CAESAR: Space Weather archive prototype for ASPIS

The project CAESAR (Comprehensive spAce wEather Studies for the ASPIS prototype Realization) is aimed to tackle all the relevant aspects of Space Weather (SWE) and realize the prototype of the scientific data centre for Space Weather of the Italian Space Agency (ASI) called ASPIS (ASI SPace Weather InfraStructure). This contribution is meant to bring attention upon the first steps in the development of the CAESAR prototype for ASPIS and will focus on the activities of the Node 2000 of CAESAR, the set of Work Packages dedicated to the technical design and implementation of the CAESAR ASPIS archive prototype. The product specifications of the intended resources that will form the archive, functional and system requirements gathered as first steps to seed the design of the prototype infrastructure, and evaluation of existing frameworks, tools and standards, will be presented as well as the status of the project in its initial stage.Comment: 4 pages, 2 figures, ADASS XXXII (2022) Proceeding

Disease Reactivation after Fingolimod Discontinuation in Pregnant Multiple Sclerosis Patients

Recent studies estimated an incidence of 4-25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013-2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and during the year after delivery. In total, 27 patients (mean age 29 years) were included. The ARR 1 year before FTY treatment was 1.3. Patients were exposed to FTY for a median of 2.9 years. The ARR was 0.04 during the last year before conception (p < 0.001 compared with the ARR before FTY treatment). Eleven patients became pregnant after a mean of 88 days following FTY discontinuation, whereas 16 patients stopped FTY after pregnancy confirmation. Relapses were observed in 22% of patients during pregnancy and in 44% in the postpartum period. ARR increased both during pregnancy (0.49; p = 0.027) and in the first year after delivery (0.67; p < 0.001) compared to the last year before pregnancy. Compared with radiological assessment before pregnancy, more patients showed new or enlarging T2 lesions (63% vs 30%; p = 0.02) and gadolinium-enhancing lesions (44% vs 0; p = 0.0001) on brain Magnetic Resonance Imaging. Relapses during pregnancy were the only significant predictor for postpartum relapses (OR 1.9, 95% CI 1.11-3.1). One case of spontaneous abortion and no cases of abnormal foetal development were observed. Despite adequate and prolonged control of disease activity, women who discontinue FTY because of pregnancy are at risk for disease reactivation. In patients who relapsed during pregnancy, the initiation of high-efficacy disease modifying drugs (DMDs) soon after delivery is advisable to prevent postpartum relapses

Development and Internal Validation of Novel Nomograms Based on Benign Prostatic Obstruction-Related Parameters to Predict the Risk of Prostate Cancer at First Prostate Biopsy

The present study aimed to determine the ability of novel nomograms based onto readily-available clinical parameters, like those related to benign prostatic obstruction (BPO), in predicting the outcome of first prostate biopsy (PBx). To do so, we analyzed our Internal Review Board-approved prospectively-maintained PBx database. Patients with PSA>20 ng/ml were excluded because of their high risk of harboring prostate cancer (PCa). A total of 2577 were found to be eligible for study analyses. The ability of age, PSA, digital rectal examination (DRE), prostate volume (PVol), post-void residual urinary volume (PVR), and peak flow rate (PFR) in predicting PCa and clinically-significant PCa (CSPCa)was tested by univariable and multivariable logistic regression analysis. The predictive accuracy of the multivariate models was assessed using receiver operator characteristic curves analysis, calibration plot, and decision-curve analyses (DCA). Nomograms predicting PCa and CSPCa were built using the coefficients of the logit function. Multivariable logistic regression analysis showed that all variables but PFR significantly predicted PCA and CSPCa. The addition of the BPO-related variables PVol and PVR to a model based on age, PSA and DRE findings increased the model predictive accuracy from 0.664 to 0.768 for PCa and from 0.7365 to 0.8002 for CSPCa. Calibration plot demonstrated excellent models' concordance. DCA demonstrated that the model predicting PCa is of value between ~15 and ~80% threshold probabilities, whereas the one predicting CSPCa is of value between ~10 and ~60% threshold probabilities. In conclusion, our novel nomograms including PVR and PVol significantly increased the accuracy of the model based on age, PSA and DRE in predicting PCa and CSPCa at first PBx. Being based onto parameters commonly assessed in the initial evaluation of men “prostate health,” these novel nomograms could represent a valuable and easy-to-use tool for physicians to help patients to understand their risk of harboring PCa and CSPCa

Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9% had a FIB-4 < 1.45, 26.4% 1.45-3.25 and 7.7% > 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to < 1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4 > 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4> 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART

Tetracosahexaenoylethanolamide, a novel -acylethanolamide, is elevated in ischemia and increases neuronal output.

-acylethanolamines (NAEs) are endogenous lipid-signaling molecules derived from fatty acids that regulate numerous biological functions, including in the brain. Interestingly, NAEs are elevated in the absence of fatty acid amide hydrolase (FAAH) and following CO-induced ischemia/hypercapnia, suggesting a neuroprotective response. Tetracosahexaenoic acid (THA) is a product and precursor to DHA; however, the NAE product, tetracosahexaenoylethanolamide (THEA), has never been reported. Presently, THEA was chemically synthesized as an authentic standard to confirm THEA presence in biological tissues. Whole brains were collected and analyzed for unesterified THA, total THA, and THEA in wild-type and FAAH-KO mice that were euthanized by either head-focused microwave fixation, CO + microwave, or CO only. PPAR activity by transient transfection assay and ex vivo neuronal output in medium spiny neurons (MSNs) of the nucleus accumbens by patch clamp electrophysiology were determined following THEA exposure. THEA in the wild-type mice was nearly doubled ( 0.05) transcriptional activity of PPARs relative to control, but 100 nM of THEA increased ( < 0.001) neuronal output in MSNs of the nucleus accumbens. Here were identify a novel NAE, THEA, in the brain that is elevated upon ischemia/hypercapnia and by KO of the FAAH enzyme. While THEA did not activate PPAR, it augmented the excitability of MSNs in the nucleus accumbens. Overall, our results suggest that THEA is a novel NAE that is produced in the brain upon ischemia/hypercapnia and regulates neuronal excitation

Radiation environment in exploration-class space missions and plants’ responses relevant for cultivation in Bioregenerative Life Support Systems

For deep space exploration, radiation effects on astronauts, and on items fundamental for life support systems, must be kept under a pre-agreed threshold to avoid detrimental outcomes. Therefore, it is fundamental to achieve a deep knowledge on the radiation spatial and temporal variability in the different mission scenarios as well as on the responses of different organisms to space-relevant radiation. In this paper, we first consider the radiation issue for space exploration from a physics point of view by giving an overview of the topics related to the spatial and temporal variability of space radiation, as well as on measurement and simulation of irradiation, then we focus on biological issues converging the attention on plants as one of the fundamental components of Bioregenerative Life Support Systems (BLSS). In fact, plants in BLSS act as regenerators of resources (i.e. oxygen production, carbon dioxide removal, water and wastes recycling) and producers of fresh food. In particular, we summarize some basic statements on plant radio-resistance deriving from recent literature and concentrate on endpoints critical for the development of Space agriculture. We finally indicate some perspective, suggesting the direction future research should follow to standardize methods and protocols for irradiation experiments moving towards studies to validate with space-relevant radiation the current knowledge. Indeed, the latter derives instead from experiments conducted with different radiation types and doses and often with not space-oriented scopes

The ALTEA experiment onboard the International Space Station

The knowledge of the composition of the radiation environment is an important information for all the radiation safety issues needed for the planning of future long manned space missions. The ALTEA detector is on board the International Space Station since July 2006 and during this period it has performed a detailed measurement of the radiation environment. In this paper we present a summary of past measures and results