Comparison of zebrafish in vitro and in vivo developmental toxicity assessments of perfluoroalkyl acids (PFAAs).

Perfluoroalkyl acids (PFAAs) are persistent environmental contaminants that are associated with various adverse health outcomes. Perfluorooctanoic acid (PFOA) is one of the most prominently detected PFAAs in the environment, which is now replaced with shorter chain carbon compounds including perfluorohexanoic acid (PFHxA) and perfluorobutyric acid (PFBA). The aim of this study was to compare the toxicity of four PFAAs as a function of chain length and head group (carboxylate versus sulfonate) with in vitro and in vivo zebrafish assessments, which were subsequently compared to other cell and aquatic models. Mortality rate increased with chain length (PFOA > PFHxA ≫ PFBA) in both whole embryo/larvae and embryonic cell models. The sulfonate group enhanced toxicity with perfluorobutane sulfonate (PFBS) showing higher toxicity than PFBA and PFHxA in both larvae and cells. Toxicity trends were similar among different aquatic models, but sensitivities varied. Discrepancies with other zebrafish studies were confirmed to be associated with a lack of neutralization of acidic pH of dosing solutions in these other investigations, demonstrating the need for rigor in reporting pH of exposure solutions in all experiments. The zebrafish embryonic cell line was also found to be similar to most other cell lines regardless of exposure length. Overall, results agree with findings in other cell lines and organisms where longer chain length and sulfonate group increase toxicity, except in investigations not neutralizing the exposure solutions for these acidic compounds.

Misrepresentation in multidisciplinary pain medicine fellowship applications to a single academic program.

BACKGROUND AND OBJECTIVES: Publication misrepresentation by residency applicants has been well documented, but fewer studies have investigated it in fellowship applicants, specifically in pain medicine. We therefore sought to evaluate the demographics of pain medicine fellowship applicants and the type, number, and accuracy of referenced publications they reported. METHODS: Applications to the Multidisciplinary Pain Medicine fellowship program in the Mayo School of Graduate Medical Education, Rochester, Minnesota were reviewed for three consecutive academic years (2009-2012). Demographic information and publications claimed by applicants were compiled, and publications were scrutinized by a medical librarian for accuracy. RESULTS: Over a 3-year period, 179 fellowship applications were received. Of the 179 applicants, more than half (106 [59%]) listed at least one publication. Of 324 listed publications, 263 were verifiable; of these, 14 (5.3%) were deemed fraudulent, and six (2.3%) contained an inaccuracy possibly conferring a competitive advantage. In our small sample size, we found no difference in the rate of publications or in the accuracy of listed publications across subspecialties, or between US medical graduates and international medical graduates. CONCLUSIONS: The lack of national data, specifically on applicant misrepresentation, due to the heretofore absence of a universal application process or match, impedes assessment of the extent to which these findings are representative of the national applicant pool. We observed notable trends (few female applicants; numerous international medical graduate applicants) different from those reported by other specialties. Despite the low rate (5.3%) of fraudulent publications, fellowship program directors and selection committees should be aware of this possibility to ensure selection of fellows with the highest degree of professional and ethical integrity.

Assessment of unique behavioral, morphological, and molecular alterations in the comparative developmental toxicity profiles of PFOA, PFHxA, and PFBA using the zebrafish model system.

Perfluoroalkyl substances (PFAS) are a class of synthetic chemicals that are persistent in the environment. Due to adverse health outcomes associated with longer chain PFAS, shorter chain chemicals were used as replacements, but developmental toxicity assessments of the shorter chain chemicals are limited. Toxicity of three perfluoroalkyl acids (PFAAs) [perfluorooctanoic acid (PFOA), composed of 8 carbon (C8), perfluorohexanoic acid (PFHxA, C6), and perfluorobutanoic acid (PFBA, C4)] was compared in developing zebrafish (Danio rerio). LC50s at 120 h post fertilization (hpf) assessed potency of each PFAA by exposing developing zebrafish (1-120 hpf) to range of concentrations. Zebrafish were then exposed to sublethal concentrations (0.4-4000 ppb, µg/L) throughout embryogenesis (1-72 hpf). Effects of the embryonic exposure on locomotor activities was completed with the visual motor response test at 120 hpf. At 72 hpf, morphological changes (total body length, head length, head width) and transcriptome profiles to compare altered molecular and disease pathways were determined. The LC50 ranking followed trend as expected based on chain length. PFOA caused hyperactivity and PFBA hypoactivity, while PFHxA did not change behavior. PFOA, PFHxA, and PFBA caused morphological and transcriptomic alterations that were unique for each chemical and were concentration-dependent indicating different toxicity mechanisms. Cancer was a top disease for PFOA and FXR/RXR activation was a top canonical pathway for PFBA. Furthermore, comparison of altered biological and molecular pathways in zebrafish exposed to PFOA matched findings reported in prior epidemiological studies and other animal models, supporting the predictive value of the transcriptome approach and for predicting adverse health outcomes associated with PFHxA or PFBA exposure.

Comparison of trauma mortality and estimated cancer mortality from computed tomography during initial evaluation of intermediate-risk trauma patients.

BACKGROUND: Computed tomography (CT) is the primary source of nontherapeutic medical radiation exposure. Radiation exposure is associated with an increased risk of cancer mortality. Although the risk of cancer mortality is negligible in comparison with that of trauma mortality in high-risk patients, the balance of risk versus benefit in patients with less severe mechanisms of injury is unknown. METHODS: This observational cohort study using a trauma center registry included blunt trauma patients prospectively triaged to an intermediate risk group (level II). Radiation dose was calculated using average dosage for each CT scan. Age-adjusted attributable radiation risk for cancer mortality was calculated using Biological Effects of Ionizing Radiation VII data. RESULTS: Six hundred forty-two level II trauma patients were analyzed, with a mean age of 43.8 years and a median Injury Severity Score of 8. Patients received a median radiation effective dose of 24.7 mSv in the first 24 hours of medical evaluation. Higher Injury Severity Score was associated with greater total radiation dose. Of the four deaths, all were 80 years or older with intracranial injuries. The estimated risk of cancer death attributable to CT exposure was 0.1%. CONCLUSIONS: The risk of mortality from trauma is six times higher than the estimated risk of radiation-induced cancer mortality in intermediate level trauma patients. The mortality due to trauma is greatest in older patients, suggesting lower clinical suspicion is needed to warrant CT studies in this population. Efforts to reduce radiation exposure to trauma patients should focus on young patients with minor injuries.

Assessment of Student Perspectives on Improving Wellness in Medical School: Qualitative Results from a Cross-Sectional Survey of Medical Students in Florida.

PURPOSE: Helping medical students maintain wellbeing has become an important concern, as many medical students report a decline in their mental health during the course of their training. To improve students' wellbeing, some schools have implemented wellness programs into their curricula. While there is growing research about the effectiveness of these programs, little is known about what medical students themselves desire to support their wellbeing. This study aimed to assess medical student perspectives regarding the most effective ways to promote wellness during medical school. PARTICIPANTS AND METHODS: To address this gap in the literature, a survey was administered to medical students at the nine medical schools in the state of Florida. Participants included 864 medical students, whose anonymous responses were analyzed descriptively as well as qualitatively to determine major themes. RESULTS: Students provided novel suggestions and recommendations, including ideas for curricular additions and changes, cultural changes within schools, promoting positive behaviors and extracurricular activities, and providing resources for students. CONCLUSION: Based on the participants' responses, it is evident that wellness is an important issue to medical students and, given the variety of suggestions, schools should strongly consider what wellness changes to implement and whether participation in them should be mandatory. The results of this study will be a resource to medical schools and educators who are considering curricular changes to address medical student wellbeing.