Amniotic fluid brain-specific proteins are biomarkers for spinal cord injury in experimental myelomeningocele

Myelomeningocele (MMC), the most severe form of spina bifida (SB), causes neurological deficit. Injury to the spinal cord is thought to begin in utero. We investigated whether brain-specific proteins (BSPs) would enable us to monitor the development of MMC-related tissue damage during pregnancy in an animal model with naturally occurring SB (curly tail/loop tail mouse; n = 256). Amniotic fluid levels of neurofilament heavy chain (NfH), glial acidic fibrillary protein (GFAP) and S100B were measured by standard ELISA techniques. The amniotic fluid levels of all BSPs were similar in SB and control mice on embryonic day (E) 12.5 and 14.5, whereas a significant increase was observed for GFAP in SB mice on E16.5. Levels of all BSPs were significantly increased in SB mice on E18.5. The rapid increase in GFAP, paralleled by a moderate increase in NfH and S100B, suggests that spinal cord damage starts to accelerate around E16.5. The macroscopic size of the MMC was related to NfH level on E16.5 and E18.5, suggesting that axonal degeneration is most severe in large MMC. Amniotic fluid BSP measurements may provide important information for balancing the risks and benefits to mother and child of in utero surgery for MMC

Forecasting Techniques Applied To Water Quality Time Series In View Of Data Quality Assessment

The main advantage of continuous water quality measurement systems is the ability to capture dynamics in water and wastewater systems, which allows for the identification of critical events, the evaluation of impacts on receiving water bodies, the identification of cause and effect relationships and the ability to discern trends. However, the challenge associated with automatic monitoring systems is the collection of data with sufficient quality for the intended application. That is, useful monitoring is dependent on cautious data quality assessment. With particular attention to its practical implementation, this paper presents a method for data quality assessment that attempts to extract useful information from individual water quality measurement time series. Based on forecasting techniques that make use of the historical behavior of the data, raw measurements are evaluated for the detection of doubtful data and outliers. Posterior treatment is then applied to remove noise and detect potential sensor faults. The proposed tool has been successfully tested on water quality time series collected from different water and wastewater systems

Rho GTPases in mammalian spinal neural tube closure

Neural tube closure is an important morphogenetic event that involves dramatic reshaping of both neural and non-neural tissues. Rho GTPases are key cytoskeletal regulators involved in cell motility and in several developmental processes, and are thus expected to play pivotal roles in neurulation. Here, we discuss 2 recent studies that shed light on the roles of distinct Rho GTPases in different tissues during neurulation. RhoA plays an essential role in regulating actomyosin dynamics in the neural epithelium of the elevating neural folds, while Rac1 is required for the formation of cell protrusions in the non-neural surface ectoderm during neural fold fusion

Valproic acid disrupts the biomechanics of late spinal neural tube closure in mouse embryos

Failure of neural tube closure in the early embryo causes neural tube defects including spina bifida. Spina bifida lesions predominate in the distal spine, particularly after exposure to the anticonvulsant valproic acid (VPA). How VPA specifically disturbs late stages of neural tube closure is unclear, as neurulation is usually viewed as a uniform 'zippering' process along the spine. We recently identified a novel closure site ("Closure 5") which forms at the caudal extremity of the mouse posterior neuropore (PNP) when completion of closure is imminent. Here we investigated whether distal spina bifida in VPA-exposed embryos involves disruption of Closure 5. Exposure of E8.5 mouse embryos to VPA in whole embryo culture had marked embryotoxic effects, whereas toxic effects were less pronounced in more developmentally advanced (E9) embryos. Only 33% of embryos exposed to VPA from E9 to E10.5 achieved PNP closure (control=90%). Short-term (8h) VPA treatment diminished supra-cellular F-actin cables which normally run along the lateral neural folds, and prevented caudal PNP narrowing normally characteristic of Closure 5 formation. Laser ablation of Closure 5 caused rapid neuropore widening. Equivalent ablations of the caudal PNP in VPA treated embryos resulted in significantly less widening, suggesting VPA prevents formation of Closure 5 as a biomechanically active structure. Thus, VPA exposure prevents morphological and biomechanical conversion of the caudal extreme of the PNP during late spinal closure. Closure 5 facilitates neural fold apposition when completion of closure is imminent, such that its disruption in VPA-exposed embryos may lead to distal spina bifida

Adherence to Antibiotic Prophylaxis in Children with Vesicoureteral Reflux

Vesicoureteral reflux (VUR) affects approximately 1% of children and may predispose a child with a bladder infection to develop pyelonephritis and renal scarring. To prevent these potential sequelae, one accepted treatment option for VUR includes low-dose continuous antibiotic prophylaxis (CAP) to maintain urine sterility until the condition resolves. Despite the widespread use of CAP, little data exists regarding adherence to long-term antibiotic therapy. Not only will poor adherence to CAP potentially preclude the intended benefit, but also nonadherence with antibiotic regimens may carry untoward effects including unnecessary treatment changes for presumed antibiotic failure, emergence of resistant organisms, and compromised clinical trial outcomes. We present an overview of medication adherence in children with VUR, discuss possible consequences of nonadherence to antibiotic prophylaxis, and suggest ways to improve adherence. We raise awareness of issues related to nonadherence relevant to healthcare providers, investigators, and the community

Preparation for cancer care: perceptions of newly qualified health care professionals

The present paper is derived from a larger survey which examined the perceptions of recently qualified health care professionals’ experience on evidence-based practice, team working and cancer care. This study reports solely on the findings relating to cancer care. The perceptions of recently qualified professionals in relation to their initial educational input on issues such as confidence, anxiety, communication skills and practice in cancer care as well as adequacy of support, professional supervision and use of reflection were gathered using a cross-sectional postal survey design. A total of 50 graduates from each professional category in nursing, occupational therapy, physiotherapy, and social work were sampled yielding a total sample of 200. Eighty-five questionnaires were returned yielding a response rate of 43%. Twenty-eight (33%) respondents stated that they were currently involved in working with people with cancer. These were as follows: 5 nurses, 8 physiotherapists, 9 occupational therapists and 6 social workers. Despite the low response rate, the findings suggest that health care professionals’ educational input and experiences of working with people with cancer were overall positive; for example, in the respondents’ confidence, communication skills, decrease in anxiety and application of knowledge gained in classroom to professional practice. Moreover, most respondents learnt about caring for cancer patients through practice rather than classroom teaching. A high percentage (i.e. 64%;18) across all groups felt supported when caring for people with cancer and reported receiving professional supervision as well as being able to actively reflect on their practice. The implications for education and practice were discussed particularly as there have been few studies conducted in relation to the specific needs and collaborative learning of these health care professional groups

Neural tube closure: cellular, molecular and biomechanical mechanisms.

Neural tube closure has been studied for many decades, across a range of vertebrates, as a paradigm of embryonic morphogenesis. Neurulation is of particular interest in view of the severe congenital malformations - 'neural tube defects' - that result when closure fails. The process of neural tube closure is complex and involves cellular events such as convergent extension, apical constriction and interkinetic nuclear migration, as well as precise molecular control via the non-canonical Wnt/planar cell polarity pathway, Shh/BMP signalling, and the transcription factors Grhl2/3, Pax3, Cdx2 and Zic2. More recently, biomechanical inputs into neural tube morphogenesis have also been identified. Here, we review these cellular, molecular and biomechanical mechanisms involved in neural tube closure, based on studies of various vertebrate species, focusing on the most recent advances in the field

Novel mouse model of encephalocele: post-neurulation origin and relationship to open neural tube defects

Encephalocele is a clinically important birth defect that can lead to severe disability in childhood and beyond. The embryonic and early fetal pathogenesis of encephalocele is poorly understood and, while usually classified as a 'neural tube defect', there is conflicting evidence on whether encephalocele results from defective neural tube closure, or is a post-neurulation defect. It is also unclear whether encephalocele can result from the same causative factors as anencephaly and open spina bifida, or whether it is aetiologically distinct. This lack of information results largely from the scarce availability of animal models of encephalocele, particularly ones that resemble the commonest, non-syndromic human defects. Here, we report a novel mouse model of occipito-parietal encephalocele, in which the small GTPase Rac1 is conditionally ablated in the (non-neural) surface ectoderm. Most mutant fetuses have open spina bifida, and some also exhibit exencephaly/anencephaly. However, a proportion of mutant fetuses exhibit brain herniation, affecting the occipito-parietal region and closely resembling encephalocele. The encephalocele phenotype does not result from defective neural tube closure, but rather from a later disruption of the surface ectoderm covering the already closed neural tube, allowing the brain to herniate. The neuroepithelium itself shows no down-regulation of Rac1 and appears morphologically normal until late gestation. A large skull defect overlies the region of brain herniation. Our work provides a new genetic model of occipito-parietal encephalocele, particularly resembling non-syndromic human cases. While encephalocele has a different, later-arising pathogenesis than open neural tube defects, both can share the same genetic causation

European Non-native Species in Aquaculture Risk Analysis Scheme - a summary of assessment protocols and decision support tools for use of alien species in aquaculture

The European Non-native Species in Aquaculture Risk Analysis Scheme (ENSARS) was developed in response to European 'Council Regulation No. 708/2007 of 11 June 2007 concerning use of alien and locally absent species in aquaculture' to provide protocols for identifying and evaluating the potential risks of using non-native species in aquaculture. ENSARS is modular in structure and adapted from non-native species risk assessment schemes developed by the European and Mediterranean Plant Protection Organisation and for the UK. Seven of the eight ENSARS modules contain protocols for evaluating the risks of escape, introduction to and establishment in open waters, of any non-native aquatic organism being used (or associated with those used) in aquaculture, that is, transport pathways, rearing facilities, infectious agents, and the potential organism, ecosystem and socio-economic impacts. A concluding module is designed to summarise the risks and consider management options. During the assessments, each question requires the assessor to provide a response and confidence ranking for that response based on expert opinion. Each module can also be used individually, and each requires a specific form of expertise. Therefore, a multidisciplinary assessment team is recommended for its completion