Genetic admixture and risk of hypertensive disorders of pregnancy among Latinas in Los Angeles County.

BACKGROUND: Latinos are a heterogeneous population in terms of demographics, culture, and genetic admixture from three racial groups (white, African, and Native American). This study examines the role of genetic ancestry and environmental risk factors in the risk of hypertensive disorder of pregnancy among Latinas in Los Angeles County. METHODS: Gestational hypertension, preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome cases (n = 125), plus unaffected controls (n = 161), were recruited from Los Angeles County + University of Southern California Women's and Children's Hospital from 1999 through 2008. Diagnoses were confirmed with extensive chart review. Personal information, demographics, and biospecimens were collected from all participants. Ancestry informative markers were used to estimate genetic ancestry proportions. RESULTS: After adjusting for European ancestry and key risk factors, African ancestry was positively associated with hypertensive disorders of pregnancy risk for the highest vs. the lowest quartiles of African ancestry (odds ratio = 2.6 [95% confidence interval = 1.1-6.1]). This association was stronger among women born in Mexico with parents born in Mexico (4.3 [1.4-13]). The results from generalized additive models showed a positive association between joint European/African ancestry and hypertensive disorders of pregnancy risk and an inverse association between Native American ancestry and risk. These associations were stronger among women of Mexican origin. CONCLUSION: Our findings suggest that higher Native American ancestry among Latinas may protect against hypertensive disorders of pregnancy. Further studies are needed to determine whether this protective effect is driven by specific alleles present in this population or by other risk factors that correlate with Native American ancestry.

Associations between ambient air pollution and Hypertensive Disorders of Pregnancy.

BACKGROUND: Exposure to ambient air pollution is linked to adverse pregnancy outcomes. Previous reports examining the relationship between ambient air pollution and Hypertensive Disorders of Pregnancy have been inconsistent. OBJECTIVES: We evaluated the effects of ambient air pollution on the odds of Hypertensive Disorder of Pregnancy and whether these associations varied by body mass index (BMI). METHODS: We conducted a retrospective, case-control study among 298 predominantly Hispanic women (136 clinically confirmed cases) who attended the Los Angeles County+University of Southern California Women's and Children's Hospital during 1996-2008. Trimester-specific carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and particulate matter with aerodynamic diameter <10 µm and <2.5 µm (PM10, PM2.5) exposure were estimated based on 24-hour exposure level at residential address. Logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for two standard deviation increase in exposure levels. RESULTS: Exposures to CO and PM2.5 in the 1st trimester were significantly associated with Hypertensive Disorders of Pregnancy, and these associations were modified by BMI. In non-obese women (BMI <30), 1st trimester exposures to PM2.5 and CO were significantly associated with increased odds of Hypertensive Disorder of Pregnancy (ORs per 2-standard deviation increase in PM2.5 (7 µg/m(3)) and CO (1 ppm) exposures were 9.10 [95% CI: 3.33-24.6] and 4.96 [95% CI: 1.85-13.31], respectively). Additionally, there was a significantly positive association between exposure to O3 in the 2nd trimester and Hypertensive Disorder of Pregnancy (OR per 15 ppb=2.05; 95% CI: 1.22-3.46). CONCLUSION: Among non-obese women, 1st trimester exposure to PM2.5 and carbon monoxide are associated with increased odds of Hypertensive Disorder of Pregnancy.

Night and day: the comparative study of strepsirrhine primates reveals socioecological and phylogenetic patterns in olfactory signals.

Studies of chemical signals in vertebrates typically target single species; however, a broader understanding of olfactory communication may derive from comparative studies. We collected urine from 12 species representing most families of strepsirrhine primates--an excellent model clade because of variation in scent marking and socioecology. Using SPDE/GC-MS, we identified the volatile chemical composition of male and female urine from six 'urine marking' species and six glandular or 'non-urine marking' species. We found no sex differences, but as predicted, urine markers expressed the most chemically complex and distinctive urine. More distantly related species had more dissimilar urinary profiles, suggesting gradual signal evolution. Reconstructing ancestral chemical profiles revealed different evolutionary trajectories for urine and non-urine markers. We suggest that urine marking is an ancestral behaviour related to solitary, nocturnal living and that parallel evolutionary shifts towards greater reliance on derived glandular marking occurred in a family (Lemuridae) characterized by diurnality and sociality.

Favorable outcome of pregnancy with an elective use of epoprostenol and sildenafil in women with severe pulmonary hypertension.

BACKGROUND: Pulmonary hypertension carries significant maternal and fetal risk during pregnancy and the postpartum period. As maternal mortality is high, specific targeted therapy for pulmonary hypertension may be required during pregnancy. CASES: We describe 2 pregnant patients who presented with severe secondary pulmonary arterial hypertension during their last trimester. They were electively treated in the late antepartum and early postpartum periods with sildenafil and intravenous epoprostenol and successfully delivered healthy infants via cesarean section without postpartum complications. CONCLUSION: Although pulmonary hypertension is associated with a risk of maternal mortality and most women are advised against pregnancy, new therapies may improve the outcome of pregnancy in patients with pulmonary hypertension.

Sudden fetal death in intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with an increased risk of fetal death. The mechanism of death is unknown. CASES: The first case involved a young primipara with pruritus and a bile acid concentration of 79 mumol/dL. While undergoing fetal heart rate monitoring, the fetus had a prolonged deceleration resulting in intrauterine death. The second case involved a young multipara with cholestasis who received ursodeoxycholic acid. Her bile acid concentration improved to13 micromol/dL. At 34 weeks of gestation, she had uterine contractions with prolonged decelerations resulting in delivery of her fetus with Apgar scores of 0, 0, and 5 at 1, 5, and 10 minutes, respectively. CONCLUSION: Fetal death from intrahepatic cholestasis of pregnancy can be abrupt and not reliably predicted by the characteristics of the fetal heart rate tracing.

Maternal and fetal variants in the TGF-beta3 gene and risk of pregnancy-induced hypertension in a predominantly Latino population.

OBJECTIVE: We sought to determine whether polymorphisms in the transforming growth factor (TGF)-beta3 gene are associated with risk of pregnancy-induced hypertension (PIH) in case-control mother-baby dyads. STUDY DESIGN: Patients (n = 136) and control subjects (n = 169) were recruited from our hospital. We genotyped 4 TGF-beta3 polymorphisms and examined association with PIH using logistic regression, adjusting for parity, maternal age, gestational age at delivery, fetal (or maternal) genotypes for the polymorphism in question, and the 3 other polymorphisms within the TGF-beta3 gene. RESULTS: Only 1 of the TGF-beta3 polymorphisms (rs11466414) was associated with PIH. Mothers who carried a baby with a minor allele were at decreased risk (odds ratio(multi-locus adj), 0.32; 95% confidence interval, 0.14-0.77). Maternal TGF-beta3 variants had no effect on risk of PIH. CONCLUSION: A fetal TGF-beta3 polymorphism (rs11466414) is associated with PIH in a predominantly Hispanic population.

Free T4 immunoassays are flawed during pregnancy.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracies of 2 free thyroxine immunoassays during pregnancy. STUDY DESIGN: Serum was collected from healthy, thyroid peroxidase antibody-negative women during each trimester and nonpregnant controls. Thyrotropin, total T4 (TT4), free T4 index (FT4I), and 2 different FT4 immunoassays were studied. RESULTS: As expected, TT4 was elevated in all 3 trimesters compared to controls (P < .001). FT4I was elevated in the 1st trimester as compared with controls (P < .05) and returned to the nonpregnant range in the 2nd and 3rd trimesters. In contrast, 1st trimester FT4 immunoassay values were either comparable or lower than controls and by the 2nd and 3rd trimesters had decreased to approximately 65% of controls. CONCLUSION: Neither FT4 immunoassay accurately reflects established free T4 changes during pregnancy. TT4 and the FT4I retained an appropriate inverse relationship with TSH throughout pregnancy and appear to provide a more reliable free T4 estimate.

Hyperemesis gravidarum.

Hyperemesis gravidarum occurs in 0.3% to 2% of pregnant women, although populations with significantly higher rates have been reported. In clinical practice, hyperemesis gravidarum is identified by otherwise unexplained intractable vomiting and dehydration. This article discusses the causes, presentation, diagnosis, and management of hyperemesis gravidarum.

The psychosocial burden of hyperemesis gravidarum.

OBJECTIVE: To describe the psychosocial burden of hyperemesis gravidarum (HG) in a large cohort of affected women, focusing on previously unreported problems. STUDY DESIGN: Women with HG described their pregnancy history in an open-ended survey administered internationally through an HG website during 2003 to 2005. RESULT: Of the 808 participants, 626 (77.5%) were American. A large majority (82.8%) reported that HG caused negative psychosocial changes, consisting of (1) socioeconomic changes, for example, job loss or difficulties, (2) attitude changes including fear regarding future pregnancies and (3) psychiatric sequelae, for example, feelings of depression and anxiety, which for some continued postpartum. Women who reported that their health-care provider was uncaring or unaware of the severity of their symptoms were nearly twice as likely to report these psychiatric sequelae (odds ratio 1.86, 95% confidence interval 1.06 to 3.29, P=0.032). CONCLUSION: Over 80% of a large cohort of women with HG reported that HG caused a negative psychosocial impact.

AKR1C1 and SRD5A1 messenger RNA expression at term in the human myometrium and chorioamniotic membranes.

We sought to determine relative mRNA expression of AKR1C1 and SRD5A1, which respectively encode for the key progesterone metabolizing enzymes, 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase type 1, in the myometrium and chorioamniotic membranes during human spontaneous or induced labor and nonlabor. Quantitative real-time reverse-transcriptase polymerase chain reaction was used to compare relative mRNA expression of AKR1C1 and SRD5A1 in the myometrium and chorioamniotic membranes from 20 subjects during three different states of labor: not in labor ( N = 10), spontaneous labor ( N = 5), or induced labor ( N = 5). Labor was defined as regular uterine contractions that resulted in cervical dilation. Myometrial AKR1C1 mRNA expression was significantly greater in spontaneously laboring subjects compared with those not in labor (2.4-fold [1.97 to 2.98], P = 0.02). There was no difference in myometrial AKR1C1 mRNA expression between those with induced labor compared with those not in labor. Regardless of labor status, no differences were observed in the chorioamniotic membrane AKR1C1 mRNA expression between the groups. SRD5A1 mRNA expression was significantly lower in the membranes of both laboring groups when compared with those not in labor (spontaneous: 0.10-fold [0.06 to 0.18], P = 0.007; induced: 0.09-fold [0.03 to 0.25], P = 0.013). Regardless of labor status, there was no difference in SRD5A1 mRNA expression in the myometrium. Our study demonstrated tissue-specific changes in progesterone metabolizing enzyme mRNA expression in human intrauterine tissue at term associated with labor status. These observed changes in mRNA expression may have important implications for progesterone metabolism at those specific sites and thereby may differentially regulate the tissue-specific progesterone concentration and/or the level of specific progesterone metabolites.

The knowledge mobilisation challenge: does producing evidence lead to its adoption within dentistry?

The transfer of evidence into clinical practice is the ultimate aim of those engaged in health research. But is this a process that occurs naturally? Can health researchers take it for granted that the evidence they produce will be embraced by clinicians and incorporated into their everyday practice? In this article, we use the example of oral healthcare in dependent older people and the issue of antibiotic prescribing by GDPs to illustrate the fact that successful knowledge transfer between researchers and practitioners cannot be automatically assumed. What is needed, so we argue, are certain tools to facilitate the knowledge transfer, exchange and implementation process. These tools may take the form of human intermediaries, who can occupy the space in between the worlds of research and practice, acting as brokers to mobilise knowledge, or through the establishment of communities of practice. We outline both of these approaches here as a potential solution to the problem of knowledge mobilisation in dentistry.

Detecting the earliest radiological signs of bisphosphonate-related osteonecrosis.

Introduction Oral bisphosphonates are the most commonly prescribed anti-resorptive drugs used in the treatment of osteoporosis, but osteonecrosis of the jaw is a serious complication. The early diagnosis of this destructive side effect is crucial in preventing excessive bone loss, pain and infection.Objective To aid dental practitioners in the early identification of bisphosphonate-related osteonecrosis of the jaw.Method A scoping review was carried out.Data sources We searched MEDLINE via OVID, EMBASE via OVID, Dentistry and Oral Sciences Source (DOSS), Proquest Dissertation and Theses Search, to identify references that described clinical and radiological findings in medication-related osteonecrosis of the jaw (MRONJ).Data selection Nineteen references mentioned the earliest radiological changes in MRONJ with a description of the observations and were included in the analysis.Data synthesis The radiographic signs included osteosclerosis/lysis, widening of the periodontal ligament and thickening of the lamina dura and cortex. To assess the quality of original data on which recommendations had been made, these 19 studies were subjected to a quality appraisal.Conclusion Using bone exposure as a criterion for diagnosis of MRONJ, leads to delayed diagnosis and a poor response to treatment. In those patients at risk of bone exposure with MRONJ, insufficient information is present in the literature to allow the general dental practitioner to reliably identify the radiographic features indicating imminent bone exposure. A well-designed prospective study is needed.

Elective pregnancy termination in a large cohort of women with hyperemesis gravidarum.

BACKGROUND: This study was conducted to describe characteristics of women who terminated their pregnancies secondary to hyperemesis gravidarum (HG). STUDY DESIGN: Data were obtained from a survey provided on an HG Web site from 2003 to 2005. RESULTS: Of 808 women who completed the survey, 123 (15.2%) had at least one termination due to HG, and 49 (6.1%) had multiple terminations. Prominent reasons given for the terminations were inability to care for the family and self (66.7%), fear that they or their baby could die (51.2%), or that the baby would be abnormal (22.0%). These same women were three times as likely to state that their health care providers were uncaring or did not understand how sick they were [64/123 (52.0%) vs. 168/685 (24.5%), odds ratio 3.34 (95% CI 2.21-5.05), p<.001]. CONCLUSION: These data suggest that the physical and psychological burden of HG has been underestimated, and that further education within the medical community may be warranted.

Implementation and trial evidence: a plea for fore-thought.

In a world where evidence-based practice is see as the foundation of modern healthcare, this paper asks when and how should we be accounting for the input of patients, the public, dental professionals, commissioners and policy-makers in the evidence generation process?

Guidelines on the timing and frequency of bitewing radiography: a systematic review.

Objectives To identify guidelines on when and how frequently bitewing radiographs should be used in dentistry for the diagnosis of caries, and to provide an objective appraisal of their quality.Data sources MEDLINE (OVID), US National Guideline Clearinghouse (www.guideline.gov) and the Royal College of Surgeons of England (https://www.rcseng.ac.uk/fds/publications-clinical-guidelines/clinical_guidelines) websites were searched using a variety of relevant search terms (2 August 2016).Data selection Publications were included if they made recommendations on the issue of when and how frequently radiographs should be used in any dentally-related specialty pertaining to the diagnosis of caries; and/or if they were aimed at the individual practitioner (any health professional working within dentistry) and/or patients.Data analysis Thirteen published guidelines were included and assessed using the AGREE II instrument.Conclusions There was a significant variation amongst the guidelines in the recommendations at what age radiography should be undertaken. There was also disagreement on the frequency of repeat radiographs and how this is influenced by the age of the patient and their caries risk.

Massive subchorionic hematoma associated with enoxaparin.

BACKGROUND: The use of low-molecular-weight heparins is increasing for the prevention of thromboembolism in pregnancy. Subchorionic hematoma as a complication of anticoagulation therapy is rarely reported. CASE: A persistent, massive subchorionic hematoma was diagnosed in a pregnant patient with atrial fibrillation and mitral stenosis. Enoxaparin was administered to maintain her trough anti-Xa level 0.5 units/mL or higher. The patient's peak anti-Xa levels never exceeded 1.05 units/mL. The patient underwent cesarean delivery at 34 6/7 weeks of gestation for preterm premature rupture of membranes. CONCLUSION: Subchorionic hematoma is a potentially serious complication that can occur in pregnant patients receiving enoxaparin for the prevention of thromboembolism.

Shoulder dystocia: the unpreventable obstetric emergency with empiric management guidelines.

OBJECTIVE: Much of our understanding and knowledge of shoulder dystocia has been blurred by inconsistent and scientific studies that are of limited scientific quality. In an evidence-based format, we sought to answer the following questions: (1) Is shoulder dystocia predictable? (2) Can shoulder dystocia be prevented? (3) When shoulder dystocia does occur, what maneuvers should be performed? and (4) What are the sequelae of shoulder dystocia? STUDY DESIGN: Electronic databases, including PUBMED and the Cochrane Database, were searched using the key word "shoulder dystocia." We also performed a manual review of articles included in the bibliographies of these selected articles to further define articles for review. Only those articles published in the English language were eligible for inclusion. RESULTS: There is a significantly increased risk of shoulder dystocia as birth weight linearly increases. From a prospective point of view, however, prepregnancy and antepartum risk factors have exceedingly poor predictive value for the prediction of shoulder dystocia. Late pregnancy ultrasound likewise displays low sensitivity, decreasing accuracy with increasing birth weight, and an overall tendency to overestimate the birth weight. Induction of labor for suspected fetal macrosomia has not been shown to alter the incidence of shoulder dystocia among nondiabetic patients. The concept of prophylactic cesarean delivery as a means to prevent shoulder dystocia and therefore avoid brachial plexus injury has not been supported by either clinical or theoretic data. Although many maneuvers have been described for the successful alleviation of shoulder dystocia, there have been no randomized controlled trials or laboratory experiments that have directly compared these techniques. Despite the introduction of ancillary obstetric maneuvers, such as McRoberts maneuver and a generalized trend towards the avoidance of fundal pressure, it has been shown that the rate of shoulder-dystocia associated brachial plexus palsy has not decreased. The simple occurrence of a shoulder dystocia event before any iatrogenic intervention may be associated with brachial plexus injury. CONCLUSION: For many years, long-standing opinions based solely on empiric reasoning have dictated our understanding of the detailed aspects of shoulder dystocia prevention and management. Despite its infrequent occurrence, all healthcare providers attending pregnancies must be prepared to handle vaginal deliveries complicated by shoulder dystocia.

The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population.

OBJECTIVE: To establish the prevalence of intrahepatic cholestasis of pregnancy (ICP) in a primarily Latina population in the United States. STUDY DESIGN: Over a period of 16 months, a convenience sample of subjects admitted to labor and delivery in the third trimester was enrolled. Each subject completed a questionnaire rating their severity of pruritus on a numeric scale of 1 to 10. Serum was analyzed via radioimmunoassay for total bile acid concentration. ICP was defined as pruritus score >4 and a total serum bile acid concentration of >or=20 micromol/l. Ethnicity was determined from hospital record demographic data. RESULTS: All invited participants enrolled in the study. Three hundred and forty subjects were enrolled. Three hundred and sixteen subjects (93%) were identified as Latina. The serum bile acid concentration range for the entire study population was 1 to 580 micromol/l with a mean of 10.4+/-34.9 micromol/l. Twenty-four (7.1%) subjects had a serum bile acid concentration >or=20 micromol/l. A pruritus score >4 was found in 19.7% (67/340). Of the 24 subjects with a bile acid concentration >or=20 micromol/l, 19 also had a pruritus score >4. Thus, the prevalence of ICP in this population was 5.6% (19/340). In subjects with ICP, the mean serum bile acid concentration was 89.5+/-124.0 micromol/l. When controlling for confounders, women with ICP were associated with higher rates of chorioamnionitis (P=0.043) and their fetuses had higher rates of thick meconium (P=0.053). CONCLUSIONS: The overall prevalence of ICP in this population was 5.6%, 10 to 100 times higher than previously reported data from the United States. Larger studies of perinatal morbidity examining the diagnostic criteria of cholestasis need to be conducted.

An active retrotransposon in Candida albicans.

Tca2 is a Ty1/copia-type retrotransposon from the pathogenic yeast Candida albicans. It was originally identified as an abundant, linear, extrachromosomal, double-stranded DNA molecule. Here we show that Tca2 is widespread in C.albicans, but that the abundance of extrachromosomal Tca2 DNA varies greatly among different strains and is strongly dependent on the growth temperature. The relative levels of Tca2 RNA vary in a similar pattern to the extrachromosomal DNA, raising the possibility that the variations in extrachromosomal DNA levels are introduced predominantly at the level of transcription. We have also analysed the retrotranspositional activity of the element by developing a transposition assay involving a cloned Tca2 element tagged with a selectable marker gene that is activated by passage through an RNA intermediate. We show that the marked Tca2 is transpositionally active as transposed copies of the marked element became integrated at a variety of new positions in the genome and an intron in the donor element was precisely removed in the newly transposed copies. This is the first report of transposition in C.albicans.