Hemostasis is a dynamic age-related process, which gradually evolves from fetal life throughout childhood until adulthood. Although at birth there is a hemostatic deficit of most coagulation factors, studies have shown that this “hemostatic immaturity” is functionally counterbalanced in healthy term or preterm newborns. This delicate hemostatic balance is, however, deranged in sick neonates, resulting in an enhanced risk of hemorrhage and/or thrombosis. In critically ill neonates, conventional coagulation tests do not seem to provide reliable information or indications regarding the functional status of platelets or fibrinolysis. In contrast, viscoelastic tests, namely thromboelastography/thromboelastometry (TEG/TEM) hold promise for rapid assessment of the whole hemostatic potential, allowing immediate intervention should this be required. However, neonatal data are limited due to lack of reference values, especially in premature neonates. In this narrative review, we provide some insights around current knowledge regarding TEG/TEM applications in healthy and sick newborns. Overall, the use of viscoelastic tests in diagnosis and management of coagulation disorders in neonates is definitely worth further exploration. Consideration should be made to include these tests in the routine laboratory investigation of neonates and specific transfusion algorithms should also be developed in order to avoid treatment pitfalls. For this type of study formal consent is not required. A.K. and R.S. contributed to the conception and design of the study. All authors contributed to the interpretation of data for the work, drafted the manuscript and critically revised the article for important intellectual content, and approved the final version to be published. ^* These authors share equal contribution.

Background: Microgravity (µG) negatively influences bone metabolism by affecting normal osteoblast and osteoclast function. µG effects on bone metabolism has been an extensive field of study in recent years, due to the challenges presented by space flight. Methods: We systematically reviewed research data from genomic studies performed in real or simulated µG, on osteoblast and osteoclast cells. Our search yielded 50 studies, of which 39 concerned cells of the osteoblast family and 11 osteoclast precursors. Results: Osteoblastic cells under µG show a decreased differentiation phenotype, proved by diminished expression levels of Alkaline Phosphatase (ALP) and Osteocalcin (OCN) but no apoptosis. Receptor Activator of NF-κB Ligand (RANKL)/ Osteoprotegerine (OPG) ratio is elevated in favor of RANKL in a time-dependent manner, and further RANKL production is caused by upregulation of Interleukin- 6 (IL-6) and the inflammation pathway. Extracellular signals and changes in the gravitational environment are perceived by mechanosensitive proteins of the cytoskeleton and converted to intracellular signals through the Mitogen Activated Protein Kinase pathway (MAPK). This is followed by changes in the expression of nuclear transcription factors of the Activator Protein-1 (AP-1) family and in turn of the NF-κB, thus affecting osteoblast differentiation, cell cycle, proliferation and maturation. Pre-osteoclastic cells show increased expression of the marker proteins such as Tryptophan Regulated Attenuation Protein (TRAP), cathepsin K, Matrix Metalloproteinase-9 (MMP-9) under µG conditions and become sensitized to RANKL. Conclusion: Suppressing the expression of fusion genes such as syncytine-A which acts independently of RANKL, could be possible future therapeutic targets for microgravity side effects.