BackgroundOxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor that upregulates a battery of antioxidative genes and cytoprotective enzymes that constitute the cellular response to oxidative stress. Our previous studies have shown that disruption of Nrf2 in mice (Nrf2 −/−) causes increased susceptibility to pulmonary emphysema, asthma and sepsis due to increased oxidative stress and inflammation. Here we have tested the hypothesis that disruption of Nrf2 in mice causes increased atherosclerosis.Principal FindingsTo investigate the role of Nrf2 in the development of atherosclerosis, we crossed Nrf2 −/− mice with apoliporotein E-deficient (ApoE −/−) mice. ApoE −/− and ApoE −/− Nrf2 −/− mice were fed an atherogenic diet for 20 weeks, and plaque area was assessed in the aortas. Surprisingly, ApoE −/− Nrf2 −/− mice exhibited significantly smaller plaque area than ApoE −/− controls (11.5% vs 29.5%). This decrease in plaque area observed in ApoE −/− Nrf2 −/− mice was associated with a significant decrease in uptake of modified low density lipoproteins (AcLDL) by isolated macrophages from ApoE −/− Nrf2 −/− mice. Furthermore, atherosclerotic plaques and isolated macrophages from ApoE −/− Nrf2 −/− mice exhibited decreased expression of the scavenger receptor CD36.ConclusionsNrf2 is pro-atherogenic in mice, despite its antioxidative function. The net pro-atherogenic effect of Nrf2 may be mediated via positive regulation of CD36. Our data demonstrates that the potential effects of Nrf2-targeted therapies on cardiovascular disease need to be investigated.

Adenomyosis represents a unique pathophysiological condition in which normal-appearing endometrial mucosa resides within myometrium and is thus protected from menstrual shedding. The resulting ectopic presence of endometrial tissue composed of glands and stroma is thought to affect normal contractile function and peristalsis of uterine smooth muscle, causing menometrorrhagia, infertility, and adverse obstetric outcomes. Since the first description of adenomyosis more than 150 years ago, pathologists have studied this lesion by examining tissue specimens, and have proposed multiple explanations to account for its pathogenesis. However, as compared with endometriosis, progress of adenomyosis research has been, at best, incremental mainly due to the lack of standardized protocols in sampling tissue and a lack of consensus diagnostic criteria in pathology practice. Despite these limitations, recent advances in revealing the detailed anatomy and biology of eutopic endometrium offer an unprecedented opportunity to study this common but relatively understudied disorder. Here, we briefly summarize the pathological aspects of adenomyosis from an historical background, and discuss conventional morphology and recent tissue-based molecular studies with a special emphasis on elucidating its tissue of origin from a pathologist's perspective. We also discuss unmet needs in pathology studies that would be important for advancing adenomyosis research.

Objective: To determine whether in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A) is cost effective to achieve a live birth compared with IVF alone in fresh donor oocyte cycles. Design: Theoretical cost-effectiveness study. Setting: Not applicable. Patient(s): None. Intervention(s): Comparison between the cost of IVF with PGT-A vs. IVF alone to achieve a live birth. The model analyzed a hypothetical single fresh oocyte donor IVF cycle with PGT-A vs. IVF alone and followed the progression of a single embryo through the different decision nodes. Cost estimates assigned to each clinical event were based on data obtained from the literature and institutional costs. Main Outcome Measure(s): Cost per live birth.