Co-designing technology to improve psychological therapy for psychosis: SloMo, a blended digital therapy for fear of harm from others.

Digital technology is positioned as a potential solution to improving access, experience, and outcomes of psychological therapies for psychosis. Digital solutions need to be fit for purpose and tailored to context to deliver real world benefits. To address this, co-production is often used, where stakeholder involvement informs intervention development.

A crisis planning and monitoring intervention to reduce compulsory hospital readmissions (FINCH study): protocol for a randomised controlled feasibility study.

Background: Rates of compulsory (also known as involuntary) detention under mental health legislation have been rising over several decades in countries including England. Avoiding such detentions should be a high priority given their potentially traumatic nature and departure from usual ethical principles of consent and collaboration. Those who have been detained previously are at high risk of being detained again, and thus a priority group for preventive interventions.

Pilot of urgent care center evaluation for acute coronary syndrome.

Objectives: Patients with chest pain and concern for potential coronary ischemia are frequently referred to the emergency department (ED), resulting in substantial resource utilization and cost. The objective of this study was to implement a protocol for urgent care center (UCC) evaluation of potential acute coronary syndrome (ACS) and describe its performance.

Study Design: This is a descriptive, retrospective review of consecutive cases included in a protocol for UCC evaluation of ACS.

Using deuterium in drug discovery: leaving the label in the drug.

Deuterium, the stable isotope of hydrogen, is known to medicinal chemists for its utility in mechanistic, spectroscopic, and tracer studies. In fact, well-known applications utilizing deuterium exist within every subdiscipline in pharmaceutical discovery and development. Recent emphasis on incorporation of deuterium into the active pharmaceutical ingredient has come about as a result of inquiries into the potential for substantial benefits of the deuterium kinetic isotope effect on the safety and disposition of the drug substance.

Potent and cellularly active 4-aminoimidazole inhibitors of cyclin-dependent kinase 5/p25 for the treatment of Alzheimer's disease.

Utilizing structure-based drug design, a 4-aminoimidazole heterocyclic core was synthesized as a replacement for a 2-aminothiazole due to potential metabolically mediated toxicity. The synthetic route utilized allowed for ready synthesis of 1-substituted-4-aminoimidazoles. SAR exploration resulted in the identification of a novel cis-substituted cyclobutyl group that gave improved enzyme and cellular potency against cdk5/p25 with up to 30-fold selectivity over cdk2/cyclin E.

Discovery of novel isothiazole inhibitors of the TrkA kinase: structure-activity relationship, computer modeling, optimization, and identification of highly potent antagonists.

The design, synthesis, and biological evaluation of potent inhibitors of the TrkA kinase is presented. A homology model is created to aid in the enhancement of potency and selectivity of isothiazole inhibitors found during a high-throughput screen. Three different syntheses are utilized to make diverse analogs within this series.

Expression, purification, and enzymatic characterization of the dual specificity mitogen-activated protein kinase phosphatase, MKP-4.

Mitogen-activated protein kinase phosphatase-4 (MKP-4) is a dual specificity phosphatase, which acts as a negative regulator of insulin-stimulated pathways. Here, we describe expression, purification, and biochemical characterization of MKP-4. We used the Baculovirus expression system and purification with a combination of affinity and gel filtration chromatography to generate pure MKP-4 and MKP-4/p38 complex.

Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer's disease.

High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC(50)=ca. 320nM).