Background: Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of re- suscitation of very... Show moreBackground: Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of re- suscitation of very and extremely preterm infants (<32 weeks' gestation). However, despite more than 10 randomized controlled trials on this question, the ideal initial oxygen concentration for this group of vulnerable infants remains uncertain. Aims: This study aims to assess the effect of various initial oxygen concentrations on (1) all-cause mortality, chronic lung disease, intraventricular hemorrhage, and retinopathy of prematurity; and (2) reaching the prescribed oxygen saturation targets by 5 min after birth, in preterm infants requiring resuscitation. Methods: We will conduct a system- atic review and network meta-analysis using individual participant data. Studies of preterm infants <32 weeks' gestation, randomized to initial oxygen concentration, will be included. We will systematically search medical databases and trial registriesfor eligible studies (published or unpublished). Records will be screened by two independent reviewers, with conflicts resolved by the inclusion of a third reviewer. Identified initial oxygen concentrations will be grouped into the following nodes: low (<= 30%), intermediate (60%), and high (>= 90%) oxygen. A two-step random-effects contrastbased network meta-regression will be calculated to compare and rank different oxygen concentrations. Analyses will be intention-to-treat, with the primary outcome of all-cause mortality. Discussion: This is the first individual participant data network meta-analysis of initial oxygen concentrations for the resuscitation of preterm infants. This novel approach may address long-standing uncertainty regarding optimal oxygen supplementation practice for the resuscitation of preterm infants <32 weeks' gestation. (C) 2022 S. Karger AG, Basel Show less
During development of the cellular slime mold Dictyostelium discoideum, cAMP induces chemotaxis and expression of different classes of genes by means of interaction with surface cAMP receptors. We... Show moreDuring development of the cellular slime mold Dictyostelium discoideum, cAMP induces chemotaxis and expression of different classes of genes by means of interaction with surface cAMP receptors. We describe a cAMP derivative, 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate (8-CPT-cAMP), which inhibits cAMP-induced chemotaxis at low concentrations but induces chemotaxis at supersaturating concentrations. This compound, moreover, selectively activates expression of aggregative genes but not of postaggregative genes. 8-CPT-cAMP induces normal cGMP and cAMP accumulation but in contrast to cAMP, which increases inositol 1,4,5-trisphosphate levels, 8-CPT-cAMP decreases inositol 1,4,5-trisphosphate levels. The derivative induces reduced activation of guanine nucleotide regulatory proteins, which may cause its defective activation of inositol 1,4,5-trisphosphate production. Our data suggest that disruption of inositolphospholipid signaling impairs chemotaxis and expression of a subclass of cAMP-regulated genes. Show less
