The Clumsy Horse: A Professional Development Tool for Facilitators of Self-Directed, Case-Based Learning.

Introduction: With the constant evolution of science and advancing technology, future physicians must learn to navigate an ever-changing health care environment by continuous learning throughout their professional careers. Lifelong, self-directed learning is a critical component of medical education to ensure future physicians are adept at identifying knowledge gaps and seeking, analyzing, and communicating new information. To train faculty who teach case-based, self-directed learning, we designed the Clumsy Horse Case. Methods: The Clumsy Horse Case was created as part of a faculty development program for facilitators of a new case-based, self-directed curriculum known as Patient-Centered Education (PaCE) Cases. An unfamiliar veterinary medicine case was designed to level the playing field for faculty from different specialty areas in order to provide an authentic self-directed learning experience. To determine effectiveness, faculty participants completed a standardized eight-question evaluation survey after the Clumsy Horse Case session, and facilitators received student feedback at the end of each semester via a standard faculty evaluation form. Results: Student ratings indicated that faculty were adequately prepared to be effective facilitators. The Clumsy Horse Case was an integral part of facilitator preparation and provided an engaging learning experience for over 60 faculty. Survey ratings and comments from faculty participants indicated a high level of engagement and satisfaction with the learning experience. Discussion: The Clumsy Horse Case is generalizable for developing faculty in any curriculum with a case-based, self-directed learning component. It can be modified to fit any school's curriculum and integrated into a professional development program.

Symptomatic hyperprolactinemia from an ectopic pituitary adenoma located in the clivus.

OBJECTIVE: To report a case of an ectopic pituitary adenoma in the clivus. METHODS: The clinical, laboratory, and imaging findings of the case are reviewed, and the embryogenesis of the pituitary gland, the pathophysiologic features of this condition, the diagnosis, and the treatment options are discussed. RESULTS: A 20-year-old man presented to a local physician because of a milky nipple discharge of 2 months' duration. He was otherwise healthy. Findings on physical examination were unremarkable except for the milky discharge from both nipples on expression. Serum prolactin, insulinlike growth factor-I, and alpha-fetoprotein were measured. Magnetic resonance imaging of the brain revealed a 13-mm erosive mass in the clivus. Surgical excision of the lesion was undertaken because of the propensity for aggressive lesions in this anatomic location and the high likelihood of complete resection. After the resected tissue was examined, the patient was diagnosed as having an ectopic prolactin-producing pituitary adenoma. His endocrinologic function normalized after resection, and no further therapy was needed. CONCLUSION: Ectopic prolactinoma in the clivus is an uncommon lesion. Surgical resection was undertaken in our patient because of the uncertainty of the diagnosis and the aggressive natural history of more common tumors of the clivus, such as chordomas. Resection provided a cure in this patient. Although it is possible that a successful trial of dopaminergic therapy would have obviated surgical intervention, this approach would be associated with additional risks if the diagnosis were incorrect.

Aqueous access pathways in ATP synthase subunit a. Reactivity of cysteine substituted into transmembrane helices 1, 3, and 5.

Subunit a is thought to play a key role in H+ transport-driven rotation of the subunit c ring in Escherichia coli F1F0 ATP synthase. In the membrane-traversing F0 sector of the enzyme, H+ binding and release occurs at Asp-61 in the middle of the second transmembrane helix (TMH) of subunit c. Protons are thought to reach Asp-61 via aqueous channels formed at least in part by one or more of the five TMHs of subunit a. Aqueous access to surfaces of TMHs 2, 4, and 5 was previously suggested based upon the chemical reactivity of cysteine residues substituted into these helices. Here we have substituted Cys into TMH1 and TMH3 and extended the substitutions in TMH5 to the cytoplasmic surface. One region of TMH3 proved to be moderately Ag+-sensitive and may connect with the Ag+-sensitive region found previously on the periplasmic side of TMH2. A single Cys substitution in TMH1 proved to be both N-ethylmaleimide (NEM)-sensitive and Ag+-sensitive and suggests a possible packing interaction of TMH1 with TMH2 and TMH3. New Ag+- and NEM-sensitive residues were found at the cytoplasmic end of TMH5 and suggest a possible connection of this region to the NEM- and Ag+-sensitive region of TMH4 described previously. From the now complete pattern of TMH residue reactivity, we conclude that aqueous access from the periplasmic side of F0 to cAsp-61 at the center of the membrane is likely to be mediated by residues of TMHs 2, 3, 4, and 5 at the center of a four-helix bundle. Further, aqueous access between cAsp-61 and the cytoplasmic surface is likely to be mediated by residues in TMH4 and TMH5 at the exterior of the four-helix bundle that are in contact with the c-ring.

Aqueous access pathways in subunit a of rotary ATP synthase extend to both sides of the membrane.

The role of subunit a in promoting proton translocation and rotary motion in the Escherichia coli F1Fo ATP synthase is poorly understood. In the membrane-bound Fo sector of the enzyme, H+ binding and release occur at Asp-61 in the middle of the second transmembrane helix (TMH) of subunit c. Protons are thought to reach Asp-61 at the center of the membrane via aqueous channels formed at least in part by one or more of the five TMHs of subunit a. Aqueous access pathways have previously been mapped to surfaces of aTMH4. Here we have substituted Cys into the second and fifth TMHs of subunit a and carried out chemical modification with Ag+ and N-ethylmaleimide to define the aqueous accessibility of residues along these helices. Access to cAsp-61 at the center of the membrane may be mediated in part by Ag+-sensitive residues 248, 249, 251, and 252 in aTMH5. From the periplasmic surface, aqueous access to cAsp-61 may be mediated by silver-sensitive residues 115, 116, 119, 120, 122, and 126 in aTMH2. The Ag+-sensitive residues in TMH2, -4, and -5 form a continuum extending from the periplasmic to the cytoplasmic side of the membrane. In an arrangement of helices supported by second-site revertant and crosslinking analyses, these residues cluster at the interior of a four-helix bundle formed by TMH2-5. The aqueous access pathways at the interior of subunit a may be gated by a swiveling of helices in this bundle, alternately exposing cytoplasmic and periplasmic half channels to cAsp-61 during the H+ transport cycle.