Zebrafish () are a good model for cancer research including studies on chemotherapy treatments. We treated wild-type and deletion mutant zebrafish embryos at 24 h post-fertilization with 1 µM of the topoisomerase I inhibitor, camptothecin (CPT), for 4 h to catalogue gene expression changes induced by this DNA damage treatment and to understand if these changes are influenced by loss of miR-34a. The 4 sample groups of 3 independent biological samples consisting of 30 embryos each were analyzed by RNA-sequencing using the recently updated zebrafish transcriptome annotation based on GRCz11, which enabled a more complete and sensitive read mapping and gene assignment than standard annotations.
View Article and Find Full Text PDFLi-Fraumeni syndrome is caused by inherited TP53 tumor suppressor gene mutations. MicroRNA miR-34a is a p53 target and modifier gene. Interestingly, miR-34 triple-null mice exhibit normal p53 responses and no overt cancer development, but the lack of miR-34 promotes tumorigenesis in cancer-susceptible backgrounds.
View Article and Find Full Text PDFGestational diabetes mellitus is a condition similar to type 2 diabetes mellitus (T2DM) in that patients are unable to compensate for the degree of insulin resistance, and both conditions are often treated with metformin. The comparative pharmacodynamic response to metformin in these 2 populations has not been studied. This study characterized insulin sensitivity, β-cell responsivity, and disposition index following a mixed-meal tolerance test utilizing a minimal model of glucose, insulin, and C-peptide kinetics before and during treatment with metformin.
View Article and Find Full Text PDFEur J Obstet Gynecol Reprod Biol
June 2015
Objective: To determine whether 1,5-anhydroglucitol is predictive of neonatal birth weight.
Study Design: A retrospective cohort study including 85 pregnancies complicated by diabetes (Type 1=37, Type 2=24, gestational=24). Women had simultaneous hemoglobin A1c and 1,5-anhydroglucitol measurements every 4-8 weeks throughout pregnancy until delivery.
Objective: To determine the association of 1,5-anhydroglucitol (1,5-AG) with neonatal birth weight (NBW) and neonatal hypoglycemia (+NH) in pregnancies complicated by diabetes.
Methods: We assessed a retrospective cohort of 102 females, 17 with gestational diabetes (GDM), 48 with type 1 diabetes mellitus (T1DM), and 37 with type 2 diabetes mellitus (T2DM). 1,5-AG and glycated hemoglobin A1C (A1C) values throughout pregnancy were extracted.
Infect Dis Obstet Gynecol
August 2011
Objective: To compare genital HSV shedding among HIV-positive and HIV-negative women.
Methods: Women with and without known HIV infection who delivered at the University of Washington Medical Center between 1989-1996 had HSV serologies done as part of clinical care. Genital swabs from HSV-2-seropositive women were evaluated by real-time quantitative HSV DNA PCR.
Background: Neonatal herpes simplex virus (HSV) is a rare but devastating disease. We have conducted pooled analyses of data from 3 cohorts to evaluate the effects of maternal HSV serostatus and HSV type on risk of neonatal HSV acquisition and severity.
Methods: Data from cohorts in Seattle, WA, and Stanford, CA, USA, and Stockholm, Sweden were pooled using Mantel-Haenszel methods.
Varicella zoster virus (VZV) infection can be serious for pregnant women and their babies, although it is rare. The implications of primary VZV infection vary with the gestational age at infection. For the mother, the risk of severe illness is greatest after mid-pregnancy, when she is relatively immunocompromised.
View Article and Find Full Text PDFGenital herpes is common and is becoming more so, with a seroprevalence of 25% in middle class primary care settings. Primary genital herpes in pregnancy most often is subclinical, but it also can cause severe illness. Further, active genital herpes at the time of vaginal delivery poses significant risk of neonatal infection, especially if the mother acquired the infection in the third trimester.
View Article and Find Full Text PDFBackground: Nephropathy complicates 5% to 10% of pregnancies in women with diabetes and is associated with adverse outcomes. Given the importance of blood pressure (BP) control in reducing cardiovascular and renal complications outside of pregnancy, we hypothesized that poorly controlled hypertension in early pregnancy among women with diabetic nephropathy would be associated with adverse outcomes.
Methods: To examine the impact of hypertensive control in early pregnancy on perinatal outcomes, we performed a retrospective cohort study of pregnancies complicated by diabetic nephropathy with "Above Target" mean arterial pressure (> or = 100 mm Hg; N = 21) and "Below Target" mean arterial pressure (< 100 mm Hg; N = 22), which approximates the American Diabetes Association and the Seventh Report of the Joint National Committee recommended target of 130/80 mm Hg, measured at < 20 weeks' gestation.
Am J Obstet Gynecol
December 2005
Objective: This study was undertaken to determine risk factors for herpes simplex virus (HSV) acquisition among at risk pregnant women.
Study Design: Women in a prospective study of HSV acquisition in pregnancy invited their sexual partners for HSV type-specific serologic testing. Risk factors for HSV susceptibility, exposure, and acquisition were examined.
Approximately 22% of pregnant women are infected with herpes simplex virus (HSV)-2, and 2% of women will acquire HSV during pregnancy. Remarkably, up to 90% of these women are undiagnosed because they are asymptomatic or have subtle symptoms attributed to other vulvovaginal disorders. Diagnosis of genital herpes relies on laboratory confirmation with culture or polymerase chain reaction assay of genital lesions and type-specific glycoprotein G-based serologic testing.
View Article and Find Full Text PDFNeonatal herpes is a devastating disease, the most serious complication of genital herpes, one of the most common serious congenital or perinatal infections, and the most frequent complication of sexually transmitted infections among children. Nevertheless, neonatal herpes is not reportable to health authorities in most states. The potential for prevention has been enhanced by recent diagnostic and therapeutic advances, and the disease meets widely accepted criteria for reporting, including incidence rates that exceed those of comparable conditions, epidemiologic instability, disease severity, direct and indirect socioeconomic costs, concern by persons at risk, the potential for prevention by public health interventions, and the prospect that the resulting data would influence public health policy.
View Article and Find Full Text PDFIn recent proficiency testing of herpes simplex virus type-specific serologic evidence by the College of American Pathologists, commercially available herpes simplex virus antibody assays that were not glycoprotein-G based demonstrated high false-positive rates (14%-88%) for herpes simplex virus type-2 antibodies in sera that were positive for herpes simplex virus type-1 antibodies but negative for herpes simplex virus type-2 antibodies. Herpes simplex virus serologic testing should be performed with only glycoprotein-G-based tests.
View Article and Find Full Text PDFObjective: To estimate the accuracy of clinical diagnosis of genital herpes for herpes simplex virus (HSV) detection among women in labor.
Methods: Viral detection by culture and HSV DNA polymerase chain reaction (PCR) among women who underwent cesarean delivery for genital herpes was compared with women without HSV symptoms in labor who had genital swabs collected for HSV culture and to a subset of these women who had genital specimens available for PCR analysis, regardless of culture results.
Results: From 1989 to 1999, 126 of 19,568 (0.
Objective: The purpose of this study was to determine whether serologic testing for herpes simplex virus type 2 (HSV-2) in pregnant women and their partners is cost-effective.
Study Design: A decision analysis model was developed to investigate the cost-effectiveness of providing type-specific serologic testing at week 15 of pregnancy for all women unaware of their HSV-2 status, and offering antiviral suppressive therapy from week 36 until delivery to all seropositive women. This scenario was compared with current care, in which only a minority of women diagnosed with genital herpes (GH) receives antiviral suppressive therapy (AST).
Neonatal herpes simplex virus (HSV) infection can have severe consequences. Skin, eye and mouth infection is rarely fatal, but disseminated or central nervous system (CNS) disease has a mortality rate of 80% in the absence of therapy, and most surviving infants have neurological sequelae. Aciclovir therapy can improve the outcome of neonatal herpes, but is often delayed due to the early non-specific symptoms of the disease.
View Article and Find Full Text PDFBackground: Oral acyclovir is commonly used for genital herpes and other herpesvirus infections. Data on potential fetal risk are extremely limited. From 1984 to 1998, the Acyclovir in Pregnancy Registry monitored birth outcomes of women exposed to oral or intravenous acyclovir during pregnancy.
View Article and Find Full Text PDFObjective: The purpose of this study was to assess the efficacy of acyclovir in the reduction of herpes simplex virus culture and polymerase chain reaction positivity and cesarean delivery.
Study Design: Women with recurrent genital herpes simplex virus were randomized to acyclovir 400 mg three times daily or placebo from 36 weeks of gestation until delivery. A subset of daily specimens for herpes simplex virus culture and DNA polymerase chain reaction was self-collected.
Context: Neonatal herpes most commonly results from fetal exposure to infected maternal genital secretions at the time of delivery. The risk of transmission from mother to infant as it relates to maternal herpes simplex virus (HSV) serologic status and exposure to HSV in the maternal genital tract at the time of labor has not been quantified. Furthermore, no data exist on whether cesarean delivery, the standard of care for women with genital herpes lesions at the time of delivery, reduces HSV transmission.
View Article and Find Full Text PDFIt is now known that the physical presentation of genital herpes simplex (HSV) infection can be misleading in making the diagnosis of genital herpes. An incorrect diagnosis can be particularly damaging in pregnancy where it may result in extended exposure of the fetus to antiviral agents, an inappropriate route and timing of delivery and a significant increase in fetal exposure to HSV during labour and delivery. Case 1 describes a 32-year-old woman at 30 weeks in her first pregnancy who had the appearance and clinical course typically ascribed to primary genital HSV infection.
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