Autophagy as a pharmacological target in hematopoiesis and hematological disorders

Orsini, Marion,Morceau, Franck,Dicato, Mario,Diederich, Marc Elsevier 2018 Biochemical pharmacology Vol.152 No.-

<P><B>Abstract</B></P> <P>Autophagy is involved in many cellular processes, including cell homeostasis, cell death/survival balance and differentiation. Autophagy is essential for hematopoietic stem cell survival, quiescence, activation and differentiation. The deregulation of this process is associated with numerous hematological disorders and pathologies, including cancers. Thus, the use of autophagy modulators to induce or inhibit autophagy emerges as a potential therapeutic approach for treating these diseases and could be particularly interesting for differentiation therapy of leukemia cells. This review presents therapeutic strategies and pharmacological agents in the context of hematological disorders. The pros and cons of autophagy modulators in therapy will also be discussed.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A comparative study of salt tolerance parameters in 11 wild relatives of <i>Arabidopsis thaliana</i>

Orsini, Francesco,D'Urzo, Matilde Paino,Inan, Gunsu,Serra, Sara,Oh, Dong-Ha,Mickelbart, Michael V.,Consiglio, Federica,Li, Xia,Jeong, Jae Cheol,Yun, Dae-Jin,Bohnert, Hans J.,Bressan, Ray A.,Maggio, Al Oxford University Press 2010 Journal of experimental botany Vol.61 No.13

<P>Salinity is an abiotic stress that limits both yield and the expansion of agricultural crops to new areas. In the last 20 years our basic understanding of the mechanisms underlying plant tolerance and adaptation to saline environments has greatly improved owing to active development of advanced tools in molecular, genomics, and bioinformatics analyses. However, the full potential of investigative power has not been fully exploited, because the use of halophytes as model systems in plant salt tolerance research is largely neglected. The recent introduction of halophytic <I>Arabidopsis</I>-Relative Model Species (ARMS) has begun to compare and relate several unique genetic resources to the well-developed <I>Arabidopsis</I> model. In a search for candidates to begin to understand, through genetic analyses, the biological bases of salt tolerance, 11 wild relatives of <I>Arabidopsis thaliana</I> were compared: <I>Barbarea verna, Capsella bursa-pastoris, Hirschfeldia incana, Lepidium densiflorum, Malcolmia triloba, Lepidium virginicum, Descurainia pinnata, Sisymbrium officinale, Thellungiella parvula, Thellungiella salsuginea</I> (previously <I>T. halophila</I>)<I/>, and <I>Thlaspi arvense</I>. Among these species, highly salt-tolerant (<I>L. densiflorum</I> and <I>L. virginicum</I>) and moderately salt-tolerant (<I>M. triloba</I> and <I>H. incana</I>) species were identified. Only <I>T. parvula</I> revealed a true halophytic habitus, comparable to the better studied <I>Thellungiella salsuginea</I>. Major differences in growth, water transport properties, and ion accumulation are observed and discussed to describe the distinctive traits and physiological responses that can now be studied genetically in salt stress research.</P>

Common models and approaches for the clinical educator to plan effective feedback encounters

Cesar Orsini,Veena Rodrigues,Jorge Tricio,Margarita Rosel 한국보건의료인국가시험원 2022 보건의료교육평가 Vol.19 No.-

Giving constructive feedback is crucial for learners to bridge the gap between their current performance and the desired standards of competence. Giving effective feedback is a skill that can be learned, practiced, and improved. Therefore, our aim was to explore models in clinical settings and assess their transferability to different clinical feedback encounters. We identified the 6 most common and accepted feedback models, including the Feedback Sandwich, the Pendleton Rules, the One-Minute Preceptor, the SET-GO model, the R2C2 (Rapport/Reaction/Content/Coach), and the ALOBA (Agenda Led Outcome-based Analysis) model. We present a handy resource describing their structure, strengths and weaknesses, requirements for educators and learners, and suitable feedback encounters for use for each model. These feedback models represent practical frameworks for educators to adopt but also to adapt to their preferred style, combining and modifying them if necessary to suit their needs and context.

벨기에의 사회보험료 감면정책(고용보너스: Werkbonus)

Kristian Orsini 한국노동연구원 2011 국제노동브리프 Vol.9 No.10

Implementation and lessons learned from 2 online interprofessional faculty development programs for improving educational practice in the health professions in Chile and the United Kingdom from 2018 to 2021

Cesar Orsini 한국보건의료인국가시험원 2021 보건의료교육평가 Vol.18 No.-

This study presents the design, implementation, and lessons learned from 2 fit-for-purpose online interprofessional faculty development programs for educational practice improvement in the health professions in Chile and the United Kingdom from 2018 to 2021. Both programs were designed to enhance teaching and learning practices in an interprofessional environment based on 4 pillars: professional diversity, egalitarianism, blended/online learning, and active learning strategies. A multidisciplinary mix of educators participated, showing similar results. The 3 main lessons learned were that the following factors facilitated an interprofessional environment: aprofessions-inclusive teaching style, a flexible learning climate, and interprofessional peer work. These lessons may be transferable toother programs seeking to enhance and support interprofessionality. Faculty development initiatives preparing educators for interprofessional practice should be an integral component of health professions education, as delivering these courses within professional silosis no longer justifiable. As the relevance of interprofessional education grows, an effective way of promoting interprofessonal educationis to train the trainers in formal interprofessional settings.

How dental students’ course experiences and satisfaction of their basic psychological needs influence passion for studying in Chile

Cesar Orsini,Jorge Tricio,Doris Tapia,Cristina Segura 한국보건의료인국가시험원 2019 보건의료교육평가 Vol.16 No.-

Purpose: This study aimed to determine how the general course experiences of dental students in Chile and the satisfaction or frustration of their basic psychological needs influenced their passion for studying, and how passion influenced students’ study strategies. Methods: A correlational cross-sectional study was conducted at 3 Chilean dental schools between April and June 2018, in which 935 undergraduate students participated. Students responded to Spanish-language versions of 4 psychological scale tools: the Course Experience Questionnaire, the Basic Psychological Needs Satisfac¬tion and Frustration Scale, the Passion Scale, and the Revised Study Process Questionnaire. Data were analysed with bivariate correlations and structural equation modelling, controlling for age, gender, year of study, and type of university. Results: Students’ general course experiences (i.e., good teaching, clear goals and standards, appropriate assessment, and appropriate workload) positively predicted basic need satisfaction and negatively predicted need frustration. Need satisfaction positively predicted passion in students, with stronger scores for harmonious passion. Basic need frustration positively predicted obsessive passion and negatively predicted harmonious passion. Harmonious passion positively predicted deep study strategies and negatively predicted surface study strategies, while obsessive passion positively predicted both deep and surface study strategies. Conclusion: Dental students’ optimal course experiences positively influenced the satisfaction of their basic psychological needs, which favoured harmonious over obsessive passion. In turn, harmonious over obsessive passion positively influenced deep study strategies. Therefore, efforts should be made to provide course experiences that support students’ basic needs and harmonious passion for studying, both in classroom and chair-side teaching.

Risk factors associated with development of coinfection in critically Ill patients with COVID-19

Erica M. Orsini,Gretchen L. Sacha,Xiaozhen Han,Wang Xiaofeng,Abhijit Duggal,Prabalini Rajendram 대한중환자의학회 2022 Acute and Critical Care Vol.37 No.3

Background: At outset of the coronavirus disease 2019 (COVID-19) pandemic, the significance of bacterial and fungal coinfections in individuals with COVID-19 was unknown. Initial reports indicated that the prevalence of coinfection in the general population was low, but there was uncertainty regarding the risk of coinfection in critically ill patients.Methods: Nine hundred critically ill adult patients with COVID-19 infection were enrolled in this observational case-control study. Patients with a coinfection (case) and patients without a coinfection (control) were compared using univariate and multivariable analyses. A subgroup analysis was performed on patients with coinfection, dividing them into early (infection within 7 days) and late (infection after 7 days) infection groups.Results: Two hundred and thirty-three patients (25.9%) had a bacterial or fungal coinfection. Vasopressor use (P<0.001) and severity of illness (higher Acute Physiology and Chronic Health Evaluation III score, P=0.009) were risk factors for the development of a coinfection. Patients with coinfection had higher mortality and length of stay. Vasopressor and corticosteroid use and central line and foley catheter placement were risk factors for late infection (>7 days). There were high rates of drug-resistant infections.Conclusions: Critically ill patients with COVID-19 are at risk for both community-acquired and hospital-acquired infections throughout their hospitalization for COVID-19. It is important to consider the development of a coinfection in clinically worsening critically ill patients with COVID-19 and consider the likelihood of drug-resistance when choosing an empiric regimen.

Trajectory Data Warehouses: Design and Implementation Issues

Orlando, Salvatore,Orsini, Renzo,Raffaeta, Alessandra,Roncato, Alessandro,Silvestri, Claudio Korean Institute of Information Scientists and Eng 2007 Journal of Computing Science and Engineering Vol.1 No.2

In this paper we investigate some issues and solutions related to the design of a Data Warehouse (DW), storing several aggregate measures about trajectories of moving objects. First we discuss the loading phase of our DW which has to deal with overwhelming streams of trajectory observations, possibly produced at different rates, and arriving in an unpredictable and unbounded way. Then, we focus on the measure presence, the most complex measure stored in our DW. Such a measure returns the number of distinct trajectories that lie in a spatial region during a given temporal interval. We devise a novel way to compute an approximate, but very accurate, presence aggregate function, which algebraically combines a bounded amount of measures stored in the base cells of the data cube. We conducted many experiments to show the effectiveness of our method to compute such an aggregate function. In addition, the feasibility of our innovative trajectory DW was validated with an implementation based on Oracle. We investigated the most challenging issues in realizing our trajectory DW using standard DW technologies: namely, the preprocessing and loading phase, and the aggregation functions to support OLAP operations.

Analysis of Acid Sphingomyelinase Activity in Dried Blood Spots Using Tandem Mass Spectrometry

Elisa Legnini,Joe J. Orsini,Adolf Mühl,Britt Johnson,Angela Dajnoki,Olaf A Bodamer 대한진단검사의학회 2012 Annals of Laboratory Medicine Vol.32 No.5

Background: Niemann Pick disease (NP) is a rare, lysosomal storage disorder due to deficiency of the intra-lysosomal enzyme acid sphingomyelinase (ASM) resulting in intracellular accumulation of sphingomyelin. We evaluated a tandem mass spectrometry (MS/MS)method to analyze ASM activity in dried blood spots (DBS) that may be suitable for laboratory diagnosis of NP including high throughput screening of at-risk populations and potentially for newborn screening. Methods: ASM activity was measured in 3.2 mm punches from DBS. The eluate was incubated with the ASM substrate (N-Hexanoyl-D-erythro-sphingosylphosphorylcholine [C6- sphingomyelin (C29H59N2O6P)]) and an internal standard (N-butyroyl-D-erythro-sphingosine [C4-ceramide (C22H43NO3)]). ASM product and IS were analyzed using MS/MS in multiple reaction monitoring mode for transitions m/z 370.6>264.3 (ASM internal standard) and m/z 398.6>264.3 (ASM product). Results: ASM activities were stable for up to 2 months at or below 4˚C. Position of the punch in the DBS and/or hematocrit of the DBS had a limited effect on ASM activities. Both intraand inter-assay variability were below 10%. There was no carry-over. The median ASM activity in 2,085 newborn infants was 9.5 μmol/h/L (mean 10.6) with a SD of 5.06 μmol/h/L. Six of 2,085 (0.3%) infants were found to have ASM activities below the cut-off of 2.5 μmol/h/L. ASM activities were below the cut-off level in all 10 previously diagnosed cases with NP (range: 0.16 to 2.08 μmol/h/L). Conclusions: This MS/MS method for the measurement of ASM activity in DBS is robust and suitable for laboratory diagnosis of NP. Background: Niemann Pick disease (NP) is a rare, lysosomal storage disorder due to deficiency of the intra-lysosomal enzyme acid sphingomyelinase (ASM) resulting in intracellular accumulation of sphingomyelin. We evaluated a tandem mass spectrometry (MS/MS)method to analyze ASM activity in dried blood spots (DBS) that may be suitable for laboratory diagnosis of NP including high throughput screening of at-risk populations and potentially for newborn screening. Methods: ASM activity was measured in 3.2 mm punches from DBS. The eluate was incubated with the ASM substrate (N-Hexanoyl-D-erythro-sphingosylphosphorylcholine [C6- sphingomyelin (C29H59N2O6P)]) and an internal standard (N-butyroyl-D-erythro-sphingosine [C4-ceramide (C22H43NO3)]). ASM product and IS were analyzed using MS/MS in multiple reaction monitoring mode for transitions m/z 370.6>264.3 (ASM internal standard) and m/z 398.6>264.3 (ASM product). Results: ASM activities were stable for up to 2 months at or below 4˚C. Position of the punch in the DBS and/or hematocrit of the DBS had a limited effect on ASM activities. Both intraand inter-assay variability were below 10%. There was no carry-over. The median ASM activity in 2,085 newborn infants was 9.5 μmol/h/L (mean 10.6) with a SD of 5.06 μmol/h/L. Six of 2,085 (0.3%) infants were found to have ASM activities below the cut-off of 2.5 μmol/h/L. ASM activities were below the cut-off level in all 10 previously diagnosed cases with NP (range: 0.16 to 2.08 μmol/h/L). Conclusions: This MS/MS method for the measurement of ASM activity in DBS is robust and suitable for laboratory diagnosis of NP.

Natural compounds and pharmaceuticals reprogram leukemia cell differentiation pathways

Morceau, F.,Chateauvieux, S.,Orsini, M.,Trecul, A.,Dicato, M.,Diederich, M. Pergamon Press ; Elsevier Science Ltd 2015 BIOTECHNOLOGY ADVANCES Vol.33 No.6

In addition to apoptosis resistance and cell proliferation capacities, the undifferentiated state also characterizes most cancer cells, especially leukemia cells. Cell differentiation is a multifaceted process that depends on complex regulatory networks that involve transcriptional, post-transcriptional and epigenetic regulation of gene expression. The time- and spatially-dependent expression of lineage-specific genes and genes that control cell growth and cell death is implicated in the process of maturation. The induction of cancer cell differentiation is considered an alternative approach to elicit cell death and proliferation arrest. Differentiation therapy has mainly been developed to treat acute myeloid leukemia, notably with all-trans retinoic acid (ATRA). Numerous molecules from diverse natural or synthetic origins are effective alone or in association with ATRA in both in vitro and in vivo experiments. During the last two decades, pharmaceuticals and natural compounds with various chemical structures, including alkaloids, flavonoids and polyphenols, were identified as potential differentiating agents of hematopoietic pathways and osteogenesis.