Action of clathrodin and analogues on voltage-gated sodium channels.

Clathrodin is a marine alkaloid and believed to be a modulator of voltage-gated sodium (Na(V)) channels. Since there is an urgent need for small molecule Na(V) channel ligands as novel therapeutics, clathrodin could represent an interesting lead compound. Therefore, clathrodin was reinvestigated for its potency and Na(V) channel subtype selectivity. Clathrodin and its synthetic analogues were subjected to screening on a broad range of Na(V) channel isoforms, both in voltage clamp and patch clamp conditions. Even though clathrodin was not found to exert any activity, some analogues were capable of modulating the Na(V) channels, hereby validating the pyrrole-2-aminoimidazole alkaloid structure as a core structure for future small molecule-based Na(V) channel modulators.

Patient journeys: diagnosis and treatment of pernicious anaemia.

BACKGROUND: Instigating a patient support group for patients with pernicious anaemia (PA) revealed dissatisfaction with its current diagnosis and treatment. The authors investigated the clinical features, patient experience of diagnosis and treatment of PA in the UK. METHODS: A total of 889 patients registered with the PA Society support group completed an online survey or postal questionnaire. Outcome measures included clinical features, length of time to diagnosis and patient satisfaction with current treatment RESULTS: One-third of patients experienced symptoms for up to 1 year before diagnosis; 14% waited more than 10 years for a diagnosis. Neurological features were highly prevalent, the most common being memory loss and poor concentration. Nearly two-thirds of respondents were dissatisfied with current treatment; 10% used a non-licensed form of B12 to supplement their prescribed injections. CONCLUSION: The diagnosis and treatment of PA should be subject to a thorough review. This article discusses the patient survey and results and makes recommendations for how the diagnosis and treatment of PA may be evaluated.

Initial Studies Directed toward the Rational Design of Aqueous Graphene Dispersants.

This study presents preliminary experimental data suggesting that sodium 4-(pyrene-1-yl)butane-1-sulfonate (PBSA), 5, an analogue of sodium pyrene-1-sulfonate (PSA), 1, enhances the stability of aqueous reduced graphene oxide (RGO) graphene dispersions. We find that RGO and exfoliated graphene dispersions prepared in the presence of 5 are approximately double the concentration of those made with commercially available PSA, 1. Quantum mechanical and molecular dynamics simulations provide key insights into the behavior of these molecules on the graphene surface. The seemingly obvious introduction of a polar sulfonate head group linked via an appropriate alkyl spacer to the aromatic core results in both more efficient binding of 5 to the graphene surface and more efficient solvation of the polar head group by bulk solvent (water). Overall, this improves the stabilization of the graphene flakes by disfavoring dissociation of the stabilizer from the graphene surface and inhibiting reaggregation by electrostatic and steric repulsion. These insights are currently the subject of further investigations in an attempt to develop a rational approach to the design of more effective dispersing agents for rGO and graphene in aqueous solution.

The Relationship Between Subthreshold Autistic Traits, Ambiguous Figure Perception and Divergent Thinking.

This research investigates the paradox of creativity in autism. That is, whether people with subclinical autistic traits have cognitive styles conducive to creativity or whether they are disadvantaged by the implied cognitive and behavioural rigidity of the autism phenotype. The relationship between divergent thinking (a cognitive component of creativity), perception of ambiguous figures, and self-reported autistic traits was evaluated in 312 individuals in a non-clinical sample. High levels of autistic traits were significantly associated with lower fluency scores on the divergent thinking tasks. However autistic traits were associated with high numbers of unusual responses on the divergent thinking tasks. Generation of novel ideas is a prerequisite for creative problem solving and may be an adaptive advantage associated with autistic traits.