Medical student and medical school teaching faculty perceptions of conflict of interest.

BACKGROUND: Attitudes towards conflict of interest (COI) and COI policy are shaped during medical school and influence both the education of medical students and their future medical practice. Understanding the current attitudes of medical students and medical school teaching faculty may provide insight into what is taught about COI and COI policy within the 'hidden' medical curriculum. Differences between medical student and medical school teaching faculty perceptions of COI and COI policy have not been compared in detail. The authors surveyed first year medical students and medical school teaching faculty at one academic medical center. RESULTS: The response rate was 98.7% (150/152) for students and 34.2% (69/202) for faculty. Students were less likely than faculty to agree that lecturers should disclose COI to any learners (4.06 vs. 4.31, p = 0.01), but more likely to agree that COI disclosure decreases the presentation of biased material (3.80 vs. 3.21, p < 0.001). Student and faculty responses for all other questions were not different. Many of these responses suggest student and faculty support for stronger COI policy at academic medical centers. CONCLUSIONS: Students and faculty perceptions regarding COI and COI policy are largely similar, but differ in terms of the perceived effectiveness of COI disclosure. This study also suggests that medical students and medical school teaching faculty support for stronger COI policy at academic medical centers.

Youth Football Injuries: A Prospective Cohort.

BACKGROUND: There are approximately 2.8 million youth football players between the ages of 7 and 14 years in the United States. Rates of injury in this population are poorly described. Recent studies have reported injury rates between 2.3% and 30.4% per season and between 8.5 and 43 per 1000 exposures. HYPOTHESIS: Youth flag football has a lower injury rate than youth tackle football. The concussion rates in flag football are lower than in tackle football. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Three large youth (grades 2-7) football leagues with a total of 3794 players were enrolled. Research personnel partnered with the leagues to provide electronic attendance and injury reporting systems. Researchers had access to deidentified player data and injury information. Injury rates for both the tackle and flag leagues were calculated and compared using Poisson regression with a log link. The probability an injury was severe and an injury resulted in a concussion were modeled using logistic regression. For these 2 responses, best subset model selection was performed, and the model with the minimum Akaike information criterion value was chosen as best. Kaplan-Meier curves were examined to compare time loss due to injury for various subgroups of the population. Finally, time loss was modeled using Cox proportional hazards regression models. RESULTS: A total of 46,416 exposures and 128 injuries were reported. The mean age at injury was 10.64 years. The hazard ratio for tackle football (compared with flag football) was 0.45 (95% CI, 0.25-0.80; P = .0065). The rate of severe injuries per exposure for tackle football was 1.1 (95% CI, 0.33-3.4; P = .93) times that of the flag league. The rate for concussions in tackle football per exposure was 0.51 (95% CI, 0.16-1.7; P = .27) times that of the flag league. CONCLUSION: Injury is more likely to occur in youth flag football than in youth tackle football. Severe injuries and concussions were not significantly different between leagues. Concussion was more likely to occur during games than during practice. Players in the sixth or seventh grade were more likely to suffer a concussion than were younger players.

Dual specificity phosphatase 15 regulates Erk activation in Schwann cells.

Schwann cells and oligodendrocytes are the myelinating cells of the peripheral and central nervous system, respectively. Despite having different myelin components and different transcription factors driving their terminal differentiation there are shared molecular mechanisms between the two. Sox10 is one common transcription factor required for several steps in development of myelinating glia. However, other factors are divergent as Schwann cells need the transcription factor early growth response 2/Krox20 and oligodendrocytes require Myrf. Likewise, some signaling pathways, like the Erk1/2 kinases, are necessary in both cell types for proper myelination. Nonetheless, the molecular mechanisms that control this shared signaling pathway in myelinating cells remain only partially characterized. The hypothesis of this study is that signaling pathways that are similarly regulated in both Schwann cells and oligodendrocytes play central roles in coordinating the differentiation of myelinating glia. To address this hypothesis, we have used genome-wide binding data to identify a relatively small set of genes that are similarly regulated by Sox10 in myelinating glia. We chose one such gene encoding Dual specificity phosphatase 15 (Dusp15) for further analysis in Schwann cell signaling. RNA interference and gene deletion by genome editing in cultured RT4 and primary Schwann cells showed Dusp15 is necessary for full activation of Erk1/2 phosphorylation. In addition, we show that Dusp15 represses expression of several myelin genes, including myelin basic protein. The data shown here support a mechanism by which early growth response 2 activates myelin genes, but also induces a negative feedback loop through Dusp15 to limit over-expression of myelin genes.

Patient-Reported Allergies Predict Worse Outcomes After Hip and Knee Arthroplasty: Results From a Prospective Cohort Study.

BACKGROUND: Retrospective analyses have demonstrated correlation between patient-reported allergies and negative outcomes after total joint arthroplasty. We sought to validate these observations in a prospective cohort. METHODS: One hundred forty-four patients undergoing total hip arthroplasty and 302 patients undergoing total knee arthroplasty were prospectively enrolled. Preoperatively, patients listed their allergies and completed the Medical Outcomes Study Short Form 36 (SF-36) and the Charlson Comorbidity Index (CCI) Questionnaire. At a mean of 17 months (range 12-25 months) postoperatively, SF-36, CCI, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were obtained by telephone survey. Regression analysis was used to determine the strength of correlation between patient age, comorbidity burden, and number of allergies and outcome measurements. RESULTS: In 446 patients, 273 reported at least 1 allergy. The number of allergies reported ranged from 0 to 33. Penicillin or its derivative was the most frequently reported allergy followed by sulfa, environmental allergen, and narcotic pain medication. Patients reporting at least 1 allergy had a significantly lower postoperative SF-36 Physical Component Score compared to those reporting no allergies (51.3 vs 49.4, P = .01). The SF-36 postoperative Mental Component Score was no different between groups. Multivariate regression analysis showed that age and patient reported allergies, but not comorbidities, were independently associated with worse postoperative SF-36 Physical Component Summary (PCS) and WOMAC score. Patients with allergies experienced the same improvement in SF-36 PCS as those without an allergy. Comorbidities did not correlate with patient-reported function postoperatively. CONCLUSION: Patients who report allergies have lower postoperative outcome scores but may experience the same increment in improvement after total joint arthroplasty.

Small Molecules Revealed in a Screen Targeting Epithelial Scattering Are Inhibitors of Microtubule Polymerization.

Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in the detachment of cell-cell junctions and initiation of cell migration. Instead of coordinating collective cell behavior within a tissue, cells become solitary and have few cell-cell interactions. Since epithelial scattering is recapitulated in cancer progression and since HGF signaling drives cancer metastasis in many cases, inhibitors of HGF signaling have been proposed to act as anticancer agents. We previously sought to better understand critical components required for HGF-induced epithelial scattering by performing a forward chemical genetics screen, which resulted in the identification of compounds with no previously reported biological activity that we report here. In efforts to determine the mechanism of these compounds, we find that many compounds have broad antiproliferative effects on cancer cell lines by arrest of cell division in G2/M with minimal induction of apoptosis. This effect is reminiscent of microtubule-targeting agents, and we find that several of these scaffolds directly inhibit microtubule polymerization. Compounds are assessed for their toxicity and pharmacokinetics in vivo. The identification of novel small-molecule inhibitors of microtubule polymerization highlights the role of the microtubule cytoskeleton in HGF-induced epithelial scattering.

Spectroscopic evidence for Fe(II)-Fe(III) electron transfer at clay mineral edge and basal sites.

Despite the importance of Fe redox cycling in clay minerals, the mechanism and location of electron transfer remain unclear. More specifically, there is some controversy whether electron transfer can occur through both basal and edge surfaces. Here we used Mössbauer spectroscopy combined with selective chemical extractions to study electron transfer from Fe(II) sorbed to basal planes and edge OH-groups of clay mineral NAu-1. Fe(II) sorbed predominantly to basal planes at pH values below 6.0 and to edge OH-groups at pH value 7.5. Significant electron transfer occurred from edge OH-group bound Fe(II) at pH 7.5, whereas electron transfer from basal plane-sorbed Fe(II) to structural Fe(III) in clay mineral NAu-1 at pH 4.0 and 6.0 occurred but to a much lower extent than from edge-bound Fe(II). Mössbauer hyperfine parameters for Fe(II)-reacted NAu-1 at pH 7.5 were consistent with structural Fe(II), whereas values found at pH 4.0 and 6.0 were indicative of binding environments similar to basal plane-sorbed Fe(II). Reference experiments with Fe-free synthetic montmorillonite SYn-1 provided supporting evidence for the assignment of the hyperfine parameters to Fe(II) bound to basal planes and edge OH-groups. Our findings demonstrate that electron transfer to structural Fe in clay minerals can occur from Fe(II) sorbed to both basal planes and edge OH-groups. These findings require us to reassess the mechanisms of abiotic and microbial Fe reduction in clay minerals as well as the importance of Fe-bearing clay minerals as a renewable source of redox equivalents in subsurface environments.