Des chaperons pharmacologiques agissant sur les récepteurs V2 de la vasopressine offrent un traitement potentiel pour le diabète insipide néphrogénique

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Beneficial effects of ivabradine in patients with heart failure, low ejection fraction, and heart rate above 77 b.p.m.

Aims: Ivabradine has been approved in heart failure with reduced ejection fraction (HFrEF) and elevated heart rate despite guideline‐directed medical therapy (GDMT) to reduce cardiovascular (CV) death and hospitalization for worsening HF. The median value of 77 b.p.m. is the lower bound selected for the regulatory approval in Canada, South Africa, and Australia. Patient‐reported outcomes (PROs) including symptoms, quality of life, and global assessment are considered of major interest in the global plan of care of patients with HF. However, the specific impact of GDMT, and specifically ivabradine, on PRO remains poorly studied. In the subgroup of patients from the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) who had heart rate above the median of 77 b.p.m. (pre‐specified analysis) and for whom the potential for improvement was expected to be larger, we aimed (i) to evaluate the effects of ivabradine on PRO (symptoms, quality of life, and global assessment); (ii) to consolidate the effects of ivabradine on the primary composite endpoint of CV death and hospitalization for HF; and (iii) to reassess the effects of ivabradine on left ventricular (LV) remodelling. Methods and results: Comparisons were made according to therapy, and proportional hazards models (adjusted for baseline beta‐blocker therapy) were used to estimate the association between ivabradine and various outcomes. In SHIFT, n = 3357 (51.6%) patients had a baseline heart rate > 77 b.p.m. After a median follow‐up of 22.9 months (inter‐quartile range 18–28 months), ivabradine on top of GDMT improved symptoms (28% vs. 23% improvement in New York Heart Association functional class, P = 0.0003), quality of life (5.3 vs. 2.2 improvement in Kansas City Cardiomyopathy Questionnaire overall summary score, P = 0.005), and global assessment [from both patient (improved in 72.3%) and physician (improved in 61.0%) perspectives] significantly more than did placebo (both P < 0.0001). Ivabradine induced a 25% reduction in the combined endpoint of CV death and hospitalization for HF (hazard ratio 0.75; P < 0.0001), which translates into a number of patients needed to be treated for 1 year of 17. Patients under ivabradine treatment demonstrated a significant reduction in LV dimensions when reassessed at 8 months (P < 0.05). Conclusions: In patients with chronic HFrEF, sinus rhythm, and a heart rate > 77 b.p.m. while on GDMT, the present analysis brings novel insights into the role of ivabradine in improving the management of HFrEF, particularly with regard to PRO (ISRCTN70429960)

Association Between Cardiac Radiation Exposure and the Risk of Arrhythmia in Breast Cancer Patients Treated With Radiotherapy:A Case-Control Study

Background: Previous studies suggested that radiation therapy (RT) for breast cancer (BC) can induce cardiac arrhythmias and conduction disorders. However, the association with mean heart dose and specific cardiac substructures doses was less studied. Materials and Methods: We conducted a nested case-control study based on French BC patients, enrolled in the European MEDIRAD-BRACE study (https://clinicaltrials.gov, Identifier: NCT03211442), who underwent three-dimensional conformal radiation therapy (3D-CRT) between 2009 and 2013 and were retrospectively followed until 2019. Cases were incident cases of cardiac arrhythmia. Controls without arrhythmia were selected with propensity-scored matching by age, duration of follow-up, chemotherapy, hypertension, and diabetes (ratio 1:4 or 5). Doses to the whole heart (WH), left and right atria (LA and RA), and left and right ventricles (LV and RV) were obtained after delineation with multi-atlas-based automatic segmentation. Results: The study included 116 patients (21 cases and 95 controls). Mean age at RT was 64 ± 10 years, mean follow-up was 7.0 ± 1.3 years, and mean interval from RT to arrhythmia was 4.3 ± 2.1 years. None of the results on association between arrhythmia and cardiac doses reached statistical significance. However, the proportion of right-sided BC was higher among patients with arrhythmia than among controls (57% vs. 51%, OR = 1.18, p = 0.73). Neither mean WH dose, nor LV, RV, and LA doses were associated with an increased risk of arrhythmia (OR = 1.00, p > 0.90). In contrast, the RA dose was slightly higher for cases compared to controls [interquartile range (0.61-1.46 Gy) vs. (0.49-1.31 Gy), p = 0.44], and a non-significant trend toward a potentially higher risk of arrhythmia with increasing RA dose was observed (OR = 1.19, p = 0.60). Subanalysis according to BC laterality showed that the association with RA dose was reinforced specifically for left-sided BC (OR = 1.76, p = 0.75), while for right-sided BC, the ratio of mean RA/WH doses may better predict arrhythmia (OR = 2.39, p = 0.35). Conclusion: Despite non-significant results, our exploratory investigation on BC patients treated with RT is the first study to suggest that right-sided BC patients and the right atrium irradiation may require special attention regarding the risk of cardiac arrhythmia and conduction disorders. Further studies are needed to expand on this topic

Effects of controlled atmosphere temperature treatment (CATT) for Phytonemus pallidus management on plant survival, yield and growth of strawberry transplants

Cyclamen mite (Phytonemus pallidus Banks) can be eliminated from strawberry (Fragaria × ananassa Duchesne) planting material when transplants are subjected to a controlled atmosphere temperature treatment (CATT) at 35 °C, 50% CO2 and 10% O2 under high relative humidity for 48 h. In our previous research, CATT reduced cyclamen mite numbers by 99.9%, but its effects on plant vigour were not assessed. The objective of this study was to assess the survival, yield and growth of different strawberry cultivars (‘Albion’, ‘Murano’, ‘Seascape’) and plant types (bareroot plants, trayplants) that received CATT before planting compared to untreated control plants. CATT slightly increased the risks of plant mortality, and plant losses were greater for trayplants than for bareroot plants. CATT resulted in increased runner production for ‘Albion’ transplants but caused no effects on other cultivars. Fruit yields were either unaffected or decreased by CATT, suggesting stimulation of vegetative rather than reproductive growth. Based on these results, disinfection of strawberry transplants using CATT would be more suitable for plants destined for propagation rather than for fruit production. Our research highlights the need to develop a universal and easily adoptable treatment effective against multiple pests and pathogens to produce clean strawberry transplants.Le tarsonème du fraisier (Phytonemus pallidus Banks) peut être éliminé des transplants de fraisiers (Fragaria × ananassa Duchesne) soumis à un traitement de température en atmosphère contrôlée (CATT) à 35 °C, 50 % de CO2 et 10 % d’O2 sous une humidité relative élevée pendant 48 h. Dans notre recherche précédente, le traitement CATT a réduit le nombre de tarsonèmes du fraisier de 99,9 %, mais ses effets sur les plants n’ont pas été évalués. L’objectif de cette étude était d’évaluer l’effet du traitement CATT sur la survie, le rendement et la croissance de différents cultivars (‘Albion’, ‘Murano’, ‘Seascape’) et types de plants (plants à racines nues, trayplants). La mortalité après la plantation était plus grande pour les plants traités. Le traitement CATT a entraîné une augmentation de la production de stolons pour les transplants du cultivar ‘Albion’, mais n’a eu aucun effet sur les autres cultivars. Les rendements en fruits n’ont pas été affectés ou ont été diminués par le traitement CATT, ce qui suggère qu’il pourrait stimuler la croissance végétative aux dépens de la croissance reproductive. La désinfection des transplants de fraisiers à l’aide du traitement CATT conviendrait donc mieux aux plantes destinées à la multiplication plutôt qu’à la production de fruits

Transgenerational Immune Priming in the Field: Maternal Environmental Experience Leads to Differential Immune Transfer to Oocytes in the Marine Annelid Hediste diversicolor

Transgenerational immune priming (TGIP) is an intriguing form of parental care which leads to the plastic adjustment of the progeny’s immunity according to parental immune experience. Such parental effect has been described in several vertebrate and invertebrate taxa. However, very few empirical studies have been conducted from the field, with natural host-parasite systems and real ecological settings, especially in invertebrates. We investigated TGIP in wild populations of the marine annelid Hediste diversicolor. Females laid eggs in a mud tube and thus shared the local microbial threats with the first developmental stages, thus meeting expectations for the evolution of TGIP. We evidenced that a maternal bacterial challenge led to the higher antibacterial defense of the produced oocytes, with higher efficiency in the case of Gram-positive bacterial challenge, pointing out a prevalent role of these bacteria in the evolutionary history of TGIP in this species. Underlying mechanisms might involve the antimicrobial peptide hedistin that was detected in the cytoplasm of oocytes and whose mRNAs were selectively stored in higher quantity in mature oocytes, after a maternal immune challenge. Finally, maternal immune transfer was significantly inhibited in females living in polluted areas, suggesting associated costs and the possible trade-off with female’s protection

Selective epitaxial growth of AlGaAs/GaAs heterostructures on 300 mm Si(001) for red optical emission

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