Systematic review of interventions for children with Fetal Alcohol Spectrum Disorders

<p>Abstract</p> <p>Background</p> <p>Children with Fetal Alcohol Spectrum Disorders (FASD) may have significant neurobehavioural problems persisting into adulthood. Early diagnosis may decrease the risk of adverse life outcomes. However, little is known about effective interventions for children with FASD. Our aim is to conduct a systematic review of the literature to identify and evaluate the evidence for pharmacological and non-pharmacological interventions for children with FASD.</p> <p>Methods</p> <p>We did an electronic search of the Cochrane Library, MEDLINE, EMBASE, PsychINFO, CINAHL and ERIC for clinical studies (Randomized controlled trials (RCT), quasi RCT, controlled trials and pre- and post-intervention studies) which evaluated pharmacological, behavioural, speech therapy, occupational therapy, physiotherapy, psychosocial and educational interventions and early intervention programs. Participants were aged under 18 years with a diagnosis of a FASD. Selection of studies for inclusion and assessment of study quality was undertaken independently by two reviewers. Meta-analysis was not possible due to diversity in the interventions and outcome measures.</p> <p>Results</p> <p>Twelve studies met the inclusion criteria. Methodological weaknesses were common, including small sample sizes; inadequate study design and short term follow up. Pharmacological interventions, evaluated in two studies (both RCT) showed some benefit from stimulant medications. Educational and learning strategies (three RCT) were evaluated in seven studies. There was some evidence to suggest that virtual reality training, cognitive control therapy, language and literacy therapy, mathematics intervention and rehearsal training for memory may be beneficial strategies. Three studies evaluating social communication and behavioural strategies (two RCT) suggested that social skills training may improve social skills and behaviour at home and Attention Process Training may improve attention.</p> <p>Conclusion</p> <p>There is limited good quality evidence for specific interventions for managing FASD, however seven randomized controlled trials that address specific functional deficits of children with FASD are underway or recently completed.</p

Combined Face-Brain Morphology and Associated Neurocognitive Correlates in Fetal Alcohol Spectrum Disorders

BACKGROUND: Since the 1970s, a range of facial, neurostructural, and neurocognitive adverse effects have been shown to be associated with prenatal alcohol exposure. Typically, these effects are studied individually and not in combination. Our objective is to improve the understanding of the teratogenic effects of prenatal alcohol exposure by simultaneously considering face-brain morphology and neurocognitive measures. METHODS: Participants were categorized as control (n = 47), fetal alcohol syndrome (FAS, n = 22), or heavily exposed (HE) prenatally, but not eligible for a FAS diagnosis (HE, n = 50). Structural brain MRI images and high-resolution 3D facial images were analyzed using dense surface models of features of the face and surface shape of the corpus callosum (CC) and caudate nucleus (CN). Asymmetry of the CN was evaluated for correlations with neurocognitive measures. RESULTS: (i) Facial growth delineations for FAS, HE, and controls are replicated for the CN and the CC. (ii) Concordance of clinical diagnosis and face-based control-FAS discrimination improves when the latter is combined with specific brain regions. In particular, midline facial regions discriminate better when combined with a midsagittal profile of the CC. (iii) A subset of HE individuals was identified with FAS-like CN dysmorphism. The average of this HE subset was FAS-like in its facial dysmorphism. (iv) Right-left asymmetry found in the CNs of controls is not apparent for FAS, is diminished for HE, and correlates with neurocognitive measures in the combined FAS and HE population. CONCLUSIONS: Shape analysis which combines facial regions with the CN, and with the CC, better identify those with FAS. CN asymmetry was reduced for FAS compared to controls and is strongly associated with general cognitive ability, verbal learning, and recall in those with prenatal alcohol exposure. This study further extends the brain-behavior relationships known to be vulnerable to alcohol teratogenesis

Imaging the Impact of Prenatal Alcohol Exposure on the Structure of the Developing Human Brain

Prenatal alcohol exposure has numerous effects on the developing brain, including damage to selective brain structure. We review structural magnetic resonance imaging (MRI) studies of brain abnormalities in subjects prenatally exposed to alcohol. The most common findings include reduced brain volume and malformations of the corpus callosum. Advanced methods have been able to detect shape, thickness and displacement changes throughout multiple brain regions. The teratogenic effects of alcohol appear to be widespread, affecting almost the entire brain. The only region that appears to be relatively spared is the occipital lobe. More recent studies have linked cognition to the underlying brain structure in alcohol-exposed subjects, and several report patterns in the severity of brain damage as it relates to facial dysmorphology or to extent of alcohol exposure. Future studies exploring relationships between brain structure, cognitive measures, dysmorphology, age, and other variables will be valuable for further comprehending the vast effects of prenatal alcohol exposure and for evaluating possible interventions

Natural coagulates for wastewater treatment; a review for application and mechanism

The increase of water demand and wastewater generation is among the global concerns in the world. The less effective management of water sources leads to serious consequences, the direct disposal of untreated wastewater is associated with the environmental pollution, elimination of aquatic life and the spread of deadly epidemics. The flocculation process is one of the most important stages in water and wastewater treatment plants, wherein this phase the plankton, colloidal particles, and pollutants are precipitated and removed. Two major types of coagulants are used in the flocculation process included the chemical and natural coagulants. Many studies have been performed to optimize the flocculation process while most of these studies have confirmed the hazardous effects of chemical coagulants utilization on the ecosystem. This chapter reviews a summary of the coagulation/flocculation processes using natural coagulants as well as reviews one of the most effective natural methods of water and wastewater treatment

Impact of in utero exposure to EtOH on corpus callosum development and paw preference in rats: protective effects of silymarin

BACKGROUND: Using a rat model we have found that the bioflavonoid silymarin (SY) ameliorates some of the negative consequences of in utero exposure to ethanol (EtOH). In the current study our aim was to determine if laterality preference and corpus callosum development were altered in rat offspring whose mothers were provided with a concomitant administration of SY with EtOH throughout gestation. METHODS: We provided pregnant Fisher/344 rats with liquid diets containing 35% ethanol derived calories (EDC) throughout the gestational period. A silymarin/phospholipid compound containing 29.8% silybin was co administered with EtOH to a separate experimental group. We tested the offspring for laterality preference at age 12 weeks. After testing the rats were sacrificed and their brains perfused for later corpus callosum extraction. RESULTS: We observed incomplete development of the splenium in the EtOH-only offspring. Callosal development was complete in all other treatment groups. Rats from the EtOH-only group displayed a left paw preference; whereas control rats were evenly divided between right and left paw preference. Inexplicably both SY groups were largely right paw preferring. CONCLUSIONS: The addition of SY to the EtOH liquid diet did confer some ameliorative effects upon the developing fetal rat brain

Imaging Mass Spectrometry Detection of Gangliosides Species in the Mouse Brain following Transient Focal Cerebral Ischemia and Long-Term Recovery

Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18∶1, d20∶1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury

Dietary and Behavioral Interventions Protect against Age Related Activation of Caspase Cascades in the Canine Brain

Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON – control environment/control diet, AOX– control environment/antioxidant diet, ENR – enriched environment/control diet, AOX/ENR– enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the first to show that lifestyle interventions can regulate caspase pathways in a higher animal model of aging