Clinical Trial: Study to Investigate the Efficacy and Safety of the Alpha-2-Delta Ligand PD-217,014 in Patients With Irritable Bowel Syndrome.

Introduction: Despite the emergence of drugs to treat irritable bowel syndrome (IBS), improving abdominal pain can still be challenging. αδ ligands, such as gabapentin and pregabalin, are sometimes used off-label to tackle this problem. However, evidence for efficacy is limited, and no large-scale studies have been published.

Evaluation of a novel malaria anti-sporozoite vaccine candidate, R21 in Matrix-M adjuvant, in the UK and Burkina Faso: two phase 1, first-in-human trials.

Background: Malaria remains a substantial public health burden among young children in sub-Saharan Africa and a highly efficacious vaccine eliciting a durable immune response would be a useful tool for controlling malaria. R21 is a malaria vaccine comprising nanoparticles, formed from a circumsporozoite protein and hepatitis B surface antigen (HBsAg) fusion protein, without any unfused HBsAg, and is administered with the saponin-based Matrix-M adjuvant. This study aimed to assess the safety and immunogenicity of the malaria vaccine candidate, R21, administered with or without adjuvant Matrix-M in adults naïve to malaria infection and in healthy adults from malaria endemic areas.

Fragment-based development of small molecule inhibitors targeting cholesterol metabolism.

() is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi- (MDR) and extensively- (XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.

Predicting airway immune responses and protection from immune parameters in blood following immunization in a pig influenza model.

Whereas the intranasally delivered influenza vaccines used in children affect transmission of influenza virus in the community as well as reducing illness, inactivated influenza vaccines administered by intramuscular injection do not prevent transmission and have a variable, sometimes low rate of vaccine effectiveness. Although mucosally administered vaccines have the potential to induce more protective immune response at the site of viral infection, quantitating such immune responses in large scale clinical trials and developing correlates of protection is challenging. Here we show that by using mathematical models immune responses measured in the blood after delivery of vaccine to the lungs by aerosol can predict immune responses in the respiratory tract in pigs.

Consideration of Cybersecurity Risks in the Benefit-Risk Analysis of Medical Devices: Scoping Review.

Background: The integration of connected medical devices (MDs) into health care brings benefits but also introduces new, often challenging-to-assess risks related to cybersecurity, which have the potential to harm patients. Current regulations in the European Union and the United States mandate the consideration of these risks in the benefit-risk analysis (BRA) required for MD approval. This important step in the approval process weighs all the defined benefits of a device with its anticipated risks to ensure that the product provides a positive argument for use.