RESUMEN
BACKGROUND: When compared to the general US working population, physicians are more likely to experience burnout and dissatisfaction with work-life balance. Our aim was to examine the association of objectively-measured sleep, activity, call load, and gender with reported resident burnout and wellness factors. METHODS: Residents were recruited to wear activity tracker bands and complete interval blinded surveys. RESULTS: Of the 30 residents recruited, 28 (93%) completed the study. Based on survey results, residents who reported high amounts of call reported equivalent levels of wellness factors to those who reported low call loads. There was no association between amount of call on training satisfaction, emotional exhaustion, self-reported burnout, or sleep quality. Analysis of sleep tracker data showed that there was no significant association with time in bed, time asleep, times awakened or sleep latency and call load or self-reported burnout. Female gender, however, was found to be associated with self-reported burnout. No significant associations were found between objectively-measured activity and burnout. CONCLUSIONS: Based on the results of our study, there was no association with burnout and objectively-measured sleep, call volume, or activity. Increased call demands had no negative association with training satisfaction or professional fulfillment. This would suggest that more hours worked does not necessarily equate to increased burnout.
Asunto(s)
Agotamiento Profesional/psicología , Satisfacción en el Trabajo , Médicos , Sueño/fisiología , Adulto , Agotamiento Profesional/etiología , Estudios de Cohortes , Femenino , Humanos , Internado y Residencia , Masculino , Médicos/psicología , Responsabilidad Social , Estados Unidos/epidemiología , Tolerancia al Trabajo ProgramadoRESUMEN
MicroRNAs (miRNAs) are important players of post-transcriptional gene regulation. Individual miRNAs can target multiple mRNAs and a single mRNA can be targeted by many miRNAs. We hypothesized that miRNAs select and regulate their targets based on their own expression levels, those of their target mRNAs and triggered feedback loops. We studied the effects of varying concentrations of let-7a-7f and the miR-17-92 cluster plasmids on the reporter genes carrying either DICER- or cMYC -3'UTR in Huh-7 cells. We showed that let-7 significantly downregulated expression of DICER 3'UTR reporter at lower concentrations, but selectively downregulated expression of a cMYC 3'UTR reporter at higher dose. This miRNA dose-dependent target selection was also confirmed in other target genes, including CCND1, CDKN1 and E2F1. After overexpressing let-7a-7f or the miR-17-92 clusters at wide-ranging doses, the target genes displayed a nonlinear correlation to the transfected miRNA. Further, by comparing the expression levels of let-7a and miR-17-5p, along with their selected target genes in 3 different cell lines, we found that the knockdown dose of each miRNA was directly related to their baseline expression level, that of the target gene and feedback loops. These findings were supported by gene modulation studies using endogenous levels of miR-29, -1 and -206 and a luciferase reporter system in multiple cell lines. Finally, we determined that the miR-17-92 cluster affected cell viability in a dose-dependent manner. In conclusion, we have shown that miRNAs potentially select their targets in a dose-dependent and nonlinear fashion that affects biological function; and this represents a novel mechanism by which miRNAs orchestrate the finely tuned balance of cell function.
Asunto(s)
Regiones no Traducidas 3' , Retroalimentación Fisiológica , Regulación de la Expresión Génica , MicroARNs/genética , Línea Celular Tumoral , Supervivencia Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo , Genes Reporteros , Humanos , Luciferasas , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Largo no Codificante , Ribonucleasa III/genética , Ribonucleasa III/metabolismo , TransfecciónRESUMEN
Multichannel conduits have been developed for experimental peripheral nerve and spinal cord repair. We present a series of methods to characterize multichannel nerve tubes for properties of bending, deformation, swelling, and degradation and introduce a new method to test the permeability of multichannel nerve tubes from the rate of diffusion of different-sized fluorescent dextran molecules (10, 40, and 70 kDa). First, single-lumen nerve tubes made with different poly(lactic-co-glycolic acid) (PLGA) ratios (50:50, 75:25, and 85:15) were compared. One ratio (75:25 PLGA) was subsequently used to compare single-lumen and multichannel nerve tubes. Nerve tubes made with lower PLGA ratios were found to be more flexible than nerve tubes made with a higher PLGA ratio. For low ratios, however, swelling was also greater as a result of a faster rate of degradation. Multichannel structure did not interfere with the permeability of the tube; the rate of diffusion into multichannel 75:25 PLGA nerve tubes appeared to be even higher than that into single-lumen ones, but this was only significant for 70-kDa molecules. Also, multichannel 75:25 PLGA nerve tubes were more flexible and, at the same time, more resistant to deformation. However, swelling significantly decreased the total cross-sectional lumen area, especially in multichannel 75:25 PLGA nerve tubes. Permeability, bending, deformation, swelling, and degradation are important properties to characterize in the development of multichannel nerve tubes. The methods presented in this study can be used as a basis for optimizing these properties for future, possibly clinical, application.
