Αξιολόγηση πειραματικής διάταξης ραδιενεργού πηγής σωματίων α 234-U για ραδιοβιολογικά πειράματα

Η παρούσα εργασία αποτελεί μια προσπάθεια επιβεβαίωσης της πειραματικής επιβεβαίωσης λειτουργίας της πειραματικής διάταξης πηγής ακτινοβολίας α 234-U που κατασκευάστηκε από την Ευαγγελία Χουλιλίτσα με σκοπό την in situ ακτινοβόληση βιολογικού υλικού. Έγινε για τα πειράματα χρήση της συσκευής αυτής, που βρίσκεται στο κτίριο Φυσικής του ΕΜΠ στο εργαστήριο του Δρ. Γεωργακίλα, για ακτινοβόληση κυττάρων CHO με δόση 1Gy. Σύμφωνα με τους υπολογισμούς που πραγματοποιήθηκαν από την Ευαγγελία Χουλιλίτσα στα πλαίσια της διπλωματικής της εργασίας, για τη συσκευή αυτή, δόση 1Gy ισοδυναμεί με παραμονή του βιολογικού υλικού κάτω από την πηγή για χρόνο 13’ 26’’. Τα σωμάτια α είναι πυρήνες He, άρα θετικά φορτισμένα σωματίδια, που εκπέμπονται από ραδιενεργά υλικά. Έχουν εξαιρετικό ενδιαφέρον στη μελέτη τους, καθώς λόγω και του μεγέθους τους είναι ικανά να σκοτώσουν ένα κύτταρο διασχίζοντας τον πυρήνα τους, αλλά ταυτόχρονα είναι δύσκολο να μελετηθούν σε βιολογικά πειράματα λόγω της μικρής διεισδυτικότητάς τους. Εξαιτίας της μεγάλης τιμής της γραμμικής εναπόθεσης ενέργειας (LET) που έχουν συγκριτικά με τις πιο μελετημένες ακτίνες Χ ή γάμα, οι ραδιοβιολογικές συνέπειες των άλφα προσέλκυσαν μεγάλο ερευνητικό ενδιαφέρον. Τα σωμάτια άλφα έχουν ενέργειες από 4 έως 9 MeV και χαρακτηρίζονται από τιμή LET της τάξης του 100 keV ανά μm που είναι υπεύθυνη για την σοβαρή βλάβη που προκαλεί η άλφα ακτινοβολία τόσο σε υγιή και κακοήθη κύτταρα, αλλά και για την εμβέλειά τους σε βιολογικό υλικό που είναι μικρότερη από 0.1 mm. Αυτό που ξεχωρίζει την άλφα ακτινοβολία από τις ακτινοβολίες με χαμηλή τιμή LET είναι ότι η επίδραση των άλφα είναι σχεδόν ανεξάρτητη της δόσης και η βιολογική τους αποτελεσματικότητα καθορίζεται λιγότερο από το στάδιο του κυτταρικού κύκλου στο οποίο βρίσκεται το κύτταρο. Επιπλέον, οι βλάβες που προκαλεί η άλφα ακτινοβολία στο DNA είναι λιγότερο ευαίσθητες στους αντίστοιχους μηχανισμούς επιδιόρθωσης.This project is an evaluation effort of an a-particle 234-U sorce experimental setup constructed by Evangelia Choulilitsa. The device was used to radiate CHO cells with the dose of 1 Gy. For this device, 1 Gy radiation is equivalent with 13'26''. The experiments' results were used to calculate the actual dose that the cells received for exposure time 13'26'', as it is expected to be less than 1 Gy

Un modèle bayésien multivarié à effets mixtes (Leaspy) pour analyser la trajectoire du déclin cognitif dans CADASIL

International audienceCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), the most frequent cerebral small artery disease is caused by stereotyped mutations of the NOTCH3 gene. The multifaceted clinical presentation of this disorder can be assessed using various measures. We used a bayesian mixed effect model(Leaspy) to model the multivariate disease progression and explore the spatiotemporal relationships between these measures. We were also able to identify different groups of individual evolution according to the time shift and acceleration rate by taking into account the gender, education level, smoking, hypertension and the mutation's position

Outcome of very high-risk patients treated by Sotrovimab for mild-to-moderate COVID-19 Omicron, a prospective cohort study (the ANRS 0003S COCOPREV study)

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Sotrovimab to Prevent Severe COVID-19 in High-Risk Patients Infected with Omicron BA.2

International audienceBefore the Omicron era, the neutralizing antibody targeting the SARS-CoV2 Spike protein Sotrovimab has been shown to reduce the risk of COVID-19-related hospitalization in patients who are at high risk for progression (1, 2). We recently showed that early administration of Sotrovimab in Omicron-infected patients with very high-risk for progression was associated with a low rate of COVID-19-related hospitalization within one month after treatment administration (3%), and with no death (1). However, the dominance of the Omicron sublineage BA.2 led health agencies to suspend Sotrovimab emergency use authorizations because of its lower neutralizing ability in vitro compared to BA.1 sublineage (3, 4). Clinical efficiency of Sotrovimab to prevent COVID-19 related complications in high-risk patients with mild-to-moderate COVID-19 Omicron BA.2 remains unknown. Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients with mild-to-moderate COVID-19 who received 500 mg of Sotrovimab IV to prevent COVID-19-related complications

Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir

International audienceObjectives: Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients who received Sotrovimab or Nirmatrelvir to prevent severe COVID-19.Methods: In the multicentric prospective ANRS 0003S CoCoPrev cohort study, patients at high-risk for progression with mild-to-moderate BA.1 or BA.2 COVID-19 who received Sotrovimab or Nirmatrelvir were included. Proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multivariable Cox proportional hazard model was used for time to negative PCR and a mixed effect model for the dynamics of viral decay.Results: Among the 255 included patients, of whom 199/255 (80%) received ≥3 vaccine doses, 195/255 (76%) received Sotrovimab and 60/255 (24%) received Nirmatrelvir. At day 28, new COVID-19-related hospitalization occurred in 4/193 (2%, 95%CI 1-5%) Sotrovimab-treated patients, and 0/55 Nirmatrelvir-treated patient (p=0.24). One out of 55 Nirmatrelvir-treated patients died (2%, 95%CI 0-10%). The median time to negative PCR was 11.5 days (95%CI 10.5-13) in Sotrovimab-treated patients vs. 4 days (95% CI 4-9) in Nirmatrelvir-treated patients (p<0.001). Viral decay was faster in patients who received Nirmatrelvir (p<0.001). In multivariable analysis Nirmatrelvir and nasopharyngeal PCR cycle threshold value were independently associated with a faster conversion to negative PCR (HR 2.35, 95%CI 1.56-3.56, p<0.0001, and HR 1.05, 95%CI 1.01-1.08, p=0.01, respectively).Conclusions: Early administration of Nirmatrelvir in high-risk patients, compared to Sotrovimab, was associated with a faster viral clearance. This may participate to decrease transmission and prevent viral resistance

Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir

International audienceObjectives: Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients who received Sotrovimab or Nirmatrelvir to prevent severe COVID-19.Methods: In the multicentric prospective ANRS 0003S CoCoPrev cohort study, patients at high-risk for progression with mild-to-moderate BA.1 or BA.2 COVID-19 who received Sotrovimab or Nirmatrelvir were included. Proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multivariable Cox proportional hazard model was used for time to negative PCR and a mixed effect model for the dynamics of viral decay.Results: Among the 255 included patients, of whom 199/255 (80%) received ≥3 vaccine doses, 195/255 (76%) received Sotrovimab and 60/255 (24%) received Nirmatrelvir. At day 28, new COVID-19-related hospitalization occurred in 4/193 (2%, 95%CI 1-5%) Sotrovimab-treated patients, and 0/55 Nirmatrelvir-treated patient (p=0.24). One out of 55 Nirmatrelvir-treated patients died (2%, 95%CI 0-10%). The median time to negative PCR was 11.5 days (95%CI 10.5-13) in Sotrovimab-treated patients vs. 4 days (95% CI 4-9) in Nirmatrelvir-treated patients (p<0.001). Viral decay was faster in patients who received Nirmatrelvir (p<0.001). In multivariable analysis Nirmatrelvir and nasopharyngeal PCR cycle threshold value were independently associated with a faster conversion to negative PCR (HR 2.35, 95%CI 1.56-3.56, p<0.0001, and HR 1.05, 95%CI 1.01-1.08, p=0.01, respectively).Conclusions: Early administration of Nirmatrelvir in high-risk patients, compared to Sotrovimab, was associated with a faster viral clearance. This may participate to decrease transmission and prevent viral resistance