Citations

To clarify effects of diet and body weight on prostate cancer development, three studies were undertaken using the TRAMP mouse model of this disease. In the first experiment, obesity was induced by injection of gold thioglucose (GTG). Age of prostate tumor detection (~33 wk) and death (~43 wk) was not significantly different among the groups. In the second study, TRAMP-C2 cells were injected into syngeneic C57BL6 mice and tumor progression was evaluated in mice fed either high-fat or low-fat diets. The high fat fed mice had larger tumors than did the low-fat fed mice. In the third study, tumor development was followed in TRAMP mice fed a high fat diet from 6 weeks of age. There were no significant effects of body weight status or diet on tumor development among the groups. When the tumors were examined for the neuroendocrine marker synaptophysin, there was no correlation with either body weight or diet. However, there was a significant correlation of the expression of synaptophysin with earlier age to tumor detection and death. In summary, TRAMP-C2 cells grew faster when the mice were fed a high-fat diet. Further synaptophysin may be a marker of poor prognosis independent of weight and diet.

A 47-year-old Hispanic woman developed a chronically obstructed left kidney, due to a long-segment ureteric stricture deemed not amenable to reimplantation, following left ovarian cyst excision in 2004. Therefore, a ureteral stent requiring exchange every 3 months was necessary, due to hydronephrosis, recurrent urosepsis, chronic pain, and a poor quality of life. Her medical history was complicated by hypertension, poorly controlled diabetes mellitus, and microalbuminuria, suggesting early diabetic nephropathy. A left nephrectomy was recommended. This was deferred, due to concern for progressive kidney failure associated with her comorbidities. A radionuclide Tc-99m MAG3 renal scan revealed differential perfusion as follows: 44% left kidney and 56% right kidney, with symmetrical uptake on the renogram phase and delayed excretion on the left, which were correctted following furosemide administration. A left ureteronephrectomy with autotransplantation of the left kidney and ureteroneocystostomy was performed in 2009. Since then, the patient has experienced no further complications or need for invasive procedures, with excellent diabetic control and stable renal function (eGFR > 60 mL/min/1.73 m2). This technique is seldom employed in the surgical management of complex ureteral injuries, but may be an alternative for appropriate cases.

Improving professional attitudes and behaviors requires critical self reflection. Research on reflection is necessary to understand professionalism among medical students. The aims of this prospective validation study at the Mayo Medical School and Cleveland Clinic Lerner College of Medicine were: (1) to develop and validate a new instrument for measuring reflection on professionalism, and (2) determine whether learner variables are associated with reflection on the gross anatomy experience. An instrument for assessing reflections on gross anatomy, which was comprised of 12 items structured on five‐point scales, was developed. Factor analysis revealed a three‐dimensional model including low reflection (four items), moderate reflection (five items), and high reflection (three items). Item mean scores ranged from 3.05 to 4.50. The overall mean for all 12 items was 3.91 (SD = 0.52). Internal consistency reliability (Cronbach's α) was satisfactory for individual factors and overall (Factor 1 α = 0.78; Factor 2 α = 0.69; Factor 3 α = 0.70; Overall α = 0.75). Simple linear regression analysis indicated that reflection scores were negatively associated with teamwork peer scores ( P = 0.018). The authors report the first validated measurement of medical student reflection on professionalism in gross anatomy. Critical reflection is a recognized component of professionalism and may be important for behavior change. This instrument may be used in future research on professionalism among medical students. Anat Sci Educ 6: 232–238. © 2012 American Association of Anatomists.

The mitotic checkpoint protein Bub1 is essential for embryogenesis and survival of proliferating cells, and bidirectional deviations from its normal level of expression cause chromosome missegregation, aneuploidy, and cancer predisposition in mice. To provide insight into the physiological significance of this critical mitotic regulator at a modular level, we generated Bub1 mutant mice that lack kinase activity using a knockin gene-targeting approach that preserves normal protein abundance. In this paper, we uncover that Bub1 kinase activity integrates attachment error correction and mitotic checkpoint signaling by controlling the localization and activity of Aurora B kinase through phosphorylation of histone H2A at threonine 121. Strikingly, despite substantial chromosome segregation errors and aneuploidization, mice deficient for Bub1 kinase activity do not exhibit increased susceptibility to spontaneous or carcinogen-induced tumorigenesis. These findings provide a unique example of a modular mitotic activity orchestrating two distinct networks that safeguard against whole chromosome instability and reveal the differential importance of distinct aneuploidy-causing Bub1 defects in tumor suppression.

Increases in weight have been associated with corresponding increases in insulin resistance in postmenopausal women. Although estrogen has significant impact on body fat and body fat distribution, the cellular mechanisms that influence this process are not yet known. We measured adipose tissue fatty acid (FA) storage and FA storage factors in 12 premenopausal and 11 postmenopausal women matched for age and body composition. Postmenopausal women had lower postprandial FA oxidation (indirect calorimetry), greater meal FA, and direct free FA (FFA) storage than premenopausal women, including two-fold greater meal FA storage in the femoral depot. The fed/fasted activities of adipose tissue lipoprotein lipase were not significantly different between premenopausal and postmenopausal women. In contrast, adipocyte acyl-CoA synthetase and diacylglycerol acyltransferase activities in postmenopausal women were significantly upregulated and were positively correlated with direct FFA storage rates. These findings suggest that the propensity for subcutaneous adipose tissue FA storage is increased in postmenopausal women, more so from changes in adipocyte FA storage factors than from adipose tissue lipoprotein lipase activity. Our results suggest that female sex steroids, most likely estrogen, have important effects on adipose tissue FA storage and FA oxidation that could promote fat gain in postmenopausal women.

Background. Repetitive facilitative exercise (RFE), a combination of high repetition rate and neurofacilitation, is a recently developed approach to the rehabilitation of stroke-related limb impairment. Preliminary investigations have been encouraging, but a randomized controlled evaluation has yet to be performed. Objectives. To compare the efficacy of RFE with that of conventional rehabilitation in adults with subacute stroke. Methods. A total of 52 adults with stroke-related upper-limb impairment (Brunnstrom stage ≥III) of 3 to 13 weeks’ duration participated in this randomized, controlled, observer-blinded trial. Participants were randomized into 2 groups and received treatment on a 4-week, 40 min/d, 5 d/wk schedule. Those assigned to RFE received 100 standardized movements of at least 5 joints of their affected upper extremity, whereas those in the control group participated in a conventional upper-extremity rehabilitation program. Primary and secondary outcomes (improvement in group Action Research Arm Test [ARAT] and Fugl-Meyer Arm [FMA] scores, respectively) were assessed at the end of training. Results. In all, 49 participants (26 receiving RFE) completed the trial. ARAT and FMA scores at baseline were 19 ± 21 and 39 ± 21 (mean ± standard deviation). Evaluation at the trial’s completion revealed significantly larger improvements in the RFE group than in the control group in both ARAT ( F = 7.52; P = .009) and FMA ( F = 5.98; P = .019) scores. Conclusions. These findings suggest that RFE may be more effective than conventional rehabilitation in lessening impairment and improving upper-limb motor function during the subacute phase of stroke.