Recent Publications by CFE Educators

Aromatic amines have been studied for more than a half-century as model carcinogens representing a class of chemicals that form bulky adducts to the C8 position of guanine in DNA. Among these guanine adducts, the N-(2'-deoxyguanosin-8-yl)-aminofluorene (G-AF) and N-2-(2'-deoxyguanosin-8-yl)-acetylaminofluorene (G-AAF) derivatives are the best studied. Although G-AF and G-AAF differ by only an acetyl group, they exert different effects on DNA replication by replicative and high-fidelity DNA polymerases. Translesion synthesis of G-AF is achieved with high-fidelity polymerases, whereas replication of G-AAF requires specialized bypass polymerases. Here we have presented structures of G-AF as it undergoes one round of accurate replication by a high-fidelity DNA polymerase. Nucleotide incorporation opposite G-AF is achieved in solution and in the crystal, revealing how the polymerase accommodates and replicates past G-AF, but not G-AAF. Like an unmodified guanine, G-AF adopts a conformation that allows it to form Watson-Crick hydrogen bonds with an opposing cytosine that results in protrusion of the bulky fluorene moiety into the major groove. Although incorporation opposite G-AF is observed, the C:G-AF base pair induces distortions to the polymerase active site that slow translesion synthesis.

OBJECTIVE

The Accreditation Council for Graduate Medical Education (ACGME) has challenged program directors to assess their residents' core competencies, including communication and interpersonal skills (CIS). We report our institution's experience using a series of standardized patient encounters in an objective structured clinical examination (OSCE) to evaluate CIS in surgical residents.

METHODS

Standardized patients rated the residents' ability to maintain a patient-centered approach across 6 challenging communication tasks. Residents received verbal feedback from the patients after each encounter and completed a survey indicating their experience and comfort with each task. Individual and group reports documented resident competency and provided aggregate information for curriculum review. Formal grades were not assigned.

RESULTS

Twenty-two residents in 2 surgical residency programs piloted the assessment. The Generalizability of the assessment was 0.81. Scores of second- and third-year residents were not significantly different. Residents found the program to be helpful and able to assess their skills.

CONCLUSIONS

The standardized patient-based OSCE is an effective method to assess communication and interpersonal skills and provides useful information for curriculum review.

BACKGROUND

Information prescriptions (IPs) are prescriptions of specific, evidence-based information to manage health problems.

OBJECTIVE

To determine whether a pediatrician-provided IP would change parents' attitudes/behaviors about using Internet health information resources.

DESIGN, SETTING, AND PARTICIPANTS

We conducted a randomized controlled trial of parents visiting an academic general pediatric practice. Both groups received a preintervention paper survey and a telephone survey 2 to 3 weeks after their clinic visit. The intervention group was offered computer training and received the IP and training summary handout.

RESULTS

Final groups included 100 control and 97 intervention subjects. Of all parents, 68.0% had used the Internet in the past 6 months for health information and 52.8% used it for children's health information. The intervention group used the Internet more for general health information (P =.05) and child health information (P.001) than the control group. At follow-up, 51 (66.2%) of 77 Internet information resources used by the intervention group were prescribed by the pediatricians. Parents who used the IP (31 [32%] of 97 intervention parents) used the Internet for general health information (P.001) and child health information (P =.001) more than nonusers. Compared with nonusers, IP users were more likely to state they would use the IP again in the future (P =.02) and had already recommended the IP to family or friends more than nonusers (P =.001).

CONCLUSIONS

Parents of children in pediatric practices commonly use the Internet for general and children's health information. In this study, IPs were associated with specific parental attitude and behavior changes resulting in increased Internet utilization for general and child health information and for specific high-quality information resources. Pediatricians can implement IPs in their office.

Aerobic respiration generates reactive oxygen species that can damage guanine residues and lead to the production of 8-oxoguanine (8oxoG), the major mutagenic oxidative lesion in the genome. Oxidative damage is implicated in ageing and cancer, and its prevalence presents a constant challenge to DNA polymerases that ensure accurate transmission of genomic information. When these polymerases encounter 8oxoG, they frequently catalyse misincorporation of adenine in preference to accurate incorporation of cytosine. This results in the propagation of G to T transversions, which are commonly observed somatic mutations associated with human cancers. Here, we present sequential snapshots of a high-fidelity DNA polymerase during both accurate and mutagenic replication of 8oxoG. Comparison of these crystal structures reveals that 8oxoG induces an inversion of the mismatch recognition mechanisms that normally proofread DNA, such that the 8oxoG.adenine mismatch mimics a cognate base pair whereas the 8oxoG.cytosine base pair behaves as a mismatch. These studies reveal a fundamental mechanism of error-prone replication and show how 8oxoG, and DNA lesions in general, can form mismatches that evade polymerase error-detection mechanisms, potentially leading to the stable incorporation of lethal mutations.

Accurate and safe diagnostic testing provides the crucial link between detection and optimal management of coronary artery disease (CAD). Noninvasive diagnostic testing for CAD may be less accurate in women than in men. Many noninvasive diagnostic modalities are available for this purpose. An exercise tolerance test provides an assessment of functional capacity and has the advantages of wide availability and low initial cost. However, exercise echocardiography may be the most cost-effective method for the initial assessment of coronary artery disease in intermediate-risk women owing to its higher sensitivity and specificity. Recent studies with electron-beam computed tomography reveal that women with no coronary calcification are very unlikely to have obstructive CAD. In symptomatic women with an intermediate likelihood of CAD, either an exercise treadmill test or exercise echocardiography is appropriate for initial screening and can provide useful prognostic information. Alternatively, an electron-beam computed tomographic scan with a 0 calcium score may spare many women with atypical chest pain or equivocal findings on an exercise tolerance test from undergoing more expensive stress imaging studies or coronary angiography. For high-risk symptomatic women, a more aggressive approach involving coronary angiography appears to be the preferred initial diagnostic strategy.

Despite its fundamental importance, the educational mission of most medical schools receives far less recognition and support than do the missions of research and patient care. This disparity is based, in part, on the predominance of discipline-based departments, which focus on the more sustainable enterprises of research and patient care. Where departmental teaching is emphasized, it tends to center on trainees directly associated with the department-leaving medical students unsupported. The authors argue that the ongoing erosion of the educational mission will never be reversed unless there are changes in the underlying structure of medical schools. Academies of medical educators are developing at a number of medical schools to advance the school-wide mission of education. The authors describe and compare key features of such organizations at eight medical schools, identified through an informal survey of the Society of Directors of Research in Medical Education, along with direct contacts with specific schools. Although these entities are relatively new, initial assessments suggest that they have already had a major impact on the recognition of teaching efforts by the faculty, fueled curricular reform, promoted educational scholarship, and garnered new resources to support teaching. The academy movement, as a structural approach to change, shows promise for reinvigorating the educational mission of academic medicine.

Current guidelines recommend that the clinician, radiologist, and pathologist work together to establish a diagnosis of idiopathic interstitial pneumonia. Three clinicians, two radiologists, and two pathologists reviewed 58 consecutive cases of suspected idiopathic interstitial pneumonia. Each participant was provided information in a sequential manner and was asked to record their diagnostic impression and level of confidence at each step. Interobserver agreement improved from the beginning to the end of the review. After the presentation of histopathologic information, radiologists changed their diagnostic impression more often than did clinicians. In general, as more information was provided the confidence level for a given diagnosis improved, and the diagnoses rendered with a high level of confidence were more likely congruent with the final pathologic consensus diagnosis. The final consensus pathologist diagnosis was idiopathic pulmonary fibrosis in 30 cases. Clinicians identified 75% and radiologists identified 48% of these cases before presentation of the histopathologic information. Histopathologic information has the greatest impact on the final diagnosis, especially when the initial clinical/radiographic diagnosis is not idiopathic pulmonary fibrosis. We conclude that dynamic interactions between clinicians, radiologists, and pathologists improve interobserver agreement and diagnostic confidence.