Dynamic self-assembled meso-structures formed across a wide concentration range in aqueous solutions of propranolol hydrochloride.

Hypothesis: Nanoscale characterisation of the self-associated species formed by amphiphilic pharmaceuticals in aqueous solution carries relevance across their entire journey from development through to manufacture - relevant, therefore, not only as regards formulation of the drug products as medicines, but also potentially relevant to their bioavailability, activity, and clinical side effects. Such knowledge and understanding, however, can only be fully secured by applying a range of experimental and theoretical methodologies.

Experiments: Herein, we apply a synergistic combination of solubility, surface tension, SANS, NMR and UV spectroscopic studies, together with MD simulation and QM calculations, to investigate the meso-structures of propranolol hydrochloride aggregates in bulk aqueous solutions, at concentrations spanning 2.

Different effects of fatty acid oxidation on hematopoietic stem cells based on age and diet.

Fatty acid oxidation is of uncertain importance in most stem cells. We show by C-palmitate tracing and metabolomic analysis that hematopoietic stem/progenitor cells (HSPCs) engage in long-chain fatty acid oxidation that depends upon carnitine palmitoyltransferase 1a (CPT1a) and hydroxyacyl-CoA dehydrogenase (HADHA) enzymes. CPT1a or HADHA deficiency had little or no effect on HSPCs or hematopoiesis in young adult mice.

Lower respiratory tract infections following respiratory syncytial virus monoclonal antibody nirsevimab immunization versus placebo: Analysis from a Phase 3 randomized clinical trial (MELODY).

Background: Nirsevimab is an extended half-life, highly potent neutralizing monoclonal antibody against the respiratory syncytial virus (RSV) fusion protein, with efficacy in preventing RSV-associated medically attended (MA) lower respiratory tract infection (LRTI) in infants and medically vulnerable children (aged ≤24 months). This post-hoc exploratory analysis examined the incidence of LRTI from RSV and other respiratory pathogens during a 2:1 randomized, double-blind, placebo-controlled, phase 3 study of nirsevimab, in healthy-term and late-preterm (i.e.

Toward target 2035: EUbOPEN - a public-private partnership to enable & unlock biology in the open.

Target 2035 is a global initiative that seeks to identify a pharmacological modulator of most human proteins by the year 2035. As part of an ongoing series of annual updates of this initiative, we summarise here the efforts of the EUbOPEN project whose objectives and results are making a strong contribution to the goals of Target 2035. EUbOPEN is a public-private partnership with four pillars of activity: (1) chemogenomic library collections, (2) chemical probe discovery and technology development for hit-to-lead chemistry, (3) profiling of bioactive compounds in patient-derived disease assays, and (4) collection, storage and dissemination of project-wide data and reagents.

Epidemiologic and genomic characterization of an outbreak of Rift Valley fever among humans and dairy cattle in northern Tanzania.

Background: A peri-urban outbreak of Rift Valley fever virus (RVFV) among dairy cattle from May through August 2018 in northern Tanzania was detected through testing samples from prospective livestock abortion surveillance. We sought to identify concurrent human infections, their phylogeny, and epidemiologic characteristics in a cohort of febrile patients enrolled from 2016-2019 at hospitals serving the epizootic area.

Methods: From September 2016 through May 2019, we conducted a prospective cohort study that enrolled febrile patients hospitalized at two hospitals in Moshi, Tanzania.