49 results on '"Amireault P"'
Search Results
2. Examining Positive Youth Development Interventions with a Physical Activity Component to Address Bullying among Pre- and Early Adolescents: A Critical Review of the Literature
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Majed, Elzahraa, Ruiz, Yumary, Amireault, Steve, Reed, Jason B., Snyder, Frank J., McDonough, Meghan H., and Blankenship, Bonnie
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This review aimed at identifying specific features of PYD interventions with a PA component that appear most promising at reducing bullying behaviors among pre- and early adolescents. We reviewed articles that included PYD interventions with a PA component among pre- and early adolescents aged 8-14 years from five databases and found seven studies representing 3892 participants. Studies collectively showed that PYD-PA interventions can promote an interactive and supportive relationship between participants and staff and foster adolescents' psychosocial development. The review's limitations include the variation of PA components and geographical contexts of interventions leading to a difficulty in synthesizing the results. PA-based PYD interventions provide a promising approach that can foster youth's psychosocial development such as the use of an interactive approach and the use of several PYD components (e.g., empathy and caring). This approach, consequently, may lower bullying behaviors. Given the nature of this review, further evaluation is warranted.
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- 2022
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3. Safe drugs with high potential to block malaria transmission revealed by a spleen-mimetic screening
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Mario Carucci, Julien Duez, Joel Tarning, Irene García-Barbazán, Aurélie Fricot-Monsinjon, Abdoulaye Sissoko, Lucie Dumas, Pablo Gamallo, Babette Beher, Pascal Amireault, Michael Dussiot, Ming Dao, Mitchell V. Hull, Case W. McNamara, Camille Roussel, Papa Alioune Ndour, Laura Maria Sanz, Francisco Javier Gamo, and Pierre Buffet
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Science - Abstract
Authors propose their splenic mimetic filtration method, microsphiltration, and utilise this approach in a drug-screen, to identify compounds that induce a stiffening effect on Plasmodium falciparum-infected erythrocytes. They proceed to assess safety and tolerability of one identified compound in a phase I clinical trial.
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- 2023
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4. Low-Dose Dietary Fish Oil Improves RBC Deformability without Improving Post-Transfusion Recovery in Mice
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Christopher Y. Kim, Hannah J. Larsen, Steven L. Spitalnik, Eldad A. Hod, Richard O. Francis, Krystalyn E. Hudson, Dominique E. Gordy, Elizabeth F. Stone, Sandy Peltier, Pascal Amireault, Angelo D’Alessandro, James C. Zimring, Paul W. Buehler, Xiaoyun Fu, and Tiffany Thomas
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fish oil ,erythrocytes ,transfusion ,RBC ,supplement ,deformability ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Long-chain polyunsaturated fatty acids (LC-PUFAs) are important modulators of red blood cell (RBC) rheology. Dietary LC-PUFAs are readily incorporated into the RBC membrane, improving RBC deformability, fluidity, and hydration. Female C57BL/6J mice consumed diets containing increasing amounts of fish oil (FO) ad libitum for 8 weeks. RBC deformability, filterability, and post-transfusion recovery (PTR) were evaluated before and after cold storage. Lipidomics and lipid peroxidation markers were evaluated in fresh and stored RBCs. High-dose dietary FO (50%, 100%) was associated with a reduction in RBC quality (i.e., in vivo lifespan, deformability, lipid peroxidation) along with a reduced 24 h PTR after cold storage. Low-dose dietary FO (6.25–12.5%) improved the filterability of fresh RBCs and reduced the lipid peroxidation of cold-stored RBCs. Although low doses of FO improved RBC deformability and reduced oxidative stress, no improvement was observed for the PTR of stored RBCs. The improvement in RBC deformability observed with low-dose FO supplementation could potentially benefit endurance athletes and patients with conditions resulting from reduced perfusion, such as peripheral vascular disease.
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- 2023
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5. Integration Process and Identity Redefinition of Chinese Adult Learners of French as a Second Language in Quebec
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Amireault, Valérie
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This study explores the perceptions of integration and cultural identity redefinitions expressed by Chinese adult learners of French as a second language (FSL) in Quebec (Canada). We present their reflections from their perspective of learning and using French, Quebec's main language. Interviews were conducted in French with 15 newly-arrived immigrants, intermediate speakers of the language. The study shows that these Chinese immigrants mostly develop a utilitarian relationship with the French language. French courses are first and foremost perceived as a first step toward their linguistic and professional integration. Results show that learning the language and using it outside of the formal learning context constitute essential components of the integration process into the host society. French learning is also perceived as a space in which to build one's identity, a sort of negotiation between the culture of origin and the host culture. Study results help to better understand Chinese learners in FSL classrooms and consider relevant pedagogical actions for these learners.
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- 2020
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6. Association between Fruit and Vegetable Intake and Physical Activity among Breast Cancer Survivors: A Longitudinal Study
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Steve Amireault, Jennifer Brunet, Jordan D. Kurth, Angela J. Fong, and Catherine M. Sabiston
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breast neoplasms ,diet ,exercise ,longitudinal studies ,survivors ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
This study examines the association between rates of change in daily fruit and vegetable intake and in weekly levels of moderate-to-vigorous intensity physical activity (MVPA) over a 15-month period in women following primary treatment completion for breast cancer. Breast cancer survivors (N = 199) self-reported fruit and vegetable intake and wore an accelerometer for 7 consecutive days to measure levels of MVPA on five occasions every 3 months. Multivariate latent growth modeling revealed that the rate of change in fruit and vegetable intake was not associated with the rate of change in levels of MVPA. Baseline (Mean = 3.46 months post-treatment) levels of MVPA were not associated with the rate of change of daily fruit and vegetable intake; likewise, baseline fruit and vegetable intake was not associated with the rate of change in levels of MVPA. Behavioral interventions promoting fruit and vegetable intake should not be assumed to yield concomitant effects in promoting MVPA or vice versa.
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- 2021
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7. Deuterated Linoleic Acid Attenuates the RBC Storage Lesion in a Mouse Model of Poor RBC Storage
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Christopher Y. Kim, Hannah Johnson, Sandy Peltier, Steven L. Spitalnik, Eldad A. Hod, Richard O. Francis, Krystalyn E. Hudson, Elizabeth F. Stone, Dominique E. Gordy, Xiaoyun Fu, James C. Zimring, Pascal Amireault, Paul W. Buehler, Robert B. Wilson, Angelo D’Alessandro, Mikhail S. Shchepinov, and Tiffany Thomas
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transfusion ,RBC ,deformability ,ROS ,lipidomics ,peroxidation ,Physiology ,QP1-981 - Abstract
Background: Long-chain polyunsaturated fatty acids (PUFAs) are important modulators of red blood cell (RBC) rheology. Dietary PUFAs are readily incorporated into the RBC membrane, improving RBC deformability, fluidity, and hydration. However, enriching the lipid membrane with PUFAs increases the potential for peroxidation in oxidative environments (e.g., refrigerated storage), resulting in membrane damage. Substitution of bis-allylic hydrogens with deuterium ions in PUFAs decreases hydrogen abstraction, thereby inhibiting peroxidation. If lipid peroxidation is a causal factor in the RBC storage lesion, incorporation of deuterated linoleic acid (DLA) into the RBC membrane should decrease lipid peroxidation, thereby improving RBC lifespan, deformability, filterability, and post-transfusion recovery (PTR) after cold storage.Study Design and Methods: Mice associated with good (C57BL/6J) and poor (FVB) RBC storage quality received diets containing 11,11-D2-LA Ethyl Ester (1.0 g/100 g diet; deuterated linoleic acid) or non-deuterated LA Ethyl Ester (control) for 8 weeks. Deformability, filterability, lipidomics, and lipid peroxidation markers were evaluated in fresh and stored RBCs.Results: DLA was incorporated into RBC membranes in both mouse strains. DLA diet decreased lipid peroxidation (malondialdehyde) by 25.4 and 31% percent in C57 mice and 12.9 and 79.9% in FVB mice before and after cold storage, respectively. In FVB, but not C57 mice, deformability filterability, and post-transfusion recovery were significantly improved.Discussion: In a mouse model of poor RBC storage, with elevated reactive oxygen species production, DLA attenuated lipid peroxidation and significantly improved RBC storage quality.
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- 2022
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8. Storage-Induced Micro-Erythrocytes Can Be Quantified and Sorted by Flow Cytometry
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Mickaël Marin, Sandy Peltier, Youcef Hadjou, Sonia Georgeault, Michaël Dussiot, Camille Roussel, Olivier Hermine, Philippe Roingeard, Pierre A. Buffet, and Pascal Amireault
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red blood cell (RBC) ,RBC storage ,RBC morphology ,flow cytometry ,imaging flow cytometry (IFC) ,RBC storage lesion ,Physiology ,QP1-981 - Abstract
Refrigerated storage of red cell concentrates before transfusion is associated with progressive alterations of red blood cells (RBC). Small RBC (type III echinocytes, sphero-echinocytes, and spherocytes) defined as storage-induced micro-erythrocytes (SME) appear during pretransfusion storage. SME accumulate with variable intensity from donor to donor, are cleared rapidly after transfusion, and their proportion correlates with transfusion recovery. They can be rapidly and objectively quantified using imaging flow cytometry (IFC). Quantifying SME using flow cytometry would further facilitate a physiologically relevant quality control of red cell concentrates. RBC stored in blood bank conditions were stained with a carboxyfluorescein succinimidyl ester (CFSE) dye and incubated at 37°C. CFSE intensity was assessed by flow cytometry and RBC morphology evaluated by IFC. We observed the accumulation of a CFSEhigh RBC subpopulation by flow cytometry that accounted for 3.3 and 47.2% at day 3 and 42 of storage, respectively. IFC brightfield images showed that this CFSEhigh subpopulation mostly contains SME while the CFSElow subpopulation mostly contains type I and II echinocytes and discocytes. Similar numbers of SME were quantified by IFC (based on projected surface area) and by flow cytometry (based on CFSE intensity). IFC and scanning electron microscopy showed that ≥95% pure subpopulations of CFSEhigh and CFSElow RBC were obtained by flow cytometry-based sorting. SME can now be quantified using a common fluorescent dye and a standard flow cytometer. The staining protocol enables specific sorting of SME, a useful tool to further characterize this RBC subpopulation targeted for premature clearance after transfusion.
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- 2022
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9. Genetic regulation of carnitine metabolism controls lipid damage repair and aging RBC hemolysis in vivo and in vitro
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Nemkov, Travis, Key, Alicia, Stephenson, Daniel, Earley, Eric J., Keele, Gregory R., Hay, Ariel, Amireault, Pascal, Casimir, Madeleine, Dussiot, Michaël, Dzieciatkowska, Monika, Reisz, Julie A., Deng, Xutao, Stone, Mars, Kleinman, Steve, Spitalnik, Steven L., Hansen, Kirk C., Norris, Philip J., Churchill, Gary A., Busch, Michael P., Roubinian, Nareg, Page, Grier P., Zimring, James C., Arduini, Arduino, and D’Alessandro, Angelo
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•Carnitine pools in stored human and murine RBCs are regulated by genetic polymorphisms in the SLC22A16 and SLC22A5 transporters.•Carnitine pools fuel the Lands cycle for damaged membrane lipid repair during RBC aging, affecting hemolysis in vitro and in vivo.
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- 2024
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10. OA3‐AM23‐MN‐13 | Morphologically altered Red Blood Cells that Accumulate During Storage Have Altered Proteostasis and Post‐transfusion Spleen Retention
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Peltier, S., primary, Marin, M., additional, Dzieciatkowska, M., additional, Dussiot, M., additional, Georgeault, S., additional, Gautier, E., additional, Spitalnik, S., additional, Buffet, P., additional, D’Alessandro, A., additional, and Amireault, P., additional
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- 2023
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11. 'Do I Have to Sign My Real Name?' Ethical and Methodological Challenges in Multilingual Research with Adult SLIFE Learning French as a Second Language
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Alexandra H. Michaud, Véronique Fortier, and Valérie Amireault
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methodological challenges ,research ethics ,second language learners ,limited formal education ,multilingual study ,Language and Literature - Abstract
In 2017, Quebec’s Auditor General reported several major issues regarding government-funded French as a second language (FSL) courses, especially those intended for adult students with limited or interrupted formal education (SLIFE). To this day, no official framework or program exists for this specific population, a situation that the government of Quebec wishes to resolve. Our research team was thereby mandated by the Ministry of Immigration to conduct a large-scale multilingual study with the objective of gaining a better understanding of the realities and needs of the various stakeholders involved in low-literate FSL classes. We met 42 teachers, 24 French learning center directors, and 10 pedagogical advisors in individual interviews; we also led 107 group interviews with SLIFE in 26 languages, allowing us to meet 464 adult SLIFE enrolled in low-literate FSL classes from 11 regions of the province of Quebec, most of them being refugees. This article reports on the decision-making process in which we engaged to overcome the ethical and methodological challenges we faced at various stages of the data collection with SLIFE participants: recruitment, informed consent, confidentiality, interview protocol design, instrument piloting, data collection, and data translation and transcription. To make informed decisions, we had to turn to literature outside SLA (i.e., refugee research and translation/interpreting literature) for guidance. In this article we discuss the limitations and contributions of our research to guide researchers who will conduct studies with similar non-academic samples/populations.
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- 2022
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12. Maintenance motives for physical activity among older adults: a protocol for a systematic review and meta-analysis
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Mary Katherine Huffman, Jason Brian Reed, Theresa Carpenter, and Steve Amireault
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Medicine - Abstract
IntroductionPhysical activity (PA) is an important aspect for health and well-being, yet many older adults do not maintain their PA long term. The identification of key factors that are associated with, and likely causally related to, older adults’ PA maintenance is a crucial first step towards developing programmes that are effective at promoting long-term PA behaviour change. The purpose of this protocol is to outline a systematic review that will examine the relationship between four motives (ie, satisfaction, enjoyment, self-determination and identity) and older adults’ PA maintenance.Methods and analysisStudies that investigated PA maintenance with a sample mean age ≥55 years will be included. Five electronic databases (PubMed, Cumulative Index to Nursing and Allied Health Literature, SPORTDiscus, PsycINFO and ProQuest Dissertations and Theses) were searched on 6 April 2018 with no publication date limit (ie, from inception). One reviewer screened 100% of titles and abstracts (k=21 470) while a random subsample (20%) was screened independently by two reviewers. An update of the search was run on 1 October 2019. All studies for which the full text was retrieved will be independently screened by two reviewers. Data pertaining to study sample, design, motives, PA (eg, measurement validity evidence, study definition of maintenance) and essential bias domains (eg, bias due to missing data) will be extracted. Study-level effect sizes will be calculated, and if the number of studies is ≥5, a random-effects meta-analysis will be performed using inverse-variance methods; a narrative synthesis will be performed otherwise.Ethics and disseminationThe university’s Human Research Protection Program determined that the proposed study qualifies as exempt from the Institutional Review Board review under Exemption Category 4 (PROPEL #: 80047007). Results will be published in a peer-review journal, and the findings will help inform future interventions with older adults.PROSPERO registration numberCRD42018088161.
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- 2020
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13. Changes in light-, moderate-, and vigorous-intensity physical activity and changes in depressive symptoms in breast cancer survivors: a prospective observational study
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Sylvester, Benjamin D., Ahmed, Rashid, Amireault, Steve, and Sabiston, Catherine M.
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- 2017
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14. Mechanical clearance of red blood cells by the human spleen: Potential therapeutic applications of a biomimetic RBC filtration method
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Duez, J., Holleran, J.P., Ndour, P.A., Pionneau, C., Diakité, S., Roussel, C., Dussiot, M., Amireault, P., Avery, V.M., and Buffet, P.A.
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- 2015
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15. Restoration of Physiological Levels of Uric Acid and Ascorbic Acid Reroutes the Metabolism of Stored Red Blood Cells
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Manon Bardyn, Jingkui Chen, Michaël Dussiot, David Crettaz, Lucas Schmid, Emmanuel Längst, Pascal Amireault, Jean-Daniel Tissot, Mario Jolicoeur, and Michel Prudent
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red blood cell ,blood storage ,transfusion ,metabolomics ,antioxidant ,uric acid ,Microbiology ,QR1-502 - Abstract
After blood donation, the red blood cells (RBCs) for transfusion are generally isolated by centrifugation and then filtrated and supplemented with additive solution. The consecutive changes of the extracellular environment participate to the occurrence of storage lesions. In this study, the hypothesis is that restoring physiological levels of uric and ascorbic acids (major plasmatic antioxidants) might correct metabolism defects and protect RBCs from the very beginning of the storage period, to maintain their quality. Leukoreduced CPD-SAGM RBC concentrates were supplemented with 416 µM uric acid and 114 µM ascorbic acid and stored during six weeks at 4 °C. Different markers, i.e., haematological parameters, metabolism, sensitivity to oxidative stress, morphology and haemolysis were analyzed. Quantitative metabolomic analysis of targeted intracellular metabolites demonstrated a direct modification of several metabolite levels following antioxidant supplementation. No significant differences were observed for the other markers. In conclusion, the results obtained show that uric and ascorbic acids supplementation partially prevented the metabolic shift triggered by plasma depletion that occurs during the RBC concentrate preparation. The treatment directly and indirectly sustains the antioxidant protective system of the stored RBCs.
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- 2020
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16. Fluorescence Exclusion: A Simple Method to Assess Projected Surface, Volume and Morphology of Red Blood Cells Stored in Blood Bank
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Camille Roussel, Sylvain Monnier, Michael Dussiot, Elisabeth Farcy, Olivier Hermine, Caroline Le Van Kim, Yves Colin, Matthieu Piel, Pascal Amireault, and Pierre A. Buffet
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red blood cell volume ,red blood cells ,transfusion ,red blood cell storage ,fluorescence exclusion ,red blood cell morphology ,Medicine (General) ,R5-920 - Abstract
Red blood cells (RBC) ability to circulate is closely related to their surface area-to-volume ratio. A decrease in this ratio induces a decrease in RBC deformability that can lead to their retention and elimination in the spleen. We recently showed that a subpopulation of “small RBC” with reduced projected surface area accumulated upon storage in blood bank concentrates, but data on the volume of these altered RBC are lacking. So far, single cell measurement of RBC volume has remained a challenging task achieved by a few sophisticated methods some being subject to potential artifacts. We aimed to develop a reproducible and ergonomic method to assess simultaneously RBC volume and morphology at the single cell level. We adapted the fluorescence exclusion measurement of volume in nucleated cells to the measurement of RBC volume. This method requires no pre-treatment of the cell and can be performed in physiological or experimental buffer. In addition to RBC volume assessment, brightfield images enabling a precise definition of the morphology and the measurement of projected surface area can be generated simultaneously. We first verified that fluorescence exclusion is precise, reproducible and can quantify volume modifications following morphological changes induced by heating or incubation in non-physiological medium. We then used the method to characterize RBC stored for 42 days in SAG-M in blood bank conditions. Simultaneous determination of the volume, projected surface area and morphology allowed to evaluate the surface area-to-volume ratio of individual RBC upon storage. We observed a similar surface area-to-volume ratio in discocytes (D) and echinocytes I (EI), which decreased in EII (7%) and EIII (24%), sphero-echinocytes (SE; 41%) and spherocytes (S; 47%). If RBC dimensions determine indeed the ability of RBC to cross the spleen, these modifications are expected to induce the rapid splenic entrapment of the most morphologically altered RBC (EIII, SE, and S) and further support the hypothesis of a rapid clearance of the “small RBC” subpopulation by the spleen following transfusion.
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- 2018
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17. Measuring Post-transfusion Recovery and Survival of Red Blood Cells: Strengths and Weaknesses of Chromium-51 Labeling and Alternative Methods
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Camille Roussel, Pierre A. Buffet, and Pascal Amireault
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transfusion recovery ,red blood cell ,spleen ,red blood cell morphology ,red blood cell deformability ,storage lesion ,Medicine (General) ,R5-920 - Abstract
The proportion of transfused red blood cells (RBCs) that remain in circulation is an important surrogate marker of transfusion efficacy and contributes to predict the potential benefit of a transfusion process. Over the last 50 years, most of the transfusion recovery data were generated by chromium-51 (51Cr)-labeling studies and were predominantly performed to validate new storage systems and new processes to prepare RBC concentrates. As a consequence, our understanding of transfusion efficacy is strongly dependent on the strengths and weaknesses of 51Cr labeling in particular. Other methods such as antigen mismatch or biotin-based labeling can bring relevant information, for example, on the long-term survival of transfused RBC. These radioactivity-free methods can be used in patients including from vulnerable groups. We provide an overview of the methods used to measure transfusion recovery in humans, compare their strengths and weaknesses, and discuss their potential limitations. Also, based on our understanding of the spleen-specific filtration of damaged RBC and historical transfusion recovery data, we propose that RBC deformability and morphology are storage lesion markers that could become useful predictors of transfusion recovery. Transfusion recovery can and should be accurately explored by more than one method. Technical optimization and clarification of concepts is still needed in this important field of transfusion and physiology.
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- 2018
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18. Validity of the Brazilian version of the Godin-Shephard Leisure-Time Physical Activity Questionnaire
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Thaís Moreira São João, Roberta Cunha Matheus Rodrigues, Maria Cecília Bueno Jayme Gallani, Cinthya Tamie Passos Miura, Gabriela de Barros Leite Domingues, Steve Amireault, and Gaston Godin
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Enfermedades Cardiovasculares ,Actividad Motora ,Estudios de Validación ,Cuestionarios ,Psicometría ,Medicine ,Public aspects of medicine ,RA1-1270 - Abstract
This study provides evidence of construct validity for the Brazilian version of the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ), a 1-item instrument used among 236 participants referred for cardiopulmonary exercise testing. The Baecke Habitual Physical Activity Questionnaire (Baecke-HPA) was used to evaluate convergent and divergent validity. The self-reported measure of walking (QCAF) evaluated the convergent validity. Cardiorespiratory fitness assessed convergent validity by the Veterans Specific Activity Questionnaire (VSAQ), peak measured (VO2peak) and maximum predicted (VO2pred) oxygen uptake. Partial adjusted correlation coefficients between the GSLTPAQ, Baecke-HPA, QCAF, VO2pred and VSAQ provided evidence for convergent validity; while divergent validity was supported by the absence of correlations between the GSLTPAQ and the Occupational Physical Activity domain (Baecke-HPA). The GSLTPAQ presents level 3 of evidence of construct validity and may be useful to assess leisure-time physical activity among patients with cardiovascular disease and healthy individuals.
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- 2015
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19. Validation of the Godin-Shephard Leisure-Time Physical Activity Questionnaire classification coding system using accelerometer assessment among breast cancer survivors
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Amireault, Steve, Godin, Gaston, Lacombe, Jason, and Sabiston, Catherine M.
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- 2015
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20. No effect of scalp cooling on survival among women with breast cancer
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Lemieux, J., Provencher, L., Perron, L., Brisson, J., Amireault, C., Blanchette, C., and Maunsell, E.
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- 2015
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21. Erratum to: The use of the Godin-Shephard Leisure-Time Physical Activity Questionnaire in oncology research: a systematic review
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Steve Amireault, Gaston Godin, Jason Lacombe, and Catherine M. Sabiston
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Medicine (General) ,R5-920 - Published
- 2016
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22. Conserver les globules rouges pour la transfusion.
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Roussel, Camille, Buffet, Pierre, and Amireault, Pascal
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Quatre-vingt-dix millions de patients reçoivent une transfusion de globules rouges chaque année. Cette procédure nécessite une étape de stockage des globules rouges entre le don et la transfusion au receveur, permettant la réalisation de contrôles de qualité et une meilleure gestion des flux. Les nombreuses améliorations techniques des dernières décennies permettent aujourd'hui le stockage réfrigéré des concentrés érythrocytaires (CGR) pendant 42 jours avant utilisation. Ce stockage s'accompagne cependant d'altérations des globules rouges, collectivement nommés les « lésions » de stockage, dont l'amplitude augmente avec la durée de conservation et serait responsable de la clairance post-transfusionnelle précoce d'une partie des globules rouges transfusés (en moyenne 18 %), diminuant d'autant le rendement transfusionnel. L'impact de la durée de conservation sur la sécurité transfusionnelle a été largement débattu au cours des dernières années et, si l'innocuité de la prise en charge standard semble établie, la question de la sécurité des CGR après 35 jours de stockage est l'objet de controverses. En Europe, le seul critère de qualité des CGR est l'hémolyse à 42 jours qui ne doit pas dépasser 0,8 %, mais ce paramètre n'a pas été corrélé au rendement transfusionnel. De nouveaux marqueurs, notamment basés sur les modifications morphologiques liées au stockage, pourraient être mieux corrélés au rendement transfusionnel. Ninety million patients receive a red blood cell transfusion every year. This procedure requires to store red blood cells (RBC) between donation and transfusion to the recipient, to allow quality control and better flow management. Numerous technical improvements in recent decades now allow refrigerated storage of RBC concentrates for 42 days before use. During this 6-week-long period, a series of modifications that alter RBC have been described, collectively referred as the storage «lesion». These alterations increase with storage duration and is responsible for the early post-transfusion clearance of a portion of the transfused RBC (on average 18 %), reducing transfusion yield. The impact of storage duration on transfusion safety has been widely debated in recent years and, while the safety of standard care management seems to be established, the question of the safety of RBC stored for more than 35 days is still controversial. In Europe, the only quality criterion for RBC concentrates is hemolysis at 42 days, which should not exceed 0.8 %, but this parameter has not been correlated with transfusion efficacy. New markers, including storage-related morphological changes, may better correlate with transfusion yield. [ABSTRACT FROM AUTHOR]
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- 2020
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23. Rapid clearance of storage-induced microerythrocytes alters transfusion recovery
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Roussel, Camille, Morel, Alexandre, Dussiot, Michaël, Marin, Mickaël, Colard, Martin, Fricot-Monsinjon, Aurélie, Martinez, Anaïs, Chambrion, Charlotte, Henry, Benoît, Casimir, Madeleine, Volle, Geoffroy, Dépond, Mallorie, Dokmak, Safi, Paye, François, Sauvanet, Alain, Le Van Kim, Caroline, Colin, Yves, Georgeault, Sonia, Roingeard, Philippe, Spitalnik, Steven L., Ndour, Papa Alioune, Hermine, Olivier, Hod, Eldad A., Buffet, Pierre A., and Amireault, Pascal
- Abstract
Permanent availability of red blood cells (RBCs) for transfusion depends on refrigerated storage, during which morphologically altered RBCs accumulate. Among these, a subpopulation of small RBCs, comprising type III echinocytes, spheroechinocytes, and spherocytes and defined as storage-induced microerythrocytes (SMEs), could be rapidly cleared from circulation posttransfusion. We quantified the proportion of SMEs in RBC concentrates from healthy human volunteers and assessed correlation with transfusion recovery, investigated the fate of SMEs upon perfusion through human spleen ex vivo, and explored where and how SMEs are cleared in a mouse model of blood storage and transfusion. In healthy human volunteers, high proportion of SMEs in long-stored RBC concentrates correlated with poor transfusion recovery. When perfused through human spleen, 15% and 61% of long-stored RBCs and SMEs were cleared in 70 minutes, respectively. High initial proportion of SMEs also correlated with high retention of RBCs by perfused human spleen. In the mouse model, SMEs accumulated during storage. Transfusion of long-stored RBCs resulted in reduced posttransfusion recovery, mostly due to SME clearance. After transfusion in mice, long-stored RBCs accumulated predominantly in spleen and were ingested mainly by splenic and hepatic macrophages. In macrophage-depleted mice, splenic accumulation and SME clearance were delayed, and transfusion recovery was improved. In healthy hosts, SMEs were cleared predominantly by macrophages in spleen and liver. When this well-demarcated subpopulation of altered RBCs was abundant in RBC concentrates, transfusion recovery was diminished. SME quantification has the potential to improve blood product quality assessment. This trial was registered at www.clinicaltrials.gov as #NCT02889133.
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- 2021
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24. Genetic Regulation of Carnitine Metabolism Controls Lipid Damage Repair Mechanisms and Hemolytic Propensity of Human Red Blood Cells during Aging In Vivo and in Vitro
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D'Alessandro, Angelo, Key, Alicia, Amireault, Pascal, Peltier, Sandy, Earley, Eric, Page, Grier P, Nemkov, Travis, Stephenson, Daniel, Deng, Xutao, Georgeault, Sonia, Roingeard, Philippe, Stone, Mars, Kleinman, Steven, Norris, Philip J, Busch, Michael Paul, and Arduini, Arduino
- Abstract
Large scale genomics studies and vein-to-vein databases have started to reveal that donor biology and genetics influence red blood cell (RBC) storability and transfusion outcomes. To further delve into this concept, here we performed metabolomics analyses of 13,091 packed RBC units from donors enrolled in the Recipient Epidemiology and Donor Evaluation (REDS) RBC Omics study. End of storage (day 42) units were tested for metabolomics and hemolytic propensity. Donors ranking in the 5 thand 95 thpercentile were contacted again and invited to donate a second unit of blood, which was stored again for 42 days (n=643). Correlation of end of storage metabolomics measurements for the first (index) and second (recalled) donation identified a core of metabolites involved in carnitine synthesis and acyl-carnitine metabolism as the most reproducible within the same donor across multiple donations ( Figure 1.A). Carnitine and its precursors, methyl- and trimethyl-lysine were the most significantly reproducible of all the metabolites tested in this study ( Figure 1.A). Association of L-carnitine measurements to genomics data (i.e., 879,000 single nucleotide polymorphisms that were assayed via a precision transfusion medicine array developed for this study - Figure 1.B) identified non-synonymous coding polymorphisms in the carnitine transporter SLC22A16 as a critical genetic factor contributing to inter-donor heterogeneity in end of storage carnitine levels ( Figure 1.B). Donors carrying two alleles of this SNP were characterized by the lowest L-carnitine levels, and associated depletion of the whole carnitine pool. Functionally, stored RBCs with the lowest levels of carnitine pools were characterized by significant elevation in in vitrohemolysis and the highest degree of vesiculation, in parallel to increases in lipid peroxidation markers (hydroxy-eicosatetraenoic - HETEs and hydroxy-octadecadienoic acids - HODEs).
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- 2023
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25. Cytokine profiling, pretreatment with anakinra, and tolerance development in platinum-induced mixed hypersensitivity reactions.
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Picard, Matthieu, Filion, Charles Alexandre, Auclair, Marie-Hélène, Noujaim, Jonathan, de Guerké, Lara, Dionne, Jean-Luc, Beaudet, Julie, Amireault, Carl, and Fortin, Suzanne
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- 2023
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26. Optimisation transfusionnelle : étude de la lésion de stockage par cytométrie morphologique (AMNIS°) et microsphiltration
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Roussel, C.A., primary, Dussiot, M., additional, Duez, J., additional, Marin, M., additional, Morel, A., additional, Ndour, A., additional, Kim, C. Le Van, additional, Hermine, O., additional, Colin, Y., additional, Buffet, P., additional, and Amireault, P., additional
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- 2015
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27. Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation
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Azouzi, Slim, Santuz, Hubert, Morandat, Sandrine, Pereira, Catia, Côté, Francine, Hermine, Olivier, El Kirat, Karim, Colin, Yves, Le Van Kim, Caroline, Etchebest, Catherine, and Amireault, Pascal
- Abstract
Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter that is involved in a growing number of functions in peripheral tissues. Recent studies have shown nonpharmacological functions of 5-HT linked to its chemical properties. Indeed, it was reported that 5-HT may, on the one hand, bind lipid membranes and, on the other hand, protect red blood cells through a mechanism independent of its specific receptors. To better understand these underevaluated properties of 5-HT, we combined biochemical, biophysical, and molecular dynamics simulations approaches to characterize, at the molecular level, the antioxidant capacity of 5-HT and its interaction with lipid membranes. To do so, 5-HT was added to red blood cells and lipid membranes bearing different degrees of unsaturation. Our results demonstrate that 5-HT acts as a potent antioxidant and binds with a superior affinity to lipids with unsaturation on both alkyl chains. We show that 5-HT locates at the hydrophobic-hydrophilic interface, below the glycerol group. This interfacial location is stabilized by hydrogen bonds between the 5-HT hydroxyl group and lipid headgroups and allows 5-HT to intercept reactive oxygen species, preventing membrane oxidation. Experimental and molecular dynamics simulations using membrane enriched with oxidized lipids converge to further reveal that 5-HT contributes to the termination of lipid peroxidation by direct interaction with active groups of these lipids and could also contribute to limit the production of new radicals. Taken together, our results identify 5-HT as a potent inhibitor of lipid peroxidation and offer a different perspective on the role of this pleiotropic molecule.
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- 2017
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28. Validity of the Brazilian version of the Godin-Shephard Leisure-Time Physical Activity Questionnaire.
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São João, Thaís Moreira, Matheus Rodrigues, Roberta Cunha, Jayme Gallani, Maria Cecília Bueno, Passos Miura, Cinthya Tamie, de Barros Leite Domingues, Gabriela, Amireault, Steve, and Godin, Gaston
- Abstract
Copyright of Cadernos de Saude Publica is the property of Escola Nacional de Saude Publica Sergio Arouca and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2015
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29. Case studies in automation of forensic toxicology practices with R
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Desharnais, Brigitte, Daigneault, Gabrielle, Lajoie, Marie-Jo, Garneau, Béatrice, Amireault, Catherine, Doyon, Alexandra, and Mireault, Pascal
- Abstract
The last decade has seen a considerable growth in data generated by scientific instrumentation. Accountability requirements have grown similarly, requiring forensic toxicology laboratories to generate summary of findings to funders, stakeholders and the general public. This work aims to show how the programming language R and its integrated development environment (IDE) RStudio can be harnessed to speed up data analysis and produce summary reports in three different forensic toxicology applications.
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- 2022
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30. Splenic Retention of Plasmodium falciparumGametocytes To Block the Transmission of Malaria
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Duez, Julien, Holleran, John P., Ndour, Papa Alioune, Loganathan, Sasdekumar, Amireault, Pascal, Français, Olivier, El Nemer, Wassim, Le Pioufle, Bruno, Amado, Inês F., Garcia, Sylvie, Chartrel, Nathalie, Le Van Kim, Caroline, Lavazec, Catherine, Avery, Vicky M., and Buffet, Pierre A.
- Abstract
ABSTRACTPlasmodium falciparumis transmitted from humans to Anophelesmosquito vectors via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration through microsphere layers (microsphiltration) had shown that circulating gametocytes are deformable. Compounds reducing gametocyte deformability would induce their splenic clearance, thus removing them from the blood circulation and blocking malaria transmission. The hand-made, single-sample prototype for microsphiltration was miniaturized to a 96-well microtiter plate format, and gametocyte retention in the microsphere filters was quantified by high-content imaging. The stiffening activity of 40 pharmacological compounds was assessed in microtiter plates, using a small molecule (calyculin) as a positive control. The stiffening activity of calyculin was assessed in spleen-mimetic microfluidic chips and in macrophage-depleted mice. Marked mechanical retention (80% to 90%) of mature gametocytes was obtained in microplates following exposure to calyculin at concentrations with no effect on parasite viability. Of the 40 compounds tested, including 20 antimalarials, only 5 endoperoxides significantly increased gametocyte retention (1.5- to 2.5-fold; 24 h of exposure at 1 μM). Mature gametocytes exposed to calyculin accumulated in microfluidic chips and were cleared from the circulation of macrophage-depleted mice as rapidly as heat-stiffened erythrocytes, thus confirming results obtained using the microsphiltration assay. An automated miniaturized approach to select compounds for their gametocyte-stiffening effect has been established. Stiffening induces gametocyte clearance both in vitroand in vivo. Based on physiologically validated tools, this screening cascade can identify novel compounds and uncover new targets to block malaria transmission. Innovative applications in hematology are also envisioned.
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- 2015
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31. The Godin-Shephard Leisure-Time Physical Activity Questionnaire: Validity Evidence Supporting its Use for Classifying Healthy Adults into Active and Insufficiently Active Categories
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Amireault, Steve and Godin, Gaston
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This study provided validity evidence for the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) to classify respondents into activeand insufficiently activecategories. Members of a fitness center [45 women and 55 men; mean (SD) age = 45.5 (10.6) yr.] completed the questionnaire. Using only moderate and strenuous scores, those with a leisure score index ≥ 24 were classified as active; those with a score ≤ 23 were classified as insufficiently active. VO2max, percentage of body fat, and electronic records of fitness center attendance were the validation variables. In a visit to the fitness center, participants completed the GSLTPAQ and a certified exercise specialist performed a physical fitness evaluation. A multivariate analysis of covariance (MANCOVA) indicated the group of respondents classified as activehad higher VO2max and lower percentage of body fat than the group of respondents classified as insufficiently active. An analysis of covariance (ANCOVA) indicated the group of respondents classified as active had higher electronic records of fitness center attendance than the group of respondents classified as insufficiently active. Therefore, these pieces of validity evidence support the use of the questionnaire's classification system among healthy adults.
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- 2015
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32. Doing more than Just Acknowledging Attrition at Follow-Up: A Comment on Lu, Cheng, and Chen (2013)
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Amireault, Steve
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Lu, Cheng, and Chen (2013) faced one of the most common challenges encountered in longitudinal studies: follow-up attrition. Using a correlational prospective design, 464 volunteers completed a questionnaire that measured the constructs of the theory of planned behavior, and subsequently 154 of them provided physical activity data at a 6-month follow-up. The proportion of participants (66.8%) for whom the investigators were not able to gather information on the behavioral outcome at follow-up may reflect a form of selection bias that may affect both the validity and generalizability of study results. Lu, et al.'s (2013) study is used here to explore the implication of follow-up attrition on the results and inference, to review what information should be reported in a scientific paper in such situations, and to give practical tips to handle follow-up attrition.
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- 2014
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33. Erythropoietin Downregulates Red Blood Cell Clearance in Mice
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Colard, Martin, Dussiot, Michaël, Martinez, Anaïs, Peyssonnaux, Carole, Mayeux, Patrick, Benghiat, Fleur Samantha, Buffet, Pierre, Hermine, Olivier, and Amireault, Pascal
- Abstract
Purpose
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- 2019
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34. Storage-Induced Micro-Erythrocytes Are Rapidly Cleared from Recipient Circulation and Predict Transfusion Recovery
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Roussel, Camille, Morel, Alexandre, Dussiot, Michaël, MARIN, Mickael, Colard, Martin, Fricot, Aurélie, Martinez, Anaïs, Chambrion, Charlotte, Henry, Benoît, Volle, Geoffroy, Depond, Mallorie, Dokmak, Safi, Paye, Francois, Sauvanet, Alain, Le Van Kim, Caroline, Colin Aronovicz, Yves, Spitalnik, Steven L., Ndour, Papa Alioune, Hod, Eldad A., Hermine, Olivier, Buffet, Pierre, and Amireault, Pascal
- Abstract
Roussel: Zimmer Biomet: Research Funding. MARIN:Zimmer Biomet: Research Funding. Spitalnik:Hemanext: Membership on an entity's Board of Directors or advisory committees; Tioma, Inc.: Consultancy. Hermine:AB science: Consultancy, Equity Ownership, Honoraria, Research Funding; Celgene: Research Funding; Novartis: Research Funding. Buffet:Zimmer Biomet: Research Funding. Amireault:Zimmer Biomet: Research Funding.
- Published
- 2019
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35. Band 3 Phosphorylation Induces Irreversible Alteration of Stored Red Blood Cells
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Azouzi, Slim, Colin Aronovicz, Yves, Pereira, Catia, Romana, Marc, Peyrard, Thierry, Amireault, Pascal, and Le Van Kim, Caroline
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No relevant conflicts of interest to declare.
- Published
- 2016
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36. Contribution of Imaging Flow Cytometry to Storage Lesion Assessment: Identification of a Sub-Population of Morphologically Altered Erythrocytes
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Amireault, Pascal, Roussel, Camille A, Dussiot, Michaël, Marin, Mickael, Morel, Alexandre, Ndour, Papa Alioune, Duez, Julien, Le Van Kim, Caroline, Hermine, Olivier, Colin-Aronovicz, Yves, and Buffet, Pierre A
- Abstract
No relevant conflicts of interest to declare.
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- 2015
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37. Proteostasis and metabolic dysfunction in a distinct subset of storage-induced senescent erythrocytes targeted for clearance.
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Peltier S, Marin M, Dzieciatkowska M, Dussiot M, Roy MK, Bruce J, Leblanc L, Hadjou Y, Georgeault S, Fricot A, Roussel C, Stephenson D, Casimir M, Sissoko A, Paye F, Dokmak S, Ndour PA, Roingeard P, Gautier EF, Spitalnik SL, Hermine O, Buffet PA, D'Alessandro A, and Amireault P
- Abstract
Although refrigerated storage slows the metabolism of volunteer donor RBCs, cellular aging still occurs throughout this in vitro process, which is essential in transfusion medicine. Storage-induced microerythrocytes (SMEs) are morphologically-altered senescent RBCs that accumulate during storage and which are cleared from circulation following transfusion. However, the molecular and cellular alterations that trigger clearance of this RBC subset remain to be identified. Using a staining protocol that sorts long-stored SMEs (i.e., CFSE
high ) and morphologically-normal RBCs (CFSElow ), these in vitro aged cells were characterized. Metabolomics analysis identified depletion of energy, lipid-repair, and antioxidant metabolites in CFSEhigh RBCs. By redox proteomics, irreversible protein oxidation primarily affected CFSEhigh RBCs. By proteomics, 96 proteins, mostly in the proteostasis family, had relocated to CFSEhigh RBC membranes. CFSEhigh RBCs exhibited decreased proteasome activity and deformability; increased phosphatidylserine exposure, osmotic fragility, and endothelial cell adherence; and were cleared from the circulation during human spleen ex vivo perfusion. Conversely, molecular, cellular, and circulatory properties of long-stored CFSElow RBCs resembled those of short-stored RBCs. CFSEhigh RBCs are morphologically and metabolically altered, have irreversibly oxidized and membrane-relocated proteins, and exhibit decreased proteasome activity. In vitro aging during storage selectively alters metabolism and proteostasis in SMEs, targeting these senescent cells for clearance.- Published
- 2024
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38. Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients.
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Casimir M, Colard M, Dussiot M, Roussel C, Martinez A, Peyssonnaux C, Mayeux P, Benghiat S, Manceau S, Francois A, Marin N, Pène F, Buffet PA, Hermine O, and Amireault P
- Subjects
- Humans, Animals, Mice, Prospective Studies, Erythropoiesis physiology, Erythrocytes, Anemia drug therapy, Anemia etiology, Erythropoietin pharmacology, Erythropoietin therapeutic use
- Abstract
Red blood cells (RBC) transfusion is used to alleviate symptoms and prevent complications in anemic patients by restoring oxygen delivery to tissues. RBC transfusion efficacy, that can be measured by a rise in hemoglobin (Hb) concentration, is influenced by donor-, product-, and recipient-related characteristics. In some studies, severe pre-transfusion anemia is associated with a greater than expected Hb increment following transfusion but the biological mechanism underpinning this relationship remains poorly understood. We conducted a prospective study in critically ill patients and quantified Hb increment following one RBC transfusion. In a murine model, we investigated the possibility that, in conjunction with the host erythropoietic response, the persistence of transfused donor RBC is improved to maintain a highest RBC biomass. We confirmed a correlation between a greater Hb increment and a deeper pre-transfusion anemia in a cohort of 17 patients. In the mouse model, Hb increment and post-transfusion recovery were increased in anemic recipients. Post-transfusion RBC recovery was improved in hypoxic mice or those receiving an erythropoiesis-stimulating agent and decreased in those treated with erythropoietin (EPO)-neutralizing antibodies, suggesting that EPO signaling is necessary to observe this effect. Irradiated recipients also showed decreased post-transfusion RBC recovery. The EPO-induced post-transfusion RBC recovery improvement was abrogated in irradiated or in macrophage-depleted recipients, but maintained in splenectomized recipients, suggesting a mechanism requiring erythroid progenitors and macrophages, but which is not spleen-specific. Our study highlights a physiological role of EPO in downregulating post-transfusion RBC clearance, contributing to maintain a vital RBC biomass to rapidly cope with hypoxemia., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
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- 2023
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39. Low-Dose Dietary Fish Oil Improves RBC Deformability without Improving Post-Transfusion Recovery in Mice.
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Kim CY, Larsen HJ, Spitalnik SL, Hod EA, Francis RO, Hudson KE, Gordy DE, Stone EF, Peltier S, Amireault P, D'Alessandro A, Zimring JC, Buehler PW, Fu X, and Thomas T
- Subjects
- Humans, Female, Mice, Animals, Mice, Inbred C57BL, Erythrocytes metabolism, Fish Oils pharmacology, Fish Oils metabolism, Fatty Acids, Unsaturated metabolism, Fatty Acids metabolism, Blood Preservation methods, Erythrocyte Deformability, Dietary Fats, Unsaturated metabolism
- Abstract
Long-chain polyunsaturated fatty acids (LC-PUFAs) are important modulators of red blood cell (RBC) rheology. Dietary LC-PUFAs are readily incorporated into the RBC membrane, improving RBC deformability, fluidity, and hydration. Female C57BL/6J mice consumed diets containing increasing amounts of fish oil (FO) ad libitum for 8 weeks. RBC deformability, filterability, and post-transfusion recovery (PTR) were evaluated before and after cold storage. Lipidomics and lipid peroxidation markers were evaluated in fresh and stored RBCs. High-dose dietary FO (50%, 100%) was associated with a reduction in RBC quality (i.e., in vivo lifespan, deformability, lipid peroxidation) along with a reduced 24 h PTR after cold storage. Low-dose dietary FO (6.25-12.5%) improved the filterability of fresh RBCs and reduced the lipid peroxidation of cold-stored RBCs. Although low doses of FO improved RBC deformability and reduced oxidative stress, no improvement was observed for the PTR of stored RBCs. The improvement in RBC deformability observed with low-dose FO supplementation could potentially benefit endurance athletes and patients with conditions resulting from reduced perfusion, such as peripheral vascular disease.
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- 2023
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40. Deuterated Linoleic Acid Attenuates the RBC Storage Lesion in a Mouse Model of Poor RBC Storage.
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Kim CY, Johnson H, Peltier S, Spitalnik SL, Hod EA, Francis RO, Hudson KE, Stone EF, Gordy DE, Fu X, Zimring JC, Amireault P, Buehler PW, Wilson RB, D'Alessandro A, Shchepinov MS, and Thomas T
- Abstract
Background: Long-chain polyunsaturated fatty acids (PUFAs) are important modulators of red blood cell (RBC) rheology. Dietary PUFAs are readily incorporated into the RBC membrane, improving RBC deformability, fluidity, and hydration. However, enriching the lipid membrane with PUFAs increases the potential for peroxidation in oxidative environments (e.g., refrigerated storage), resulting in membrane damage. Substitution of bis-allylic hydrogens with deuterium ions in PUFAs decreases hydrogen abstraction, thereby inhibiting peroxidation. If lipid peroxidation is a causal factor in the RBC storage lesion, incorporation of deuterated linoleic acid (DLA) into the RBC membrane should decrease lipid peroxidation, thereby improving RBC lifespan, deformability, filterability, and post-transfusion recovery (PTR) after cold storage. Study Design and Methods: Mice associated with good (C57BL/6J) and poor (FVB) RBC storage quality received diets containing 11,11-D2-LA Ethyl Ester (1.0 g/100 g diet; deuterated linoleic acid) or non-deuterated LA Ethyl Ester (control) for 8 weeks. Deformability, filterability, lipidomics, and lipid peroxidation markers were evaluated in fresh and stored RBCs. Results: DLA was incorporated into RBC membranes in both mouse strains. DLA diet decreased lipid peroxidation (malondialdehyde) by 25.4 and 31% percent in C57 mice and 12.9 and 79.9% in FVB mice before and after cold storage, respectively. In FVB, but not C57 mice, deformability filterability, and post-transfusion recovery were significantly improved. Discussion: In a mouse model of poor RBC storage, with elevated reactive oxygen species production, DLA attenuated lipid peroxidation and significantly improved RBC storage quality., Competing Interests: MS was employed by Retrotope Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Johnson, Peltier, Spitalnik, Hod, Francis, Hudson, Stone, Gordy, Fu, Zimring, Amireault, Buehler, Wilson, D’Alessandro, Shchepinov and Thomas.)
- Published
- 2022
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41. Storage-Induced Micro-Erythrocytes Can Be Quantified and Sorted by Flow Cytometry.
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Marin M, Peltier S, Hadjou Y, Georgeault S, Dussiot M, Roussel C, Hermine O, Roingeard P, Buffet PA, and Amireault P
- Abstract
Refrigerated storage of red cell concentrates before transfusion is associated with progressive alterations of red blood cells (RBC). Small RBC (type III echinocytes, sphero-echinocytes, and spherocytes) defined as storage-induced micro-erythrocytes (SME) appear during pretransfusion storage. SME accumulate with variable intensity from donor to donor, are cleared rapidly after transfusion, and their proportion correlates with transfusion recovery. They can be rapidly and objectively quantified using imaging flow cytometry (IFC). Quantifying SME using flow cytometry would further facilitate a physiologically relevant quality control of red cell concentrates. RBC stored in blood bank conditions were stained with a carboxyfluorescein succinimidyl ester (CFSE) dye and incubated at 37°C. CFSE intensity was assessed by flow cytometry and RBC morphology evaluated by IFC. We observed the accumulation of a CFSE
high RBC subpopulation by flow cytometry that accounted for 3.3 and 47.2% at day 3 and 42 of storage, respectively. IFC brightfield images showed that this CFSEhigh subpopulation mostly contains SME while the CFSElow subpopulation mostly contains type I and II echinocytes and discocytes. Similar numbers of SME were quantified by IFC (based on projected surface area) and by flow cytometry (based on CFSE intensity). IFC and scanning electron microscopy showed that ≥95% pure subpopulations of CFSEhigh and CFSElow RBC were obtained by flow cytometry-based sorting. SME can now be quantified using a common fluorescent dye and a standard flow cytometer. The staining protocol enables specific sorting of SME, a useful tool to further characterize this RBC subpopulation targeted for premature clearance after transfusion., Competing Interests: PA is funded in part by New Health Science. MM, SP, MD, CR, PB, and PA declare that the European patent application EP21306765 was filed on December 12th, 2021. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marin, Peltier, Hadjou, Georgeault, Dussiot, Roussel, Hermine, Roingeard, Buffet and Amireault.)- Published
- 2022
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42. Metabolic rejuvenation upgrades circulatory functions of red blood cells stored under blood bank conditions.
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Marin M, Roussel C, Dussiot M, Ndour PA, Hermine O, Colin Y, Gray A, Landrigan M, Le Van Kim C, Buffet PA, and Amireault P
- Subjects
- Adenine pharmacology, Blood Banks, Blood Preservation, Cryopreservation, Endothelial Cells metabolism, Erythrocytes cytology, Flow Cytometry, Hemolysis, Humans, Inosine pharmacology, Phosphatidylserines metabolism, Rejuvenation physiology, Time Factors, Adenosine Triphosphate metabolism, Erythrocyte Deformability drug effects, Erythrocytes drug effects, Erythrocytes metabolism
- Abstract
Background: Red blood cells (RBC) change upon hypothermic conservation, and storage for 6 weeks is associated with the short-term clearance of 15% to 20% of transfused RBCs. Metabolic rejuvenation applied to RBCs before transfusion replenishes energetic sources and reverses most storage-related alterations, but how it impacts RBC circulatory functions has not been fully elucidated., Study Design and Methods: Six RBC units stored under blood bank conditions were analyzed weekly for 6 weeks and rejuvenated on Day 42 with an adenine-inosine-rich solution. Impact of storage and rejuvenation on adenosine triphosphate (ATP) levels, morphology, accumulation of storage-induced microerythrocytes (SMEs), elongation under an osmotic gradient (by LORRCA), hemolysis, and phosphatidylserine (PS) exposure was evaluated. The impact of rejuvenation on filterability and adhesive properties of stored RBCs was also assessed., Results: Rejuvenation of RBCs restored intracellular ATP to almost normal levels and decreased the PS exposure from 2.78% to 0.41%. Upon rejuvenation, the proportion of SME dropped from 28.2% to 9.5%, while the proportion of normal-shaped RBCs (discocytes and echinocytes 1) increased from 47.7% to 67.1%. In LORCCA experiments, rejuvenation did not modify the capacity of RBCs to elongate and induced a reduction in cell volume. In functional tests, rejuvenation increased RBC filterability in a biomimetic splenic filter (+16%) and prevented their adhesion to endothelial cells (-87%)., Conclusion: Rejuvenation reduces the proportion of morphologically altered and adhesive RBCs that accumulate during storage. Along with the improvement in their filterability, these data show that rejuvenation improves RBC properties related to their capacity to persist in circulation after transfusion., (© 2020 AABB.)
- Published
- 2021
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43. Restoration of Physiological Levels of Uric Acid and Ascorbic Acid Reroutes the Metabolism of Stored Red Blood Cells.
- Author
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Bardyn M, Chen J, Dussiot M, Crettaz D, Schmid L, Längst E, Amireault P, Tissot JD, Jolicoeur M, and Prudent M
- Abstract
After blood donation, the red blood cells (RBCs) for transfusion are generally isolated by centrifugation and then filtrated and supplemented with additive solution. The consecutive changes of the extracellular environment participate to the occurrence of storage lesions. In this study, the hypothesis is that restoring physiological levels of uric and ascorbic acids (major plasmatic antioxidants) might correct metabolism defects and protect RBCs from the very beginning of the storage period, to maintain their quality. Leukoreduced CPD-SAGM RBC concentrates were supplemented with 416 µM uric acid and 114 µM ascorbic acid and stored during six weeks at 4 °C. Different markers, i.e., haematological parameters, metabolism, sensitivity to oxidative stress, morphology and haemolysis were analyzed. Quantitative metabolomic analysis of targeted intracellular metabolites demonstrated a direct modification of several metabolite levels following antioxidant supplementation. No significant differences were observed for the other markers. In conclusion, the results obtained show that uric and ascorbic acids supplementation partially prevented the metabolic shift triggered by plasma depletion that occurs during the RBC concentrate preparation. The treatment directly and indirectly sustains the antioxidant protective system of the stored RBCs.
- Published
- 2020
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44. Reexamination of the chromium-51-labeled posttransfusion red blood cell recovery method.
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Francis RO, Mahajan S, Rapido F, La Carpia F, Soffing M, Divgi C, Yeh R, Mintz A, Leslie L, Agrest I, Karafin MS, Ginzburg Y, Shaz BH, Spitalnik SL, Schwartz J, Thomas T, Fu X, Amireault P, Buffet P, Zimring JC, D'Alessandro A, and Hod EA
- Subjects
- Adenosine Triphosphate blood, Adult, Blood Banking methods, Blood Transfusion, Autologous, Female, Hemolysis, Humans, Liver physiology, Male, Middle Aged, Spleen physiology, Technetium, Time Factors, Blood Preservation methods, Chromium Radioisotopes, Erythrocyte Transfusion, Erythrocytes physiology
- Abstract
Background: The chromium-51-labeled posttransfusion recovery (PTR) study has been the gold-standard test for assessing red blood cell (RBC) quality. Despite guiding RBC storage development for decades, it has several potential sources for error., Methods: Four healthy adult volunteers each donated an autologous, leukoreduced RBC unit, aliquots were radiolabeled with technetium-99m after 1 and 6 weeks of storage, and then infused. Subjects were imaged by single-photon-emission computed tomography immediately and 4 hours after infusion. Additionally, from subjects described in a previously published study, adenosine triphosphate levels in transfusates infused into 52 healthy volunteers randomized to a single autologous, leukoreduced, RBC transfusion after 1, 2, 3, 4, 5, or 6 weeks of storage were correlated with PTR and laboratory parameters of hemolysis., Results: Evidence from one subject imaged after infusion of technetium-99m-labeled RBCs suggests that, in some individuals, RBCs may be temporarily sequestered in the liver and spleen immediately following transfusion and then subsequently released back into circulation; this could be one source of error leading to PTR results that may not accurately predict the true quantity of RBCs cleared by intra- and/or extravascular hemolysis. Indeed, adenosine triphosphate levels in the transfusates correlated more robustly with measures of extravascular hemolysis in vivo (e.g., serum iron, indirect bilirubin, non-transferrin-bound iron) than with PTR results or measures of intravascular hemolysis (e.g., plasma free hemoglobin)., Conclusions: Sources of measurement error are inherent in the chromium-51 PTR method. Transfusion of an entire unlabeled RBC unit, followed by quantifying extravascular hemolysis markers, may more accurately measure true posttransfusion RBC recovery., (© 2019 AABB.)
- Published
- 2019
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45. Fluorescence Exclusion: A Simple Method to Assess Projected Surface, Volume and Morphology of Red Blood Cells Stored in Blood Bank.
- Author
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Roussel C, Monnier S, Dussiot M, Farcy E, Hermine O, Le Van Kim C, Colin Y, Piel M, Amireault P, and Buffet PA
- Abstract
Red blood cells (RBC) ability to circulate is closely related to their surface area-to-volume ratio. A decrease in this ratio induces a decrease in RBC deformability that can lead to their retention and elimination in the spleen. We recently showed that a subpopulation of "small RBC" with reduced projected surface area accumulated upon storage in blood bank concentrates, but data on the volume of these altered RBC are lacking. So far, single cell measurement of RBC volume has remained a challenging task achieved by a few sophisticated methods some being subject to potential artifacts. We aimed to develop a reproducible and ergonomic method to assess simultaneously RBC volume and morphology at the single cell level. We adapted the fluorescence exclusion measurement of volume in nucleated cells to the measurement of RBC volume. This method requires no pre-treatment of the cell and can be performed in physiological or experimental buffer. In addition to RBC volume assessment, brightfield images enabling a precise definition of the morphology and the measurement of projected surface area can be generated simultaneously. We first verified that fluorescence exclusion is precise, reproducible and can quantify volume modifications following morphological changes induced by heating or incubation in non-physiological medium. We then used the method to characterize RBC stored for 42 days in SAG-M in blood bank conditions. Simultaneous determination of the volume, projected surface area and morphology allowed to evaluate the surface area-to-volume ratio of individual RBC upon storage. We observed a similar surface area-to-volume ratio in discocytes (D) and echinocytes I (EI), which decreased in EII (7%) and EIII (24%), sphero-echinocytes (SE; 41%) and spherocytes (S; 47%). If RBC dimensions determine indeed the ability of RBC to cross the spleen, these modifications are expected to induce the rapid splenic entrapment of the most morphologically altered RBC (EIII, SE, and S) and further support the hypothesis of a rapid clearance of the "small RBC" subpopulation by the spleen following transfusion.
- Published
- 2018
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46. Measuring Post-transfusion Recovery and Survival of Red Blood Cells: Strengths and Weaknesses of Chromium-51 Labeling and Alternative Methods.
- Author
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Roussel C, Buffet PA, and Amireault P
- Abstract
The proportion of transfused red blood cells (RBCs) that remain in circulation is an important surrogate marker of transfusion efficacy and contributes to predict the potential benefit of a transfusion process. Over the last 50 years, most of the transfusion recovery data were generated by chromium-51 (
51 Cr)-labeling studies and were predominantly performed to validate new storage systems and new processes to prepare RBC concentrates. As a consequence, our understanding of transfusion efficacy is strongly dependent on the strengths and weaknesses of51 Cr labeling in particular. Other methods such as antigen mismatch or biotin-based labeling can bring relevant information, for example, on the long-term survival of transfused RBC. These radioactivity-free methods can be used in patients including from vulnerable groups. We provide an overview of the methods used to measure transfusion recovery in humans, compare their strengths and weaknesses, and discuss their potential limitations. Also, based on our understanding of the spleen-specific filtration of damaged RBC and historical transfusion recovery data, we propose that RBC deformability and morphology are storage lesion markers that could become useful predictors of transfusion recovery. Transfusion recovery can and should be accurately explored by more than one method. Technical optimization and clarification of concepts is still needed in this important field of transfusion and physiology.- Published
- 2018
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47. Band 3 phosphorylation induces irreversible alterations of stored red blood cells.
- Author
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Azouzi S, Romana M, Arashiki N, Takakuwa Y, El Nemer W, Peyrard T, Colin Y, Amireault P, and Le Van Kim C
- Subjects
- Erythrocytes cytology, Humans, Phosphorylation, Protein Multimerization, Time Factors, Anion Exchange Protein 1, Erythrocyte metabolism, Blood Preservation, Erythrocytes metabolism
- Published
- 2018
- Full Text
- View/download PDF
48. Spherocytic shift of red blood cells during storage provides a quantitative whole cell-based marker of the storage lesion.
- Author
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Roussel C, Dussiot M, Marin M, Morel A, Ndour PA, Duez J, Le Van Kim C, Hermine O, Colin Y, Buffet PA, and Amireault P
- Subjects
- Biomarkers blood, Female, Humans, Kinetics, Male, Spherocytes metabolism, Time Factors, Blood Preservation, Cell-Derived Microparticles, Flow Cytometry methods, Spherocytes cytology
- Abstract
Background: Storage lesion may explain the rapid clearance of up to 25% of transfused red blood cells (RBCs) in recipients. Several alterations affect stored RBC but a quantitative, whole cell-based predictor of transfusion yield is lacking. Because RBCs with reduced surface area are retained by the spleen, we quantified changes in RBC dimensions during storage., Study Design and Methods: Using imaging flow cytometry we observed the dimension and morphology of RBCs upon storage, along with that of conventional biochemical and mechanical markers of storage lesion. We then validated these findings using differential interference contrast (DIC) microscopy and quantified the accumulation of microparticles (MPs)., Results: Mean projected surface area of the whole RBC population decreased from 72.4 to 68.4 µm
2 , a change resulting from the appearance of a well-demarcated subpopulation of RBCs with reduced mean projected surface (58 µm2 , 15.2%-19.9% reduction). These "small RBCs" accounted for 4.9 and 23.6% of all RBCs on Days 3 and 42 of storage, respectively. DIC microscopy confirmed that small RBCs had shifted upon storage from discocytes to echinocytes III, spheroechinocytes, and spherocytes. Glycophorin A-positive MPs and small RBCs appeared after similar kinetics., Conclusion: The reduction in surface area of small RBCs is expected to induce their retention by the spleen. We propose that small RBCs generated by MP-induced membrane loss are preferentially cleared from the circulation shortly after transfusion of long-stored blood. Their operator-independent quantification using imaging flow cytometry may provide a marker of storage lesion potentially predictive of transfusion yield., (© 2017 AABB.)- Published
- 2017
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49. Splenic retention of Plasmodium falciparum gametocytes to block the transmission of malaria.
- Author
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Duez J, Holleran JP, Ndour PA, Loganathan S, Amireault P, Français O, El Nemer W, Le Pioufle B, Amado IF, Garcia S, Chartrel N, Le Van Kim C, Lavazec C, Avery VM, and Buffet PA
- Subjects
- Animals, Antimalarials pharmacology, Automation, Enzyme Inhibitors pharmacology, Erythrocyte Count, Erythrocytes parasitology, Filtration, Flow Cytometry, Image Processing, Computer-Assisted, Macrophages parasitology, Malaria, Falciparum prevention & control, Marine Toxins, Mice, Microfluidic Analytical Techniques, Microspheres, Models, Biological, Oxazoles pharmacology, Parasite Egg Count, Spleen drug effects, Malaria, Falciparum parasitology, Malaria, Falciparum transmission, Plasmodium falciparum growth & development, Spleen parasitology
- Abstract
Plasmodium falciparum is transmitted from humans to Anopheles mosquito vectors via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration through microsphere layers (microsphiltration) had shown that circulating gametocytes are deformable. Compounds reducing gametocyte deformability would induce their splenic clearance, thus removing them from the blood circulation and blocking malaria transmission. The hand-made, single-sample prototype for microsphiltration was miniaturized to a 96-well microtiter plate format, and gametocyte retention in the microsphere filters was quantified by high-content imaging. The stiffening activity of 40 pharmacological compounds was assessed in microtiter plates, using a small molecule (calyculin) as a positive control. The stiffening activity of calyculin was assessed in spleen-mimetic microfluidic chips and in macrophage-depleted mice. Marked mechanical retention (80% to 90%) of mature gametocytes was obtained in microplates following exposure to calyculin at concentrations with no effect on parasite viability. Of the 40 compounds tested, including 20 antimalarials, only 5 endoperoxides significantly increased gametocyte retention (1.5- to 2.5-fold; 24 h of exposure at 1 μM). Mature gametocytes exposed to calyculin accumulated in microfluidic chips and were cleared from the circulation of macrophage-depleted mice as rapidly as heat-stiffened erythrocytes, thus confirming results obtained using the microsphiltration assay. An automated miniaturized approach to select compounds for their gametocyte-stiffening effect has been established. Stiffening induces gametocyte clearance both in vitro and in vivo. Based on physiologically validated tools, this screening cascade can identify novel compounds and uncover new targets to block malaria transmission. Innovative applications in hematology are also envisioned., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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