Publications by authors named "Aisling Murphy"

17 Publications

  • Page 1 of 1

Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis.

N Engl J Med 2020 10 7;383(18):1746-1756. Epub 2020 Oct 7.

From the University of California, San Francisco (T.N.S., B.R.L., S.L.D., S.P., A.F., A.M.S., P.D., U.H., J.V.Z., S.J.S., T.C.M., M.E.N.), the University of California, San Diego (R.R.A., L.C.L.), the University of California, Los Angeles (I.D., K.H., A.M.), the University of California, Irvine (J.D., J.J., C.U.), and the University of California, Davis (N.M.B., N.T.F.).

Background: The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear.

Methods: We evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited.

Results: In 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases.

Conclusions: In this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2023643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650529PMC
October 2020

Assessing the multidisciplinary team approaches to placenta accreta spectrum across five institutions within the University of California fetal Consortium (UCfC).

J Matern Fetal Neonatal Med 2019 Oct 24:1-6. Epub 2019 Oct 24.

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego , San Diego , CA , USA.

To describe the multidisciplinary approaches to placenta accreta spectrum (PAS) across five tertiary care centers that comprise the University of California fetal Consortium (UCfC) and to identify potential best practices. Retrospective review of all cases of pathologically confirmed invasive placenta delivered from 2009 to 2014 at UCfC. Differences in intraoperative management and outcomes based on prenatal suspicion were compared. Interventions assessed included ureteral stent use, intravascular balloon use, anesthetic type, gynecologic oncology (Gyn Onc) involvement, and cell saver use. Intervention variation by institution was also assessed. Analyses were adjusted for final pathologic diagnosis. Chi-square, Fisher's exact, Student's -test, and Mann-Whitney's -test were used as appropriate. Binary logistic regression and multivariable linear regression were used to adjust for confounders. One hundred and fifty-one cases of pathologically confirmed invasive placenta were identified, of which 82% (123) were suspected prenatally. There was no correlation between the degree of invasion on prenatal imaging and use of each intervention. Ureteral stents were placed in 33% (41) of cases and did not reduce GU injury. Intravascular balloons were placed in 29% (36) of cases and were associated with shorter OR time (161 versus 236 min, < .01) and lower estimated blood loss (EBL) (1800 versus 2500 ml, < .01). General endotracheal anesthesia (GETA) was used in 70% (86). EBL did not differ between GETA and regional anesthesia. Gyn Onc was involved in 58% (71) of cases and EBL adjusted for final pathology was reduced with their involvement (2200 versus 2250 ml, = .02) while OR time and intraoperative complications did not differ. Cell saver was used in 20% (24) and was associated with longer OR time (296 versus 200 min, < .01). Use of cell saver was not associated with a difference in EBL or number of units of packed red cells transfused. All analyses were adjusted for pathologic severity of invasion. Intravascular interventions such as uterine artery balloons and the inclusion of Gynecologic Oncologists as part of a multidisciplinary approach to treating PAS reduce EBL. Additionally, the placement of intravascular balloons may reduce OR time. No significant differences were seen in outcomes when comparing the use of ureteral stents, general anesthesia, or institutions. A team of experienced operators with a standard approach may be more significant than specific practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2019.1676411DOI Listing
October 2019

Nonimmune hydrops fetalis: identifying the underlying genetic etiology.

Genet Med 2019 06 9;21(6):1339-1344. Epub 2018 Nov 9.

Department of Obstetrics, Gynecology, & Reproductive Sciences, University of California, San Francisco, CA, USA.

Purpose: Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes.

Methods: Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal-Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology.

Results: Sixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach-Merritt syndrome.

Conclusion: In this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-018-0352-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509016PMC
June 2019

Pilot Study of Intra-Aortic Balloon Occlusion to Limit Morbidity in Patients with Adherent Placentation Undergoing Cesarean Hysterectomy.

AJP Rep 2018 Apr 11;8(2):e57-e63. Epub 2018 Apr 11.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of California, Los Angeles, California.

 We study whether using an intra-aortic balloon (IAB) during cesarean hysterectomy decreases delivery morbidity in patients with suspected morbidly adherent placentation.  This is a retrospective cohort study of deliveries complicated by suspected abnormal placentation between 2009 and 2016 comparing maternal and neonatal outcomes with an IAB placed prior to cesarean hysterectomy versus no IAB. The primary outcome included quantified blood loss (QBL).  Thirty-five cases were reviewed, 16 with IAB and 19 without IAB. No difference was seen in median QBL between the two groups (1,351 vs. 1,397 mL;  = 0.90). There were no significant differences in overall surgical complications (19% IAB, 21% no IAB;  = 0.86), bladder complications (12 vs. 21%;  = 0.66), intensive care unit admissions (12 vs. 26%;  = 0.41), surgical duration (2.9 vs. 2.8 hour;  = 0.83), or blood transfusions (median 2 vs. 2;  = 0.27) between the two groups. There was one groin hematoma at the balloon site that was managed conservatively. There were no complications involving thrombosis or limb ischemia in the IAB group.  While we did not detect statistically significant differences, larger studies may be warranted given the potential for extreme morbidity in these cases. This study highlights the potential use of an IAB in the management of these cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1641736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895466PMC
April 2018

Measuring human placental blood flow with multidelay 3D GRASE pseudocontinuous arterial spin labeling at 3T.

J Magn Reson Imaging 2018 06 14;47(6):1667-1676. Epub 2017 Nov 14.

Laboratory of FMRI Technology (LOFT), Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Background: Placenta influences the health of both a woman and her fetus during pregnancy. Maternal blood supply to placenta can be measured noninvasively using arterial spin labeling (ASL).

Purpose: To present a multidelay pseudocontinuous arterial spin labeling (pCASL) combined with a fast 3D inner-volume gradient- and spin-echo (GRASE) imaging technique to simultaneously measure placental blood flow (PBF) and arterial transit time (ATT), and to study PBF and ATT evolution with gestational age during the second trimester. The PBF values were compared with uterine arterial Doppler ultrasound to assess its potential clinical utility.

Study Type: This was a prospective study.

Subjects: Thirty-four pregnant women.

Field Strength/sequence: Multidelay 3D inner-volume GRASE pCASL sequence on 3T MR scanners.

Assessment: Subjects underwent two longitudinal MRI scans within the second trimester, conducted between 14-16 and 19-22 weeks of gestational age, respectively. Placental perfusion was measured using the free-breathing pCASL sequence at three postlabeling delays (PLDs), followed by offline motion correction and model fitting for estimation of PBF and ATT.

Statistical Tests: A paired t-test was conducted to evaluate the significance of PBF/ATT variations with placental development. A two-sample t-test was conducted to evaluate the significance of PBF difference in subjects with and without early diastolic notch.

Results: The mean PBF and ATT for the second trimester were 111.4 ± 26.7 ml/100g/min and 1387.5 ± 88.0 msec, respectively. The average PBF increased by 10.4% (P < 0.05), while no significant change in ATT (P = 0.72) was found along gestational ages during the second trimester. PBF decreased 20.3% (P < 0.01) in subjects with early diastolic notches in ultrasound flow waveform patterns.

Data Conclusion: Multidelay pCASL with inner-volume 3D GRASE is promising for noninvasive assessment of PBF during pregnancy. Its clinical use for the detection of aberrations in placental function and prediction of fetal developmental disorders awaits evaluation.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1667-1676.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.25893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951737PMC
June 2018

Placental Alpha Microglobulin-1 Compared With Fetal Fibronectin to Predict Preterm Delivery in Symptomatic Women.

Obstet Gynecol 2017 12;130(6):1183-1191

University of California Irvine, Orange, California; St. David's Medical Center, Austin, Texas; Summa Health, Akron, Ohio; HonorHealth Scottsdale Shea Medical Center, Scottsdale, Arizona; the University of Kansas, Kansas City, Kansas; Meritus Health, Hagerstown, Maryland; South Shore Hospital, South Weymouth, Massachusetts; Promedica-The Toledo Hospital, Toledo, Ohio; St. Luke's Hospital of Kansas City, Kansas City, Missouri; the University at Buffalo-Women and Children's Hospital of Buffalo, Buffalo, New York; Stony Brook University School of Medicine, Stony Brook, New York; the University of California, Los Angeles, Los Angeles, California; the University of California San Diego, San Diego, California; the University of California, Davis, Sacramento, California; and the University of California, San Francisco, California.

Objective: To compare the rapid bedside test for placental α microglobulin-1 with the instrumented fetal fibronectin test for prediction of imminent spontaneous preterm delivery among women with symptoms of preterm labor.

Methods: We conducted a prospective observational study on pregnant women with signs or symptoms suggestive of preterm labor between 24 and 35 weeks of gestation with intact membranes and cervical dilatation less than 3 cm. Participants were prospectively enrolled at 15 U.S. academic and community centers. Placental α microglobulin-1 samples did not require a speculum examination. Health care providers were blinded to placental α microglobulin-1 results. Fetal fibronectin samples were collected through speculum examination per manufacturer requirements and sent to a certified laboratory for testing using a cutoff of 50 ng/mL. The coprimary endpoints were positive predictive value (PPV) superiority and negative predictive value (NPV) noninferiority of placental α microglobulin-1 compared with fetal fibronectin for the prediction of spontaneous preterm birth within 7 days and within 14 days.

Results: Of 796 women included in the study cohort, 711 (89.3%) had both placental α microglobulin-1 and fetal fibronectin results and valid delivery outcomes available for analysis. The overall rate of preterm birth was 2.4% (17/711) within 7 days of testing and 4.2% (30/711) within 14 days of testing with respective rates of spontaneous preterm birth of 1.3% (9/703) and 2.9% (20/701). Fetal fibronectin was detected in 15.5% (110/711), and placental α microglobulin-1 was detected in 2.4% (17/711). The PPVs for spontaneous preterm delivery within 7 days or less among singleton gestations (n=13) for placental α microglobulin-1 and fetal fibronectin were 23.1% (3/13) and 4.3% (4/94), respectively (P<.025 for superiority). The NPVs were 99.5% (619/622) and 99.6% (539/541) for placental α microglobulin-1 and fetal fibronectin, respectively (P<.001 for noninferiority).

Conclusion: Although placental α microglobulin-1 performed the same as fetal fibronectin in ruling out spontaneous preterm delivery among symptomatic women, it demonstrated statistical superiority in predicting it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/AOG.0000000000002367DOI Listing
December 2017

Maternal and neonatal outcomes among scheduled versus unscheduled deliveries in women with prenatally diagnosed, pathologically proven placenta accreta.

J Matern Fetal Neonatal Med 2019 Mar 5;32(6):927-931. Epub 2017 Nov 5.

a Department of Reproductive Medicine , University of California , San Diego, San Diego , CA , USA.

Objective: To evaluate maternal and neonatal outcomes among scheduled versus unscheduled deliveries in cases of prenatally diagnosed, pathologically proven placenta accreta.

Study Design: Retrospective cohort of placenta accreta cases delivered in five University of California hospitals.

Results: Of 151 cases of histopathologically proven placenta accreta, 82% were prenatally diagnosed. Sixty-seven percent of women underwent scheduled deliveries and 33% were unscheduled. There were no differences in demographics between groups except a higher rate of antepartum bleeding in the unscheduled delivery group (81 versus 53%; p = .003). Scheduled deliveries were associated with a later gestational age at delivery (34.6 versus 32.6 weeks; p = .001), lower blood loss (2.0 versus 2.5 l; p = .04), higher birth weight (2488 versus 2010 g; p < .001), shorter postpartum length of stay (4 versus 5 d; p = .03) and neonatal length of stay (12 versus 20 d; p = .005).

Conclusion: Despite a prenatal diagnosis of placenta accreta, 1/3 of these cases require unscheduled delivery, portending poorer maternal and neonatal outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2017.1395847DOI Listing
March 2019

Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection.

Sci Rep 2016 Feb 15;6:21674. Epub 2016 Feb 15.

School of Biomedical and Healthcare Sciences, University of Plymouth, Devon, United Kingdom.

Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep21674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753684PMC
February 2016

Self-disseminating vaccines for emerging infectious diseases.

Expert Rev Vaccines 2016 2;15(1):31-9. Epub 2015 Nov 2.

a School of Biomedical and Healthcare Sciences , Plymouth University , Plymouth , UK.

Modern human activity fueled by economic development is profoundly altering our relationship with microorganisms. This altered interaction with microbes is believed to be the major driving force behind the increased rate of emerging infectious diseases from animals. The spate of recent infectious disease outbreaks, including Ebola virus disease and Middle East respiratory syndrome, emphasize the need for development of new innovative tools to manage these emerging diseases. Disseminating vaccines are one such novel approach to potentially interrupt animal to human (zoonotic) transmission of these pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1586/14760584.2016.1106942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732410PMC
September 2016

Urinary Excretion of Myo-Inositol and D-Chiro-Inositol in Early Pregnancy Is Enhanced in Gravidas With Gestational Diabetes Mellitus.

Reprod Sci 2016 Mar 8;23(3):365-71. Epub 2015 Sep 8.

Department of Obstetrics and Gynecology, David Geffen School of Medicine at the University of California, Los Angeles, California.

The effects of gestational diabetes mellitus (GDM) were determined on urinary excretion of putative components of insulin signaling. Random urine samples were collected from 375 gravidas at 6 to 14 weeks' gestation, 22 to 32 weeks' gestation, and ∼6 weeks' postpartum. Gestational diabetes mellitus developed in 35 women who were matched with 59 normal gravidas. Urinary concentrations of myo-inositol (MI) and D-chiro-inositol (DCI) were measured by gas chromatography/mass spectrometry and normalized to creatinine levels. Compared to postpartum values, urinary excretion of MI and DCI was increased 2.9-fold and 2-fold, respectively, in early pregnancy, and 5.5-fold and 4.5-fold, respectively, in later gestation. Gravidas with GDM had significantly greater MI and DCI excretion than controls in the first trimester but not subsequently. The results suggest that gravidas destined to develop GDM have altered synthesis, metabolism, and/or renal excretion of MI and DCI in early pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1933719115602767DOI Listing
March 2016

Role of the DNA Sensor STING in Protection from Lethal Infection following Corneal and Intracerebral Challenge with Herpes Simplex Virus 1.

J Virol 2015 Nov 26;89(21):11080-91. Epub 2015 Aug 26.

Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA

Unlabelled: STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING(-/-) mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal to STING(-/-) mice by the i.v. route. Corneally infected STING(-/-) mice also showed increased periocular disease and increased corneal and trigeminal ganglia titers, although there was no difference in brain titers. They also showed elevated expression of tumor necrosis factor alpha (TNF-α) and CXCL9 relative to control mice but surprisingly modest changes in type I interferon expression. Finally, we also showed that HSV strains lacking the ability to counter autophagy and the PKR-driven antiviral state had near-wild-type virulence following intracerebral infection of STING(-/-) mice. Together, these data show that while STING is an important component of host resistance to HSV in the cornea, its previously shown immutable role in mediating host survival by the i.v. route was not recapitulated following a mucosal infection route. Furthermore, our data are consistent with the idea that HSV counters STING-mediated induction of the antiviral state and autophagy response, both of which are critical factors for survival following direct infection of the nervous system.

Importance: HSV infections represent an incurable source of morbidity and mortality in humans and are especially severe in neonatal and immunocompromised populations. A key step in the development of an immune response is the recognition of microbial components within infected cells. The host protein STING is important in this regard for the recognition of HSV DNA and the subsequent triggering of innate responses. STING was previously shown to be essential for protection against lethal challenge from intravenous HSV-1 infection. In this study, we show that the requirement for STING depends on the infection route. In addition, STING is important for appropriate regulation of the inflammatory response in the cornea, and our data are consistent with the idea that HSV modulates STING activity through inhibition of autophagy. Our results elucidate the importance of STING in host protection from HSV-1 and demonstrate the redundancy of host protective mechanisms, especially following mucosal infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JVI.00954-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621135PMC
November 2015

Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae.

J Gen Virol 2015 Jun 27;96(Pt 6):1411-1422. Epub 2015 Jan 27.

Department of Zoology, University of Oxford, UK.

Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1099/vir.0.000071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635489PMC
June 2015

Freedom, invisibility, and community: a qualitative study of self-identification with asexuality.

Arch Sex Behav 2015 Apr 30;44(3):799-812. Epub 2014 Dec 30.

School of Psychology, National University of Ireland, University Road, Galway, Ireland,

A significant body of research is now emerging on the subjective meaning of asexuality. This study explored how self-identification as asexual is managed, both as a threat to the self-concept and a source of personal meaning. A total of 66 self-identified asexuals were recruited from an asexuality internet community and responded to open-ended questions on an online survey. Of these, 31 participants identified as female, 15 as male, 18 gave a different label such as genderqueer or androgynous, and two did not provide information on gender. A thematic analysis of the transcripts resulted in three themes. Socially, asexuality attracted denial and resistance due to incompatibility with heteronormative societal expectations. Despite the threat to self-integrity arising from asexuality being socially rejected, it was typically assimilated as a valued and meaningful orientation on an intra-personal level, aided by information and support from the online community. A second level of threat to self arose whereby other self-identifications, especially gender, had to be reconciled with a non-sexual persona. The accommodation made to other elements of the self was reflected in complex sub-identities. The findings were interpreted using identity process theory to understand how threats arising from self-identifying as asexual are managed. Although asexuality emerges as an orientation to sexuality that can be reconciled with the self, its invisibility or outright rejection in society constitute an on-going challenge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10508-014-0458-0DOI Listing
April 2015

Synergistic control of herpes simplex virus pathogenesis by IRF-3, and IRF-7 revealed through non-invasive bioluminescence imaging.

Virology 2013 Sep 16;444(1-2):71-9. Epub 2013 Jun 16.

Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, HB 7556, Lebanon, NH 03756, USA.

Interferon regulatory factors IRF-3 and IRF-7 are central to the establishment of the innate antiviral response. This study examines HSV-1 pathogenesis in IRF-3(-/-), IRF-7(-/-) and double-deleted IRF3/7(-/-) (DKO) mice. Bioluminescence imaging of infection revealed that DKO mice developed visceral infection following corneal inoculation, along with increased viral burdens in all tissues relative to single knockout mice. While all DKO mice synchronously reached endpoint criteria 5 days post infection, the IRF-7(-/-) mice survived longer, indicating that although IRF-7 is dominant, IRF-3 also plays a role in controlling disease. Higher levels of systemic pro-inflammatory cytokines were found in IRF7(-/-) and DKO mice relative to wild-type and IRF-3(-/-) mice, and IL-6 and G-CSF, indicative of sepsis, were increased in the DKO mice relative to wild-type or single-knockout mice. In addition to controlling viral replication, IRF-3 and -7 therefore play coordinating roles in modulation of inflammation during HSV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2013.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755050PMC
September 2013

First-trimester diagnosis of body stalk anomaly using 2- and 3-dimensional sonography.

J Ultrasound Med 2011 Dec;30(12):1739-43

Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

To determine the sonographic features of body stalk anomaly in the first trimester using 2-dimensional (2D) and 3-dimensional (3D) sonography, we conducted a retrospective analysis of all nuchal translucency sonographic examinations performed between January 1, 2006, and January 1, 2010, at our institution. From a total of 6952 nuchal translucency sonographic examinations, 4 cases of body stalk anomaly were identified. All cases were characterized by an absent umbilical cord and a large ventral wall defect with herniation of the abdominal contents into the extraembryonic coelom. Associated features included kyphoscoliosis, limb defects, and enlarged nuchal translucency measurements. Three-dimensional sonography was a useful adjunct to 2D techniques in determining the precise relationship of fetal structures to the amniotic cavity. Our case series emphasizes the importance of a thorough anatomic survey at the time of nuchal translucency screening and the value of 3D sonography in the delineation of first-trimester anomalies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7863/jum.2011.30.12.1739DOI Listing
December 2011

Maternal serum placental growth factor and soluble fms-like tyrosine kinase 1 as early predictors of preeclampsia.

Acta Obstet Gynecol Scand 2010 ;89(1):143-6

Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt.

Abstract The aim of this study was to identify pregnant women at risk of preeclampsia (PE) before clinical manifestations appeared using a panel of serum markers. We recruited 240 consecutive women who presented for antenatal care. We investigated whether serum levels of placental growth factor (PlGF), its inhibitor, soluble fms-like tyrosine kinase-1 (sFlt-1), measured at 13-16 weeks gestation and the expression of fms-like tyrosine kinase-1 (Flt-1) in the maternal neutrophils measured by flow cytometry could be predictive of the subsequent development of PE. Serum PlGF levels were found to be significantly lower among women who developed PE than patients with gestational hypertension or patients in the control group (p < 0.001). In contrast, serum sFlt1 levels were most elevated in patients who developed PE versus those with gestational hypertension or the control group (p < 0.001). Serum levels of neutrophil-Flt-1, however, were lower in women who developed PE than in those with gestational hypertension or those in the control group (p < 0.001). Increased serum levels of sFlt-1, decreased levels of neutrophil-Flt-1, and decreased levels of PlGF may predict women at risk of developing PE later in pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/00016340903289892DOI Listing
January 2010

Informed consent and hypoplastic left heart syndrome.

Acta Paediatr 2005 Sep;94(9):1171-5

Department of Pediatrics, University Of Alberta, and Neonatal ICU Stollery Children's Hospital, Edmonton, Canada.

Unlabelled: We present an ethical analysis from the perspective of shared decision-making and informed consent of a change in clinical management of infants born with hypoplastic left heart syndrome (HLHS). We reported a change in treatment of HLHS at the University of Alberta away from comfort care to life-saving surgery (LST) between 1987 and 1998. In a second review (1996-2001), 49/62 infants received LST, with 81% survival from the NICU and 58% at 35 mo. Eleven infants died preoperatively of non-cardiac conditions and two received elective comfort care. Sixteen infants had 18-mo Bayley Mental Development Index, mean score 84+/-19, but five scored <70. Although we continue to present the comfort care option to parents, since 2001 LST use for HLHS at our center is almost universal despite serious complications.

Conclusion: We conclude that these findings are inconsistent with an open, shared decision-making model of informed consent and we suggest that comfort care should remain an ethically valid choice until the rate of serious long-term complications of LST decreases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1651-2227.2005.tb02069.xDOI Listing
September 2005