Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient ...population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared with either normoxic or single-H/R-episode SCD mice. Zol used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment, and increased osteoclast activity resulted from local hypoxia, oxidative stress, and the release of proresorptive cytokine such as IL-6. Zol might act on both the osteoclast and osteoblast compartments as multimodal therapy to prevent SBD.
•In SCD, recurrent vaso-occlusive crisis suppresses osteogenic lineage and activates osteoclasts.•Zoledronic acid acting on both osteoclast and osteoblast compartments is a multimodal therapy to prevent SBD.
The ASTRI Mini-Array is an international collaboration led by the Italian National Institute for Astrophysics (INAF) that will operate nine telescopes to perform Cherenkov and optical stellar ...intensity interferometry (SII) observations. At the focal plane of these telescopes, we are planning to install a stellar intensity interferometry instrument. Here we present the selected design, based on Silicon Photomultiplier (SiPM) detectors matching the telescope point spread function together with dedicated front-end electronics.
This case study focuses on key personnel leaving an IT firm (TT Inc.) which possesses specialized knowledge and skills that could not be replaced internally. This problem and event created a major ...critical knowledge gap. The individuals who left expressed dissatisfaction with the increasing workload, limited resources, impossible deadlines, and unrealistic expectations from management. The remaining team members in the data networking group also shared their dissatisfaction. The methodology used to collect the data included a survey, interviews with key players, and from exit interviews. Productivity and job satisfaction at TT Inc.'s Telecom Engineering Department have declined. The dependant variables that are being explored are job satisfaction and productivity. Results of the surveys led to recommendations in the form of alternative solutions to the problems.
This case study focuses on key personnel leaving an IT firm (TT Inc.) which possesses specialized knowledge and skills that could not be replaced internally. This problem and event created a major ...critical knowledge gap. The individuals who left expressed dissatisfaction with the increasing workload, limited resources, impossible deadlines, and unrealistic expectations from management. The remaining team members in the data networking group also shared their dissatisfaction. The methodology used to collect the data included a survey, interviews with key players, and from exit interviews. Productivity and job satisfaction at TT Inc.'s Telecom Engineering Department have declined. The dependant variables that are being explored are job satisfaction and productivity. Results of the surveys led to recommendations in the form of alternative solutions to the problems.
This case study focuses on key personnel leaving an IT firm TT Inc. which possesses specialized knowledge and skills that could not be replaced internally. This problem and event created a major ...critical knowledge gap. The individuals who left expressed dissatisfaction with the increasing workload, limited resources, impossible deadlines, and unrealistic expectations from management. The remaining team members in the data networking group also shared their dissatisfaction. The methodology used to collect the data included a survey, interviews with key players, and from exit interviews. Productivity and job satisfaction at TT Inc.'s Telecom Engineering Department have declined. The dependant variables that are being explored are job satisfaction and productivity. Results of the surveys led to recommendations in the form of alternative solutions to the problems.
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