Browsing by Author "Department of Obstetrics & Gynecology, IU School of Medicine"
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Item The altered mononuclear cell-derived cytokine response to glucose ingestion is not regulated by excess adiposity in polycystic ovary syndrome(The Endocrine Society, 2014-11) González, Frank; Sia, Chang Ling; Shepard, Marguerite K.; Rote, Neal S.; Minium, Judi; Department of Obstetrics & Gynecology, IU School of MedicineCONTEXT: Excess adipose tissue is a source of inflammation. Polycystic ovary syndrome (PCOS) is a proinflammatory state and is often associated with excess abdominal adiposity (AA) alone and/or frank obesity. OBJECTIVE: To determine the effect of glucose ingestion on cytokine release from mononuclear cells (MNC) in women with PCOS with and without excess AA and/or obesity. DESIGN: A cross-sectional study. SETTING: Academic medical center. PATIENTS: Twenty-three women with PCOS (seven normal weight with normal AA, eight normal weight with excess AA, eight obese) and 24 ovulatory controls (eight normal weight with normal AA, eight normal weight with excess AA, eight obese). INTERVENTION: Three-hour 75-g oral glucose tolerance test (OGTT). MAIN OUTCOME MEASURES: Body composition was measured by dual energy x-ray absorptiometry. Insulin sensitivity was derived from the OGTT (ISOGTT). TNFα, IL-6, and IL-1β release was measured in supernatants of cultured MNC isolated from blood samples drawn while fasting and 2 hours after glucose ingestion. RESULTS: Insulin sensitivity was lower in obese subjects regardless of PCOS status and in normal-weight women with PCOS compared with normal-weight controls regardless of body composition status. In response to glucose ingestion, MNC-derived TNFα, IL-6, and IL-1β release decreased in both normal-weight control groups but failed to suppress in either normal-weight PCOS group and in obese women regardless of PCOS status. For the combined groups, the cytokine responses were negatively correlated with insulin sensitivity and positively correlated with abdominal fat and androgens. CONCLUSIONS: Women with PCOS fail to suppress MNC-derived cytokine release in response to glucose ingestion, and this response is independent of excess adiposity. Nevertheless, a similar response is also a feature of obesity per se. Circulating MNC and excess adipose tissue are separate and distinct sources of inflammation in this population.Item A description of the methods of the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b)(Elsevier, 2015-04) HAAS, David M.; PARKER, Corette B.; WING, Deborah A.; PARRY, Samuel; GROBMAN, William A.; MERCER, Brian M.; SIMHAN, Hyagriv N.; HOFFMAN, Matthew K.; SILVER, Robert M.; WADHWA, Pathik; IAMS, Jay D.; KOCH, Matthew A.; CARITIS, Steve N.; WAPNER, Ronald J.; ESPLIN, M. Sean; ELOVITZ, Michal A.; FOROUD, Tatiana; PEACEMAN, Alan M.; SAADE, George R.; WILLINGER, Marian; REDDY, Uma M.; Department of Obstetrics & Gynecology, IU School of MedicineOBJECTIVE: The primary aim of the "Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be" is to determine maternal characteristics, which include genetic, physiologic response to pregnancy, and environmental factors that predict adverse pregnancy outcomes. STUDY DESIGN: Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at 3 study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine, cervicovaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending at <37+0 weeks' gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction. RESULTS: We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported. CONCLUSION: The "Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be" cohort study methods and procedures can help investigators when they plan future projects.Item Hypoxic conditions differentially regulate TAZ and YAP in cancer cells(Elsevier, 2014-11-15) Yan, Libo; Cai, Qingchun; Xu, Yan; Department of Obstetrics & Gynecology, IU School of MedicineThe Hippo-YAP pathway is altered and implicated as an oncogenic signaling pathway in many human cancers. Hypoxia is an important microenvironmental factor that promotes tumorigenesis. However, the effects of hypoxia on the two most important Hippo-YAP effectors, YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif), have not been reported. In this work, we demonstrated that TAZ was functionally involved in cell proliferation and/or migration in epithelial ovarian cancer (EOC) or human ovarian surface epithelial (HOSE) cells. Hypoxic conditions (1% O2 or hypoxia mimics) induced a reduction of YAP phosphorylation (S127) and total YAP expression in EOC cell lines OVCAR5 and SKOV3. However, these conditions up-regulated levels of S69 phosphorylated TAZ in EOC cells. The known TAZ kinases, Lats1 and Akt, were unlikely to be involved in up-regulated pTAZ by hypoxic conditions. Together, our data revealed new and differential regulating mechanisms of TAZ and YAP in cancer cells by hypoxia conditions.Item Increasing Influenza Vaccination Rates in a Busy Urban Clinic(JNSCI.org, 2015) Pierson, Rebecca C.; Malone, Anita M.; Haas, David M.; Department of Obstetrics & Gynecology, IU School of MedicineInfluenza infection is the cause of thousands of hospitalizations and deaths each year; infection during pregnancy results in increased morbidity and mortality. Underserved women are particularly susceptible to not receiving recommended vaccinations. This project explored the effect of a simple paper based prompt on the influenza vaccination rate in a resident continuity clinic for the underserved. Using this reminder to providers to discuss the influenza vaccination with their patients, we were able to increase vaccination rates in our clinic from 2.2% to 14.2%. This implementation of a simple, low cost, low tech prompt to providers increased the rate of influenza vaccination in our clinic and we present this approach as an easy to implement method of improving vaccination rates. We also suggest this method as an alternative to an alert in the electronic medical record in situations where the electronic medical record may not be accessed during every patient encounter.Item The influence of resuscitation preferences on obstetrical management of periviable deliveries(Nature Publishing Group, 2015-03) Edmonds, Brownsyne Tucker; McKenzie, Fatima; Hendrix, Kristin S.; Perkins, Susan M.; Zimet, Gregory D.; Department of Obstetrics & Gynecology, IU School of MedicineObjective Determine the relative influence of patient's resuscitation preferences on periviable delivery management. Methods Surveyed 295 obstetrician-gynecologists about managing periviable preterm premature rupture of membranes. Across 10 vignettes, we systematically varied gestational age; occupation; method of conception; and resuscitation preference. Physicians rated their likelihood (0-10) of proceeding with induction, steroids, and cesarean. Data were analyzed via conjoint analysis. Results 205 physician responses were included. Median ratings for management decisions were: induction 1.89; steroids 5.00; cesarean for labor 3.89; cesarean for distress 4.11. Gestational age had the greatest influence on physician ratings across all decisions (importance values ranging from 72.6-86.6), followed by patient's resuscitation preference (range= 9.3-21.4). Conclusion Gestational age is weighted more heavily than patients’ resuscitation preferences in obstetricians’ decision-making for periviable delivery management. Misalignment of antenatal management with parental resuscitation preferences may adversely affect periviable outcomes. Interventions are needed to facilitate more patient-centered decision-making in periviable care.Item Insulin receptor-like ectodomain genes and splice variants are found in both arthropods and human brain cDNA(Wiley Blackwell (Blackwell Publishing), 2013-11) Västermark, Åke; Rask-Andersen, Mathias; Sawant, Rahul S.; Reiter, Jill L.; Schiöth, Helgi B.; Williams, Michael J.; Department of Obstetrics & Gynecology, IU School of MedicineTruncated receptor ectodomains have been described for several classes of cell surface receptors, including those that bind to growth factors, cytokines, immunoglobulins, and adhesion molecules. Soluble receptor isoforms are typically generated by proteolytic cleavage of the cell surface receptor or by alternative splicing of RNA transcripts arising from the same gene encoding the full-length receptor. Both the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR) families produce soluble receptor splice variants in vertebrates and truncated forms of insulin receptor-like sequences have previously been described in Drosophila. The EGFR and INSR ectodomains share significant sequence homology with each other suggestive of a common evolutionary origin. We discovered novel truncated insulin receptor-like variants in several arthropod species. We performed a phylogenetic analysis of the conserved extracellular receptor L1 and L2 subdomains in invertebrate species. While the segregation of insulin receptor-like L1 and L2 domains indicated that an internal domain duplication had occurred only once, the generation of truncated insulin receptor-like sequences has occurred multiple times. The significance of this work is the previously unknown and widespread occurrence of truncated isoforms in arthropods, signifying that these isoforms play an important functional role, potentially related to such isoforms in mammals.Item The microenvironment reprograms circuits in tumor cells(Informa UK (Taylor & Francis), 2015-01) Cai, Qingchun; Xu, Yan; Department of Obstetrics & Gynecology, IU School of MedicineIn the course of multistep oncogenesis, initially normal cells acquire several new functions that render them malignant. We have recently demonstrated that the peritoneal microenvironment promotes resistance to anoikis in ovarian cancer cells by reprogramming SRC/AKT/ERK signaling and metabolism. These findings have prognostic and therapeutic implications.Item Offering Induction of Labor for 22-Week Premature Rupture of Membranes: A Survey of Obstetricians.(NPG, 2015-08) McKenzie, Fatima; Tucker Edmonds, Brownsyne; Department of Obstetrics & Gynecology, IU School of MedicineObjective: To describe obstetricians’ induction counseling practices for 22-week preterm premature rupture of membranes (PPROM) and identify provider characteristics associated with offering induction. Methods: Surveyed 295 obstetricians on their likelihood (0–10) of offering induction for periviable PPROM across 10 vignettes. 22-week vignettes were analyzed, stratified by parental resuscitation preference. Bivariate analyses identified physician characteristics associated with reported likelihood ratings. Results: Obstetricians (N=205) were not likely to offer induction. Median ratings by preference were: resuscitation 1.0, uncertain 1.0, and comfort care 3.0. Only 41% of obstetricians were likely to offer induction to patients desiring comfort care. Additionally, several provider-level factors, including practice region, parenting status, and years in practice, were significantly associated with offering induction. Conclusions: Obstetricians do not readily offer induction when counseling patients with 22-week ruptured membranes, even when patients prefer palliation. This may place women at risk for infectious complications without accruing a neonatal benefit from prolonged latency.Item OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages.(PLOS, 2016) D’Souza, Cheryl A.; Zhao, Fei Linda; Li, Xujian; Xu, Yan; Dunn, Shannon E.; Zhang, Li; Department of Obstetrics & Gynecology, IU School of MedicineOvarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity.Item Psychotropic Medications in Pregnancy and the Postpartum Period(Libertas Academia, 2015-07) Haas, David M.; McHugh, Katherine W.; Durst, Paula J.; Rose, Sarah M.; Patil, Avinash S.; Department of Obstetrics & Gynecology, IU School of MedicineMany pregnant women suffer from mental health conditions while pregnant. As providers and patients make decisions about risks of the conditions and treatments during pregnancy, information to populate those discussions is needed. Taking into account the physiologic changes in pregnancy, we may need to optimize medication therapy. This article reviews and summarizes some of the most common mental health conditions suffered in pregnancy: depression, bipolar disorder, anxiety, and psychosis. It further discusses the different medications used to treat them, as well as risks associated with these medications.