Phase 1 and preclinical profiling of ESM-HDAC391, a myeloid-targeted histone deacetylase inhibitor, shows enhanced pharmacology and monocytopaenia.

Aims: To improve the tolerability and therapeutic application of histone deacetylase inhibitors (HDACi), by application of an esterase-sensitive motif (ESM), to target pharmacological activity directly to mononuclear myeloid cells expressing the processing enzyme carboxylesterase-1 (CES1).

Methods: This first-in-human study comprised single and multiple ascending dose cohorts to determine safety and tolerability. Pharmacodynamic parameters included acetylation, cytokine inhibition and intracellular concentrations of processed acid metabolite in isolated monocytes.

The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62 Modulates Complement Activation.

Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed that most ES-62 was bound to a single protein, C-reactive protein (CRP), in normal human serum, displaying a calcium-dependent, high-avidity interaction and ability to form large complexes.

Prospective comparison of curbside versus formal consultations.

Background: Curbside consultations are commonly requested during the care of hospitalized patients, but physicians perceive that the recommendations provided may be based on inaccurate or incomplete information.

Objective: To compare the accuracy and completeness of the information received from providers requesting a curbside consultation of hospitalists with that obtained in a formal consultation on the same patients, and to examine whether the recommendations offered in the 2 consultations differed.

Design: Prospective cohort.

Evolving practice of hospital medicine and its impact on hospital throughput and efficiencies.

Hospitalists are uniquely positioned to implement strategies to improve patient flow and efficiency. Hospital leaders have stated they expect hospitalists to comanage surgical patients, participate in observation units, and screen medical admissions, in addition to providing inpatient care for medical patients. We review how the hospitalists' role in acute inpatient care, surgical comanagement, short stay units, chest pain units, and active bed management has improved throughput and patient flow.

Robust and sensitive nylon hybridization membrane suitable for high-throughput robotic arraying applications.

An important aspect of automated macroarraying is the suitability of the nylon membrane selected on which samples are to be arrayed. PerForma is a positively charged nylon membrane that has been developed specificallyfor automated macroarraying. Tests usingfluorescent hybridization detection methods have shown that immobilized DNA amounts as low as 0.