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Background: Intimate partner violence affects 1 in 4 women at some stage in their lives. Exposure to violence has short- and long-term consequences for women themselves and their children. The objective of this study was to examine associations between fear of an intimate partner and maternal physical and psychological morbidity in early pregnancy.Method:This paper reports baseline measures from a prospective pregnancy cohort study of 1,507 nulliparous women recruited at six public hospitals in Melbourne, Australia.Results:The study showed that 18.7 percent (280/1,497) of women reported being afraid of an intimate partner at some stage in their lives; 3.1 percent (47/1,497) were afraid in early pregnancy and 15.6 percent (233/1,497) had been afraid before but not during the current pregnancy. Compared with women who had never been afraid of an intimate partner, women who reported being afraid of an intimate partner in early pregnancy (

Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole-proteome differential screening method, we identified Schistosoma japonicum helminth defense molecule 1 (SjHDM-1) as a target of antibodies expressed by S. japonicum-resistant but not S. japonicum-susceptible individuals. In a longitudinal cohort study (n = 644) conducted in a S. japonicum-endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 immunoglobulin G had higher levels of C-reactive protein than those with low anti-SjHDM-1. High anti-SjHDM-1 immunoglobulin G responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (weight-for-age and height-for-age z scores) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity rates., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Poor intrauterine growth has negative impacts for child growth and development and disproportionately affects children living in low-resource settings. In the present study, we investigated relationships between placental pathologies and indicators of poor intrauterine growth., Methods: We enrolled a longitudinal cohort of 279 mother-infant pairs from Leyte, the Philippines. Placental measures included characteristics, pathological findings, and immunohistochemistry. At birth, intrauterine growth was assessed using anthropometric measures, weight-for-gestational age, and the clinical assessment of nutritional status score (CANSCORE) for determining fetal malnutrition. Multivariate linear regression and log-binomial regression models were applied, controlling for potential confounding factors., Results: Maternal vascular malperfusion (MVM) was related to reduced birthweight (P < 0.0001), birth length (P = 0.002), head circumference (P = 0.001), and weight-to-length ratio (P = 0.016). MVM increased the risk for preterm delivery (P = 0.0005) and small for gestational age (SGA) (P = 0.016). Acute chorioamnionitis (P = 0.013) and MVM (P = 0.021) both led to an increased risk for fetal malnutrition defined by CANSORE<25. Villous tissue activated caspase-3 was associated with lower birth length (P = 0.0006), higher weight-to-length ratio (P = 0.004), reduced risks for SGA (P = 0.011) and low weight-to-length ratio for gestational age (P = 0.004)., Conclusion: The present study applied comprehensive measures for intrauterine growth and demonstrates that low placental weight and placental pathology, chiefly MVM, contribute to poor intrauterine growth. A better understanding of the mechanistic role of specific placental pathologies on adverse newborn outcomes will provide opportunities for reducing incidence of poor intrauterine growth and associated long-term morbidities., (© 2023 International Federation of Gynecology and Obstetrics.)

Objectives: Fetal alcohol spectrum disorder (FASD) captures the broad range of emotional, cognitive, behavioral, and congenital abnormalities associated with maternal alcohol consumption, and women living in resource-limited settings may be higher risk. This study aims to examine knowledge, attitudes, practices, and beliefs (KAPB) of women in Leyte, The Philippines regarding prenatal alcohol consumption., Methods: One hundred postpartum women were recruited from a birth cohort in Leyte. A prenatal alcohol use KAPB survey was constructed in Waray, the local language. The survey was administered in June-September 2019. Descriptive statistics, chi-squared test, and Fisher's exact test were used to analyze responses., Results: Seventy-five percent of subjects reported drinking tuba, a local palm wine, during pregnancy. Most participants (75%) did not believe tuba contained alcohol. Women who believed tuba contains no alcohol were more likely to drink tuba during pregnancy (81.3%) than women who believed tuba contains alcohol (56.0%), X 2 (1, N  = 100) = 6.41, p  = .011. Women who drank tuba during pregnancy were more likely to believe tuba has health benefits (60%) than women who did not drink tuba during pregnancy (12%), Fisher's exact p  < .05, citing increased red blood cell count and unproven antiparasitic qualities. Fifteen percent of subjects reported having fed their babies tuba. Nearly all (98%) were willing to attenuate tuba/alcohol consumption if told that this practice negatively impacts pregnancies., Conclusion: Misinformation about tuba appears widespread in Leyte. Educating women of reproductive age in Leyte regarding prenatal tuba use may lead to a reduction in tuba use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Huang, Neale, Darveau, Sagliba, Moreno, Urbina Paz, Tallo, McDonald, Jiz and Friedman.)

Infants exposed to opioids in utero are an increasing clinical population and these infants are often diagnosed with Neonatal Abstinence Syndrome (NAS). Infants with NAS have diverse negative health consequences, including respiratory distress. However, many factors contribute to NAS, confounding the ability to understand how maternal opioids directly impact the neonatal respiratory system. Breathing is controlled centrally by respiratory networks in the brainstem and spinal cord, but the impact of maternal opioids on developing perinatal respiratory networks has not been studied. Using progressively more isolated respiratory network circuitry, we tested the hypothesis that maternal opioids directly impair neonatal central respiratory control networks. Fictive respiratory-related motor activity from isolated central respiratory networks was age-dependently impaired in neonates after maternal opioids within more complete respiratory networks (brainstem and spinal cords), but unaffected in more isolated networks (medullary slices containing the preBötzinger Complex). These deficits were due, in part, to lingering opioids within neonatal respiratory control networks immediately after birth and involved lasting impairments to respiratory pattern. Since opioids are routinely given to infants with NAS to curb withdrawal symptoms and our previous work demonstrated acute blunting of opioid-induced respiratory depression in neonatal breathing, we further tested the responses of isolated networks to exogenous opioids. Isolated respiratory control networks also demonstrated age-dependent blunted responses to exogenous opioids that correlated with changes in opioid receptor expression within a primary respiratory rhythm generating region, the preBötzinger Complex. Thus, maternal opioids age-dependently impair neonatal central respiratory control and responses to exogenous opioids, suggesting central respiratory impairments contribute to neonatal breathing destabilization after maternal opioids and likely contribute to respiratory distress in infants with NAS. These studies represent a significant advancement of our understanding of the complex effects of maternal opioids, even late in gestation, contributing to neonatal breathing deficits, necessary first steps in developing novel therapeutics to support breathing in infants with NAS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Beyeler, Naidoo, Morrison, McDonald, Albarrán and Huxtable.)

Undernutrition is responsible for up to 45% of deaths in children under five, with low- and middle-income countries disproportionately affected. Adipokines are known modulators of metabolism and have been linked to growth rates and neurocognition during infancy. We examined the relationship(s) between cord blood adiponectin and leptin and both longitudinal growth and cognition during the first year of life using generalized estimating equations. Infants were classified as underweight (weight-for-age z-score [WAZ]), stunted (height-for-age z-score [HAZ]) or wasted (weight-for-height z-score [WHZ]) using WHOAnthro software. Cord blood adiponectin and leptin levels were highly correlated (r = 0.35, P &lt; 0.0001) and positively associated with birth WAZ (r = 0.34 and r = 0.45, P &lt; 0.0001, respectively). Adipokines were independently, inversely associated with weight gain. Infants in the highest quintile of adipokine production had a lower risk of being stunted, while neither was associated with lower WAZ or WHZ in final adjusted models. Cognition was not found to be independently related to cord blood leptin or adiponectin. The negative association with adipokines and rate of weight gain during infancy may reflect heightened nutritional status at birth rather than a direct hormonal influence. The relationship between leptin or adiponectin and longitudinal length gains suggests that both adipokines may promote linear growth during infancy., (© 2022. The Author(s).)

Background: Transport of iron across the placenta is critical for appropriate development of the fetus. Iron deficiency during pregnancy remains a major public health concern, particularly in low- and middle-income countries, often exacerbated by infectious diseases leading to altered iron trafficking via inflammatory responses. Herein, we investigate the role of hepcidin, a master regulator of iron homeostasis, on regulation of iron transport across trophoblast cells., Methods: We utilized the Jeg-3 choriocarcinoma cell line for analysis of the expression of transferrin receptor, ferritin, and ferroportin as well as the export of 59 Fe in the presence of hepcidin. Placental tissue from human term pregnancies was utilized for immunohistochemistry., Results: Hepcidin treatment of Jeg-3 cells decreased the expression of ferroportin and transferrin receptor (TfR) and reduced the cellular export of iron. Lower expression of TfR on the syncytiotrophoblast was associated with the highest levels of hepcidin in maternal circulation, and ferroportin expression was positively associated with placental TfR. Placentas from small-for-gestational-age newborns had significantly lower levels of ferroportin and ferritin gene expression at delivery., Conclusions: Our data suggest that hepcidin plays an important role in the regulation of iron transport across the placenta, making it a critical link in movement of iron into fetal circulation., Impact: Hepcidin has a direct impact on iron transport across the human placenta. This study provides the first evidence of direct regulation of iron efflux from human trophoblast cells by hepcidin. These data extend our understanding of iron transport across the maternal-fetal interface, a process critical for fetal health and development., (© 2020. International Pediatric Research Foundation, Inc.)

Hookworm infection is associated with poor nutritional outcomes, anemia, and impaired cognitive performance. We examined the association between maternal hookworm infection and birth outcomes in a cohort of women in Leyte, Philippines. We observed poor intrauterine growth characteristics associated with maternal hookworm only among male offspring, with lower birth weight, head circumference, and placental surface area. Male neonates also had higher insulin-like growth factor 2 (IGF-2) and lower adiponectin in cord blood. These data intriguingly suggest nutritional impacts of maternal hookworm infection during pregnancy may be divergent based on sex of the offspring., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We evaluated the association between etiology of maternal anemia and iron status throughout infancy., Methods: Samples from a study designed to examine Praziquantel treatment during pregnancy were used (n = 359). All women were infected with schistosomiasis and randomized to Praziquantel or placebo at 16 ± 2 weeks' gestation. Hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, C-reactive protein, and interleukin-6 were measured in maternal and infant blood. The relationship between both maternal Praziquantel treatment and etiology of anemia and infant iron status was evaluated., Results: Maternal iron-deficiency anemia was associated with increased risk of infant anemia at 6 months of age. Infants of mothers with the lowest levels of circulating hepcidin during gestation, likely a marker for iron deficiency, had higher sTfR:SF levels and lower hemoglobin levels, particularly at 12 months of age. Maternal non-iron-deficiency anemia (NIDA) did not impact infant anemia risk or iron status. Maternal treatment for schistosomiasis had no effect on infant hematologic status., Conclusions: Maternal iron deficiency anemia was associated with an increased risk for anemia or iron deficiency during late infancy. We did not observe an association between maternal NIDA and increased risk for iron deficiency during infancy.

Background: The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment., Methods/findings: This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12-16 weeks' gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks' gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-γ. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated., Conclusions: Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface., Clinical Trial Registry Number and Website: ClinicalTrials.gov (NCT00486863)., Competing Interests: The authors have declared that no competing interests exist.

Background: In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive., Methods: We enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania. We collected cord blood, measured antibodies to Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1), and related these antibodies to the risk of severe malaria in the first year of life. In addition, we vaccinated female mice with PbSEA-1, mated them, and challenged their pups with P. berghei ANKA parasites to assess the impact of maternal PbSEA-1 vaccination on newborns' resistance to malaria., Results: Children with high cord-blood anti-PfSEA-1 antibody levels had 51.4% fewer cases of SM compared to individuals with lower anti-PfSEA-1 levels over 12 months of follow-up (P = .03). In 3 trials, pups born to PbSEA-1-vaccinated dams had significantly lower parasitemia and longer survival following a P. berghei challenge compared to pups born to control dams., Conclusions: We demonstrate that maternally-derived, cord-blood anti-PfSEA-1 antibodies predict decreased risk of SM in infants and vaccination of mice with PbSEA-1 prior to pregnancy protects their offspring from lethal P. berghei challenge. These results identify, for the first time, a parasite-specific target of maternal antibodies that protect infants from SM and suggest that vaccination of pregnant women with PfSEA-1 may afford a survival advantage to their offspring., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Few longitudinal studies have examined women's experiences of sex after childbirth. Much of the advice given to couples about what to expect in relation to sex after childbirth is based on cross-sectional studies., Objective: To investigate timing of resumption of sex after a second birth and assess associations with obstetric factors (method of birth and perineal trauma) and time interval between first and second births., Method: Prospective cohort of 1507 nulliparous women recruited before 25 weeks' gestation in Melbourne, Australia followed up at 3, 6, 9, and 12 months after first births, and 6 and 12 months after second births. Measures include: obstetric factors and resumption of vaginal sex after first and second births., Results: By 8 weeks after their second birth, 56% of women had resumed vaginal sex, compared with 65% after their first birth. Women were more likely to resume sex later than 8 weeks postpartum if they had a spontaneous vaginal birth with episiotomy or sutured perineal tear (aOR: 2.21, 95% CI: 1.5-3.2), operative vaginal birth (aOR: 2.60, 95% CI: 1.3-5.3) or cesarean delivery (aOR: 2.15, 95% CI: 1.4-3.3) compared with a vaginal birth with minimal or no perineal trauma. There was no association between timing of resumption of sex and the time interval between births., Conclusion: For almost half of the cohort, sex was not resumed until at least 8 weeks after the second birth. Timing of resumption of sex was influenced by obstetric factors, but not the time interval between births., (© 2018 Wiley Periodicals, Inc.)

Low- and middle-income countries (LMICs) carry a high burden of infectious diseases associated with impaired gut integrity, leading to microbial translocation. Pregnancies in this setting are at high risk of fetal growth restriction (FGR). We examined the association among specific risk factors for impaired gut integrity (schistosomiasis, hookworm infection, and alcohol consumption), blood endotoxin levels, and FGR. Endotoxins, lipopolysaccharide-binding proteins (LBPs), and cytokines were measured in blood from women at 32 weeks gestation, the maternal-fetal interface (MFI) at delivery, and cord blood at delivery. Resolution of schistosomiasis had no impact on endotoxin levels; however, maternal hookworm infection and alcohol consumption were associated with modest increases in endotoxin at the MFI. Cytokines responses within the maternal peripheral blood and blood from the MFI were positively associated with endotoxins, but many cord blood cytokines were negatively associated with endotoxins. Newborns with FGR also had higher levels of endotoxins at the MFI. Risk factors for microbial translocation may lead to increased levels of endotoxins at the MFI, which may contribute to poor growth in utero.

Background: To our knowledge, no studies have addressed whether maternal anemia of inflammation (AI) affects newborn iron status, and few have addressed risk factors for specific etiologies of maternal anemia., Objectives: The study aims were to evaluate 1) the contribution of AI and iron deficiency anemia (IDA) to newborn iron endowment, 2) hepcidin as a biomarker to distinguish AI from IDA among pregnant women, and 3) risk factors for specific etiologies of maternal anemia., Methods: We measured hematologic biomarkers in maternal blood at 12 and 32 wk of gestation and in cord blood from a randomized trial of praziquantel in 358 pregnant women with Schistosoma japonicum in The Philippines. IDA was defined as anemia with serum ferritin <30 ng/mL and non-IDA (NIDA), largely due to AI, as anemia with ferritin ≥30 ng/mL. We identified cutoffs for biomarkers to distinguish IDA from NIDA by using area under the curve (AUC) analyses and examined the impact of different causes of anemia on newborn iron status (primary outcome) by using multivariate regression modeling., Results: Of the 358 mothers, 38% (n = 136) had IDA and 9% (n = 32) had NIDA at 32 wk of gestation. At 32 wk of gestation, serum hepcidin performed better than soluble transferrin receptor (sTfR) in identifying women with NIDA compared with the rest of the cohort (AUCs: 0.75 and 0.70, respectively) and in identifying women with NIDA among women with anemia (0.73 and 0.72, respectively). The cutoff that optimally distinguished women with NIDA from women with IDA in our cohort was 6.1 µg/L. Maternal IDA, but not NIDA, was associated with significantly lower newborn ferritin (114.4 ng/mL compared with 148.4 µg/L; P = 0.042)., Conclusions: Hepcidin performed better than sTfR in identifying pregnant women with NIDA, but its cost may limit its use. Maternal IDA, but not NIDA, is associated with decreased newborn iron stores, emphasizing the need to identify this cause and provide iron therapy. This trial was registered at www.clinicaltrials.gov as NCT00486863.

Aims: To evaluate how young adults perceive and compare harms and benefits of marijuana and tobacco products in the context of a legal marijuana market in Colorado., Design: Semi-structured qualitative interviews., Setting: Denver, CO, USA., Participants: Thirty-two young adults (aged 18-26 years) who used tobacco/marijuana/vaporizers., Measurements: Semi-structured interviews addressed perceived harms and benefits of various tobacco and marijuana products and personal experiences with these products., Findings: Young adults evaluated harms and benefits using five dimensions: (1) combustion-smoking was considered more harmful than non-combustible products (e.g. e-cigarettes, vaporizers and edibles); (2) potency-edibles and marijuana concentrates were perceived as more harmful than smoking marijuana flower because of potential to receive too large a dose of tetrahydrocannabinol (THC); (3) chemicals-products containing chemical additives were seen as more harmful than 'pure' or 'natural' plant products; (4) addiction-participants recognized physiological addiction to nicotine, but talked primarily about psychological or life-style dependence on marijuana; and (5) source of knowledge-personal experiences, warning labels, campaigns, the media and opinions of product retailers and medical practitioners affected perceptions of harms and benefits., Conclusions: Among young adults in Colorado, USA, perceived harms and benefits of tobacco and marijuana include multiple dimensions. Health educational campaigns could benefit from addressing these dimensions, such as the potency of nicotine and cannabis concentrates and harmful chemicals present in the organic material of tobacco and marijuana. Descriptors such as 'natural' and 'pure' in the promotion or packaging of tobacco and marijuana products might be misleading., (© 2017 Society for the Study of Addiction.)

Course-based undergraduate research experiences (CUREs) for non-science majors (nonmajors) are potentially distinct from CUREs for developing scientists in their goals, learning objectives, and assessment strategies. While national calls to improve science, technology, engineering, and mathematics education have led to an increase in research revealing the positive effects of CUREs for science majors, less work has specifically examined whether nonmajors are impacted in the same way. To address this gap in our understanding, a working group focused on nonmajors CUREs was convened to discuss the following questions: 1) What are our laboratory-learning goals for nonmajors? 2) What are our research priorities to determine best practices for nonmajors CUREs? 3) How can we collaborate to define and disseminate best practices for nonmajors in CUREs? We defined three broad student outcomes of prime importance to the nonmajors CURE: improvement of scientific literacy skills, proscience attitudes, and evidence-based decision making. We evaluated the state of knowledge of best practices for nonmajors, and identified research priorities for the future. The report that follows is a summary of the conclusions and future directions from our discussion., (© 2017 C. J. Ballen et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Objective: To explore the intersection of tobacco, legalised marijuana and electronic vaporiser use among young adults in the 'natural laboratory' of Colorado, the first state with legalised retail marijuana., Methods: We conducted semistructured interviews with 32 young adults (18-26 years old) in Denver, Colorado, in 2015 to understand the beliefs and practices related to the use of tobacco, marijuana and vaporisers., Results: We found ambiguity about whether the phrase 'to smoke' refers to the use of tobacco or marijuana products. Smoking marijuana blunts (emptied cigarillo or tobacco wrap filled with marijuana) was common, but few interpreted this as tobacco use. Marijuana vaporisers were used to circumvent public consumption laws (eg, while at work or when driving). Young adults considered secondhand tobacco smoke dangerous, but perceived secondhand marijuana smoke as benign., Discussion: Using tobacco products as a delivery method for marijuana (eg, blunts) might be increasing and normalising tobacco use among young adults. Surveillance should explicitly ask about use of tobacco products for marijuana. Marijuana vaporisers, often indistinguishable from nicotine vaporisers, may be used to circumvent public consumption laws; communities concerned about use of marijuana in public spaces should include vaporisers (for nicotine or marijuana) in smoke-free regulations. Tobacco, marijuana and electronic vaporisers should be studied together, rather than separately. This approach is essential in informing research and policy as more US states and countries worldwide move to legalise marijuana., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Binding of gonadotropin-releasing hormone (GnRH) to its receptor (GnRHR) on gonadotropes within the anterior pituitary gland is essential to reproduction. In pigs, the GnRHR gene is also located near a genetic marker for ovulation rate, a primary determinant of prolificacy. We hypothesized that pituitary expression of the GnRHR gene is alternatively regulated in genetic strains with elevated ovulation rates (Chinese Meishan and Nebraska Index) vs. standard white crossbred swine (Control)., Methods: Luciferase reporter vectors containing 5118 bp of GnRHR gene promoter from either the Control, Index or Meishan swine lines were generated. Transient transfection of line-specific, full length, deletion and mutation constructs into gonadotrope-derived αT3-1 cells were performed to compare promoter activity and identify regions necessary for divergent regulation of the porcine GnRHR gene. Additionally, transcription factors that bind the GnRHR promoter from each line were identified with electrophoretic mobility shift assays (EMSA)., Results: Dramatic differences in luciferase activity among Control, Index and Meishan promoters (19-, 27- and 49-fold over promoterless control, respectively; P < 0.05) were established. A single bp substitution (-1690) within a previously identified upstream enhancer (-1779/-1667) bound GATA-4 in the Meishan promoter and the p52/p65 subunits of nuclear factor (NF)-κB in the homologous Control/Index promoters. Transient transfection of vectors containing block replacement mutations of either the GATA-4 or NF-κB binding sites within the context of their native promoters resulted in a 50 and 60 % reduction of luciferase activity, respectively (P < 0.05). Furthermore, two single-bp substitutions in the Meishan compared to Control/Index promoters resulted in binding of the p52 and p65 subunits of NF-κB and a specificity protein 1 (SP1)-like factor (-1235) as well as GATA-4 (-845). Vectors containing the full-length Meishan promoter harboring individual mutations spanning these regions reduced luciferase activity by 25 and 20 %, respectively, compared to native sequence (P < 0.05)., Conclusions: Elevated activity of the Meishan GnRHR gene promoter over Control/Index promoters in αT3-1 cells is partially due to three single nucleotide polymorphisms resulting in the unique binding of GATA-4 (-1690), the p52/p65 subunits of NF-kB in combination with a SP1-like factor (-1235), and GATA-4 (-845).

Objective: to describe the frequency, severity and persistence of dyspareunia in the first 18 months after the birth of a first child., Design: prospective pregnancy cohort study., Setting: Melbourne, Victoria, Australia., Population: 1507 nulliparous women., Methods: women ≤24 weeks gestation were recruited from six public hospitals. Self-administered written questionnaires were completed at recruitment and at three, six, 12 and 18 months post partum., Outcome Measures: study-designed self-report measure of dyspareunia on first vaginal sex, and on second and subsequent sex at all time-points, utilising the rating scale from the McGill Pain Intensity Scale., Findings: overall, 961/1122 (85.7%) of women experienced pain on first vaginal sex postnatally. The proportion of women experiencing dyspareunia reduced over time, from 431/964 (44.7%) at three months post partum to 261/1155 (22.6%) at 18 months post partum. Of the women who reported dyspareunia at each time-point, around 10% of women described the pain as׳distressing׳,׳horrible׳ or׳excruciating׳. Women who had a caesarean section were more likely to report more intense dyspareunia at six months post partum (aOR=2.35, 95% CI=1.2-4.6)., Conclusions: postnatal dyspareunia decreases over time, but persists beyond 12 months for one in five women. Caesarean section appears to be associated with more intense dyspareunia., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Despite WHO recommendations to offer pregnant women treatment with praziquantel, many nations continue to withhold treatment, awaiting data from controlled trials addressing safety and efficacy. The objectives of this study were to assess whether treatment of pregnant women with schistosomiasis at 12-16 weeks gestation leads to improved maternal and newborn outcomes and to collect maternal and newborn safety data., Methods: This phase 2, randomised, double-blind, placebo-controlled trial was done in 72 baranguays (villages) serviced by six municipal health centres in a schistosomiasis endemic region of northeastern Leyte, Philippines. Pregnant women (at 12-16 weeks gestation) who were otherwise healthy but infected with Schistosoma japonicum were enrolled and randomly assigned (1:1) to receive either over-encapsulated praziquantel (total dose 60 mg/kg given as two split doses) or placebo. Participants, investigators, midwives, and laboratory staff were all masked to treatment. The primary outcome was birthweight. Safety data were collected including immediate reactogenicity, post-dosing toxicology ascertained 24 h after study drug administration, and maternal and newborn serious adverse events. Analysis followed the intention-to-treat principle. Analyses were done using hierarchical generalised linear models to adjust for identified confounders and account for potential clustering of observations within villages and municipalities. This trial is registered with ClinicalTrials.gov, number NCT00486863., Findings: Between Aug 13, 2007, and Dec 3, 2012, 370 pregnant women were enrolled and randomly assigned to each treatment group (184 to the placebo group, 186 to the praziquantel group). Most women had low-intensity infections (n=334, 90%). Treatment with praziquantel did not have a significant effect on birthweight (2·85 kg in both groups, β=-0·002 [95% CI -0·088 to 0·083]; p=0·962). Treatment was well tolerated with reactogenicity rates similar to those seen in non-pregnant participants (severe reactions occurred in five patients in the praziquantel group and two in the placebo group, and included headache, fever, and malaise). There were no significant differences in key safety outcomes including abortion, fetal death in utero, and congenital anomalies., Interpretation: Results from this study provide important data from a controlled trial in support of the expansion of treatment policies to include pregnant women as recommended by WHO., Funding: National Institutes of Health, National Institute of Allergy and Infectious Diseases (U01AI066050)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: This qualitative research explores the use of electronic cigarettes and other similar 'vapor' delivery devices among young adults in New York City., Methods: We employed 17 focus groups followed by 12 semistructured interviews to understand the beliefs, opinions and practices related to the use of electronic cigarettes among young adult smokers (N=87)., Results: Participants were mainly daily (52%) and non-daily (41%) smokers. While experimentation with electronic cigarette devices was frequently reported, participants related an overall lack of information about the devices and what they did know often reflected messages in e-cigarette marketing campaigns. Participants also used their own bodily sensations as a way to gauge potential risks and benefits of the products. Finally, young adults, steeped in a culture of personal technologies, perceived e-cigarettes as one more 'toy' among other technologies integrated into their everyday lives., Discussion: E-cigarettes were also frequently used with other tobacco products, including conventional cigarettes. Our research indicates that public health campaigns may be needed to counter current industry marketing and inform the public that electronic cigarettes are currently unregulated, understudied and contain toxicants and carcinogens., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Regulation of gonadotropin-releasing hormone (GnRH) receptor (GnRHR) numbers on gonadotropes within the anterior pituitary gland represents a critical point for control of reproductive function. Binding of GnRH to its receptor regulates follicle stimulating hormone (FSH) and luteinizing hormone (LH) release and levels of this G-protein coupled receptor on the surface of gonadotropes determines their sensitivity to GnRH pulses. While transcriptional regulation of this gene has been studied in mice, rats, humans and sheep, little is known about its regulation in the pig, an important agricultural species and human research model., Methods: We isolated 5118 bp of 5' flanking sequence for the porcine GnRHR gene and generated luciferase reporter vectors. Deletion and mutation constructs were evaluated in gonadotrope-derived alphaT3-1 cells to determine regions important for gene transcription. Additionally, electrophoretic mobility shift assays (EMSAs) were performed to identify transcription factors binding to the GnRHR promoter., Results: Transient transfections revealed that the GnRHR promoter was functional in alphaT3-1 cells but not in cells of non-gonadotrope origin. Mutation of the highly conserved gonadotrope specific element (GSE) located at -179/-171 of proximal promoter completely ablated luciferase activity, whereas mutation of another GSE at -315/-310 reduced activity by 34%. Consistent with this, EMSAs using alphaT3-1 nuclear extracts and a steroidogenic factor (SF)1 antibody confirmed SF1 binding to both GSEs. EMSAs also demonstrated that a retinoid X receptor (RXR) binding site at -279/-274 binds RXRalpha and RXRbeta and mutation of this site eliminated promoter activity. Transient transfection of alphaT3-1 cells with reporter vectors containing selective removal of 5' flanking region for the porcine GnRHR gene indicated that the -1915/-1431 segment was important for promoter activity. Definition of this region via transfection assays and EMSAs revealed an upstream enhancing region located at -1779/-1667 that increases porcine GnRHR gene expression in alphaT3-1 cells and includes a SF1 binding site at -1760/-1753., Conclusions: Porcine GnRHR promoter activity in alphaT3-1 cells is partially conferred by a distal GSE, two proximal GSEs and a RXR binding site. Basal gonadotrope expression of the porcine GnRHR gene uniquely involves three GSEs and RXR is newly identified as a regulator of GnRHR promoter activity.

Objective: To investigate the relationship between mode of delivery, perineal trauma and dyspareunia., Design: Prospective cohort study., Setting: Six maternity hospitals in Melbourne, Australia., Sample: A total of 1507 nulliparous women recruited in the first and second trimesters of pregnancy., Method: Data from baseline and postnatal questionnaires (3, 6, 12 and 18 months) were analysed using univariable and multivariable logistic regression., Main Outcome Measure: Study-designed self-report measure of dyspareunia at 18 months postpartum., Results: In all, 1244/1507 (83%) women completed the baseline and all four postpartum questionnaires; 1211/1237 (98%) had resumed vaginal intercourse by 18 months postpartum, with 289/1211 (24%) women reporting dyspareunia. Compared with women who had a spontaneous vaginal delivery with an intact perineum or unsutured tear, women who had an emergency caesarean section (adjusted odds ratio [aOR] 2.41, 95% confidence interval [95% CI] 1.4-4.0; P = 0.001), vacuum extraction (aOR 2.28, 95% CI 1.3-4.1; P = 0.005) or elective caesarean section (aOR 1.71, 95% CI 0.9-3.2; P = 0.087) had increased odds of reporting dyspareunia at 18 months postpartum, adjusting for maternal age and other potential confounders., Conclusions: Obstetric intervention is associated with persisting dyspareunia. Greater recognition and increased understanding of the roles of mode of delivery and perineal trauma in contributing to postpartum maternal morbidities, and ways to prevent postpartum dyspareunia where possible, are warranted., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Multiple sclerosis was without effective disease-modifying therapy for many years. The introduction of the injectable therapies (interferon and glatiramer acetate) some 20 years ago was considered a major advance. Recent years have heralded a revolution in treatment options with the introduction of intravenous natalizumab and, even more recently, three oral agents. We are currently in a period of determining the best use of these therapies to ensure prevention of disease progression while maintaining patient safety. Despite these new treatments, there are still many patients living with disability as a result of multiple sclerosis and significant attention must be given to symptomatic management., (© 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)

Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-1A had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion., (Copyright © 2014, American Association for the Advancement of Science.)

Schistosomiasis affects approximately 40 million women of reproductive age and has been linked to elevated levels of circulating endotoxin in nonpregnant individuals. We have evaluated endotoxin levels in maternal, placental, and newborn blood collected from women residing in Leyte, Philippines. Endotoxin levels in both maternal and placental compartments in pregnant women with schistosomiasis were 1.3- and 2.4-fold higher, respectively, than in uninfected women. In addition, higher concentrations of endotoxin in placental blood were associated with premature birth, acute chorioamnionitis, and elevated proinflammatory cytokines. By promoting endotoxemia, schistosomiasis may exert additional, maladaptive influences on pregnancy outcomes.

The global burden of schistosomiasis is significant, with fibrosis a major associated morbidity and the primary cause of mortality. We have previously shown that schistosomiasis during pregnancy upregulates proinflammatory cytokines in the cord blood. In this study, we extend these findings to include a large panel of fibrosis-associated markers. We developed a multiplex bead-based assay to measure the levels of 35 proteins associated with fibrosis. Cord blood from 109 neonates born to mothers residing in an area of Schistosoma japonicum endemicity was assessed for these molecules. Ten mediators were elevated in the cord blood from schistosome-infected pregnancies, including insulin-like growth factor 1 (IGF-1), tumor growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), procollagen I carboxy-terminal propeptide (PICP), amino-telopeptide of type 1 collagen (ICTP), collagen VI, desmosine, matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinases 1 (TIMP-1), and TIMP-4. Many of these were also positively correlated with preterm birth (PICP, ICTP, MMP-2, TGF-β1, desmosine, CTGF, TIMP-1). In addition, birth weight was 168 g lower for infants with detectable levels of CTGF than for those with CTGF levels below the level of detection. Maternal schistosomiasis results in upregulation of fibrosis-associated proteins in the cord blood of the neonate, a subset of which are also associated with adverse birth outcomes. As the first report of fibrosis-associated molecules altered in the newborn of infected mothers, this study has broad implications for the health of the fetus, stretching from gestation to adulthood.

Background: Schistosomiasis affects nearly 40 million women of reproductive age, and is known to elicit a pro-inflammatory signature in the placenta. We have previously shown that antigens from schistosome eggs can elicit pro-inflammatory cytokine production from trophoblast cells specifically; however, the influence of these antigens on other characteristics of trophoblast function, particularly as it pertains to placentation in early gestation, is unknown. We therefore sought to determine the impact of schistosome antigens on key characteristics of first trimester trophoblast cells, including migration and invasion., Methods: First trimester HTR8/SVneo trophoblast cells were co-cultured with plasma from pregnant women with and without schistosomiasis or schistosome soluble egg antigens (SEA) and measured cytokine, cellular migration, and invasion responses., Results: Exposure of HTR8 cells to SEA resulted in a pro-inflammatory, anti-invasive signature, characterized by increased pro-inflammatory cytokines (IL-6, IL-8, MCP-1) and TIMP-1. Additionally, these cells displayed 62% decreased migration and 2.7-fold decreased invasion in vitro after treatment with SEA. These results are supported by increased IL-6 and IL-8 in the culture media of HTR8 cells exposed to plasma from Schistosoma japonica infected pregnant women., Conclusions: Soluble egg antigens found in circulation during schistosome infection increase pro-inflammatory cytokine production and inhibit the mobility and invasive characteristics of the first trimester HTR8/SVneo trophoblast cell line. This is the first study to assess the impact of schistosome soluble egg antigens on the behavior of an extravillous trophoblast model and suggests that schistosomiasis in the pre-pregnancy period may adversely impact placentation and the subsequent health of the mother and newborn.

Objective: To investigate the timing of resumption of vaginal sex and assess associations with method of birth, perineal trauma and other obstetric and social factors., Design: Prospective pregnancy cohort study of nulliparous women., Setting: Melbourne, Australia., Sample: A total of 1507 nulliparous women recruited in early pregnancy (≤24 weeks)., Method: Women were recruited from six public hospitals. Data from hospital records and self-administered questionnaires at recruitment and 3, 6 and 12 months postpartum were analysed using univariable and multivariable logistic regression., Main Outcome Measure: Resumption of vaginal sex., Results: Sexual activity was resumed earlier than vaginal sex, with 53% resuming sexual activity by 6 weeks postpartum, and 41% attempting vaginal sex. By 8 weeks a majority of women had attempted vaginal sex (65%), increasing to 78% by 12 weeks, and 94% by 6 months. Compared with women who had a spontaneous vaginal birth with an intact perineum, women who had a spontaneous vaginal birth with an episiotomy (adjusted odds ratio 3.43, 95% confidence interval 1.9-6.2) or sutured perineal tear (adjusted odds ratio 3.18, 95% confidence interval 2.1-4.9) were more likely not to have resumed vaginal sex by 6 weeks postpartum. Similarly, women who had an assisted vaginal birth or caesarean section had raised odds of delaying resumption of sex., Conclusions: Most women having a first birth do not resume vaginal sex until later than 6 weeks postpartum. Women who have an operative vaginal birth, caesarean section or perineal tear or episiotomy appear to delay longer., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Schistosomiasis affects nearly 40 million women of reproductive age. Many of these women are infected while pregnant and lactating. Several studies have demonstrated transplacental trafficking of schistosome antigens; however, little is known regarding how these antigens affect the developing fetus and placenta. To evaluate the impact of schistosomiasis on trophoblasts of the human placenta, we isolated primary trophoblast cells from healthy placentas delivered at term. These trophoblasts were placed in culture and treated with Schistosoma japonicum soluble egg antigens (SEA) or plasma from S. japonicum-infected pregnant women. Outcomes measured included cytokine production and activation of signal transduction pathways. Treatment of primary human trophoblast cells with SEA resulted in upregulation of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8 and the chemokine macrophage inflammatory protein 1α (MIP-1α). Cytokine production in response to SEA was dose dependent and reminiscent of production in response to other proinflammatory stimuli, such as Toll-like receptor 2 (TLR2) and TLR4 agonists. In addition, the signaling pathways extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal protein kinase (JNK), p38, and NF-κB were all activated by SEA in primary trophoblasts. These effects appeared to be mediated through both carbohydrate and protein epitopes of SEA. Finally, primary trophoblasts cocultured with plasma from S. japonicum-infected pregnant women produced increased levels of IL-8 compared to trophoblasts cocultured with plasma from uninfected pregnant women. We report here a direct impact of SEA on primary human trophoblast cells, which are critical for many aspects of a healthy pregnancy. Our data indicate that schistosome antigens can activate proinflammatory responses in trophoblasts, which might compromise maternal-fetal health in pregnancies complicated by schistosomiasis.

Problem: A successful pregnancy is contingent on maternal tolerance of the immunologically foreign fetus. Prevalent diseases such as preeclampsia arise in part due to an inappropriate immune response by the placenta. A number of molecules have been proposed to temper cellular response to pro-inflammatory mediators, including CD24 and Siglec10., Methods: Cytotrophoblast cells from healthy term placentas were treated with adiponectin in vitro and analyzed with qPCR and ELISA-based assays. Immunohistochemistry was performed on term villous sections and cultured trophoblasts., Results: Treatment with adiponectin increased expression of IL-1β and IL-8. Term villi express CD24 in cytotrophoblasts and the syncytiotrophoblast, and Siglec10 by the syncytiotrophoblast. Treatment of trophoblast cells with adiponectin increased Siglec10 expression., Conclusion: These data describe a role for adiponectin in enhancing pro-inflammatory signals in in vitro syncytialized trophoblasts. Additionally, this represents the first time the CD24/Siglec10 pathway has been implicated in a trophoblast response to a pro-inflammatory mediator., (© 2011 John Wiley & Sons A/S.)

Schistosomes infect ∼40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial in Schistosoma mansoni did not detect this association. We conducted an observational study among 99 pregnant women living in an area of Schistosoma japonicum endemicity in the Philippines. We enrolled women at 32 weeks gestation and measured S. japonicum and geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-α] and interleukin 10 [IL-10]), placental (TNF-α, IL-6, TNF-α receptor II [RII], and IL-1β), and cord (IL-1β and TNF-α RII) blood, as well as acute subchorionitis and increased TNF-α production by syncytiotrophoblasts assessed by immunohistochemistry (all P < 0.05). After adjusting for confounders, placental IL-1β, and TNF-α production by syncytiotrophoblasts was independently associated with decreased birth weight (both P < 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.

People with multiple sclerosis (MS) tend to have lower participation in paid employment compared to those with other chronic diseases. In two large-sample, self-report surveys of MS patients performed 4 years apart, employment rates were measured both cross-sectionally and longitudinally. The reasons for employment loss and perceived risk of future employment loss were also assessed. A total of 1,135 patients responded to the first survey, 1,329 to the second, and 667 to both. Longitudinal loss of employment was 5.4% over the 4 years 2003-2007, a period of relative national economic prosperity. By 2007, 56% of MS patients had lost employment due to MS and 64% were not in the paid labour force. Regression analysis indicated that men were more likely than women to leave their employment because of their MS, and older people were more likely than younger ones to do so. Level of occupational skill using Australian Bureau of Statistics categorisation was not predictive of maintaining or losing employment. The main reasons reported by people with MS for their loss of employment involved the ineffective management of symptoms of MS in the workplace, rather than workplace-related factors including insufficient flexibility of employment conditions or being asked to leave or sacked. The most frequently listed symptoms relating to employment loss, and perceived risk of losing current employment, were fatigue, mobility-related symptoms, arm and hand difficulties, and cognitive deficits. These findings imply that many employees with MS are leaving their planning for effective symptom management, and for appropriate accommodations in the workplace, until such planning is too late to be effective. The potential advantages of early, supported disclosure of diagnosis to employers before MS symptoms become a problem are discussed.

Introduction: Few studies have examined associations of prepregnancy urinary incontinence (UI)., Methods: Multicentre prospective pregnancy cohort study (n = 1,507) using standardised measures to assess frequency and severity of UI., Results: Prevalence of UI increased from 10.8% in the 12 months before the index pregnancy to 55.9% in the third trimester. Stress incontinence (36.9%) and mixed incontinence (13.1%) were more common during pregnancy than urge incontinence alone (5.9%). UI before pregnancy was associated with childhood enuresis (adjusted odds ratio (AdjOR) = 2.4, 95% confidence interval (CI) 1.6-3.4), higher maternal body mass index (AdjOR = 2.3, 95% CI 1.4-3.8), and previous miscarriages or terminations (AdjOR = 1.6, 95% CI 1.1-2.3). The strongest predictor of incident UI in pregnancy was occasional leakage (less than once a month) before pregnancy (AdjOR = 3.6, 95% CI 2.8-4.7)., Conclusions: Further research is needed to elucidate the complex interplay of prepregnancy and pregnancy-related factors in the aetiology of UI in nulliparous women.

The hormone adiponectin has been shown to be important in maintaining insulin sensitivity throughout the body, whereas potential effects on the placenta have not been assessed. Pregnancy constitutes a unique physiological environment in which metabolism has a profound effect on the health of both the mother and the developing fetus. It is imperative that a delicate balance in glucose delivery be maintained between maternal tissues and the fetal/placental unit. Adiponectin's role in regulating peripheral insulin responsiveness suggests it may be a factor in maintaining this balance during gestation as well. Examination of human cytotrophoblast cells revealed that mRNA for both adiponectin receptors, adipoR1 and adipoR2, are abundantly expressed at term. We were, however, unable to reliably detect mRNA for adiponectin in primary cytotrophoblasts. Expression of both receptors was maintained after induction of syncytium formation by exogenous epidermal growth factor treatment. Treatment of cytotrophoblasts with adiponectin resulted in a significant drop, as assessed by quantitative RT-PCR, in expression for a number of genes involved in the endocrine function of the placenta, including the chorionic gonadotropin subunits, placental lactogen, and some steroidogenic enzymes. Immunofluorescent staining for connexin 43 and desmoplakin in primary trophoblasts revealed that adiponectin does not inhibit syncytialization of trophoblast cells in culture. Taken together, these data describe a novel role for maternal adiponectin in regulating the placental environment. Determination of the effects of such adipokines on the maternal-fetal interface is increasingly important, because the incidence of pregnancies complicated by gestational diabetes remains a significant health problem in developed countries.

Background: Electronic prescribing has been advocated as an important tool for improving the safety and quality of medication use in ambulatory settings. However, widespread adoption of e-prescribing in ambulatory settings has yet to be realized. The determinants of successful implementation and use in these settings are not well understood., Objective: To describe the practice characteristics associated with implementation and use of e-prescribing in ambulatory settings., Design: Multi-method qualitative case study of ambulatory practices before and after e-prescribing implementation., Participants: Sixteen physicians and 31 staff members working in 12 practices scheduled for implementation of an e-prescribing program and purposively sampled to ensure a mix of practice size and physician specialty., Measurements: Field researchers used observational and interview techniques to collect data on prescription-related clinical workflow, information technology experience, and expectations., Results: Five practices fully implemented e-prescribing, 3 installed but with only some prescribers or staff members using the program, 2 installed and then discontinued use, 2 failed to install. Compared to practice members in other groups, members of successful practices exhibited greater familiarity with the capabilities of health information technologies and had more modest expectations about the benefits likely to accrue from e-prescribing. Members of unsuccessful practices reported limited understanding of e-prescribing capabilities, expected that the program would increase the speed of clinical care and reported difficulties with technical aspects of the implementation and insufficient technical support., Conclusions: Practice leaders should plan implementation carefully, ensuring that practice members prepare for the effective integration of this technology into clinical workflow.

Background: To determine (i) the rate of delayed HIV diagnosis; (ii) the missed opportunities for HIV diagnosis; and (iii) to identify who initiates HIV testing and what triggers them to do so., Methods: An analysis of the case records of all HIV-positive patients who attended Canberra Sexual Health Centre (CSHC) between 1985 and 2005 was conducted., Results: During the study period, 319/355 CSHC patients diagnosed with HIV had sufficient data to allow analysis regarding the timeliness of their diagnosis. Of these, 52 (16.3%) received a delayed diagnosis. The rate of delayed diagnosis was 9.7% (95% CI 5.1-15.3) in the 1980s and 25.6% (95% CI 13-42.1) between 2000 and 2004. There were no statistically significant differences in sociodemographic or behavioural characteristics between patients with delayed and timely HIV diagnoses. To determine who initiated testing, and if there were missed opportunities for testing, the records of CSHC patients diagnosed with HIV between 1995 and 2005 were examined. Of the 115 people diagnosed in this period, only 71 had documentation concerning missed opportunities for testing. Forty-one of these (58%) had been in contact with a health professional while infected, but before their diagnosis of HIV and 39/41 (95%) had a significant risk factor in their history that could have initiated an HIV test. Clinicians initiated testing for 43.5% of the patients, 11.3% were identified through contact tracing and only 28.7% were self referred for testing., Conclusions: Late diagnosis of HIV is common in the Australian Capital Territory and may have increased over time. Clinicians need to be aware of the sometimes-subtle manifestations of early and late HIV infection and have a lower threshold for HIV antibody testing.

Background: In the first year after childbirth, 94% of women experience one or more major health problems (urinary incontinence, faecal incontinence, perineal pain, back pain). Difficulties in intimate partner relationships and changes affecting sexual health are also common. The aim of this study is to investigate changes in women's health from early pregnancy until four years after the birth of a first child., Methods/design: The Maternal Health Study is a longitudinal study designed to fill in some of the gaps in current research evidence regarding women's physical and psychological health and recovery after childbirth. A prospective pregnancy cohort of >1500 nulliparous women has been recruited in early pregnancy at six metropolitan public hospitals in Melbourne, Australia between April 2003 and December 2005. In the first phase of the study participants are being followed up at 30-32 weeks gestation in pregnancy, and at three, six, nine, 12 and 18 months postpartum using a combination of self-administered questionnaires and telephone interviews. Women consenting to extended follow-up (phase 2) will be followed up six and 12 months after any subsequent births and when their first child is four years old. Study instruments incorporate assessment of the frequency and severity of urinary and bowel symptoms, sexual health issues, perineal and abdominal pain, depression and intimate partner violence. Pregnancy and birth outcome data will be obtained by review of hospital case notes., Discussion: Features of the study which distinguish it from prior research include: the capacity to identify incident cases of morbidity and clustering of health problems; a large enough sample to detect clinically important differences in maternal health outcomes associated with the method of birth; careful exposure measurement involving manual abstraction of data from medical records in order to explore mediating factors and possible causal pathways; and use of a variety of strategies to improve ascertainment of health outcomes.

The lung perfusion scans requested over a 5-year period for children with known congenital heart disease were reviewed retrospectively. Altogether, 102 lung perfusion scans were performed and comparable pulmonary arteriograms were available in 63 cases. There was agreement between scintigraphy and angiography in 50 (79%) cases and discrepancy in 13 (21%) cases. Scintigraphy was more sensitive in detecting small perfusion defects, particularly those seen only on oblique views. Pulmonary arteriography was more specific in identifying the cause of the perfusion abnormalities. The two techniques yield complementary information about lung perfusion. Perfusion scintigraphy is safe in children with congenital heart disease even with known pulmonary to systemic shunting. Many pitfalls could be avoided by careful choice of injection site, by knowledge of previous surgery and comparison with relevant angiograms.

Objectives: To determine the benefits of using a single venous catheter and a single angiogram during catheter occlusion of a patient arterial duct with the Rashkind double umbrella compared with those of venous and arterial catheters and multiple angiograms., Design: Retrospective review of case notes., Patients: 103 consecutive patients. The long sheath could not be advanced adequately in two patients. 101 patients had 104 implantations. Median (range) age was 35 (7-549) months and median (range) weight 13 (7-62) kg. Fifty four implantations were performed using the venous and arterial method and 50 using the venous only method., Results: Median procedure times (70 v 90 min), number of angiograms (one v four), and angiographic dye volume used (2 v 7 ml/kg) were significantly reduced using the venous only method compared with those of the venous and arterial method. There was no significant difference in fluoroscopy time (venous only 9 v venous and arterial 10 min)., Conclusions: Considerable improvements can be made in the technique of catheter closure of patent arterial ducts using the Rashkind double umbrella without compromising outcome using venous cannulation alone and a single angiogram, rather than venous and arterial cannulation and multiple angiograms. reduced risk to arteries from cannulation, The benefits are reduced radiation exposure, reduced risk to arteries from cannulation, shorter procedures, and lower equipment costs.