Challenge of Chimpanzees Immunized with a Recombinant Canarypox-HIV-1 Virus

AbstractTo evaluate the potential protective efficacy of a live recombinant human immunodeficiency virus type 1 (HIV-1) canarypox vaccine candidate, two chimpanzees were immunized five times with ALVAC-HIV-1 vCP250, a recombinant canarypox virus that expresses the HIV-1IIIB(LAI)gp120/TM,gag,and protease gene products. One month after the last booster inoculation, the animals were challenged by intravenous injection of cell-associated virus in the form of peripheral blood mononuclear cells from an HIV-1IIIB(LAI)-infected chimpanzee. One chimpanzee with a neutralizing antibody titer to HIV-1IIIB(LAI)of 128 at the time of challenge was protected, whereas both the second animal, with a neutralizing antibody titer of 32, and a naive control animal became infected. At 5 months after challenge, the protected chimpanzee and a third animal, previously immunized with various HIV-1MNantigens, were given a booster inoculation. The two animals were challenged intravenously 5 weeks later with twenty 50% tissue culture infectious doses of cell-free HIV-1DH12, a heterologous subtype B isolate. Neither chimpanzee had neutralizing antibodies to HIV-1DH12, and neither one was protected from infection with this isolate. The immune responses elicited by vaccination against HIV-1IIIB(LAI)or HIV-1MNdid not, therefore, protect the animals from challenge with the heterologous cell-free HIV-1DH12

Comparison of reconstruction methods used during liver transplantation in case of a graft with replaced or accessory right hepatic artery:A retrospective study

Variations in graft arterial anatomy can increase the risk of postoperative hepatic arterial thrombosis (HAT), especially in presence of a replaced or accessory right hepatic artery (RHA). We retrospectively analyzed 223 cases of liver transplantations with the presence of an RHA on the graft. Patient outcomes were compared according to the four different reconstruction methods used: (i) the re-implantation of the RHA into the splenic or gastroduodenal artery (n = 106); (ii) the interposition of the superior mesenteric artery (SMA) (n = 83); (iii) dual anastomosis (n = 24); (iv) use of an aortic patch including the origins of both the SMA and the coeliac trunk (n = 10). A competing risk analysis and Inverse Probability Weighting (IPW) were used. We found that the interposition of the SMA method was associated with a significantly lower incidence of HAT, at 4.8% compared to the re-implantation method at 17.9%, dual anastomosis at 12.5%, and aortic patch at 20%, p =.03. In the competing risk analysis with IPW, the only risk factor for RHA thrombosis was the type of reconstruction. Taking the SMA interposition group as the reference, the sub-hazard ratio (sHR) was 5.05 (CI 95 [1.72; 14.78], p &lt;.01) for the re-implantation group, sHR = 2.37 (CI 95 [0.51; 11.09], p =.27) for the dual anastomosis group and sHR = 2.24 (CI 95 [0.35; 14.33], p =.40) for the aortic patch group. There were no differences for intraoperative transfusion, hospitalization duration (p =.37) or incidence of severe complications (p =.1). The long-term graft (p =.69) and patient (p =.52) survival was not different. In conclusion, the SMA interposition method was associated with a lower incidence of RHA thrombosis.</p

Comparison of reconstruction methods used during liver transplantation in case of a graft with replaced or accessory right hepatic artery:A retrospective study

Variations in graft arterial anatomy can increase the risk of postoperative hepatic arterial thrombosis (HAT), especially in presence of a replaced or accessory right hepatic artery (RHA). We retrospectively analyzed 223 cases of liver transplantations with the presence of an RHA on the graft. Patient outcomes were compared according to the four different reconstruction methods used: (i) the re-implantation of the RHA into the splenic or gastroduodenal artery (n = 106); (ii) the interposition of the superior mesenteric artery (SMA) (n = 83); (iii) dual anastomosis (n = 24); (iv) use of an aortic patch including the origins of both the SMA and the coeliac trunk (n = 10). A competing risk analysis and Inverse Probability Weighting (IPW) were used. We found that the interposition of the SMA method was associated with a significantly lower incidence of HAT, at 4.8% compared to the re-implantation method at 17.9%, dual anastomosis at 12.5%, and aortic patch at 20%, p =.03. In the competing risk analysis with IPW, the only risk factor for RHA thrombosis was the type of reconstruction. Taking the SMA interposition group as the reference, the sub-hazard ratio (sHR) was 5.05 (CI 95 [1.72; 14.78], p &lt;.01) for the re-implantation group, sHR = 2.37 (CI 95 [0.51; 11.09], p =.27) for the dual anastomosis group and sHR = 2.24 (CI 95 [0.35; 14.33], p =.40) for the aortic patch group. There were no differences for intraoperative transfusion, hospitalization duration (p =.37) or incidence of severe complications (p =.1). The long-term graft (p =.69) and patient (p =.52) survival was not different. In conclusion, the SMA interposition method was associated with a lower incidence of RHA thrombosis.</p

Therapeutic anticoagulation after liver transplantation is not useful among patients with pre-transplant Yerdel-grade I/II portal vein thrombosis:A two-center retrospective study

BACKGROUND: Portal vein thrombosis (PVT) is no longer a contraindication for liver transplantation (LT). While therapeutic anticoagulation (tAC) is recommended during the waiting period, there is no evidence for its usefulness in the prevention of PVT recurrence after LT. OBJECTIVES: The aim of our study was to evaluate the role of tAC post-LT in the prevention of PVT recurrence. PATIENTS/METHODS: All adult LTs performed in 2 high volume centres between 2003 and 2018, were retrospectively analysed. Only patients with PVT classified as Yerdel grade I or II and with standard portal reconstruction were included. PVT recurrence and tAC-associated morbidity within 1 year were compared between patients receiving tAC or not. RESULTS: During the study period, out of 2612 LTs performed, 235 (9%) patients with PVT were included. 113 patients (48.1%) received post-LT tAC (tAC group) while 122 (51.9%) did not (non-tAC group). The incidence of bleeding events was significantly higher in the tAC group (26 (23%) vs. 5 (4.1%), p<0.01) and the initial hospitalization duration was longer (21 vs. 17.5 days, p<0.01). Within the first year, PVT recurrence was observed for 9 (3.8%) patients without any difference between the tAC and non-tAC groups (6 (5.1%) vs. 3 (2.5%), p=0.39). The only identified risk factor for PVT recurrence was the recipients' age (OR=0.94, p=0.03). Graft (p=0.11) and patient (p=0.44) survival were similar between the 2 groups. CONCLUSION: Therapeutic anticoagulation is not necessary in the prevention of grade I/II PVT recurrence and is associated with higher morbidity and longer hospital stay

A Human TREK-1/HEK Cell Line: A Highly Efficient Screening Tool for Drug Development in Neurological Diseases

TREK-1 potassium channels are involved in a number of physiopathological processes such as neuroprotection, pain and depression. Molecules able to open or to block these channels can be clinically important. Having a cell model for screening such molecules is of particular interest. Here, we describe the development of the first available cell line that constituvely expresses the TREK-1 channel. The TREK-1 channel expressed by the h-TREK-1/HEK cell line has conserved all its modulation properties. It is opened by stretch, pH, polyunsaturated fatty acids and by the neuroprotective molecule, riluzole and it is blocked by spadin or fluoxetine. We also demonstrate that the h-TREK-1/HEK cell line is protected against ischemia by using the oxygen-glucose deprivation model

Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT

© 2021 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.Background: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine. Methods: There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients. Results: None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41×10-9) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70×10-8), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant. Conclusions: We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.info:eu-repo/semantics/publishedVersio

Apprendre à faire la classe : analyse de l’évolution de l’activité des enseignants stagiaires en formation initiale d’instituteur primaire en FWB

This thesis work reports on research aiming at understanding how students in initial training as primary teachers in the Wallonia-Brussels Federation learn to teach during the traineeship that punctuate their formation. Our qualitative research approach is in line with the non-deficit perspective (Malo, 2006) and the activity approach (Barbier & Durand, 2003; Hubault, 1996), which are primarily interested in the resources that trainees mobilize and transform to learn their profession by experimenting with it. In particular, we mobilize the semiological framework of the course of action (Theureau, 2004, 2006), because of its interest in the dynamics of meaning construction by an actor that emerges from asymmetrical structural coupling with a situation that he experiences. Our results highlight (1) a shift from the mobilization of insecure and isolated professional gestures to configurations of organized gestures, with conditions of use and variations, (2) progress in different dimensions addressed by trainees such as as the management of the unexpected, the ability to deal with several competing concerns, the construction and mobilization of reference systems or the management of student learning and (3) five typical situated learning experiences that are lived according to temporalities and different levels of immersion in the activity.(PSYE - Sciences psychologiques et de l'éducation) -- UCL, 202