On the Outcome Project

Background: In 2001, graduate medical education in the United States was renovated to better complement 21st century developments in American medicine, society, and culture. As in 1910, when Abraham Flexner was charged to address a relatively non-standardized system that lacked accountability and threatened credibility of the profession, Dr. David Leach led the Accreditation Council of Graduate Medical Education (ACGME) Outcome Project in a process that has substantially changed medical pedagogy in the United States.Methods: Brief review of the Flexner Report of 1910 and 6 hours of interviews with leaders of the Outcome Project (4 hours with Dr. David Leach and 1-hour interviews with Drs. Paul Batalden and Susan Swing).Results: Medical educational leaders and the ACGME concluded in the late 1990s that medical education was not preparing clinicians sufficiently for lifelong learning in the 21st century. A confluence of medical, social, and historic factors required definitions and a common vocabulary for teaching and evaluating medical competency. After a deliberate consensus-driven process, the ACGME and its leaders produced a system requiring greater accountability of learners and teachers, in six explicitly defined domains of medical “competence.” While imperfect, this construct has started to take hold, creating a common vocabulary for longitudinal learning, from undergraduate to post-graduate (residency) education and in the assessment of performance following graduate training.     

Early childhood development project in Uganda as a strategy for reducing children's poor growth indicators: an explanatory study

This study shall explore the activities of the Uganda nutrition and early childhood development project using explanatory program effects, qualitative research methods to determine the role/interplay of project factors and community dynamics in relation to poor growth and social indicators in Ugandan children. This project aimed to improve the quality of life for children age less than 6 years by improving their nutrition, health, cognitive and psychosocial development. The key concern remains how successful and sustainable are the outcomes? Data shall be collected using interviews, focus groups and document reviews. Data analysis shall employ the thematic networks analytical tool, which is aided by the ATLAS.ti software. The key hypotheses and recommendations from the analysis shall then be tested in a suitable community location and period in line with the research questions.     

Biochemical and structural studies of N5-carboxyaminoimidazole ribonucleotide mutase from the acidophilic bacterium Acetobacter aceti

N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) mutase (PurE) catalyzes the reversible interconversion of acid-labile compounds N5-CAIR and 4-carboxy-5-aminoimidazole ribonucleotide (CAIR). We have examined PurE from the acidophilic bacterium Acetobacter aceti (AaPurE), focusing on its adaptation to acid pH and the roles of conserved residues His59 and His89. Both AaPurE and Escherichia coli PurE showed quasi-reversible acid-mediated inactivation, but wt AaPurE was much more stable at pH 3.5, with a > or = 20 degrees C higher thermal unfolding temperature at all pHs. His89 is not essential and does not function as part of a proton relay system. The kcat pH-rate profile was consistent with the assignment of pK1 to unproductive protonation of bound nucleotide and pK2 to deprotonation of His59. A 1.85 A resolution crystal structure of the inactive mutant H59N-AaPurE soaked in CAIR showed that protonation of CAIR C4 can occur in the absence of His59. The resulting species, modeled as isoCAIR [4(R)-carboxy-5-iminoimidazoline ribonucleotide], is strongly stabilized by extensive interactions with the enzyme and a water molecule. The carboxylate moiety is positioned in a small pocket proposed to facilitate nucleotide decarboxylation in the forward direction (N5-CAIR --> CAIR) [Meyer, E., Kappock, T. J., Osuji, C., and Stubbe, J. (1999) Biochemistry 38, 3012-3018]. Comparisons with model studies suggest that in the reverse (nonbiosynthetic) direction PurE favors protonation of CAIR C4. We suggest that the essential role of protonated His59 is to lower the barrier to decarboxylation by stabilizing a CO2-azaenolate intermediate.     

A Reproducible Computerized Method for Quantitation of Capillary Density using Nailfold Capillaroscopy

Capillaroscopy is a non-invasive, efficient, relatively inexpensive and easy to learn methodology for directly visualizing the microcirculation. The capillaroscopy technique can provide insight into a patient’s microvascular health, leading to a variety of potentially valuable dermatologic, ophthalmologic, rheumatologic and cardiovascular clinical applications. In addition, tumor growth may be dependent on angiogenesis, which can be quantitated by measuring microvessel density within the tumor. However, there is currently little to no standardization of techniques, and only one publication to date reports the reliability of a currently available, complex computer based algorithms for quantitating capillaroscopy data.¹ This paper describes a new, simpler, reliable, standardized capillary counting algorithm for quantitating nailfold capillaroscopy data. A simple, reproducible computerized capillaroscopy algorithm such as this would facilitate more widespread use of the technique among researchers and clinicians. Many researchers currently analyze capillaroscopy images by hand, promoting user fatigue and subjectivity of the results. This paper describes a novel, easy-to-use automated image processing algorithm in addition to a reproducible, semi-automated counting algorithm. This algorithm enables analysis of images in minutes while reducing subjectivity; only a minimal amount of training time (in our experience, less than 1 hr) is needed to learn the technique.     

Photosynthetic activity in synchronized cultures of algae and its dependence on light intensity

Summary Photosynthetic capacity at several levels of illuminance was investigated in cells of the successive developmental stages of the high temperature strain, Chlorella 7-11-05. The saturating light intensity, rates of photosynthesis at light saturation and at half-saturation, and the slope of the light dependent portion of the light intensity curves were proved to be bound with the developmental status of cells. The effect of the choosing of the basis for calculations of photosynthetic activity — whether packed cell volume, dry weight, nitrogen, or chlorophyll content—was discussed. The fact was stressed that with the available synchronization technique the observable amplitude of changes in metabolic activity in the course of cell development is a minimal one and the actual fluctuations in photosynthetic rates in non-synchronized suspensions in the course of the life cycle of the individual cells are expected to be higher than those recorded for synchronized populations.     

Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins

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Cholera and pertussis toxins modify regulation of glucose transport activity in rat adipose cells: evidence for mediation of a cAMP-independent process by G-proteins.

Adenylyl cyclase in rat adipose cells is stimulated by ligands for Rs receptors (e.g. isoproterenol) and inhibited by ligands for Ri receptors (e.g. adenosine). In contrast, Rs receptors mediate inhibition and Ri receptors mediate augmentation of insulin-stimulated glucose transport activity by a process independent of changes in cellular cAMP-dependent protein kinase activity [Kuroda M., Honnor R. C., Cushman S. W., Londos C. and Simpson I. A. (1987) J. biol. Chem. 262, 245-253]. The present study examines the possible role of G-proteins in the regulation of insulin-stimulated glucose transport activity by Rs and Ri receptors. First, conditions were established that permit intoxication of isolated rat adipocytes by cholera and pertussis toxins without compromising cell integrity. Effectiveness of toxin treatment was monitored by examining adenylyl cyclase activity in isolated plasma membranes. Secondly, neither toxin interfered with the ability of a maximal concentration insulin to initiate the glucose transport response. Thirdly, pertussis toxin eliminated the augmenting effects of adenosine on insulin-stimulated glucose transport activity, but enhanced the inhibitory effects of isoproterenol. Findings with ligands for other Ri receptors (nicotinic acid and prostaglandin E2) mirrored those with adenosine. Finally, cholera toxin elicited a modest depression of transport activity, and only in the absence of an Ri ligand (e.g. adenosine). Furthermore, in contrast to the enhanced stimulation of adenylyl cyclase by isoproterenol and GTP, cholera toxin eliminated the inhibitory effect of isoproterenol on transport activity. The augmentative effects of adenosine on transport activity were unchanged. Measurements of (-/+cAMP) cAMP-dependent protein kinase activity ratios reinforce the notion that modulation of glucose transport activity is independent of changes in cAMP. We conclude that regulation of glucose transport activity by Rs and Ri receptors is mediated by the G-proteins, Gs and Gi (or other toxin substrates), respectively. Inasmuch as such regulation occurs at the plasma membrane and appears to be cAMP-independent, it is suggested that glucose transporters may be direct targets for receptor: G-protein interactions.