A Novel Neural Substrate for the Transformation of Olfactory Inputs into Motor Output

Anatomical and physiological experiments in the lamprey reveal the neural circuit involved in transforming olfactory inputs into motor outputs, which was previously unknown in a vertebrate

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Background: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. Methods: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0–5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. Findings: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88–1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4–10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9–19·7, p=0·059). Interpretation: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. Funding: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation

Hormones, blood products, and therapeutic enzymes

Therapeutic uses of biological medicines are diverse and include active substances from different classes. This chapter provides an overview on the clinical applications of biological medicines containing hormones, blood products, and therapeutic enzymes. Currently, therapeutic hormones have 78 approved medicines, including insulin and analogs, glucagon and analogs, growth hormone, gonadotropins (follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin), thyroid-stimulating hormone, and parathyroid hormone. In contrast, recombinant blood products, and particularly blood factors, anticoagulants, and thrombolytic agents, incorporate 49 approved biological medicines. Regarding recombinant therapeutic enzymes, there are 22 approved medicines. Among the referred biological medicines, there are six biosimilar hormones, and no biosimilars have been approved for recombinant blood products and therapeutic enzymes, which is unexpected.Current investigations on recombinant hormones, recombinant blood products, and therapeutic enzymes seem to follow the same directions, searching for alternative non-injectable administration routes, development of new recombinant molecules with improved pharmacokinetic properties and discovering new clinical applications for approved medicines. These approaches are showing positive results and new medicines are expected to reach clinical approval in the coming years. Future prospects also include the approval of more biosimilar medicines.info:eu-repo/semantics/publishedVersio