Search

Automated compounding device (ACD) are increasingly used for parenteral nutrition (PN) bag production, and their acquisition must be sufficiently thought. The law requires the qualification of these ACD, but did not specify the tests to be performed. The quality by design (QbD) risk based approach allowed to define the quality target product profile in order to acquire the best ACD for each unit, and thanks a risk analysis permitted to define the critical quality attributes (CQA). These CQA will allowed to define tests performed during qualification. The ACD qualified was a 12 pump volumetric system. The CQA for PN bags consisted in sterile, precisely and accurately production with enough stability. During operational qualification volumetric accuracy test was performed, and during the performance qualification: flush volume, media fill, microbiological integrity of environment, sterility of control bag and production test were performed. At the end, all tests were conclusive (excepted for some results mostly due to analytical bias) and the ACD was considered to produce sterile bags in a control environment, precisely (relative standard deviation < 4%) and accurately (mean bias < 1% for weight and < 7% for other controls) with a sufficient stability. The QbD risk based approach allowed to acquire the best ACD for our need, and qualify relevant elements regarding the production process., Competing Interests: Declaration of Competing Interest Authors state no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The 68 Ga/ 177 Lu-PSMA-1 combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Specifically, 177 Lu-PSMA-1 is used in the treatment of castration-resistant prostate cancer that is ineffective or intolerant to the latest generation of chemotherapy and/or hormone therapy. This radiopharmaceutical is manufactured in a radiopharmaceutical synthesizing unit and must pass a quality control where the radiochemical purity (RCP) is assessed prior to release of the batch. RCP evaluation is performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Since there is no monograph for 177 Lu-PSMA-1 in the European Pharmacopoeia, we validate the analytical methods according to the EANM recommendations adapted from ICH Q2. Specificity, linearity, accuracy, precision, intermediate precision, limit of quantification (LOQ) and robustness were described for HPLC and TLC in this study. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of 177 Lu-PSMA-1.

Background: To assess the prevalence, the appearance, and the distribution, as well as the fluctuation over time of early repolarization patterns after four years in a female population derived from the French aviation sector., Methods: This was a retrospective longitudinal study from 1998 to 2010 of a population of female employees who received a full clinical examination and an electrocardiogram (ECG) upon their recruitment and after a period of four years., Results: A total of 306 women were included (average of 25.87 ± 3.3 years of age). The prevalence of early repolarization was 9.2%. The most common appearance was J-point slurring for 64.3% (i.e. 20/28 subjects) that occurred in the inferior leads for 28.6% (i.e. 8/28 subjects). After four years, the prevalence was 7.5%, with a regression of this aspect in five of the subjects. There were no changes in the ECG in terms of the distribution and the appearance among the 23 subjects for whom the aspect persisted. Over the course of this four year period all of the subjects remained asymptomatic., Conclusions: Early repolarization in this largely physically inactive female population was common, and it fluctuated over time. At present, no particular restrictions can be placed on asymptomatic flight crew who exhibit this feature in the absence of a prior medical history for heart disease., (© 2017 Wiley Periodicals, Inc.)

Background: The French military population is a young and athletic population with a high prevalence of early repolarization patterns (ERP) compared to the general population. Screening of military officers at risk of sudden death (SD) is a priority in military medical expertise. The aim of our study was to evaluate the prevalence of ERP and its evolution over a period of 5 years in a specific asymptomatic population, free of heart disease and cardiovascular risk factors., Methods: From March to December 2008, we prospectively collected the electrocardiograms (ECGs) of military officers enlisted into the submarine forces of France. For 5 years (until 2012), the military officers included in the study underwent a clinical examination twice per year. A new ECG was carried out 5 years after the initial one., Results: A total of 250 male subjects were included (mean age 22.87 ± 0.5 years). The prevalence of ERP was 19.2%. The most common appearance was an elevation of a slurring type J point (31/48 or 64.5%) in inferolateral leads (18/48 or 37.8%). After 5 years, the prevalence of ERP was identical to that of the previous period (19.2%) with no change in appearance, distribution, and amplitude in 47 subjects (97.9%). Repolarization changed in two patients (one occurrence of ERP and one disappearance). During the 5 years of follow-up, the subjects remained asymptomatic, Conclusion: ERP is common in our population of young, athletic, and asymptomatic military officers and changes little in 5 years., (© 2014 Wiley Periodicals, Inc.)

A high MAPK1/3 (also known as ERK2/1, respectively) activity, preventing spontaneous activation, is essential to maintain cell cycle arrest of mature oocytes of mammals, frogs or invertebrates such as starfish. Mature oocytes would undergo a "suicide"-like cell death if not fertilized. We previously have reported that downregulation of MAPK1/3 in unfertilized sea urchin eggs induces a calcium-dependent entry into mitosis. We show here that this event is followed by a series of pseudo-mitotic cell cycles associated with transient Cai increases, preceding CASP3/caspase-3 activation and apoptosis. However, cell death was delayed after inhibition of the Cai transients or of cyclin-dependent kinases (CDK), with roscovitine. In these conditions, eggs enter an autophagy program as suggested by detection of processed LC3B by western blot, immunofluorescence and immunogold staining, visualization of autophagy vesicles by electron microscopy, and an increase in acidic vesicular organelles (AVOs). We found that bafilomycin A 1 or an association of leupeptin and pepstatin, which are widely used to study autophagy, may act upon calcium signaling or cell cycle events, respectively, and not only on autophagy events. Finally, inhibition of PtdIns 3-kinase with wortmannin or LY294002 powerfully stimulated cell death of unfertilized eggs, which suggests that this activity does not negatively regulate autophagy as is often reported, but rather stimulates survival in unfertilized eggs. We suggest that apoptosis of unfertilized eggs is the consequence of an aberrant short attempt of development that occurs if MAPK1/3 is inactivated, but these eggs can use autophagy as a survival program when the cell cycle is blocked.

Background: Early repolarization pattern (ERP) associated with a risk of sudden death has recently been described. Very few studies have examined the prevalence of this pattern in a military population characterized by a predominance of young, active male subjects. Therefore, the main objective of this study was to evaluate the prevalence of ERP in a healthy military population free of heart disease but subjected to extreme and potentially arrhythmogenic physical activity., Methods: This prospective, multicenter study was carried out from November 2010 to November 2011 and included 746 individuals undergoing ECG screening; 466 were men (62.4%) and 280 were women (37.5%). Each ECG was interpreted twice by trained cardiologists., Results: The total prevalence of ERP was 13.8% (103/746); 16% (46/280) in women and 12% (57/466) in men (P > 0.05). It declined with age and the pattern of slurring in inferior location was the most common. Heart rate was significantly lower in military officers with ERP., Conclusions: ERP was commonly found in this healthy military population. Preventing the risk of sudden death in this population requires systematic ECG screening, medical history analysis and clinical examination to identify symptomatic patients., (©2013 Wiley Periodicals, Inc.)