PGC-1α4 gene expression is suppressed by the IL-6-MEK-ERK 1/2 MAPK signalling axis and altered by resistance exercise, obesity and muscle injury.

AIM: PGC-1α4 is a novel regulator of muscle hypertrophy; however, there is limited understanding of the regulation of its expression and role in many (patho)physiological conditions. Therefore, our purpose was to elicit signalling mechanisms regulating gene expression of Pgc1α4 and examine its response to (patho)physiological stimuli associated with altered muscle mass. METHODS: IL-6 knockout mice and pharmacological experiments in C2C12 myocytes were used to identify regulation of Pgc1α4 transcription. To examine Pgc1α4 gene expression in (patho)physiological conditions, obese and lean Zucker rats with/without resistance exercise (RE), ageing mice and muscle regeneration from injury were examined. RESULTS: In IL-6 knockout mice, Pgc1α4mRNA was ~sevenfold greater than wild type. In C2C12 cells, Pgc1α4mRNA was suppressed ~70% by IL-6. Suppression of Pgc1α4 by IL-6 was prevented by MEK-ERK-MAPK inhibition. RE led to ~260% greater Pgc1α4mRNA content in lean rats. However, obese Zucker rats exhibited ~270% greater Pgc1α4mRNA than lean, sedentary with no further augmentation by RE. No difference was seen in IL-6mRNA or ERK-MAPK phosphorylation in Zucker rats. Aged mice demonstrated ~50% lower Pgc1α4mRNA and ~fivefold greater ERK-MAPK phosphorylation than young despite unchanged Il-6mRNA. During muscle regeneration, Pgc1α4 content is ~30% and IL-6mRNA >threefold of uninjured controls 3 days following injury; at 5 days, Pgc1α4 was >twofold greater in injured mice with no difference in IL-6mRNA. CONCLUSION: Our findings reveal a novel mechanism suppressing Pgc1α4 gene expression via IL-6-ERK-MAPK and suggest this signalling axis may inhibit Pgc1α4 in some, but not all, (patho)physiological conditions.

Yield of the screening review of systems: a study on a general medical service.

STUDY OBJECTIVE: To determine the usefulness of screening reviews of the cardiopulmonary and gastrointestinal systems during medical admissions. DESIGN: Case series. SETTING: General internal medicine ward of a university hospital. PATIENTS: 550 consecutive medical patients were initially screened at admission. The authors excluded 265 patients with life-limiting medical conditions, and they studied 98 patients with no known cardiopulmonary disease and 207 patients with no known gastrointestinal disease. INTERVENTIONS: Positive responses to screening systems review questions were evaluated using a standardized testing algorithm. MAIN OUTCOME MEASURES: Numbers of new diagnoses; potential for patient benefit. MAIN RESULTS: The authors made 26 new diagnoses for 25 patients (95% confidence limits, 16 to 37 patients), two of whom may have gained years of life as a result. CONCLUSIONS: The absolute yield of the screening cardiopulmonary and gastrointestinal reviews of systems of 550 patients admitted to an internal medicine service of a university hospital was a new diagnosis in about 5% of patients. An estimate of the cost-effectiveness compares favorably with those of other accepted screening practices.

Standardized patient encounters. A method for teaching and evaluation.

The primary goal of medical education is to foster development of clinical competence in trainees at all levels. Variable clinical experience, inconsistent methods of instruction, and ambiguous evaluation criteria undermine this goal. Standardized patients, trained to consistently portray a wide variety of clinical cases, can help overcome many of these educational problems. This article describes the development and application of standardized patients throughout medical training at The University of Texas Medical Branch, Galveston, in the freshman interviewing course, the second-year physical diagnosis course, third-year clerkships, a fourth-year final exercise, and residency training. Development of this program is discussed in the context of a broader literature in medical education, and investigation of variables affecting standardized patient and student performance is reported. Future directions for use of standardized patients in monitoring and promoting the development of clinical competence are discussed.

Reliability and validity of an objective structured clinical examination for assessing the clinical performance of residents.

Clinical performance of residents should be assessed as reliably and validly as possible. This study investigated the reliability and validity of an objective structured clinical examination (OSCE) for assessing clinical performance of internal medicine residents. Residents were required to take a 17-patient OSCE in their first and second year. Reliability of the OSCE was 0.40. Validity studies indicated second-year students were significantly better than third-year students for five of six OSCE skill scores; first-year students were significantly better for three scores. Resident's scores for diagnosis, plan, and total significantly increased on their second OSCE. Generally faculty overall ratings of residents' clinical performance did not correlate with OSCE scores. American Board of Internal Medicine certifying examination scores were consistently positively correlated only with diagnosis. This 17-case OSCE is a feasible method for obtaining moderately reliable, valid data not available from other sources about the clinical performance of residents. More cases should be added to increase its reliability.

An objective measure of clinical performance.

Studies repeatedly have shown the clinical performance of students and residents to be less than expected by faculty. Because evaluation methods substantially influence education, poor performance can be improved with better clinical evaluation methods. This study evaluated a standardized method to measure clinical performance in which trained actual and simulated patients were organized in a multiple-station format for efficient testing of examinees on 17 cases in less than four hours. Specific checklists completed by patients and predetermined scoring protocols yielded reliable data and reduced faculty time. Data from 204 students in three clerkships were consistent with previous research showing case specificity and substantial case-to-case variability. As a group however, the students' overall total scores were very similar. This suggests that clinical education is inconsistent and that a profile of an examinee's performance is more accurate than a single overall score. Validity of this standardized clinical examination was supported by significant but moderate correlations with faculty ratings of ward performance and the medicine subtest of the National Board of Medical Examiners test, part II. Direct per-student costs were $21.00. This standardized objective examination of clinical skills is feasible for use in training programs and will provide reliable and valid data on clinical performance not available through typical methods.