Critical appraisal of continuing medical education in the rheumatic diseases for primary care physicians

Objective. To critically appraise evidence of the effectiveness of continuing medical education (CME) in rheumatic diseases for primary care physicians. Methods. Three physicians independently applied preset criteria to evaluated CME interventions published between January 1966 and August 1993. Results. Eight of 166 articles identified were critically appraised, 7 of which had positive results. Marked heterogeneity in educational interventions, evaluative methods, and outcomes was noted. Conclusion. Despite generally positive results, weak methodology precludes drawing firm conclusions about the effectiveness of CME in rheumatic diseases.     

Prenatal hypoxia may aggravate the cognitive impairment and Alzheimer’s disease neuropathology in APP/PS1 transgenic mice

Most cases of Alzheimer's disease (AD) arise through interactions between genetic and environmental factors. It is believed that hypoxia is an important environmental factor influencing the development of AD. Our group has previously demonstrated that hypoxia increased β-amyloid (Aβ) generation in aged AD mice. Here, we further investigate the pathological role of prenatal hypoxia in AD. We exposed the pregnant APP^Swe/PS1^A246E transgenic mice to high-altitude hypoxia in a hypobaric chamber during days 7–20 of gestation. We found that prenatal hypoxic mice exhibited a remarkable deficit in spatial learning and memory and a significant decrease in synapses. We also documented a significantly higher level of amyloid precursor protein, lower level of the Aβ-degrading enzyme neprilysin, and increased Aβ accumulation in the brain of prenatal hypoxic mice. Finally, we demonstrated striking neuropathologic changes in prenatal hypoxic AD mice, showing increased phosphorylation of tau, decreased hypoxia-induced factor, and enhanced activation of astrocytes and microglia. These data suggest that although the characteristic features of AD appear later in life, hypoxemia in the prenatal stage may contribute to the pathogenesis of the disease, supporting the notion that environmental factors can trigger or aggravate AD.     

International medical graduates (IMGs) needs assessment study: comparison between current IMG trainees and program directors

Background  

International Medical Graduates (IMGs) training within the Canadian medical education system face unique difficulties. The purpose of this study was to explore the challenges IMGs encounter from the perspective of trainees and their Program Directors.     

The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine

Mitochondrial DNA is replicated and repaired by DNA polymerase gamma (pol gamma), encoded by the POLG gene. The Y955C substitution in POLG leads to autosomal dominant progressive external ophthalmoplegia (PEO) with other severe phenotypes. PEO patients with this mutation can further develop parkinsonism or premature ovarian failure. Mouse and yeast models with this mutation show enhanced amounts of oxidative lesions and increased mtDNA damage. In DNA pol gamma, Tyr955 plays a critical role in catalysis and high fidelity DNA synthesis. 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) is one of the most common oxidative lesions in DNA and can promote transversion mutations. Mitochondria are thought to be a major source of endogenous reactive oxygen species that can react with dG to form 8-oxo-dG as one of the more common products. DNA polymerases can mitigate mutagenesis by 8-oxo-dG through allosteric interactions from amino acid side chains, which limit the anti-conformation of the 8-oxo-dG template base during translesion DNA synthesis. Here, we show that the Y955C pol gamma displays relaxed discrimination when either incorporating 8-oxo-dGTP or translesion synthesis opposite 8-oxo-dG. Molecular modeling and biochemical analysis suggest that this residue, Tyr955, in conjunction with Phe961 helps attenuate the anti-conformation in human pol gamma for error free bypass of 8-oxo-dG and substitution to Cys allows the mutagenic syn conformation. Collectively, these results offer a biochemical link between the observed oxidative stress in model systems and parkinsonism in patients, suggesting that patients harboring the Y955C POLG mutation may undergo enhanced oxidative stress and DNA mutagenesis.     

Characterizing Short-Term Outcomes Following Surgery for Rectal Cancer: the Role of Race and Insurance Status

Background

There is a paucity of data demonstrating the effect race and insurance status have on postoperative outcomes for patients with rectal cancer. We evaluated factors impacting short-term outcomes following rectal cancer surgery.

Design

Patients who underwent surgery for rectal cancer using the University Health System Consortium database from 2011 to 2012 were studied. Univariate and multivariable analyses were used to identify patient related risk factors for 30-day outcomes after proctectomy: complication rate, 30-day readmission, ICU stay, and length of hospital stay (LOS).

Results

A total of 9272 proctectomies were identified in this cohort. After adjustment for potential confounders, black patients were more likely to have 30-day readmissions (OR 1.51, 95 % CI 1.26–1.81), ICU stays (OR 1.25, 95 % CI 1.03–1.51), and longer LOS (+1.67 days, 95 % CI 1.21–2.13) when compared to whites. Compared to those with private insurance, patients with public or military insurance or who were self-pay had a higher likelihood of having postoperative complications.

Conclusions

In patients who undergo elective proctectomy for rectal cancer, non-white and non-privately insured status are associated with significantly worse short-term outcomes. Further studies are needed to determine the implications with respect to receipt of adjuvant therapy and survival.