Animal Mitochondrial DNA Replication.

Recent advances in the field of mitochondrial DNA (mtDNA) replication highlight the diversity of both the mechanisms utilized and the structural and functional organization of the proteins at mtDNA replication fork, despite the relative simplicity of the animal mtDNA genome. DNA polymerase γ, mtDNA helicase and mitochondrial single-stranded DNA-binding protein-the key replisome proteins, have evolved distinct structural features and biochemical properties. These appear to be correlated with mtDNA genomic features in different metazoan taxa and with their modes of DNA replication, although substantial integrative research is warranted to establish firmly these links. To date, several modes of mtDNA replication have been described for animals: rolling circle, theta, strand-displacement, and RITOLS/bootlace. Resolution of a continuing controversy relevant to mtDNA replication in mammals/vertebrates will have a direct impact on the mechanistic interpretation of mtDNA-related human diseases. Here we review these subjects, integrating earlier and recent data to provide a perspective on the major challenges for future research.

Patient- and physician-level determinants of blood pressure response to treatment in normal weight and overweight patients (the PREVIEW study).

BACKGROUND AND AIMS: Obesity combined with hypertension places patients at greater risk for target-organ damage and cardiovascular disease. The purpose of this secondary analysis was to identify physician- and patient-levels determinants of blood pressure (BP) values and predictors of uncontrolled BP through subgroup analysis by body mass index (BMI). METHODS AND RESULTS: We conducted a subgroup analysis of 3006 patients with High-BMI (BMI >25 kg/m(2); n=2124) and Normal-BMI (BMI<25 kg/m(2); n=882) treated by 504 physicians and enrolled in PREVIEW, a Belgian prospective, multi-center, pharmaco-epidemiological study of 90-day second-line treatment with valsartan. Physician- and patient-level determinants of BP values and BP control were identified by means of hierarchical linear and logistic regression. Blood pressure values and control after 90 days of treatment were consistently lower for the High-BMI group. The 25.5% of variance in 90-day systolic and 28.3% of the variance in 90-day diastolic BP were attributable to physician-level determinants for the High-BMI group; versus 27.3% and 29.8% for the Normal-BMI group (ICC=0.273 and 0.298, respectively). Determinants of 90-day BP values and predictors of uncontrolled BP varied considerably by BMI status. CONCLUSION: Several common and unique patient- and physician-level determinants of BP values and control were identified for the High-BMI and Normal-BMI groups. These findings highlight the need for differentiating healthcare interventions to account for patient and physician variables, particularly with respect to effective BP management in vulnerable populations.