Purpose of reviewIn recent years, new studies have investigated the role and influence of sleep on female fertility and early pregnancy outcomes, providing a growing body of knowledge demonstrating how regulation by sleep of hormones are important to reproduction, and how disruptions in sleep, circadian rhythms, and genes regulating circadian rhythmicity can negatively impact fertility and early pregnancy outcomes. This review aims to summarize the most recent research on the relationship among circadian rhythms, fertility, and early pregnancy outcomes in women, and to explore possible fertility interventions. Recent findingsRecent studies have found altered levels of FSH, LH, and prolactin with sleep disturbance or circadian dysrhythmia. Disruption of circadian rhythms in the form of shift work, jet lag, and daylight savings time changes have been associated with poorer fertility and early pregnancy outcomes. Alterations in the expression of circadian rhythm-regulating circadian locomotor output cycles kaput (CLOCK) genes have been associated with decreased fertility and increased rates of miscarriage. SummaryOverall, undisrupted sleep and circadian rhythmicity appear to optimize fertility and early pregnancy outcomes and may play an important role in the success of fertility treatment.

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ImportanceSocially responsible surgery (SRS) integrates surgery and public health, providing a framework for research, advocacy, education, and clinical practice to address the social barriers of health that decrease surgical access and worsen surgical outcomes in underserved patient populations. These patients face disparities in both health and in health care, which can be effectively addressed by surgeons in collaboration with allied health professionals.ObjectiveWe reviewed the current state of surgical access and outcomes of underserved populations in American rural communities, American urban communities, and in low- and middle-income countries.Evidence reviewWe searched PubMed using standardized search terms and reviewed the reference lists of highly relevant articles. We reviewed the reports of two recent global surgery commissions.ConclusionThere is an opportunity for scholarship in rural surgery, urban surgery, and global surgery to be unified under the concept of SRS. The burden of surgical disease and the challenges to management demonstrate that achieving optimal health outcomes requires more than excellent perioperative care. Surgeons can and should regularly address the social determinants of health experienced by their patients. Formalized research and training opportunities are needed to meet the growing enthusiasm among surgeons and trainees to develop their practice as socially responsible surgeons.

Metabolic phenotype can be affected by multiple factors, including allelic variation and interactions with inhibitors. Human CYP2D6 is responsible for approximately 20% of cytochrome P450-mediated drug metabolism but consists of more than 100 known variants; several variants are commonly found in the population, whereas others are quite rare. Four CYP2D6 allelic variants-three with a series of mutations distal to the active site (*34, *17-2, *17-3) and one ultra-metabolizer with mutations near the active site (*53), along with reference *1 and an active site mutant of *1 (Thr309Ala)-were expressed, purified, and studied for interactions with the typical substrates dextromethorphan and bufuralol and the inactivator SCH 66712. We found that *34, *17-2, and *17-3 displayed reduced enzyme activity and NADPH coupling while producing the same metabolites as *1, suggesting a possible role for Arg296 in NADPH coupling. A higher-activity variant, *53, displayed similar NADPH coupling to *1 but was less susceptible to inactivation by SCH 66712. The Thr309Ala mutant showed similar activity to that of *1 but with greatly reduced NADPH coupling. Overall, these results suggest that kinetic and metabolic analysis of individual CYP2D6 variants is required to understand their possible contributions to variable drug response and the complexity of personalized medicine.