Morphological and Geochemical Evidence of Eumelanin Preservation in the Feathers of the Early Cretaceous Bird, Gansus yumenensis

Recent studies have shown evidence for the preservation of colour in fossilized soft tissues by imaging melanosomes, melanin pigment containing organelles. This study combines geochemical analyses with morphological observations to investigate the preservation of melanosomes and melanin within feathers of the Early Cretaceous bird, Gansus yumenensis. Scanning electron microscopy reveals structures concordant with those previously identified as eumelanosomes within visually dark areas of the feathers but not in lighter areas or sedimentary matrices. Fourier transform infrared analyses show different spectra for the feathers and their matrices; melanic functional groups appear in the feather including carboxylic acid and ketone groups that are not seen in the matrix. When mapped, the carboxylic acid group absorption faithfully replicates the visually dark areas of the feathers. Electron Paramagnetic Resonance spectroscopy of one specimen demonstrates the presence of organic signals but proved too insensitive to resolve melanin. Pyrolysis gas chromatography mass spectrometry shows a similar distribution of aliphatic material within both feathers that are different from those of their respective matrices. In combination, these techniques strongly suggest that not only do the feathers contain endogenous organic material, but that both geochemical and morphological evidence supports the preservation of original eumelanic pigment residue

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Effects of cocaine on c-fos and NGFI-B mRNA expression in transgenic mice underexpressing glucocorticoid receptors

Numerous evidences suggest that stress and stress-related hormones can modulate the activity of the brain reward pathway and thus may account for individual vulnerability towards the reinforcing effects of drugs of abuse. Transgenic (TG) mice expressing an antisense mRNA against the glucocorticoid receptor (GR), which partially blocks GR expression, were used to assess the role of GR dysfunction on cocaine (COC)-induced c-fos and Nerve-Growth Factor Inducible-B (NGFI-B, or Nur77) gene expression. These two genes belong to different families of transcription factors and have been shown to be modulated by various dopaminergic drugs. TG and wild-type (WT) mice were both acutely and repeatedly treated with COC (20 mg/kg, i.p.). In the chronic experiment, mice received a 5-day treatment of COC and were challenged 5 days later with COC or vehicle. Locomotor activity was assessed during the entire chronic experiment in the mouse home cages. Animals were sacrificed 1 h after the last injection and NGFI-B and c-fos mRNA levels in the prefrontal cortex, the nucleus accumbens and the striatum were measured by in situ hybridization. Acute COC administration led to significantly smaller c-fos increases in TG mice compared to WT, whereas repeated COC treatment potentiated c-fos induction both in TG and WT mice to equivalent levels. TG mice displayed higher basal NGFI-B expression in the nucleus accumbens and the level of NGFI-B mRNA was differently modulated by COC in TG mice compared to WT mice. In accordance with data on c-fos expression, behavioral data indicate a blunted locomotor effect on the first COC injection in TG mice, a phenomenon corrected by the repeated COC treatment. These results suggest that an alteration of the hypothalamus-pituitary-adrenal axis can modify COC-induced regulation of the transcription factors c-fos and NGFI-B, and that these changes parallel those seen at the behavioral level. It also demonstrates that the differences at the behavioral and molecular levels noted between TG and WT mice after acute COC injection disappear following repeated COC administration, suggesting that repeated COC has a greater impact in TG mice underexpressing GRs