). Here we present the preliminary results of a compact C-band system aiming to reach an high accelerating gradient and an high pulse current necessary to deliver high dose per pulse and ultra-high dose rate required for FLASH effect. We propose a system composed of a low energy high current injector linac followed by a modular section of high accelerating gradient structures. CST code is used to define the required LINAC’s RF parameters and beam dynamics simulations are performed using TSTEP and ASTRA.
Psoriasis is a chronic inflammatory skin disease associated with reactive oxygen species (ROS) increase and a higher risk of cardiovascular (CV) events. We previously showed that the miR-200 family ...(miR-200s) is induced by ROS, miR-200c being the most upregulated member responsible for apoptosis, senescence, ROS increase, and nitric oxide decrease, finally causing endothelial dysfunction. Moreover, circulating miR-200c increases in familial hypercholesterolemic children and in plaques and plasma of atherosclerotic patients, two pathologies associated with increased ROS. Given miR-200s’ role in endothelial dysfunction, ROS, and inflammation, we hypothesized that miR-200s were modulated in lesional skin (LS) and plasma of psoriatic patients (Pso) and that their levels correlated with some CV risk determinants at a subclinical level. All Pso had severe psoriasis, i.e., Psoriasis Area and Severity Index PASI>10, and one of the following: at least two systemic psoriasis treatments, age at onset<40 years, and disease duration>10 years. RNA was extracted from plasma (Pso, N=29; Ctrl, N=29) and from nonlesional skin (NLS) and LS of 6 Pso and 6 healthy subject skin (HS) biopsies. miR-200 levels were assayed by quantitative RT-PCR. We found that all miR-200s were increased in LS vs. NLS and miR-200c was the most expressed and upregulated in LS vs. HS. In addition, circulating miR-200c and miR-200a were upregulated in Pso vs. Ctrl. Further, miR-200c positively correlated with PASI, disease duration, left ventricular (LV) mass, LV relative wall thickness (RWT), and E/e′, a marker of diastolic dysfunction. Multiple regression analysis indicates a direct association between miR-200c and both RWT and LV mass. Circulating miR-200a correlated positively only with LV mass and arterial pressure augmentation index, a measure of stiffness, although the correlations were nearly significant (P=0.06). In conclusion, miR-200c is upregulated in LS and plasma of Pso, suggesting its role in ROS increase and inflammation associated with CV risk in psoriasis.
Background
Persistent ST‐segment elevation in acute coronary syndrome is associated with both short and long‐term complications. By contrast, there is limited information about ST‐elevation and its ...evolution during takotsubo (stress) cardiomyopathy (TTC).
Aim
To evaluate whether persistent downsloping ST‐elevation in the early stages of TTC might correlate with short and long‐term clinical events.
Methods
One‐hundred fifty‐eight consecutive subjects with TTC were prospectively enrolled and assessed by electrocardiogram. Patients were classified in two groups according to the presence of downsloping ST‐elevation ≥5 mm lasting at least 24 hr (“lambda‐wave” ST‐elevation group vs. without downsloping ST‐elevation) in at least one/two contiguous leads.
Results
Five (3.2%) patients, all female with a mean left ventricular ejection fraction 32 ± 5%, were included in the lambda‐wave ST‐elevation group. These patients were characterized by a higher prevalence of physical stressor (100% vs. 49%, p = 0.04) and higher admission and peak levels of troponin‐I levels during hospitalization. Peak of ST‐elevation in the lambda‐wave ST‐elevation group was reached 6 hr after admission and gradually decreased after 24 hr. In‐hospital complications were observed in all the patients presenting lambda ST‐elevation (100% vs. 23%, p = 0.03, OR: 29.1, p = 0.04); one patient presented endoventricular thrombosis and two died of cardiogenic shock. At long‐term follow‐up (mean 443 days), adverse events were observed in 80% of patients with lambda‐wave ST‐elevation (RR of adverse events at follow‐up 32, p < 0.01).
Conclusion
Persistent downsloping lambda‐wave ST‐elevation during the acute phase of stress cardiomyopathy may be associated with a higher risk of adverse events at short and long‐term follow‐up.
Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this ...technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms.
The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account.
The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far.
•A fast GPU based MC has been developed for IOeRT breast treatment planning.•The input is an ultrasound image with defined PTV and OARs.•Different applicator positions, dimensions and angles and beam energies are tested.•Plan is optimised using absorbed dose maps and related DVHs.•Results in the context of conventional and FLASH irradiations are discussed.
Transformation characteristics and morphological features of ferrite/carbide aggregate (FCA) in low carbon-manganese steels have been investigated. Work shows that FCA has neither the lamellae ...structure of pearlite nor the lath structure of bainite and martensite. It consists of a fine dispersion of cementite particles in a smooth ferrite matrix. Carbide morphologies range from arrays of globular particles or short fibers to extended, branched, and densely interconnected fibers. Work demonstrates that FCA forms over similar cooling rate ranges to Widmanstätten ferrite. Rapid transformation of both phases occurs at temperatures between 798 K and 973 K (525 °C and 700 °C). FCA reaction is not simultaneous with Widmanstätten ferrite but occurs at temperatures intermediate between Widmanstätten ferrite and bainite. Austenite carbon content calculations verify that cementite precipitation is thermodynamically possible at FCA reaction temperatures without bainite formation. The pattern of precipitation is confirmed to be discontinuous. CCT diagrams have been constructed that incorporate FCA. At low steel manganese content, Widmanstätten ferrite and bainite bay sizes are significantly reduced so that large amounts of FCA are formed over a wide range of cooling rates.
Background: Dark chocolate is reported to decrease platelet activation but the underlying mechanism is still undefined. Dark chocolate is rich in polyphenols that could exert an antiplatelet action ...via inhibition of oxidative stress. The aim of the present study was to assess if dark chocolate inhibits platelet reactive oxidant species (ROS) formation and platelet activation. Methods: Twenty healthy subjects (HS) and 20 smokers were randomly allocated to receive 40 g of dark (cocoa > 85%) or milk chocolate (cocoa < 35%) in a cross‐over, single‐blind study. There was an interval of 7 days between the two phases of the study. At baseline and 2 h after chocolate ingestion, platelet recruitment (PR), platelet ROS, platelet isoprostane 8‐ISO‐prostaglandin F2α (8‐iso‐PGF2α), Thromboxane (TxA2) and platelet activation of NOX2, the catalytic sub‐unit of NADPH oxidase, and serum epicatechin were measured. Results: Compared with HS, smokers showed enhanced PR, platelet formation of ROS and eicosanoids and NOX2 activation. After dark chocolate, platelet ROS (−48%, P < 0.001), 8‐iso‐PGF2α (−10%, P < 0.001) and NOX2 activation (−22%, P < 0.001) significantly decreased; dark chocolate did not affect platelet variables in HS. No effect of milk chocolate was detected in both groups. Serum epicatechin increased after dark chocolate in HS (from 0.454 ± 0.3 nm to 118.3 ± 53.7 nm) and smokers (from 0.5 ± 0.28 nm to 120.9 ± 54.2 nm). Platelet incubation with 0.1–10 μm catechin significantly reduced PR, platelet 8‐iso‐PGF2α and ROS formation and NOX2 activation only in platelets from smokers. Conclusions: Dark chocolate inhibits platelet function by lowering oxidative stress only in smokers; this effect seems to be dependent on its polyphenolic content.
This paper reports the development of dosimeters based on plastic scintillating fibers imaged by a charge-coupled device camera, and their performance evaluation through irradiations with the ...electron Flash research accelerator located at the Centro Pisano Flash Radiotherapy. The dosimeter prototypes were composed of a piece of plastic scintillating fiber optically coupled to a clear optical fiber which transported the scintillation signal to the readout systems (an imaging system and a photodiode). The following properties were tested: linearity, capability to reconstruct the percentage depth dose curve in solid water and to sample in time the single beam pulse. The stem effect contribution was evaluated with three methods, and a proof-of-concept one-dimensional array was developed and tested for online beam profiling. Results show linearity up to 10 Gy per pulse, and good capability to reconstruct both the timing and spatial profiles of the beam, thus suggesting that plastic scintillating fibers may be good candidates for low-energy electron Flash dosimetry.
•Flash radiotherapy may be groundbreaking for improving cancer treatment.•Conventional dosimeters do not function properly in the Flash regime.•Dosimeters based on plastic scintillating fibers were developed and characterized.•No quenching or energy dependence was observed in the Flash regime.•The beam time structure could be properly sampled.
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