Four glutamate residues (EEEE locus) are essential for ion selectivity in voltage-gated Ca 2؉ channels, with ion-specific differences in binding to the locus providing the basis of selectivity. Whether side chain carboxylates or alternatively main chain carbonyls of these glutamates project into the pore to form the ion-binding locus has been uncertain. We have addressed this question by examining effects of sulfhydryl-modifying agents (methanethiosulfonates) on 20 cysteine-substituted mutant forms of an L-type Ca 2؉ channel. Sulfhydryl modifiers partially blocked whole oocyte Ba 2؉ currents carried by wild type channels, but this block was largely reversed with washout. In contrast, each of the four EEEE locus glutamate 3 cysteine mutants (0 position) was persistently blocked by sulfhydryl modifiers, indicating covalent attachment of a modifying group to the side chain of the substituted cysteine. Cysteine substitutions at positions immediately adjacent to the EEEE locus glutamates (؎1 positions) were also generally susceptible to sulfhydryl modification. Sulfhydryl modifiers had lesser effects on channels substituted one position further from the EEEE locus (؎2 positions). These results indicate that the carboxylate-bearing side chains of the EEEE locus glutamates and their immediate neighbors project into the water-filled lumen of the pore to form an ion-binding locus. Thus the structure of the Ca 2؉ channel selectivity filter differs substantially from that of ancestral K ؉ channels.
Many patients with diabetes do not receive recommended standards of care. Diabetes patients were seen by a pharmacist in a diabetes assessment service (DAS) 1 week prior to a physician appointment to complete diabetes standards. Completion rates of American Diabetes Association (ADA) standards were compared between patients of 5 physicians offered the DAS intervention and a concurrent cohort of randomly selected patients of nonparticipating physicians. A total of 94 patients were seen by DAS; 210 patients comprised the controls. DAS patients had a significantly higher proportion of each standard completed (glycosylated hemoglobin, lipids, foot exam, eye referral, pneumococcal and influenza vaccination, and urine microalbumin) compared with the control group (P < .001). An average of 3.3 ± 1.8 diabetes standards per patient were completed. A planned visit with a pharmacist prior to a physician appointment, with the goal of completing ADA standards of care, was feasible and effective in this university-based family medicine center.
Outcomes from The Center for Advancement of Pharmacy Education (CAPE) are intended to represent the terminal knowledge, skills, and attitudes pharmacy students should possess and have guided delivery of pharmacy education for more than two decades. Advanced pharmacy practice experiences (APPEs) are the endpoint of pharmacy curricula where demonstration and assessment of terminal learning occurs. This review examines published literature in relation to the most recent CAPE outcomes to determine the extent to which they have been addressed during APPEs since 1996. Details related to the APPE focus, intervention(s)/learning setting(s), and assessments are summarized according to the 15 CAPE outcomes. Further, the assessments are categorized according to the level of learning achieved using an available method. Common CAPE outcomes are highlighted, as well as those for which published reports are lacking for APPEs. The range and quality of assessments are discussed and emphasize the need for continuous improvement of scholarly design and assessment.
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