Our approach used lacosamide agents containing “affinity bait” (AB) and “chemical reporter” (CR) units. The affinity bait moiety is designed to irreversibly react with the target, and the CR group

permits protein detection and capture. In this study, we report the preparation and evaluation of (R)-N-(4-azido)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-3) and show that this compound exhibits potent anticonvulsant Histone Methyltransf inhibitor activities in the MES seizure model in rodents. We compared the utility of (R)-3 with its isostere, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-2), in proteomic studies designed to identify potential (R)-1 targets. We showed that despite the two-fold improved anticonvulsant activity of (R)-3 compared with (R)-2.(R)-2 was superior in revealing potential binding targets in the mouse brain soluble proteome.

The difference in these agents’ utility has been attributed to the reactivity of the affinity baits (i.e., JPH203 inhibitor (R)-2: aryl isothiocyanate moiety; (R)-3: photoactivated aryl azide intermediates) in the irreversible protein modification step, and we conclude that this factor is a critical determinant of successful target detection where ligand (drug) binding is modest. The utility of (R)-2 and (R)-3 in in situ proteome studies is explored.”
“Objective. To study whether the physician’s evaluation of the consultation correlates to patient outcome one month later concerning symptom relief, Bafilomycin A1 sick leave, and drug compliance as perceived by the patient. The study also investigated whether the patient’s evaluation

of the consultation correlated to patient outcome. Design. A longitudinal study using questionnaires. Setting. A county in south-western Sweden. Subjects. Forty-six physicians and 316 primary care patients aged 16 years or more with a new complaint lasting one week or more were invited. A total of 289 patients completed a questionnaire presented at the consultation; 273 patients were reached in a follow-up telephone interview one month after the consultation. Main outcome measures. The association between each statement in the physician-patient questionnaire (PPQ) from the consultation and the answers obtained from the telephone interview were analysed by either multiple linear or logistic regression analysis. Results. Five out of 10 items in the PPQ were significantly associated with patient outcome. Physician’s self-evaluation of the consultation was much more strongly associated with patient outcome than the patient’s evaluation. Conclusion. The difference between the physician’s and patient’s evaluation of the consultation to predict patient outcomes indicates that the physician’s self-evaluation of the consultation is of importance.”
“Objective: To illustrate the association between hydroxyurea and the development of ulcers.