Association between hypothermia in the first day of life and survival in the preterm infant.

OBJECTIVE: Hypothermia is associated with elevated mortality in the preterm infant. The preterm infant's thermoregulatory capacity is limited, and the thermal environment in an incubator is often perturbed by nursing procedures. We evaluated the incidence of a postnatal low body temperature and hypothermia in preterm infants and its association with mortality. METHODS: We measured the lowest body temperature during the first 24h of life (TBody Nadir 24h) and hypothermia (TBody Nadir 24h<36.0°C) in preterm infants (gestational age: 230-316 weeks) in a neonatal intensive care unit. Prenatal and neonatal characteristics associated with mortality were identified in univariate and multivariable analyses. RESULTS: A total of 102 preterm infants were included, with a mean gestational age at birth of 28.4±2.3 weeks. The incidence of hypothermia during the first 24h was 53%. A Cox multivariate regression model indicated that TBody Nadir 24h (hazard ratio (HR) [95% confidence interval]: 0.57 [0.36-0.90]; P=0.017), gestational age (0.62 [0.50-0.76]; P<0.001), and amine use (4.55 [2.01-10.28]; P=0.001) were significantly associated with mortality. When considering a threshold for TBody Nadir 24h, a value of 35.0°C had the highest HR (3.30 [1.42-7.68]; P<0.01). CONCLUSION: In preterm infants, the incidence of hypothermia during the first 24h of life was 53%. TBody Nadir 24h had an influence on mortality, independently of other factors (notably birth weight and amine use). Within the framework of a quality improvement strategy, the implementation of a thermoregulation bundle is required to prevent hypothermia and decrease mortality in preterm infants.

Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.

BACKGROUND: In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). PATIENTS AND METHODS: Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. RESULTS: From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported. CONCLUSIONS: Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. CLINICAL TRIAL NUMBER: NCT02034981.

TRANSPARENT TESTA 16 and 15 act through different mechanisms to control proanthocyanidin accumulation in Arabidopsis testa.

Flavonoids are secondary metabolites that fulfil a multitude of functions during the plant life cycle. In Arabidopsis proanthocyanidins (PAs) are flavonoids that specifically accumulate in the innermost integuments of the seed testa (i.e. endothelium), as well as in the chalaza and micropyle areas, and play a vital role in protecting the embryo against various biotic and abiotic stresses. PAs accumulation in the endothelium requires the activity of the MADS box transcription factor TRANSPARENT TESTA (TT) 16 (ARABIDOPSIS B-SISTER/AGAMOUS-LIKE 32) and the UDP-glycosyltransferase TT15 (UGT80B1). Interestingly tt16 and tt15 mutants display a very similar flavonoid profiles and patterns of PA accumulation. By using a combination of genetic, molecular, biochemical, and histochemical methods, we showed that both TT16 and TT15 act upstream the PA biosynthetic pathway, but through two distinct genetic routes. We also demonstrated that the activity of TT16 in regulating cell fate determination and PA accumulation in the endothelium is required in the chalaza prior to the globular stage of embryo development. Finally this study provides new insight showing that TT16 and TT15 functions extend beyond PA biosynthesis in the inner integuments of the Arabidopsis seed coat.

A new system for fast and quantitative analysis of heterologous gene expression in plants.

• Large-scale analysis of transcription factor-cis-acting element interactions in plants, or the dissection of complex transcriptional regulatory mechanisms, requires rapid, robust and reliable systems for the quantification of gene expression. • Here, we describe a new system for transient expression analysis of transcription factors, which takes advantage of the fast and easy production and transfection of Physcomitrella patens protoplasts, coupled to flow cytometry quantification of a fluorescent protein (green fluorescent protein). Two small-sized and high-copy Gateway® vectors were specifically designed, although standard binary vectors can also be employed. • As a proof of concept, the regulation of BANYULS (BAN), a key structural gene involved in proanthocyanidin biosynthesis in Arabidopsis thaliana seeds, was used. In P. patens, BAN expression is activated by a complex composed of three proteins (TT2/AtMYB123, TT8/bHLH042 and TTG1), and is inhibited by MYBL2, a transcriptional repressor, as in Arabidopsis. Using this approach, two new regulatory sequences that are necessary and sufficient for specific BAN expression in proanthocyanidin-accumulating cells were identified. • This one hybrid-like plant system was successfully employed to quantitatively assess the transcriptional activity of four regulatory proteins, and to identify their target recognition sites on the BAN promoter.

Drought differentially affects expression of a PR-10 protein, in needles of maritime pine (Pinus pinaster Ait.) seedlings.

A full length cDNA encoding a PR-10 protein was isolated from maritime pine drought-stressed seedlings. The predicted protein contained 150 amino acids, has a molecular mass of 16.7 kDa and an isoelectric point of 5.28. The transcript level of PR-10 displayed a transient accumulation in needles of drought-stressed plants, and was not detectable in root and stem tissues.

Separation and characterization of needle and xylem maritime pine proteins.

Two-dimensional gel electrophoresis (2-DE) and image analysis are currently used for proteome analysis in maritime pine (Pinus pinaster Ait.). This study presents a database of expressed proteins extracted from needles and xylem, two important tissues for growth and wood formation. Electrophoresis was carried out by isoelectric focusing (IEF) in the first dimension and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the second. Silver staining made it possible to detect an average of 900 and 600 spots on 2-DE gels from needles and xylem, respectively. A total of 28 xylem and 35 needle proteins were characterized by internal peptide microsequencing. Out of these 63 proteins, 57 (90%) could be identified based on amino acid similarity with known proteins, of which 24 (42%) have already been described in conifers. Overall comparison of both tissues indicated that 29% and 36% of the spots were specific to xylem and needles, respectively, while the other spots were of identical molecular weight and isoelectric point. The homology of spot location in 2-DE patterns was further validated by sequence analysis of proteins present in both tissues. A proteomic database of maritime pine is accessible on the internet (http://www.pierroton.inra.fr/genetics/2D/).

[Chronic obstructive bronchopneumopathy after acute inhalation of sulfur anhydride. Apropos of a case]. / Bronchopneumopathie chronique obstructive après inhalation aiguë d'anhydride sulfureux. A propos d'un cas.

We report on an acute accidental inhalation of sulfurous anhydride, by a man aged thirty in the course of his work. This intoxication, followed by acute respiratory distress, first showed an improvement, then re-aggravation 26 days after the accident. This episode has not been explained. The patient then developed a chronic obstructive bronchopathy. Ten years of regular observation allows us to maintain that the severe obstructive syndrome which the patient presents has never regressed (FEV1/FVC = 32%), and must be associated with a chronic toxic obstructive bronchopneumopathy.

[Myocardial infarction and vinorelbine. Report of a case]. / Infarctus myocardique et vinorelbine. Rapport d'un cas.

The authors report a case of a patient dying as a result of a myocardial infarction which was probably related to the administration of vinorelbine, the vinca alkaloid recently introduced into the treatment of non small cell bronchial cancers.

Localization of gamma-rays induced chromatid breaks using a three consecutive staining technique.

Three staining techniques (Giemsa, Q-banding and R-banding) are used consecutively to localize the breakage points in chromosomes of human lymphocytes, irradiated during G2-phase with gamma-rays, at doses ranging from 50 to 200 rad. The large majority, about 85% of the breaks, occurs at the interbands, between R- and Q-bands. The discrepancy of this result, with regard to previously reported ones, is attributed to the strong bias of analysis when only one staining technique is used.