Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Physician career satisfaction within specialties

<p>Abstract</p> <p>Background</p> <p>Specialty-specific data on career satisfaction may be useful for understanding physician workforce trends and for counseling medical students about career options.</p> <p>Methods</p> <p>We analyzed cross-sectional data from 6,590 physicians (response rate, 53%) in Round 4 (2004-2005) of the Community Tracking Study Physician Survey. The dependent variable ranged from +1 to -1 and measured satisfaction and dissatisfaction with career. Forty-two specialties were analyzed with survey-adjusted linear regressions</p> <p>Results</p> <p>After adjusting for physician, practice, and community characteristics, the following specialties had significantly higher satisfaction levels than family medicine: pediatric emergency medicine (regression coefficient = 0.349); geriatric medicine (0.323); other pediatric subspecialties (0.270); neonatal/prenatal medicine (0.266); internal medicine and pediatrics (combined practice) (0.250); pediatrics (0.250); dermatology (0.249);and child and adolescent psychiatry (0.203). The following specialties had significantly lower satisfaction levels than family medicine: neurological surgery (-0.707); pulmonary critical care medicine (-0.273); nephrology (-0.206); and obstetrics and gynecology (-0.188). We also found satisfaction was significantly and positively related to income and employment in a medical school but negatively associated with more than 50 work-hours per-week, being a full-owner of the practice, greater reliance on managed care revenue, and uncontrollable lifestyle. We observed no statistically significant gender differences and no differences between African-Americans and whites.</p> <p>Conclusion</p> <p>Career satisfaction varied across specialties. A number of stakeholders will likely be interested in these findings including physicians in specialties that rank high and low and students contemplating specialty. Our findings regarding "less satisfied" specialties should elicit concern from residency directors and policy makers since they appear to be in critical areas of medicine.</p