The presence of optical polarization anisotropies, such as Faraday or Kerr effects, linear birefringence, and magnetoelectric birefringence are evidence for broken symmetry states of matter. The ...recent discovery of a Kerr effect using near-IR light in the pseudogap phase of the cuprates can be regarded as a strong evidence for a spontaneous symmetry breaking and the existence of an anomalous long-range ordered state. In this work we present a high precision study of the polarimetry properties of the cuprates in the THz regime. While no Faraday effect was found in this frequency range to the limits of our experimental uncertainty (1.3 milli-radian or 0.07°), a small but significant polarization rotation was detected that derives from an anomalous linear dichroism. In YBa2Cu3Oy the effect has a temperature onset that mirrors the pseudogap temperature T* and is enhanced in magnitude in underdoped samples. In x=1/8 La2-xBaxCuO4, the effect onsets above room temperature, but shows a dramatic enhancement near a temperature scale known to be associated with spin- and charge-ordered states. These features are consistent with a loss of both C4 rotation and mirror symmetry in the electronic structure of the CuO2 planes in the pseudogap state.
Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking. Method Between 1999 and 2008 all pregnant ...Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy.
The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development β 0.24, 95% confidence interval (CI) 0.12-0.51, communication (β 0.20, 95% CI 0.01-0.39), externalizing behaviour (β 0.28, 95% CI 0.15-0.42), internalizing behaviour (β 0.14, 95% CI 0.01-0.28), and higher activity levels (β 0.24, 95% CI 0.11-0.38). Children exposed prenatally to short-term use of paracetamol (1-27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02-0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes.
Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age.
Abstract Hair analyses for exogenous compounds, specifically drugs of abuse, have been a useful tool in detecting long-term drug exposure. More recently, studies have delved into the exposure of ...endogenous compounds in hair. Cortisol is synthesized in the adrenal cortex in response to stress-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis. While catecholamines generally indicate acute stress, cortisol can be used as an indicator for sub-acute and chronic stress. Studies on the effects of chronic stress are most often subjective in nature, relying on questionnaires asking the participant to recall on past stressors. This can lead to the issue of recall and reporting bias. A new objective measure of chronic stress is needed for a more accurate understanding of the effects of chronic stress on the body. This review uses emerging evidence to describe the usefulness of hair analysis for cortisol and discusses the current methods used.
It is generally accepted that plants use the complex signaling system regulated by light and abscisic acid (ABA) signaling components to optimize growth and development in different situations. The ...role of ABA-light interactions is evident in the coupling of stress defense reactions with seed germination and root development, maintaining of stem cell identity and stem cell specification, stem elongation and leaf development, flowering and fruit formation, senescence, and shade avoidance. All these processes are regulated jointly by the ABA-light signaling system. Although a lot of work has been devoted to ABA-light signal interactions, there is still no systematic description of central signaling components and protein modules, which jointly regulate plant development. New data have emerged to promote understanding of how ABA and light signals are integrated at the molecular level, representing an extensively growing area of research. This work is intended to fill existing gaps by using literature data combined with bioinformatics analysis.
Despite extensive research efforts over decades, the teratogenic profile of valproic acid (VPA) remains obscure. We performed cumulative and conventional meta‐analyses of cohort studies to determine ...the time profiles of signal emergence of VPA‐associated congenital malformations (CMs) and to define risk estimates of each of the CMs. Fifty‐nine studies were identified and analyzed. We found that the significant risk signals began to emerge over the last 10–20 years even before large‐scale studies were performed: neural tube defect (the significant risk signal emerged in 1992); genitourinary and musculoskeletal anomalies (2004); cleft lip and/or palate (2005); and congenital heart defects (2006). At present, the risks of VPA‐associated CMs are 2–7‐fold higher than other common antiepileptic drugs. VPA should not be used as a first‐line therapy in women of childbearing age unless it is the only option for the patient.
Objective To examine the risk for persistent pulmonary hypertension of the newborn associated with antenatal exposure to antidepressants.Design Systematic review and meta-analysis.Data sources ...Embase, Medline, PsycINFO, and CINAHL from inception to 30 December 2012.Eligibility English language studies reporting persistent pulmonary hypertension of the newborn associated with exposure to antidepressants. Two independent reviewers extracted data and assessed the quality of each article.Results Of the 3077 abstracts reviewed, 738 papers were retrieved and seven included. All seven studies were above our quality threshold. Quantitative analysis was only possible for selective serotonin reuptake inhibitors (SSRIs). Although exposure to SSRIs in early pregnancy was not associated with persistent pulmonary hypertension of the newborn (odds ratio 1.23, 95% confidence interval 0.58 to 2.60; P=0.58), exposure in late pregnancy was (2.50, 1.32 to 4.73; P=0.005). Effects were not significant for any of the moderator variables examined, including study design, congenital malformations, and meconium aspiration. It was not possible to assess for the effect of caesarean section, body mass index, or preterm delivery. The absolute risk difference for development of persistent pulmonary hypertension of the newborn after exposure to SSRIs in late pregnancy was 2.9 to 3.5 per 1000 infants; therefore an estimated 286 to 351 women would need to be treated with an SSRI in late pregnancy to result in an average of one additional case of persistent pulmonary hypertension of the newborn.Conclusions The risk of persistent pulmonary hypertension of the newborn seems to be increased for infants exposed to SSRIs in late pregnancy, independent of the potential moderator variables examined. A significant relation for exposure to SSRIs in early pregnancy was not evident. Although the statistical association was significant, clinically the absolute risk of persistent pulmonary hypertension of the newborn remained low even in the context of late exposure to SSRIs.
Dual perfusion of a single placental lobule is the only experimental model to study human placental transfer of substances in organized placental tissue. To date, there has not been any attempt at a ...systematic evaluation of this model. The aim of this study was to systematically evaluate the perfusion model in predicting placental drug transfer and to develop a pharmacokinetic model to account for nonplacental pharmacokinetic parameters in the perfusion results. In general, the fetal‐to‐maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant. After modeling for differences in maternal and fetal/neonatal protein binding and blood pH, the perfusion results were able to accurately predict in vivo transfer at steady state (R2 = 0.85, P < 0.0001). Placental perfusion experiments can be used to predict placental drug transfer when adjusting for extra parameters and can be useful for assessing drug therapy risks and benefits in pregnancy.
Clinical Pharmacology & Therapeutics (2011) 90 1, 67–76. doi:10.1038/clpt.2011.66
A large number of women receive codeine for obstetric pain while breastfeeding. Following a case of fatal opioid poisoning in a breastfed neonate whose codeine prescribed mother was a CYP2D6 ...ultrarapid metabolizer (UM), we examined characteristics of mothers and infants with or without signs of central nervous system (CNS) depression following codeine exposure while breastfeeding in a case–control study. Mothers of symptomatic infants (n = 17) consumed a mean 59% higher codeine dose than mothers of asymptomatic infants (n = 55) (1.62 (0.79) mg/kg/day vs. 1.02 (0.54) mg/kg/day; P = 0.004). There was 71% concordance between maternal and neonatal CNS depression. Two mothers whose infants exhibited severe neonatal toxicity were CYP2D6 UMs and of the UGT2B7*2/*2 genotype. There may be a dose–response relationship between maternal codeine use and neonatal toxicity, and strong concordance between maternal‐infant CNS depressive symptoms. Breastfed infants of mothers who are CYP2D6 UMs combined with the UGT2B7*2/*2 are at increased risk of potentially life‐threatening CNS depression.
Clinical Pharmacology & Therapeutics (2008); 85, 1, 31–35 doi:10.1038/clpt.2008.157
The use of herbal medicines for health prevention and ailments is an increasing trend worldwide. Women in pregnancy are no exception; the reported prevalence of herbal medicine use in pregnancy ...ranges from 1 to 60 %. Despite a common perception of safety, herbal medicines may have potent pharmacological actions, and historically, have been used for this reason.
A multinational, cross-sectional study on how women treat disease and pregnancy-related health ailments was conducted between October 2011 and February 2012 in Europe, North America, and Australia. This study's primary aim was to evaluate and classify the herbal medicines used according to their safety in pregnancy and, secondly, to investigate risk factors associated with the use of contraindicated herbal medicines during pregnancy.
In total, 29.3 % of the women (n = 2673) reported the use of herbal medicines in pregnancy; of which we were able to identify 126 specific herbal medicines used by 2379 women (89.0 %). Twenty seven out of 126 herbal medicines were classified as contraindicated in pregnancy, and were used by 476 women (20.0 %). Twenty-eight were classified as safe for use in pregnancy and used by the largest number of women (n = 1128, 47.4 %). The greatest number was classified as requiring caution in pregnancy; these sixty herbal medicines were used by 751 women (31.6 %). Maternal factors associated with the use of contraindicated herbal medicines in pregnancy were found to be working in the home, having a university education, not using folic acid, and consuming alcohol. Interestingly, the recommendation to take a contraindicated herbal medicine was three times more likely to be from a healthcare practitioner (HCP) than an informal source.
Based on the current literature the majority of women in this study used an herbal medicine that was classified as safe for use in pregnancy. Women who reported taking a contraindicated herb were more likely to have been recommended it use by an HCP rather than informal source(s), indicating an urgent need for more education among HCPs. The paucity of human studies on herbal medicines safety in pregnancy stands in stark contrast to the widespread use of these products among pregnant women.
Background
Although the literature suggests that non‐steroidal anti‐inflammatory drugs (NSAIDs) are effective in controlling post‐operative pain in the paediatric population, physicians have been ...reluctant to utilise these medications after tonsillectomy due to concerns of increased bleeding rates. While many surgeons prescribe opioid analgesics postoperatively, these are associated with a number of potential adverse side‐effects including nausea, vomiting, constipation, excessive sedation and respiratory compromise.
Objective of review
To compare bleeding rates and severity between recipients of NSAIDs versus placebo or opioid analgesics for tonsillectomy.
Search strategy
Two authors independently searched electronic databases including PubMed, OVID, EMBASE and Cochrane Review from inception to July 2012. The keywords used included: Adenotonsillectomy, Tonsillectomy, Analgesia, Bleeding, Perioperative and Postoperative. These were then combined in various combinations with specific NSAIDs.
Evaluation method
A systematic review and meta‐analysis of all randomised control trials comparing bleeding rates and severity between NSAIDs versus placebo or opioids post‐tonsillectomy.
Results
A total of 36 studies met our inclusion criteria including 1747 children and 1446 adults. When all of the studies were combined in a meta‐analysis using the most severe outcome, there was no increased risk of bleeding in those using NSAIDs after tonsillectomy. Use of NSAIDs in general 1.30 (0.90–1.88) or in children 1.06 (0.65–1.74) was not associated with increased risk of bleeding in general, most severe bleeding, secondary haemorrhage, readmission or need of reoperation due to bleeding. Similarly, there was no increased bleeding risk for specific NSAIDs in adults. In the studies looking at paediatric subjects, the overall odds ratio of bleeding was even lower than in the general population and not significant. This result is based on 18 studies, six of which had zero outcomes in either treatment arm. Similar to the general population analysis, there was no significant difference in any of the subanalyses: bleeds treated with reoperation, readmission or bleeds in children that could be managed conservatively. There were also no significant differences in the subanalyses of individual NSAIDs. Similarly, there was no significant difference in rates of bleeding in the subanalysis of studies that gave NSAIDs multiple times, for instance, both before and after surgery.
Conclusions
These results suggest that NSAIDs can be considered as a safe method of analgesia among children undergoing tonsillectomy.
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