Assessing motor skills to inform a fetal alcohol spectrum disorder diagnosis focusing on persons older than 12 years: A systematic review of the literature

Background Motor impairments are one of the difficulties present in people prenatally exposed to alcohol, and are included in the diagnostic criteria for Fetal Alcohol Spectrum Disorder. Objectives The aim of this review was to examine the extent and common types of motor impairment present in persons aged over 12 years prenatally exposed to alcohol as evidence for determining the skills that should be assessed and addressed in intervention. Methods A systematic review of curren t evidence using various electronic databases was conducted. Studies were appraised using a recognized clinical appraisal tool. Results Seven studies published between 1998 and 2014 met the inclusion criteria. There is some evidence that difficulties with fine motor skills, visual motor integration, and balance skills persist in people who have been prenatally exposed to alcohol. Most studies did not focus on adolescent or adult participants in isolation, making it difficult to generalize results. Varied methodological designs made it difficult to compare studies as few used common standardized assessments. Conclusion A review of functional difficulties in each individual would be required to determine if a motor assessment is warranted. Further research is required using assessments recommended in diagnostic guidelines to determine the common motor difficulties seen in adolescents and adults

Comparative estrogenic activity of wine extracts and organochlorine pesticide residues in food.

The human diet contains industrial-derived, endocrine-active chemicals and higher levels of naturally occurring compounds that modulate multiple endocrine pathways. Hazard and risk assessment of these mixtures is complicated by noadditive interactions between different endocrine-mediated responses. This study focused on estrogenic chemicals in the diet and compared the relative potencies or estrogen equivalents (EQs) of the daily consumption of xenoestrogenic organochlorine pesticides in food (2.44 micrograms/day) with the EQs in a single 200-ml glass of red cabernet wine. The reconstituted organochlorine mixture contained 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, endosulfan-1, endosulfan-2, p,p'-methoxychlor, and toxaphene; the relative proportion of each chemical in the mixture resembled the composition reported in a recent U.S. Food and Drug Administration market basket survey. The following battery of in vitro 17 beta-estradiol (E2)-responsive bioassays were utilized in this study: competitive binding to mouse uterine estrogen receptor (ER); proliferation in T47D human breast cancer cells; luciferase (Luc) induction in human HepG2 cells transiently cotransfected with C3-Luc and the human ER, rat ER-alpha, or rat ER-beta; induction of chloramphenicol acetyltransferase (CAT) activity in MCF-7 human breast cancer cells transfected with E2-responsive cathepsin D-CAT or creatine kinase B-CAT plasmids. For these seven in vitro assays, the calculated EQs in extracts from 200 ml of red cabernet wine varied from 0.15 to 3.68 micrograms/day. In contrast, EQs for consumption of organochlorine pesticides (2.44 micrograms/day) varied from nondetectable to 1.24 ng/day. Based on results of the in vitro bioassays, organochlorine pesticides in food contribute minimally to dietary EQ intake

Secondary non-invasive prenatal screening for fetal trisomy: an effectiveness study in a public health setting.

OBJECTIVE: To evaluate the effectiveness of secondary screening using non-invasive prenatal testing (NIPT) in a routine NHS setting including test performance, turn-around times (TATs) and no-call (failure to obtain result) rates. To examine the influence of maternal and fetal characteristics on test performance. DESIGN: Retrospective cohort. SETTING: London teaching hospital. SAMPLE: A total of 8651 pregnancies undergoing screening for fetal trisomy using NIPT provided by an NHS cell-free DNA screening laboratory - the SAFE laboratory. METHODS: Screening test evaluation and TATs. Univariate and multivariate logistic regression analysis to identify significant predictors of no-call results and reported by low fetal fraction (40%) and processing failure. MAIN OUTCOME MEASURES: Test performance, TATs and no-call rates, factors affecting no-call results. RESULTS: Average TAT was 4.0 days (95% CI 4.0-4.2 days). Test sensitivities for trisomies 21 and 13/18 were 98.9% (95% CI 95.9-99.9%) and 90.4% (95% CI 80.0-96.8%), respectively. The overall no-call rate was 32/8651 (0.37%, 95% CI 0.26-0.52%). The overall risk of a no-call result was influenced by gestational age, dichorionic twin pregnancy, history of malignancy and pregnancies affected by trisomy 13/18, but not by maternal weight or use of low-molecular-weight heparin. CONCLUSIONS: High-throughput NIPT can be effectively embedded into a public health NHS setting. TATs of 4 days and no-calls of <0.5% were well within clinically desirable tolerances. Gestational age, maternal weight, assisted reproductive techniques, use of low-molecular-weight heparin and past history of malignancy did not have major impacts on test no-call rates and should not constitute reasons for withholding the option of NIPT from women. TWEETABLE ABSTRACT: Turn-around times of 4 days, no-call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS

Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases

<p>Abstract</p> <p>Background</p> <p>An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI). During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI.</p> <p>Methods</p> <p>Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors.</p> <p>Results</p> <p>Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness). However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified.</p> <p>Conclusions</p> <p>Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post-injection observation period.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID; URL: <url>http://http//www.clinicaltrials.gov/</url>: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.</p

Study protocol for screening and diagnosis of fetal alcohol spectrum disorders (FASD) among young people sentenced to detention in Western Australia

Introduction: Prenatal alcohol exposure can cause lifelong disability, including physical, cognitive and behavioural deficits, known as fetal alcohol spectrum disorders (FASD). Among individuals with FASD, engagement with justice services is common. Little is known about the prevalence of FASD among young people engaged with the Australian justice system. This study aims to establish FASD prevalence among sentenced young people in detention in Western Australia (WA), and use the findings to develop a screening tool for use among young people entering detention. Translation of these results will guide the management and support of young people in detention and will have significant implications on the lives of young people with FASD and the future of Australian youth justice services. Methods and analysis: Any sentenced young person in WA aged 10-17...years 11...months is eligible to participate. Young people are assessed for FASD by a multidisciplinary team. Standardised assessment tools refined for the Australian context are used, acknowledging the language and social complexities involved. Australian diagnostic guidelines for FASD will be applied. Information is obtained from young people, responsible adults, teachers and custodial officers. Individualised results and management plans for each young person are communicated to the young person and responsible adult. Prevalence of FASD will be reported and multivariate methods used to identify variables most predictive of FASD and to optimise the predictive value of screening. Ethics and dissemination: Approvals have been granted by the WA Aboriginal Health Ethics Committee, University of WA Human Research Ethics Committee, Department of Corrective Services, and Department for Child Protection and Family Support. Anonymised findings will be disseminated through peer-reviewed manuscripts, presentations and the media. Extensive consultation with stakeholders (including government agencies, detention centre staff, community service providers, the young people and their families or carers) will be ongoing until findings are disseminated and translated

Cover to Volume 3

The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth