Objective To assess the relationship between unintended pregnancy and postpartum depression. Design Secondary analysis of data from a prospective pregnancy cohort. Setting The study was performed at the University of North Carolina prenatal care clinics. Population/Sample Pregnant women enrolled for prenatal care at the University of North Carolina Hospital Center. Methods Participants were questioned about pregnancy intention at 15–19 weeks gestational age, and classified as having an intended, mistimed, or unwanted pregnancy. They were evaluated for postpartum depression at three and twelve months postpartum. Log binomial regression was used to assess the relationship between unintended pregnancy and depression, controlling for confounding by demographic factors and reproductive history. Main Outcome Measures Depression at three and twelve months postpartum, defined as Edinburgh Postpartum Depression Scale (EPDS) score >13. Results Data were analyzed for 688 women at three months and 550 women at twelve months. Depression was more likely in women with unintended pregnancies at both three months (RR 2.1, 95% CI 1.2, 3.6) and twelve months (RR 3.6, 95% CI 1.8, 7.1). Using multivariable analysis adjusting for confounding by age, poverty and education level, women with unintended pregnancy were twice as likely to have postpartum depression at twelve months (RR 2.0, 95% CI 0.96, 4.0). Conclusion While many elements may contribute to postpartum depression, unintended pregnancy could also be a contributing factor. Women with unintended pregnancy may have an increased risk of depression up to one year postpartum.
Hsp90 is a dimeric ATPase responsible for the activation or maturation of a specific set of substrate proteins termed ‘clients’. This molecular chaperone acts in the context of a structurally dynamic and highly regulated cycle involving ATP, co-chaperone proteins and clients. Co-chaperone proteins regulate conformational transitions that may be impaired in mutant forms of Hsp90. We report here that the in vivo impairment of commonly studied Hsp90 variants harbouring the G313S or A587T mutation are exacerbated by the co-chaperone Hch1p. Deletion of HCH1, but not AHA1, mitigates the temperature sensitive phenotype and high sensitivity to Hsp90 inhibitor drugs observed in Saccharomyces cerevisiae that express either of these two Hsp90 variants. Moreover, the deletion of HCH1 results in high resistance to Hsp90 inhibitors in yeast that express wildtype Hsp90. Conversely, the overexpression of Hch1p greatly increases sensitivity to Hsp90 inhibition in yeast expressing wildtype Hsp90. We conclude that despite the similarity between these two co-chaperones, Hch1p and Aha1p regulate Hsp90 function in distinct ways and likely independent of their roles as ATPase stimulators. We further conclude that Hch1p plays a critical role in regulating Hsp90 inhibitor drug sensitivity in yeast.
Hsp90 is a dimeric molecular chaperone that is essential for the folding and activation of hundreds of client proteins. Co-chaperone proteins regulate the ATP-driven Hsp90 client activation cycle. Aha-type co-chaperones are the most potent stimulators of the Hsp90 ATPase activity but the relationship between ATPase regulation and in vivo activity is poorly understood. We report here that the most strongly conserved region of Aha-type co-chaperones, the N terminal NxNNWHW motif, modulates the apparent affinity of Hsp90 for nucleotide substrates. The ability of yeast Aha-type co-chaperones to act in vivo is ablated when the N terminal NxNNWHW motif is removed. This work suggests that nucleotide exchange during the Hsp90 functional cycle may be more important than rate of catalysis.
OBJECTIVE Abortion laws are proliferating in the United States, but little is known about their impact on abortion providers. In 2011, North Carolina instituted the Woman’s Right to Know (WRTK) Act, which mandates a 24-hour waiting period and counseling with state-prescribed information prior to abortion. We performed a qualitative study to explore the experiences of abortion providers practicing under this law. STUDY DESIGN We conducted semi-structured interviews with 31 abortion providers (17 physicians, 9 nurses, 1 physician assistant, 1 counselor, and 3 clinic administrators) in North Carolina. Interviews were audio-recorded and transcribed. Interview transcripts were analyzed using a grounded theory approach. We identified emergent themes, coded all transcripts, and developed a thematic framework. RESULTS Two major themes define provider experiences with the WRTK law: provider objections / challenges and provider adaptations. Most providers described the law in negative terms, though providers varied in the extent to which they were affected. Many providers described extensive alterations in clinic practices to balance compliance with minimization of burdens for patients. Providers indicated that biased language and inappropriate content in counseling can negatively impact the patient-physician relationship by interfering with trust and rapport. Most providers developed verbal strategies to mitigate the emotional impacts for patients. CONCLUSIONS Abortion providers in North Carolina perceive WRTK to have a negative impact on their clinical practice. Compliance is burdensome, and providers perceive potential harm to patients. The overall impact of WRTK is shaped by interaction between the requirements of the law and the adaptations providers make in order to comply with the law while continuing to provide comprehensive abortion care.
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