The Study of the Epidemiology of Pediatric Hypertension Registry (SUPERHERO): Rationale and Methods.

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.

The impact of severe perinatal events on maternity care providers: a scoping review.

BACKGROUND: Severe events during the perinatal period can be experienced as traumatic by pregnant women, their partners or others who are closely involved. This includes maternity care providers who can be affected by being involved in or observing these events. This may have an impact on their personal well-being and professional practice, influencing quality of care. The aim of this study is to map research investigating the impact of severe events during the perinatal period on maternity care providers, and how these experiences affect their well-being and professional practice. METHOD: A scoping review following the manual of the Joanna Briggs Institute was undertaken. The electronic bibliographic databases included PubMed/MEDLINE, CINAHL, PsycINFO, PsycARTICLES, SocINDEX, Cochrane, Scopus, Web of Science and databases for grey literature. Records passing the two-stage screening process were assessed, and their reference lists hand searched. We included primary research papers that presented data from maternity care professionals on the impact of severe perinatal traumatic events. A descriptive content analysis and synthesis was undertaken. RESULTS: Following a detailed systematic search and screening of 1,611 records, 57 papers were included in the scoping review. Results of the analysis identified four categories, which highlighted the impact of traumatic perinatal events on maternity care providers, mainly midwives, obstetricians and nurses: Traumatic events, Impact of traumatic events on care providers, Changes in care providers' practice and Support for care providers; each including several subcategories. CONCLUSION: The impact of traumatic perinatal events on maternity care providers ranged from severe negative responses where care providers moved position or resigned from their employment in maternity care, to responses where they felt they became a better clinician. However, a substantial number appeared to be negatively affected by traumatic events without getting adequate support. Given the shortage of maternity staff and the importance of a sustainable workforce for effective maternity care, the impact of traumatic perinatal events requires serious consideration in maintaining their wellbeing and positive engagement when conducting their profession. Future research should explore which maternity care providers are mostly at risk for the impact of traumatic events and which interventions can contribute to prevention.

Data-Driven Implementation Strategy to Optimise Clinician Behaviour Change at Scale in Complex Clinical Environments: A Multicentre Emergency Care Study.

AIM: To develop an evidence-driven, behaviour change focused strategy to maximise implementation and uptake of HIRAID (History including Infection risk, Red flags, Assessment, Interventions, Diagnostics, communication and reassessment) in 30 Australian rural, regional and metropolitan emergency departments. DESIGN: An embedded, mixed-methods study. METHODS: This study is the first phase of a step-wedge cluster randomised control trial of HIRAID involving over 1300 emergency nurses. Concurrent quantitative and qualitative data were collected via an electronic survey sent to all nurses to identify preliminary barriers and enablers to HIRAID implementation. The survey was informed by the Theoretical Domains Framework, which is a synthesis of behavioural change theories that applies the science of intervention implementation in health care to effect change. Quantitative data were analysed using descriptive statistics and qualitative data with inductive content analysis. Data were then integrated to generate barriers and enablers to HIRAID implementation which were mapped to the Theoretical Domains Framework. Corresponding intervention functions and Behaviour Change techniques were selected and an overarching implementation strategy was developed through stakeholder consultation and application of the APEASE criteria (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects/safety and Equity). RESULTS: Six barriers to HIRAID implementation were identified by 670 respondents (response rate ~58%) representing all 30 sites: (i) lack of knowledge about HIRAID; (ii) high workload, (iii) lack of belief anything would change; (iv) not suitable for workplace; (v), uncertainty about what to do and (vi) lack of support or time for education. The three enablers were as follows: (i) willingness to learn and adopt something new; (ii) recognition of the need for something new and (iii) wanting to do what is best for patient care. The 10 corresponding domains were mapped to seven intervention functions, 21 behaviour change techniques and 45 mechanisms. The major components of the implementation strategy were a scaffolded education programme, clinical support and environmental modifications. CONCLUSIONS: A systematic process guided by the behaviour change wheel resulted in the generation of a multifaceted implementation strategy to implement HIRAID across rural, regional and metropolitan emergency departments. Implementation fidelity, reach and impact now require evaluation. IMPACT: HIRAID emergency nursing assessment framework reduced clinical deterioration relating to emergency care and improved self-confidence and documentation in emergency departments in pilot studies. Successful implementation of any intervention in the emergency department is notoriously difficult due to workload unpredictability, the undifferentiated nature of patients and high staff turnover. Key barriers and enablers were identified, and a successful implementation strategy was developed. This study uses theoretical frameworks to identify barriers and enablers to develop a data-driven, behavioural-focused implementation strategy to optimise the uptake of HIRAID in geographically diverse emergency departments which can be used to inform future implementation efforts involving emergency nurses. REPORTING METHOD: The CROSS reporting method (Supporting Information S3) was used to adhere to EQUATOR guidelines. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. TRIAL REGISTRATION: Australian New Zealand; Clinical Trials Registry (ANZCTR) number: ACTRN12621001456842, registered 25/10/2021.

Applying Sydney Triage to Admission Risk Tool (START) to improve patient flow in emergency departments: a multicentre randomised, implementation study.

BACKGROUND: To determine the effectiveness of applying the Sydney Triage to Admission Risk Tool (START) in conjunction with senior early assessment in different Emergency Departments (EDs). METHODS: This multicentre implementation study, conducted in two metropolitan EDs, used a convenience sample of ED patients. Patients who were admitted, after presenting to both EDs, and were assessed using the existing senior ED clinician assessment, were included in the study. Patients in the intervention group were assessed with the assistance of START, while patients in the control group were assessed without the assistance of START. Outcomes measured were ED length of stay and proportion of patients correctly identified as an in-patient admission by START. RESULTS: A total of 773 patients were evaluated using the START tool at triage across both sites (Intervention group n = 355 and control group n = 418 patients). The proportion of patients meeting the 4-hour length of stay thresholds was similar between the intervention and control groups (30.1% vs. 28.2%; p = 0.62). The intervention group was associated with a reduced ED length of stay when compared to the control group (351 min, interquartile range (IQR) 221.0-565.0 min versus 383 min, IQR 229.25-580.0 min; p = 0.85). When stratified into admitted and discharged patients, similar results were seen. CONCLUSION: In this extension of the START model of care implementation study in two metropolitan EDs, START, when used in conjunction with senior early assessment was associated with some reduced ED length of stay.

Instruments measuring practitioner performance of the complete examination and screening of neonates: A systematic review.

AIM: The complete examination and screening of the neonate is a recommended assessment of neonatal well-being conducted by appropriately trained medical, midwifery and nursing personnel at specific intervals during the first 6-week post-birth. Our aim was to identify and critically evaluate instruments that measure practitioner performance of this important assessment of neonatal health. METHODS: Using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology, a systematic review was undertaken. RESULTS: Four studies were identified as suitable for data extraction and analysis. This paper briefly describes the four instruments, discusses and compares the COSMIN analysis and ratings of each instrument. A recommendation for the instrument identified as the most suitable to measure practitioner performance is provided. CONCLUSION: Most instruments were designed by educators to measure the performance of practitioners developing competence in the complete examination and screening of the neonate. Further development and piloting of instruments designed to measure the performance and continuing competence of qualified practitioners of the newborn examination are required.

Responsible Inclusion of Pregnant Individuals in Eradicating HCV.

HCV infections have increased in recent years due to injection drug use and the opioid epidemic. Simultaneously, HCV cure has become a reality, with the advent of direct-acting antivirals (DAAs) and expansion of treatment programs. As a result, HCV screening recommendations now include all adults, including pregnant individuals; and many countries have endorsed widespread DAA access as a strategy to achieve HCV eradication. However, almost universally, pregnant individuals have been systematically excluded from HCV clinical research and treatment programs. This omission runs counter to public health strategies focused on elimination of HCV but is consistent with a historical pattern of exclusion of pregnant individuals from research. Our systematic review of publications on HCV treatment with DAAs in pregnancy revealed only one interventional study, which evaluated sofosbuvir/ledipasvir in 8 pregnant individuals. Given the paucity of research on this issue of great public health importance, we aimed to appraise the current landscape of HCV research/treatment and analyze the ethical considerations for responsibly including pregnant individuals. We propose that pregnancy may be an opportune time to offer HCV treatment given improved access, motivation, and other health care monitoring occurring in the antenatal period. Moreover, treatment of pregnant individuals may support the goal of eliminating perinatal HCV transmission and overcome the established challenges with transitioning care after delivery. The exclusion of pregnant individuals without justification denies them and their offspring access to potential health benefits, raising justice concerns considering growing data on DAA safety and global efforts to promote equitable and comprehensive HCV eradication. Finally, we propose a path forward for research and treatment programs during pregnancy to help advance the goal of HCV elimination.

Parents' experiences of care offered after stillbirth: An international online survey of high and middle-income countries.

BACKGROUND: Stillbirth, the death of a baby before birth, is associated with significant psychological and social consequences that can be mitigated by respectful and supportive bereavement care. The absence of high-level evidence to support the broad scope of perinatal bereavement practices means that offering a range of options identified as valued by parents has become an important indicator of care quality. This study aimed to describe bereavement care practices offered to parents across different high-income and middle-income countries. METHODS: An online survey of parents of stillborn babies was conducted between December 2014 and February 2015. Frequencies of nine practices were compared between high-income and middle-income countries. Differences in proportions of reported practices and their associated odds ratios were calculated to compare high-income and middle-income countries. RESULTS: Over three thousand parents (3041) with a self-reported stillbirth in the preceding five years from 40 countries responded. Fifteen countries had atleast 40 responses. Significant differences in the prevalence of offering nine bereavement care practices were reported by women in high-income countries (HICs) compared with women in middle-income countries (MICs). All nine practices were reported to occur significantly more frequently by women in HICs, including opportunity to see and hold their baby (OR = 4.8, 95% CI 4.0-5.9). The widespread occurrence of all nine practices was reported only for The Netherlands. CONCLUSIONS: Bereavement care after stillbirth varies between countries. Future research should look at why these differences occur, their impact on parents, and whether differences should be addressed, particularly how to support effective communication, decision-making, and follow-up care.

Midwives' experiences of caring for women's emotional and mental well-being during pregnancy.

AIMS AND OBJECTIVES: To explore midwives' experiences of caring for women's emotional and mental well-being during pregnancy. BACKGROUND: Transitioning to motherhood is a major life event for any woman and while it is a joyful experience for the majority, 15%-25% of women will experience a perinatal mental health problem. Providing psychological support to mothers by midwives is acknowledged internationally. The 2016 Irish National Maternity Strategy identifies midwives as being ideally placed to assess women's emotional needs. The research revealed a paucity of qualitative research from an Irish context in this area; therefore, this study addressed this gap in the literature. DESIGN: Qualitative descriptive design. METHODS: Semi-structured interviews were conducted with a purposive sample of 10 midwives recruited from the Irish midwifery e-group. Data were analysed using Burnard (Nurse Educ. Today, 11, 1991, 461) thematic content analysis. Transcripts were coded, and meanings were formulated to reflect significant statements, which were categorised. Categories were then evolved into subthemes, and eventually, three themes were emerged using the COREQ checklist. RESULTS: Three salient themes emerged from the data are as follows: 'awareness of Perinatal Mental Health', 'discussing emotional well-being' and 'the woman has something to divulge'. The themes convey the midwife's awareness, recognition and perceptions of mental well-being during pregnancy. How midwives discuss and assess emotional well-being, the observational skills they use, and what they perceive as the barriers and facilitators to discussing mental well-being were all identified. CONCLUSIONS: Midwives reported an awareness and acceptance that women's emotional health was as important as their physical health. Midwives used every antenatal opportunity to raise awareness about perinatal mental health, whilst also identifying key challenges in getting women to talk. RELEVANCE TO CLINICAL PRACTICE: Care pathways for assessing and identifying Perinatal Mental Health issues should be available in all maternity services. More support for midwives is required to debrief, which would assist them in supporting women's emotional well-being.

Interdisciplinary clinical debriefing in the emergency department: an observational study of learning topics and outcomes.

BACKGROUND: Defined as a 'guided reflective learning conversation', 'debriefing' is most often undertaken in small groups following healthcare simulation training. Clinical debriefing (CD) following experiences in the working environment has the potential to enhance learning and improve performance. METHODS: Prior to the study, a literature review was completed resulting in a standardised approach to CD that was used for training faculty. A pilot study of CD (n = 10) was then performed to derive a list of discussion topics and optimise the faculty training. The resulting debriefing approach was based on the "S.T.O.P." structure (Summarise the case; Things that went well; Opportunities for improvement; Points of action). A debriefing aid, with suggested scripting, was provided. A subsequent observational study assessed CD within 1-h of clinical events. 'Significantly distressing' or 'violent' events were excluded. Data was collected on participant characteristics, discussion topics, and team recommendations. Study forms were non-identifiable. Subsequent analysis was performed by two investigators using content analysis of the debriefing forms (n = 71). Discussion topics (learning points) were coded using a modified version of the Promoting Excellence and Reflective Learning in Simulation (PEARLS) framework. One month after completion of the study, ED management staff were surveyed for reports of "harm" as the result of CD. RESULTS: During the study period, 71 CDs were recorded with a total of 506 participants. Mean debriefing length was 10.93 min (SD 5.6). Mean attendance was 7.13 (SD 3.3) participants. CD topics discussed were divided into 'plus' (well-done) and 'delta' (need to improve) groupings. 232 plus domains were recorded of which 195 (84.1%) aligned with the PEARLS debriefing framework, suggesting simulation debriefing skills may be translatable to a clinical setting. Topics discussed outside the PEARLS framework included family issues, patient outcome and environmental factors. CD reports led to preventative interventions for equipment problems and to changes in existing protocols. There were no recorded incidents of participant harm resulting from CD. CONCLUSIONS: Topics discussed in CD predominantly aligned to those commonly observed in simulation-based medical education. Collective recommendations from CD can be used as evidence for improving existing protocols and models of care.

Simulation-based medical education can be used to improve the mental health competency of emergency physicians.

OBJECTIVE: We explored the feasibility of developing, running and evaluating a simulation-based medical education (SBME) workshop to improve the knowledge, skills and attitudes of emergency department (ED) doctors when called on to assess patients in psychiatric crisis. METHOD: We designed a four-hour workshop incorporating SBME and a blend of pre-reading, short didactic elements and multiple-choice questions (MCQs). Emergency department nurses (operating as SBME faculty) used prepared scripts to portray patients presenting in psychiatric crisis. They were interviewed in front of, and by, ED doctors. We collected structured course evaluations, Debriefing Assessment for Simulation in Healthcare (DASH) scores, and pre- and post-course MCQs. RESULTS: The pilot workshop was delivered to 12 ED registrars using only existing resources of the Psychiatry and Emergency Departments. Participants highly valued both 'level of appropriateness' (Likert rating µ = 4.8/5.0) and 'overall usefulness' (µ = 4.7/5.0) of the programme. They reported an improved understanding of the mental state and of relevant legal issues and rated the debriefings highly (participant DASH rating: n = 193; score µ = 6.3/7.0). Median MCQ scores improved non-significantly pre- and post-course (7.5/12 vs 10/12, p = 0.261). CONCLUSION: An SBME workshop with these aims could be delivered and evaluated using the existing resources of the Psychiatry and Emergency Departments.

Nondestructive Extraction and Identification of Microplastics from Freshwater Sport Fish Stomachs.

Microplastics were extracted from freshwater sport fish stomachs containing substantial biomass and identified using optical microscopy, scanning electron microscopy plus energy-dispersive X-ray spectroscopy (SEM/EDS), and Fourier transform infrared (FTIR) micro-spectroscopy with automated spectral mapping. An extraction method is presented that uses a negatively pressurized sieve stack and purified water to preserve plastic surface characteristics and any adsorbed persistent organic pollutants (POPs). This nondestructive extraction method for large predators' stomachs enables multiple trophic-level studies from one fish sampling event and provides other dietary and behavioral data. FTIR-identified microplastics 50-1500 µm, including polyethylene (two with plastic additive POPs), styrene acrylonitrile, polystyrene, and nylon and polyethylene terephthalate fibers 10-50 µm wide. SEM/EDS revealed characteristic surface weathering on the plastic surfaces. The nylon fibers appear to be from human fishing activities, suggesting options for management. Some particles visually identified as potential plastics were revealed by micro-spectroscopy to be mineralized, natural polyamide proteins, or nonplastic shell pieces. A low-cost, reflective sample preparation method with stable particle mounting was developed to enable automated mapping, improved FTIR throughput, and lower detection size limit. This study yielded 37 intact prey items set aside for future analyses.

Randomised controlled trial of simulation-based education for mechanical cardiopulmonary resuscitation training.

INTRODUCTION: Mechanical cardiopulmonary resuscitation (M-CPR) is increasingly used in the management of cardiac arrest. There are no previously reported randomised studies investigating M-CPR training. This study of newly trained M-CPR providers hypothesised that a brief simulation-based intervention after 4 months would improve M-CPR performance at 6 months. METHODS: This study used a simulated 'in situ' cardiac arrest model. The M-CPR device used was a proprietary Lund University Cardiac Assist System 3 machine (Physio Control, Redmond, Washington, USA). Standardised baseline training was provided to all participants. Following training, baseline performance was assessed. The primary outcome measure was the time taken to initiate M-CPR and the secondary outcome was performance against a checklist of errors. Participants were then randomised to intervention group (simulation training) or control group (routine clinical use of M-CPR). After 6 months the outcome measures were reassessed. Comparative statistical tests used an intention-to-treat analysis. RESULTS: 112 participants were enrolled. The intervention group (n=60) and control group (n=52) had similar demographic characteristics. At the 6-month assessment, median time to M-CPR initiation was 27.0 s (IQR 22.0-31.0) in the intervention group and 31.0 s (IQR 25.6-46.0) in the control group (p=0.003). The intervention group demonstrated fewer errors compared with controls at 6 months (p<0.001) CONCLUSION: In this randomised study of approaches to M-CPR training, providers receiving additional simulation-based training had higher retention levels of M-CPR skills. Therefore, when resuscitation skills are newly learnt, provision follow-up training should be an important consideration.

A model of neglect during postnatal life heightens obesity-induced hypertension and is linked to a greater metabolic compromise in female mice.

.: Exposure to early life stress (ELS) is associated with behavioral-related alterations, increases in body mass index and higher systolic blood pressure in humans. Postnatal maternal separation and early weaning (MSEW) is a mouse model of neglect characterized by a long-term dysregulation of the neuroendocrine system. OBJECTIVES: Given the contribution of adrenal-derived hormones to the development of obesity, we hypothesized that exposure to MSEW could contribute to  the worsening of cardiometabolic function in response to chronic high-fat diet (HF) feeding by promoting adipose tissue expansion and insulin resistance. SUBJECTS: MSEW was performed in C57BL/6 mice from postnatal days 2-16 and weaned at postnatal day 17. Undisturbed litters weaned at postnatal day 21 served as the control (C) group. At the weaning day, mice were placed on a low-fat diet (LF) or HF for 16 weeks. RESULTS: When fed a LF, male and female mice exposed to MSEW display similar body weight but increased fat mass compared to controls. However, when fed a HF, only female MSEW mice display increased body weight, fat mass, and adipocyte hypertrophy compared with controls. Also, female MSEW mice display evidence of an early onset of cardiometabolic risk factors, including hyperinsulinemia, glucose intolerance, and hypercholesterolemia. Yet, both male and female MSEW mice fed a HF show increased blood pressure compared with controls. CONCLUSIONS: This study shows that MSEW promotes a sex-specific dysregulation of the adipose tissue expansion and glucose homeostasis that precedes the development of obesity-induced hypertension.

Care prior to and during subsequent pregnancies following stillbirth for improving outcomes.

BACKGROUND: Stillbirth affects at least 2.6 million families worldwide every year and has enduring consequences for parents and health services. Parents entering a subsequent pregnancy following stillbirth face a risk of stillbirth recurrence, alongside increased risks of other adverse pregnancy outcomes and psychosocial challenges. These parents may benefit from a range of interventions to optimise their short- and longer-term medical health and psychosocial well-being. OBJECTIVES: To assess the effects of different interventions or models of care prior to and during subsequent pregnancies following stillbirth on maternal, fetal, neonatal and family health outcomes, and health service utilisation. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 June 2018), along with ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (18 June 2018). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-randomised controlled trials (qRCTs). Trials using a cluster-randomised design were eligible for inclusion, but we found no such reports. We included trials published as abstract only, provided sufficient information was available to allow assessment of trial eligibility and risk of bias. We excluded cross-over trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and undertook data extraction and 'Risk of bias' assessments. We extracted data from published reports, or sourced data directly from trialists. We checked the data for accuracy and resolved discrepancies by discussion or correspondence with trialists, or both. We conducted an assessment of the quality of the evidence using the GRADE approach. MAIN RESULTS: We included nine RCTs and one qRCT, and judged them to be at low to moderate risk of bias. Trials were carried out between the years 1964 and 2015 and took place predominantly in high-income countries in Europe. All trials assessed medical interventions; no trials assessed psychosocial interventions or incorporated psychosocial aspects of care. Trials evaluated the use of antiplatelet agents (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH), or both), third-party leukocyte immunisation, intravenous immunoglobulin, and progestogen. Trial participants were women who were either pregnant or attempting to conceive following a pregnancy loss, fetal death, or adverse outcome in a previous pregnancy.We extracted data for 222 women who had experienced a previous stillbirth of 20 weeks' gestation or more from the broader trial data sets, and included them in this review. Our GRADE assessments of the quality of evidence ranged from very low to low, due largely to serious imprecision in effect estimates as a result of small sample sizes, low numbers of events, and wide confidence intervals (CIs) crossing the line of no effect. Most of the analyses in this review were not sufficiently powered to detect differences in the outcomes assessed. The results presented are therefore largely uncertain.Main comparisonsLMWH versus no treatment/standard care (three RCTs, 123 women, depending on the outcome)It was uncertain whether LMWH reduced the risk of stillbirth (risk ratio (RR) 2.58, 95% CI 0.40 to 16.62; 3 trials; 122 participants; low-quality evidence), adverse perinatal outcome (RR 0.81, 95% CI 0.20 to 3.32; 2 trials; 77 participants; low-quality evidence), adverse maternal psychological effects (RR 1.00, 95% CI 0.07 to 14.90; 1 trial; 40 participants; very low-quality evidence), perinatal mortality (RR 2.58, 95% CI 0.40 to 16.62; 3 trials; 122 participants; low-quality evidence), or any preterm birth (< 37 weeks) (RR 1.01, 0.58 to 1.74; 3 trials; 114 participants; low-quality evidence). No neonatal deaths were reported in the trials assessed and no data were available for maternal-infant attachment. There was no clear evidence of a difference between the groups among the remaining secondary outcomes.LDA versus placebo (one RCT, 24 women)It was uncertain whether LDA reduced the risk of stillbirth (RR 0.85, 95% CI 0.06 to 12.01), neonatal death (RR 0.29, 95% CI 0.01 to 6.38), adverse perinatal outcome (RR 0.28, 95% CI 0.03 to 2.34), perinatal mortality, or any preterm birth (< 37 weeks) (both of the latter RR 0.42, 95% CI 0.04 to 4.06; all very low-quality evidence). No data were available for adverse maternal psychological effects or maternal-infant attachment. LDA appeared to be associated with an increase in birthweight (mean difference (MD) 790.00 g, 95% CI 295.03 to 1284.97 g) when compared to placebo, but this result was very unstable due to the extremely small sample size. Whether LDA has any effect on the remaining secondary outcomes was also uncertain.Other comparisonsLDA appeared to be associated with an increase in birthweight when compared to LDA + LMWH (MD -650.00 g, 95% CI -1210.33 to -89.67 g; 1 trial; 29 infants), as did third-party leukocyte immunisation when compared to placebo (MD 1195.00 g, 95% CI 273.35 to 2116.65 g; 1 trial, 4 infants), but these results were again very unstable due to extremely small sample sizes. The effects of the interventions on the remaining outcomes were also uncertain. AUTHORS' CONCLUSIONS: There is insufficient evidence in this review to inform clinical practice about the effectiveness of interventions to improve care prior to and during subsequent pregnancies following a stillbirth. There is a clear and urgent need for well-designed trials addressing this research question. The evaluation of medical interventions such as LDA, in the specific context of stillbirth prevention (and recurrent stillbirth prevention), is warranted. However, appropriate methodologies to evaluate such therapies need to be determined, particularly where clinical equipoise may be lacking. Careful trial design and multicentre collaboration is necessary to carry out trials that would be sufficiently large to detect differences in statistically rare outcomes such as stillbirth and neonatal death. The evaluation of psychosocial interventions addressing maternal-fetal attachment and parental anxiety and depression is also an urgent priority. In a randomised-trial context, such trials may allocate parents to different forms of support, to determine which have the greatest benefit with the least financial cost. Importantly, consistency in nomenclature and in data collection across all future trials (randomised and non-randomised) may be facilitated by a core outcomes data set for stillbirth research. All future trials should assess short- and longer-term psychosocial outcomes for parents and families, alongside economic costs of interventions.

Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress.

Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2-14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats (P < 0.05). Also, HFD increased plasma corticosterone (196 ± 51 vs. 79 ± 18 pg/ml, P < 0.05) and leptin levels (1.8 ± 0.4 vs. 1.3 ± 0.1 ng/ml, P < 0.05) in female MatSep compared with control rats, whereas insulin and adiponectin levels were similar between groups. Female control and MatSep offspring were treated with MTP (50 µg/g ip) 30 min before the daily separation. MTP treatment significantly attenuated diet-induced obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease.

Sex-specific effects of stress on metabolic and cardiovascular disease: are women at higher risk?

Cardiovascular disease (CVD) has traditionally been viewed as a male disease; however, the relative risk for obesity and hypertension morbidity and mortality, major risk factors for CVD, is higher for women in the United States. Emerging epidemiological data strongly support stressful experiences as a modifiable risk factor for obesity, insulin resistance, and heart disease in women at all ages. Therefore, primary prevention of these diseases may be associated with both identifying and increasing the knowledge regarding the sex differences in emotional functioning associated with physiological responses to stress. The purpose of this review is to highlight the growing body of clinical and experimental studies showing that stress, obesity-associated metabolic disturbances, and CVD comorbidities are more prevalent in females. Overall, this review reveals the need for investigations to decipher the early origins of these comorbidities. Targeting the sources of behavioral/emotional stress through the trajectory of life has the potential to reduce the alarming projected rates for chronic disease in women.

Occurrence, Distribution, and Fate of Organic UV Filters in Coral Communities.

Organic ultraviolet (UV) filters are widely used in personal care products and occur ubiquitously in the aquatic environment. In this study, concentrations of seven commonly used organic UV filters were determined in seawater, sediment and five coral species collected from the eastern Pearl River Estuary of South China Sea. Five compounds, benzophenone-1, -3, and -8 (BP-1, -3, and -8), octocrylene (OC) and octyl dimethyl-p-aminobenzoic acid (ODPABA), were detected in the coral tissues with the highest detection frequencies (>65%) and concentrations (31.8 ± 8.6 and 24.7 ± 10.6 ng/g ww, respectively) found for BP-3 and BP-8. Significantly higher concentrations of BP-3 were observed in coral tissues in the wet season, indicating that higher inputs of sunscreen agents could be attributed to the increased coastal recreational activities. Accumulation of UV filters was only observed in soft coral tissues with bioaccumulation factors (log10-values) ranging from 2.21 to 3.01. The results of a preliminary risk assessment indicated that over 20% of coral samples from the study sites contained BP-3 concentrations exceeding the threshold values for causing larval deformities and mortality in the worst-case scenario. Higher probabilities of negative impacts of BP-3 on coral communities are predicted to occur in wet season.

Profiling of Selected Functional Metabolites in the Central Nervous System of Marine Medaka (Oryzias melastigma) for Environmental Neurotoxicological Assessments.

The simultaneous profiling of 43 functional metabolites in the brain of the small model vertebrate organism, marine medaka (Oryzais melastigma), has been accomplished via dansyl chloride derivatization and LC-MS/MS quantification. This technique was applied to examine effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), one of the most abundant polybrominated diphenyl ether flame retardants in the natural environment, on the central nervous system (CNS) of vertebrates. The model teleosts were fed with bioencapsulated Artemia nauplii for up to 21 days. Multivariate statistical analysis has demonstrated that levels of numerous classical neurotransmitters and their metabolites in the CNS of the fish were perturbed even at the early phase of dietary exposure. Subsequent metabolic pathway analysis further implied potential impairment of the arginine and proline metabolism; glycine, serine and threonine metabolism; D-glutamine and D-glutamate metabolism; alanine, aspartate, and glutamate metabolism; valine, leucine, and isoleucine biosynthesis, and the cysteine and methionine metabolism in the brain of the test organism. Our results demonstrate that targeted profiling of functional metabolites in the CNS may shed light on how the various neurological pathways of vertebrates, including humans, are affected by toxicant/stress exposure.

Glucuronide and Sulfate Conjugates of Bisphenol A: Chemical Synthesis and Correlation Between Their Urinary Levels and Plasma Bisphenol A Content in Voluntary Human Donors.

Bisphenol A (BPA) glucuronide and sulfate conjugates are major products of Phase II metabolism of BPA in humans. In the past, their determination in body fluids usually involves tedious enzymatic hydrolysis and multiresidual analysis. The recent availability of authentic standards of these conjugates enables our better understand of the human metabolism of BPA and the distribution of their metabolites in body fluids. In this work, we report the chemical synthesis and purification of BPA mono- and di-glucuronide and BPA mono- and di-sulfate. Their levels, as well as that of BPA, in 140 paired human plasma and urine samples collected randomly from voluntary donors in Hong Kong SAR, China, were determined by solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). BPA was found in more than 135 human plasma and urine samples. Its Phase II metabolites, ranging from N.D. to 36.7 µg g-1-creatinine, also were detected in 139 of the 140 urine samples. Good correlation (r = 0.911) between molar concentration of BPA in the plasma and that of "total urinary BPA" (i.e., ln [(BPA + ∑ BPA phase II conjugate)molar concentration]) was observed. Direct quantification of Phase II metabolites of BPA in human urine can be a useful assessment tool for population exposure to this potent endocrine disrupting chemical.