Thresholds of glycemia,insulin therapy,and risk for severe retinopathy in premature infants: A cohort study

BackgroundHyperglycemia in preterm infants may be associated with severe retinopathy of prematurity (ROP) and other morbidities. However, it is uncertain which concentration of blood glucose is associated with increased risk of tissue damage, with little consensus on the cutoff level to treat hyperglycemia. The objective of our study was to examine the association between hyperglycemia and severe ROP in premature infants.Methods and findingsIn 2 independent, monocentric cohorts of preterm infants born at <30 weeks’ gestation (Nantes University Hospital, 2006–2016, primary, and Lyon-HFME University Hospital, 2009–2017, validation), we first analyzed the association between severe (stage 3 or higher) ROP and 2 markers of glucose exposure between birth and day 21—maximum value of glycemia (MaxGly_1–21) and mean of daily maximum values of glycemia (MeanMaxGly_1–21)—using logistic regression models. In both the primary (n = 863 infants, mean gestational age 27.5 ± 1.4 weeks, boys 52.5%; 38 with severe ROP; 54,083 glucose measurements) and the validation cohort (n = 316 infants, mean gestational age 27.4 ± 1.4 weeks, boys 51.3%), MaxGly_1–21 and MeanMaxGly_1–21 were significantly associated with an increased risk of severe ROP: odds ratio (OR) 1.21 (95% CI 1.14–1.27, p < 0.001) and OR 1.70 (95% CI 1.48–1.94, p < 0.001), respectively, in the primary cohort and OR 1.17 (95% CI 1.05–1.32, p = 0.008) and OR 1.53 (95% CI 1.20–1.95, p < 0.001), respectively, in the validation cohort. These associations remained significant after adjustment for confounders in both cohorts. Second, we identified optimal cutoff values of duration of exposure above each concentration of glycemia between 7 and 13 mmol/l using receiver operating characteristic curve analyses in the primary cohort. Optimal cutoff values for predicting stage 3 or higher ROP were 9, 6, 5, 3, 2, 2, and 1 days above a glycemic threshold of 7, 8, 9, 10, 11, 12, and 13 mmol/l, respectively. Severe exposure was defined as at least 1 exposure above 1 of the optimal cutoffs. Severe ROP was significantly more common in infants with severe exposure in both the primary (10.9% versus 0.6%, p < 0.001) and validation (5.2% versus 0.9%, p = 0.030) cohorts. Finally, we analyzed the association between insulin therapy and severe ROP in a national population-based prospectively recruited cohort (EPIPAGE-2, 2011, n = 1,441, mean gestational age 27.3 ± 1.4, boys 52.5%) using propensity score weighting. Insulin use was significantly associated with severe ROP in overall cohort crude analyses (OR 2.51 [95% CI 1.13–5.58], p = 0.024). Adjustment for inverse propensity score (gestational age, sex, birth weight percentile, multiple birth, spontaneous preterm birth, main pregnancy complications, surfactant therapy, duration of oxygen exposure between birth and day 28, digestive state at day 7, caloric intake at day 7, and highest glycemia during the first week) and duration of oxygen therapy had a large but not significant effect on the association between insulin treatment and severe ROP (OR 0.40 [95% CI 0.13–1.24], p = 0.106). Limitations of this study include its observational nature and, despite the large number of patients included compared to earlier similar studies, the lack of power to analyze the association between insulin use and retinopathy.ConclusionsIn this study, we observed that exposure to high glucose concentration is an independent risk factor for severe ROP, and we identified cutoff levels that are significantly associated with increased risk. The clinical impact of avoiding exceeding these thresholds to prevent ROP deserves further evaluation.

In this cohort study, Elsa Kermorvant-Duchemin and colleagues examine the association between hyperglycemia and severe retinopathy of prematurity in infants.     

Functional analysis of RXLR effectors from the New Zealand kauri dieback pathogen Phytophthora agathidicida

New Zealand kauri is an ancient, iconic, gymnosperm tree species that is under threat from a lethal dieback disease caused by the oomycete Phytophthora agathidicida. To gain insight into this pathogen, we determined whether proteinaceous effectors of P. agathidicida interact with the immune system of a model angiosperm, Nicotiana, as previously shown for Phytophthora pathogens of angiosperms. From the P. agathidicida genome, we defined and analysed a set of RXLR effectors, a class of proteins that typically have important roles in suppressing or activating the plant immune system. RXLRs were screened for their ability to activate or suppress the Nicotiana plant immune system using Agrobacterium tumefaciens transient transformation assays. Nine P. agathidicida RXLRs triggered cell death or suppressed plant immunity in Nicotiana, of which three were expressed in kauri. For the most highly expressed, P. agathidicida (Pa) RXLR24, candidate cognate immune receptors associated with cell death were identified in Nicotiana benthamiana using RNA silencing-based approaches. Our results show that RXLRs of a pathogen of gymnosperms can interact with the immune system of an angiosperm species. This study provides an important foundation for studying the molecular basis of plant–pathogen interactions in gymnosperm forest trees, including kauri.     

Bacterivory in the common foraminifer Ammonia tepida: Isotope tracer experiment and the controlling factors

The majority of sediment dweller foraminifera are deposit feeders. They use their pseudopodia to gather sediment with associated algae, organic detritus and bacteria. Uptake of bacteria by foraminifera have been observed but rarely quantified. We measured uptake of bacteria by the common foraminifera Ammonia tepida using ¹⁵N pre-enriched bacteria as tracers. In intertidal flats, seasonal, tidal and circadian cycles induce strong variations in environmental parameters. Grazing experiments were performed in order to measure effects of abiotic (temperature, salinity and irradiance) and biotic (bacterial and algal abundances) factors on uptake rates of bacteria. In mean conditions, A. tepida grazed 78 pgC ind^− 1 h^− 1 during the first eight hours of incubation, after which this uptake rate decreased. Uptake of bacteria was optimal at 30 °C, decreased with salinity and was unaffected by light. Above 7 × 10⁸ bacteria ml wt sed^− 1, uptake of bacteria remained unchanged when bacterial abundance increased. Algal abundance strongly affected algal uptake but did not affect uptake of bacteria. As uptake of bacteria represented 8 to 19% of microbes (algae plus bacteria) uptake, Ammonia seemed to be mainly dependant on algal resource.     

Genome of the rainbow trout (Oncorhynchus mykiss) encodes two distinct muscle regulatory factors with homology to MyoD

Previously we identified a trout myogenic factor related to MyoD. We now present a cDNA encoding a novel trout myogenic factor (TMyoD2) expressed in embryonic muscle. Nucleotide analysis and amino acid comparison showed that this cDNA encodes a MyoD-like protein of 275 amino acids that is distinct but related to TMyoD with 78% identity over the entire length. The protein sequence conservation between TMyoD2 and TMyoD was calculated to be 90% within the basic/ helix-loop-helix domain that is involved in DNA binding and heterooligomerisation. At the nucleotide level, comparison of TMyoD with TMyoD2 reveals that the translated regions are flanked by highly divergent 3′ and 5′ ends. The substantial differences observed at translated and especially untranslated regions strongly suggest that TMyoD and TMyoD2 mRNA originate from different loci. The TMyoD and TMyoD2 mRNA are likely transcribed from two distinct genes which were duplicated during the tetraploïdization of the salmonid genome.