Sofosbuvir as post-exposure prophylaxis for yellow fever-associated viscerotropic disease (YEL-AVD).

Objectives: Yellow fever-associated viscerotropic disease (YEL-AVD) is a rare but serious complication arising from administration of live-attenuated yellow fever vaccine to individuals with risk factors such as thymectomy. At present there is no evidence-based treatment, and case fatality rates are high. Sofosbuvir, an NS5B nucleotide inhibitor, has activity against yellow fever virus in vitro and in vivo.

Preterm preeclampsia screening and prevention: a comprehensive approach to implementation in a real-world setting.

Background: Preeclampsia significantly impacts maternal and perinatal health. Early screening using advanced models and primary prevention with low-dose acetylsalicylic acid for high-risk populations is crucial to reduce the disease's incidence. This study assesses the feasibility of implementing preterm preeclampsia screening and prevention by leveraging information from our current aneuploidy screening program in a real-world setting with geographic separation clinical site and laboratory analysis site.

Phenotype-Led Identification of IL-10 Upregulators in Human CD4 T-cells and Elucidation of Their Pharmacology as Highly Selective CDK8/CDK19 Inhibitors.

Therapeutics promoting the endogenous production of IL-10 have the potential to restore homeostasis in inflammatory disorders such as inflammatory bowel disease (IBD). Here we describe the identification of a series of IL-10 upregulators based on a pyrimidyl-piperidine scaffold through a high throughput phenotypic CD4 T-cell multiplex assay. optimization of the initial hit yielded a lead with good potency and an clearance profile, compound 3-7, which additionally demonstrated efficacy in a murine endotoxin challenge PK-PD mechanistic model.

Helicopter emergency medical services demonstrate reduced time to emergency anaesthesia in an undifferentiated trauma population: a retrospective observational analysis across three major trauma networks.

Background: Early rapid sequence induction of anaesthesia (RSI) and tracheal intubation for patients with airway or ventilatory compromise following major trauma is recommended, with guidance suggesting a 45-min timeframe. Whilst on-scene RSI is recommended, the potential time benefit offered by Helicopter Emergency Medical Services (HEMS) has not been studied. We compared the time from 999/112 emergency call to delivery of RSI between patients intubated either in the Emergency Department or pre-hospital by HEMS.

The Once and Future Fish: Assessing a Millennium of Atlantic Herring Exploitation Through Mixed-Stock Analysis and Ancient DNA.

Small pelagic fish support profitable fisheries and are important for food security around the world. Yet, their sustainable management can be hindered by the indiscriminate impacts of simultaneous exploitation of fish from multiple distinct biological populations over extended periods of time. The quantification of such impacts is greatly facilitated by recently developed molecular tools-including diagnostic single nucleotide polymorphism (SNP) panels for mixed-stock analysis (MSA)-that can accurately detect the population identity of individual fish.